WHO Model List of Essential Medicines
The WHO Model List of Essential Medicines is a periodically updated compendium published by the World Health Organization that identifies a limited set of pharmaceutical products deemed necessary for addressing priority health conditions in basic healthcare systems, emphasizing those with the highest efficacy, safety, and cost-effectiveness relative to available alternatives.[1] First issued in 1977 following recommendations from a WHO expert committee, the list distinguishes a core selection of minimum needs from complementary medicines requiring specialized facilities, and it now includes a separate pediatric version introduced in 2007.[2] The 24th adult list and 10th children's list, released in September 2025, encompass 523 and 374 medicines respectively, guiding procurement, pricing, and reimbursement policies in resource-constrained environments to prioritize rational drug use over expansive market availability.[3] By focusing on evidence-based criteria such as disease burden, comparative effectiveness, and population-level impact, the list has shaped national essential medicines policies in over 150 countries, contributing to improved access in low- and middle-income settings and reducing reliance on less essential or duplicative therapies.[4] Nonetheless, inclusions of certain high-cost biologics and analogues—such as short-acting insulin variants and GLP-1 agonists in the 2025 update—have drawn scrutiny for insufficient demonstration of superior outcomes over cheaper human insulins, potentially straining budgets without proportional health gains and highlighting tensions in balancing innovation with fiscal realism.00292-X/fulltext)[5]Background and History
Origins and establishment in 1977
The World Health Organization (WHO) established the Model List of Essential Medicines in response to widespread inefficiencies in pharmaceutical procurement and use, particularly in low-income countries during the 1970s, where limited budgets led to overemphasis on expensive or marginally effective drugs amid issues like irrational prescribing and inappropriate donations.[6][5] This initiative built on earlier WHO efforts to promote rational drug policies, aiming to prioritize a core set of medicines that addressed the most prevalent health needs with proven efficacy, safety, and affordability.[6] The concept challenged the prevailing view that all registered drugs were equally necessary, advocating instead for evidence-based selection to optimize resource allocation in basic health systems.[4] The foundational list emerged from the first meeting of the WHO Expert Committee on the Selection of Essential Drugs, convened in Geneva from October 17 to 21, 1977.[7] Comprising pharmacologists, clinicians, and public health experts, the committee evaluated medicines based on criteria including therapeutic value, population-level disease burden, and comparative cost-effectiveness, resulting in a model list of approximately 200 drugs covering essential categories such as analgesics, antibiotics, antimalarials, and vaccines.[6][8] Published as WHO Technical Report Series No. 615, the document emphasized that the list was not exhaustive but a flexible guide for national adaptation, intended to inform procurement, training, and regulatory decisions without restricting access to other beneficial therapies when feasible.[7] Upon release, the 1977 list was hailed as a "peaceful revolution" in international public health for shifting focus from market-driven abundance to prioritized essentials, though it drew criticism from pharmaceutical interests concerned about reduced demand for non-listed products.[5][9] By formalizing the principle that a limited, rationally selected formulary could meet most priority needs, it laid the groundwork for subsequent global adoption, with over a dozen countries developing their own lists within years.[10] The establishment marked WHO's proactive role in countering inequities in drug access, grounded in empirical assessments of health priorities rather than commercial imperatives.[6]Key milestones and periodic updates
The inaugural WHO Model List of Essential Medicines was published in 1977, comprising 208 pharmaceutical products selected for their efficacy, safety, and relevance to priority health conditions in resource-limited settings.[6] This list represented a foundational policy tool, promoting the rational selection of a core set of medicines over expansive formularies to enhance accessibility and cost control in primary health care.[6] A pivotal development occurred in 2007 with the release of the first Model List of Essential Medicines for Children, which addressed formulation gaps and dosing requirements specific to pediatric populations, expanding the framework beyond adult-centric selections.[2] By that year, the 15th adult list had grown to 340 medicines, reflecting incremental additions driven by emerging clinical evidence and global health priorities.[11] The lists undergo biennial revisions through the WHO Expert Committee on Selection and Use of Essential Medicines, incorporating peer-reviewed data on therapeutic value, population impact, and comparative effectiveness to add, remove, or reclassify items.[2] This schedule ensures responsiveness to advances in pharmacology and epidemiology, with the 23rd adult list and 9th children's list issued in 2023, followed by the 24th adult list and 10th children's list on September 5, 2025, which integrated treatments for conditions including certain cancers, diabetes, and antimicrobial resistance.[3] Over nearly five decades, the core adult list has expanded from under 200 items to 523 medicines by 2025, underscoring evolving evidence bases while maintaining focus on minimum needs for basic systems.[12]Developments leading to the 24th edition (2025)
The 25th WHO Expert Committee on the Selection and Use of Essential Medicines convened from May 5 to 9, 2025, at WHO headquarters in Geneva, Switzerland, to review applications for updates to the Model Lists following the 23rd edition published in July 2023.[12][13] The committee evaluated submissions based on criteria including public health relevance, comparative efficacy, safety profiles, and comparative cost-effectiveness, prioritizing medicines addressing prevalent conditions in low- and middle-income countries.[14] An open session on May 5 allowed stakeholder input, including from industry groups like the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), which emphasized the role of innovative therapies in transforming disease management.[15] Applications focused on emerging needs in noncommunicable diseases (NCDs), with seven submissions for oncology medicines, including immune checkpoint inhibitors for cancers such as breast, lung, and colorectal types.[16] Additional proposals targeted diabetes and obesity management, cystic fibrosis, hemophilia, mental health, and preventive therapies like cytisine for tobacco cessation and therapeutic sunscreens for albinism-related skin cancer risk.[3][17] Advocacy efforts, such as those by the World Federation of Hemophilia for emicizumab and the Union for International Cancer Control for targeted cancer agents, influenced reviews by highlighting evidence from clinical trials demonstrating superior outcomes over existing options.[17][16] The committee recommended 20 additions to the adult list (16 core, 4 complementary) and 15 to the children's list, incorporating therapies like GLP-1 receptor agonists (e.g., semaglutide) for type 2 diabetes and obesity, elexacaftor/tezacaftor/ivacaftor (Trikafta) for cystic fibrosis, and rapid-acting insulins, expanding totals to 523 adult and 374 pediatric medicines.[18][19] These changes reflected growing global burdens of NCDs, with diabetes affecting over 500 million adults and obesity tripling since 1975, alongside new trial data supporting efficacy in diverse populations.[3] However, inclusions of high-cost biologics and injectables drew critique for potentially straining procurement budgets in resource-poor settings, where annual prices for GLP-1 agents can exceed $10,000, raising questions about alignment with the list's foundational emphasis on affordable basics.00292-X/fulltext)00292-X/fulltext) The updated 24th Model List and 10th children's list were published on September 5, 2025, in the committee's report, aiming to guide national essential medicines policies amid rising demands for equitable access to evidence-based innovations.[20]Purpose and Global Role
Objectives for basic health systems
The WHO Model List of Essential Medicines establishes objectives centered on equipping basic health systems—typically primary care facilities in resource-constrained settings—with a minimal, prioritized set of pharmaceuticals to address prevalent diseases and public health priorities. The core list specifically delineates the minimum medicine requirements for such systems, emphasizing the most efficacious, safe, and cost-effective options for priority conditions like infectious diseases, maternal and child health issues, and basic palliative care needs.[21] This approach ensures that even under-resourced infrastructures can deliver targeted interventions without diverting limited budgets to less essential or redundant therapies.[6] A primary objective is to promote uninterrupted availability of these medicines in adequate quantities, appropriate dosage forms, and assured quality at the point of care, thereby enabling basic health systems to maintain operational continuity and respond effectively to routine and epidemic threats.[21] Affordability forms another cornerstone, with selections prioritizing options that impose minimal financial strain on individuals, communities, and public budgets, facilitating sustainable procurement and equitable access in low-income contexts.[6] By focusing on evidence of clinical benefits relative to harms and costs, the list supports rational prescribing practices, reducing overuse or misuse that could strain supply chains in primary facilities.[2] These objectives align with broader goals of strengthening basic health systems' capacity to achieve population-level health gains, such as lowering mortality from treatable conditions through standardized protocols for conditions like malaria, tuberculosis, and essential surgeries.[6] The list's biennial updates incorporate epidemiological shifts and new evidence, ensuring relevance to evolving burdens in basic care environments, while encouraging national adaptations to local disease profiles without expanding beyond core essentials.[21] Over 150 countries have drawn from the model to formulate their own lists, which in turn guide procurement policies that prioritize these fundamentals, thereby enhancing system resilience and efficiency.[6]Influence on national policies and procurement
Over 150 countries have developed national essential medicines lists modeled on the WHO Model List, adapting its core selections to local disease burdens, healthcare capacities, and resource constraints.[6] This adaptation process informs national drug policies by prioritizing medicines that address prevalent public health needs, such as infectious diseases in low- and middle-income countries (LMICs), thereby shaping formularies for public health systems.[22] For instance, national committees in these countries review WHO recommendations biennially, incorporating epidemiological data and cost analyses to refine selections, which has led to more than 137 documented national lists aligned with WHO criteria as of recent assessments.[2] The Model List exerts direct influence on procurement strategies by serving as a benchmark for public sector purchasing, enabling governments to focus budgets on a limited set of high-impact, cost-effective drugs rather than expansive inventories.[6] In LMICs, where medicines constitute 20–60% of total health expenditures, this guidance facilitates bulk procurement mechanisms, price negotiations with suppliers, and integration into supply chains, reducing waste and enhancing availability of essentials like antimalarials and antibiotics.[6] Evidence from implementation studies indicates that countries aligning procurement with the Model List achieve higher tracer medicine availability in facilities, though challenges persist due to funding shortfalls and supply disruptions.[22] On the policy front, the List underpins reimbursement schemes, insurance coverage, and regulatory frameworks by endorsing evidence-based prioritization, which discourages inclusion of marginally beneficial or high-cost alternatives without proven population-level gains.[6] This has promoted rational use policies in adopting nations, correlating with improved access to priority treatments amid fiscal pressures, as seen in global surveys where Model List-aligned policies correlate with sustained essential drug stocks despite economic variability.[23] However, adoption varies, with some countries facing barriers from pharmaceutical industry lobbying or outdated national reviews, underscoring the List's role as an aspirational rather than mandatory standard.[22]Selection Process and Governance
Role of the WHO Expert Committee
The WHO Expert Committee on the Selection and Use of Essential Medicines serves as the primary advisory body responsible for recommending updates to the Model List of Essential Medicines (EML) and the Model List of Essential Medicines for Children (EMLc). Convened by the World Health Organization (WHO), the committee evaluates proposed additions, amendments, or deletions to ensure the lists prioritize medicines that address public health needs with optimal efficacy, safety, and value. Its recommendations guide the WHO Director-General in finalizing the biennial updates, which are then disseminated as normative tools for global health systems.[14] Committee members, typically numbering 8 to 20 individuals, are selected from WHO's Expert Advisory Panels on drug evaluation, essential medicines, and related fields, emphasizing professional expertise in pharmacology, clinical therapeutics, public health, and pharmacoeconomics. Selection prioritizes independence, geographical representation across WHO regions, gender balance, and coverage of varying income levels to mitigate potential biases in decision-making. Members undergo declaration of interests to maintain objectivity, though analyses have noted variability in expertise depth across committees, with calls for greater scrutiny of academic and institutional affiliations that could influence priorities toward certain therapeutic areas.[14][24][25] The committee convenes every two years, reviewing applications submitted by WHO departments, member states, professional organizations, and other stakeholders for medicines meeting essentiality criteria. Prior to meetings, WHO secretariats and subgroups conduct preliminary assessments of submitted evidence, including systematic reviews of clinical trials, comparative effectiveness data, and pharmacovigilance reports. During sessions, such as the 24th meeting in 2025 which evaluated 59 applications, the committee deliberates on public health relevance—factoring in disease prevalence and population impact—alongside rigorous evidence of superior efficacy and safety profiles relative to existing options, and comparative cost-effectiveness for resource-limited settings.[2][12][14] Outcomes include prioritized inclusions for high-burden conditions, deletions of obsolete or inferior agents, and annotations specifying formulations, strengths, or usage guidelines. For instance, recommendations emphasize medicines with strong evidence from randomized controlled trials and real-world data, rejecting those lacking robust comparative studies or where benefits do not justify costs at scale. These evidence-based judgments aim to promote rational use and access, though critics argue that evolving applicant influences—often from pharmaceutical entities or advocacy groups—may skew toward newer, patented drugs over generics, potentially undermining cost priorities in low-income contexts. The committee's reports, published post-meeting, detail rationales and underpin national essential medicines lists in over 150 countries.[26][25]00292-X/fulltext)Application submissions and review procedures
Applications for inclusion, deletion, or modification of medicines on the WHO Model List of Essential Medicines are submitted by interested parties, including WHO departments, academic institutions, public health organizations, and pharmaceutical entities, to the EML Secretariat via email in PDF and Word formats.[24][27] Submissions must adhere to mandatory guidelines specifying required evidence on public health relevance, efficacy, safety, and comparative cost-effectiveness, with detailed formats for new medicines or new indications of existing ones.[28] Application calls occur biennially ahead of Expert Committee meetings; for the 2025 update (25th meeting, 5-9 May 2025), the period opened on 9 May 2024 with a deadline of 1 November 2024 at 18:00 UTC.[27] Upon receipt, the WHO Secretariat reviews submissions for completeness and prepares dossiers, often making application data and reviews publicly available to allow input from interested parties.[25] The independent, multidisciplinary WHO Expert Committee on Selection and Use of Essential Medicines then evaluates applications during its closed sessions, drawing on submitted evidence, external expert reviews where needed, and committee deliberations to assess alignment with selection criteria.[29][30] An open session precedes the meeting for stakeholder statements, promoting transparency, though final decisions remain evidence-based and insulated from direct advocacy.[15] The Committee issues non-binding recommendations to the WHO Director-General, who approves the updated lists for publication, typically incorporating only a fraction of applications based on rigorous evidentiary thresholds; for instance, not all submitted cancer medicines were recommended in recent cycles due to insufficient comparative data.[29][31] This process ensures decisions prioritize population-level impact over individual or commercial interests, with historical analyses noting that applicant-driven priorities may not always reflect global disease burdens, prompting periodic procedural reviews.[32]Criteria for Essentiality
Evidence-based evaluation of efficacy and safety
The WHO Expert Committee on the Selection and Use of Essential Medicines evaluates medicines for inclusion based on scientific evidence of comparative efficacy, meaning demonstrated therapeutic benefits relative to existing treatments or placebo, typically derived from randomized controlled trials, systematic reviews, or meta-analyses where available.[26] This assessment prioritizes outcomes such as mortality reduction, symptom relief, or disease progression halt, with insufficient evidence from observational studies alone often leading to rejection.[29] For instance, applications must submit data showing statistically significant improvements in clinically relevant endpoints, adjusted for population-specific factors like disease prevalence in low-resource settings.[6] Safety evaluation focuses on the risk-benefit ratio, incorporating pharmacovigilance data on adverse events, drug interactions, and contraindications, with emphasis on real-world tolerability in diverse populations including children, pregnant individuals, and those with comorbidities.[26] Medicines with high rates of severe side effects, such as organ toxicity or dependency risks exceeding benefits, are excluded unless no superior alternatives exist; for example, the committee has rejected proposals lacking long-term safety data from post-marketing surveillance.[29] Comparative safety is scrutinized against standard-of-care options, favoring agents with lower incidence of harms like antimicrobial resistance or hypersensitivity reactions.[25] The process requires applicants—often WHO departments, academic groups, or professional societies—to provide comprehensive dossiers with peer-reviewed evidence, graded by quality using tools akin to GRADE (Grading of Recommendations Assessment, Development and Evaluation), though the committee applies independent scrutiny to mitigate biases in submitted studies.[14] Rejections frequently cite inadequate comparative data, as seen in analyses of non-recommended applications where over 40% failed due to insufficient efficacy or safety proof against comparators.[29] This evidence threshold ensures selections align with causal mechanisms supported by empirical outcomes rather than surrogate markers alone, though for priority public health needs like pandemics, expedited reviews may incorporate emerging data with caveats on uncertainty.[26]Cost-effectiveness and population-level impact
The selection criteria for medicines on the WHO Model List of Essential Medicines (EML) incorporate comparative cost-effectiveness, evaluated through evidence of efficacy relative to cost, public health relevance, and affordability, particularly for resource-limited settings where medicines constitute 20–60% of total health expenditures.[6][33] This approach favors generics and off-patent drugs with established production costs far below market prices in many cases, enabling national procurement policies to prioritize high-value interventions over more expensive alternatives.[34] Empirical analyses of EML implementation demonstrate cost reductions by restricting formularies to essential items; in a resource-constrained district hospital in India, annual medicine spending totaled approximately USD 416,000, with anti-infectives accounting for 40.7%—primarily cost-effective antiretrovirals and antibiotics—while limiting procurement to 21 high-impact drugs that comprised half the budget, thereby curbing waste on less essential options.[33] Broader adoption guides pricing regulations and tendering, as seen in over 150 countries' national lists, which align procurement with EML recommendations to lower unit costs through bulk generic sourcing.[6] Population-level impacts arise from targeting medicines for prevalent conditions with substantial morbidity burdens, such as infectious diseases and cardiovascular disorders, where expanded essential lists correlate with improved access and potential mortality reductions—though causality is confounded by concurrent health system factors like infrastructure.[35] For cardiovascular disease, countries listing more EML-aligned medicines exhibit associations with lower age-standardized mortality rates, reflecting enhanced treatment coverage for priority needs.[35] Overall, EML-guided policies promote rational prescribing and availability, averting untreated cases in high-prevalence settings, but realization depends on national adaptation, with persistent gaps in affordability for newer inclusions despite cost-effectiveness thresholds.[6][22]Structure and Features of the List
Core list versus complementary list
The WHO Model List of Essential Medicines divides its entries into a core list and a complementary list to distinguish between pharmaceuticals suitable for basic versus advanced health systems. The core list specifies the minimum medicine needs for a basic health-care system, encompassing the most efficacious, safe, and cost-effective agents for priority conditions essential to primary care delivery.[21] This categorization prioritizes accessibility in resource-limited settings, focusing on interventions that can be administered with standard facilities and trained personnel.[21] The complementary list, by contrast, enumerates essential medicines for priority diseases where specialized diagnostic or monitoring facilities, and/or specialist medical care or training, are required for safe and effective use.[36] It includes higher-cost alternatives to core list items or treatments for conditions demanding advanced infrastructure, such as certain oncology or infectious disease therapies.[21] In instances of uncertainty regarding a medicine's fit for basic systems, the WHO Expert Committee defaults to complementary listing to avoid overburdening primary care while ensuring availability in capable settings.[36] This dual structure facilitates graduated implementation: countries with rudimentary health infrastructures emphasize the core list for procurement and policy, while those with developed systems integrate complementary items to address complex pathologies.[2] The 23rd edition, published in July 2023, exemplifies this by listing 78 core medicines across 30 therapeutic categories and 44 complementary entries, reflecting evidence-based prioritization without mandating universal adoption.[21] National lists adapt these models, often retaining the core-complementary distinction to balance equity and capability.[2]Separate children's formulary
The WHO Model List of Essential Medicines for Children (EMLc) constitutes a distinct formulary within the broader essential medicines framework, specifically designed to prioritize pharmaceuticals suitable for individuals under 12 years of age. Unlike the adult-oriented Model List of Essential Medicines (EML), the EMLc emphasizes formulations that account for pediatric physiological differences, such as immature organ systems, variable pharmacokinetics, and the necessity for palatable, easy-to-administer dosage forms like oral liquids, dispersible tablets, and suppositories. This separation recognizes that adult medicines often prove inadequate or unsafe for children due to challenges in dosing accuracy, swallowing difficulties, and taste acceptability, which can compromise treatment adherence and efficacy.[2][37] Initiated in 2007 following recognition of persistent gaps in child-specific drug availability—despite the adult EML's existence since 1977—the EMLc was developed to rectify underrepresentation of pediatric needs in global health procurement and policy. Prior to its establishment, children comprised a disproportionate burden of disease in low- and middle-income countries, yet suitable formulations were scarce, leading to off-label use of adult products or improvised preparations with risks of dosing errors and toxicity. The inaugural EMLc included approximately 250 medicines, focusing on high-burden conditions like infectious diseases, malnutrition, and neonatal care, and has since expanded to address emerging priorities such as antimicrobial resistance and non-communicable diseases in youth. Biennial updates by the WHO Expert Committee ensure alignment with evolving evidence, with the 10th edition, released in September 2025, encompassing 374 entries across core and complementary categories.[2][38][12] Selection for the EMLc adheres to the same foundational criteria as the adult list—public health relevance, proven efficacy, safety profile, and cost-effectiveness—but incorporates child-specific evaluations, including bioavailability in immature metabolism, excipient safety to avoid allergens or irritants, and stability in pediatric delivery systems. Applications must demonstrate comparative advantages over existing options, with priority given to single-dose or fixed-dose combinations that minimize administration errors in resource-limited settings. For instance, the list specifies dispersible zinc tablets for diarrhea management in infants, reflecting evidence that such forms enhance absorption and compliance over crushed adult tablets. Where data gaps persist, particularly for neonates or rare pediatric conditions, the committee relies on extrapolated adult trials supplemented by pharmacokinetic studies, though this approach has drawn scrutiny for potential underestimation of age-related variances. The EMLc also differentiates core items (prioritized for basic health systems) from complementary ones (requiring specialized diagnostics or facilities), aiding targeted procurement.[39][40] Empirical data underscore the EMLc's role in influencing national pediatric formularies, though implementation varies; as of 2025, only a minority of countries' essential lists explicitly mandate child-appropriate formulations, potentially perpetuating access barriers. Analyses indicate that adherence to EMLc recommendations correlates with reduced child mortality from treatable conditions, such as pneumonia and malaria, by facilitating bulk procurement of affordable generics. Nonetheless, ongoing challenges include limited innovation in pediatric drug development, with many inclusions relying on older, off-patent molecules due to manufacturers' reluctance to invest in low-volume child markets. The WHO continues to advocate for research into priority gaps, such as improved antimalarials for infants, to enhance the list's causal impact on global child health outcomes.[41][42]Annotation systems and recommendations
The WHO Model List of Essential Medicines employs annotation systems to convey nuanced guidance on selection, equivalence, and usage constraints, enabling adaptation by national authorities while maintaining evidence-based priorities. A primary annotation is the square box symbol (□), which identifies a listed medicine as representative of a pharmacological class where therapeutically equivalent alternatives exist, allowing substitution based on local availability, pricing, or regulatory factors without loss of clinical performance.[36][43] This system, implemented since 1983, promotes procurement efficiency by emphasizing class-level interchangeability over specific agents, provided equivalence is demonstrated through comparative data on efficacy and safety.[44] The complementary list, presented separately from the core list, annotates medicines essential for priority conditions requiring specialized diagnostic, monitoring, or therapeutic infrastructure, such as advanced cancer care or complex infections. These annotations underscore that inclusion does not imply routine availability in primary facilities but rather targeted deployment where expertise exists, reflecting assessments of population-level need balanced against resource demands.[36] In the 24th list (2025), specific superscripts like 'a' denote age or weight restrictions on use, with detailed criteria outlined in appended tables to guide pediatric or vulnerable population applications.[45] Recommendations within the list derive from the WHO Expert Committee's biennial reviews, which evaluate submissions against criteria including comparative effectiveness, safety profiles from randomized trials, and cost-effectiveness metrics like incremental cost-effectiveness ratios.[21] Annotations often incorporate committee rationales, such as notes on formulation preferences or monitoring requirements, to signal evidence gaps—ensuring inclusions prioritize medicines with robust data over those with preliminary or context-specific support. For instance, square box usage has evolved to address heterogeneous applications, with periodic reviews clarifying its role in avoiding over-restriction of viable equivalents.[43] This framework supports causal prioritization of interventions demonstrably reducing morbidity and mortality at scale, without formal graded scales but through explicit evidentiary commentary.Anaesthetics, Preoperative Medicines, and Medical Gases
General anaesthetics, oxygen, and related inhalational/injectable options
In the WHO Model List of Essential Medicines, the subcategory of general anaesthetics, oxygen, and related inhalational or injectable options encompasses agents critical for inducing and maintaining reversible loss of consciousness and analgesia during surgical procedures, as well as oxygen for perioperative oxygenation and emergency resuscitation. These selections prioritize agents with established efficacy in diverse clinical settings, favorable safety profiles relative to alternatives, and feasibility for use in resource-limited environments where advanced monitoring may be unavailable.[21] The 24th list, updated in September 2025, reflects evidence-based refinements, including the removal of halothane due to its obsolescence, higher hepatotoxicity risk compared to modern volatile agents, and global phase-out trends supported by pharmacovigilance data showing rare but severe adverse events like fulminant hepatic failure.[46] Inhalational options include:- Oxygen, supplied as inhalation gas, indispensable for averting hypoxemia during anaesthesia induction, maintenance, and recovery, as well as in non-surgical contexts like pneumonia or shock; its inclusion stems from fundamental physiological needs, with shortages linked to excess mortality in low-income settings per observational studies from the COVID-19 era.[47]
- Isoflurane, inhalation vapour, a halogenated ether valued for rapid onset and offset, hemodynamic stability, and lower malignant hyperthermia risk than older agents; randomized controlled trials demonstrate comparable efficacy to sevoflurane with better cost-effectiveness in developing countries.[21]
- Nitrous oxide, inhalation gas, used adjunctively for its analgesic and mild hypnotic effects, though limited by diffusion hypoxia risks and environmental concerns; retained for its non-flammable profile and utility in obstetrics and pediatrics where full general anaesthesia is impractical.[21]
- Ketamine, injection 50 mg (as hydrochloride)/mL, a dissociative agent enabling anaesthesia without significant respiratory depression, preserving airway reflexes and spontaneous ventilation—key advantages in austere environments, as evidenced by meta-analyses of battlefield and rural surgery outcomes showing reduced intubation needs.[21]
- Propofol, injection 10 mg/mL, an intravenous hypnotic for rapid induction and maintenance via infusion, with pharmacokinetic data from pharmacokinetic-pharmacodynamic models confirming short recovery times and antiemetic properties; its essentiality is justified by prospective cohort studies indicating superior patient satisfaction and efficiency in ambulatory procedures versus barbiturates.[21]
Local anaesthetics and preoperative sedation
The WHO Model List of Essential Medicines designates bupivacaine and lidocaine as core local anaesthetics for providing targeted, reversible nerve conduction blockade in procedures ranging from minor surgery to dental extractions and obstetric interventions. Bupivacaine, a long-acting amide anaesthetic, is listed in injectable forms at 0.25%, 0.5%, and 0.75% hydrochloride concentrations for infiltration, peripheral nerve blocks, epidural administration, and intrathecal use in spinal anaesthesia, offering durations of anaesthesia up to 4-8 hours depending on dose and site. Its inclusion stems from demonstrated efficacy in randomized controlled trials for postoperative pain control and reduced systemic toxicity compared to shorter-acting alternatives when used appropriately, with a therapeutic index supporting safe application in low-resource settings where general anaesthesia may be unavailable.[21] Lidocaine, a shorter-acting amide anaesthetic, complements bupivacaine and is recommended in multiple formulations: injectable solutions at 1% and 2% hydrochloride for infiltration and nerve blocks; topical applications at 2-4% for surface anaesthesia; dental cartridges at 2% for oral procedures; and combinations with epinephrine (1:200,000 or 1:100,000) to prolong effect and minimize vascular uptake, reducing toxicity risks such as convulsions from inadvertent intravascular injection. These forms enable versatile use in emergency intubations, wound repair, and biopsy, with epinephrine-enhanced versions specifically noted for haemostasis in vascular-rich areas. Lidocaine's broad utility is evidenced by its low cost (often under $1 per dose) and high availability, making it indispensable for primary care-level interventions where sterile equipment limits systemic options.[21] For preoperative sedation and preparation in short-term procedures, the list prioritizes atropine, diazepam, and limited use of morphine to mitigate anxiety, excessive secretions, and vagal responses without compromising recovery. Atropine sulfate injection (1 mg in 1-ml ampoule) serves as an anticholinergic premedicant to dry respiratory secretions and counteract bradycardia during induction or spinal anaesthesia, particularly in obstetrics to prevent hypotension; its selection reflects pharmacokinetic data showing rapid onset (2-4 minutes intravenously) and minimal central effects at low doses (0.01-0.02 mg/kg). Diazepam injection (5 mg/ml) provides anxiolysis and anterograde amnesia via GABA receptor enhancement, dosed at 0.1-0.2 mg/kg preoperatively to facilitate cooperation in unsedated patients, with evidence from clinical guidelines confirming reduced procedural distress in resource-constrained environments. Morphine injection (10 mg/ml) is conditionally included for analgesic premedication in painful interventions, titrated at 0.1 mg/kg to avoid respiratory depression, underscoring the list's emphasis on balanced risk-benefit profiles derived from pharmacovigilance data.[21]| Medicine | Form and Strength | Primary Indications |
|---|---|---|
| Bupivacaine | Injection: 0.25%; 0.5%; 0.75% (hydrochloride); spinal: 0.5% with glucose | Regional blocks, epidural/spinal anaesthesia |
| Lidocaine | Injection: 1%; 2% (hydrochloride); topical: 2-4%; dental: 2%; + epinephrine: 1%+0.001%; 2%+0.001% | Infiltration, surface anaesthesia, dental procedures |
| Atropine | Injection: 1 mg (sulfate) in 1-ml ampoule | Antisialogogue, prevent bradycardia/hypotension |
| Diazepam | Injection: 5 mg/ml | Sedation, anxiolysis for short procedures |
| Morphine | Injection: 10 mg/ml | Analgesic premedication (limited use) |
Medical gases and supportive agents
Oxygen and nitrous oxide are the primary medical gases included in this subsection of the WHO Model List of Essential Medicines (24th list, 2025). Oxygen, supplied as an inhalation medical gas, is essential for treating hypoxaemia across various clinical scenarios, including respiratory distress, perioperative care, and emergency resuscitation. Its inclusion reflects extensive empirical evidence from randomized controlled trials demonstrating reduced mortality in conditions like pneumonia and acute respiratory failure when titrated appropriately to maintain saturations of 92-95% in adults, avoiding hyperoxia which can exacerbate oxidative stress and organ damage. For neonates ≤32 weeks gestation, the list specifies limiting initial resuscitation to no more than 30% oxygen concentration, supported by meta-analyses of trials such as the TOBY and SUPPORT studies showing decreased risk of severe retinopathy of prematurity and bronchopulmonary dysplasia with targeted lower oxygen levels compared to higher fractions. Nitrous oxide, administered by inhalation, functions as an analgesic adjunct and carrier gas in general anaesthesia, offering rapid onset and minimal cardiovascular depression. Its essential status is justified by cost-effectiveness in low-resource settings for short procedures and obstetrics, where randomized trials confirm efficacy in reducing opioid requirements and improving pain scores without significant respiratory depression when combined with oxygen. However, the list annotates environmental concerns, noting piped nitrous oxide as a potent greenhouse gas contributing to healthcare emissions; point-of-care cylinders are recommended over central piping to mitigate leaks, aligning with lifecycle assessments quantifying nitrous oxide's global warming potential 298 times that of CO2 over 100 years. Despite these drawbacks, no superior low-cost alternatives match its profile for resource-limited anaesthesia. Supportive agents in this category address common perioperative complications. Atropine injection (1 mg sulfate in 1 mL ampoule) counters bradycardia and vagal reflexes during induction or airway manipulation, with evidence from observational studies in surgical cohorts showing reduced incidence of asystole when prophylactically administered in high-risk cases. Ephedrine injection (30 mg hydrochloride in 1 mL ampoule) treats or prevents hypotension from spinal or epidural anaesthesia via alpha- and beta-adrenergic stimulation, supported by meta-analyses of randomized trials indicating faster blood pressure recovery compared to crystalloids alone, though with risks of tachycardia in susceptible patients. Epinephrine (adrenaline) injection (1 mg in 1 mL ampoule) is vital for anaphylaxis, cardiac arrest, or severe hypotension in anaesthesia, with guidelines derived from Advanced Cardiac Life Support protocols and trials confirming its vasoconstrictive and inotropic effects improve survival rates in perioperative arrests by 20-30%. These agents' formulations prioritize stability and ease of use in austere environments, selected for their narrow therapeutic indices balanced against high unmet need in essential surgical care.Medicines for Pain and Palliative Care
Non-opioids, NSAIDs, and opioid analgesics
The WHO Model List of Essential Medicines designates specific non-opioids, non-steroidal anti-inflammatory drugs (NSAIDs), and opioid analgesics as critical for pain management in primary health care and palliative settings, prioritizing agents effective for mild to severe pain with established safety profiles when used appropriately.[48] These selections emphasize accessibility, cost-effectiveness, and evidence-based efficacy, drawing from clinical guidelines that favor stepwise escalation from non-opioids for mild pain to opioids for intractable cases.[21] Non-opioids, primarily paracetamol (acetaminophen), serve as first-line treatment for mild pain and fever, available in multiple formulations to accommodate various administration routes and patient needs. Paracetamol is listed in oral liquid (125 mg/5 mL; 120 mg/5 mL; 250 mg/5 mL), rectal suppository (100 mg; 250 mg), dispersible tablet (100 mg; 250 mg), and tablet (250 mg; 325 mg; 500 mg) forms.[49] Its inclusion reflects broad utility and low risk of gastrointestinal side effects compared to NSAIDs, though hepatic toxicity limits high-dose chronic use.[50] NSAIDs such as acetylsalicylic acid (aspirin) and ibuprofen address pain with an inflammatory component, offering anti-pyretic and analgesic effects through cyclooxygenase inhibition. Acetylsalicylic acid is provided as oral solid (100–500 mg) and rectal suppository (50–150 mg), while ibuprofen includes oral liquid (200 mg/5 mL; 100 mg/5 mL) and tablets (200 mg; 400 mg; 600 mg).[51] These agents are essential for conditions like musculoskeletal pain but require caution due to risks of gastrointestinal bleeding and renal impairment, particularly in vulnerable populations.[52]| Medicine | Forms |
|---|---|
| Acetylsalicylic acid | Oral solid: 100–500 mg; Rectal suppository: 50–150 mg |
| Ibuprofen | Oral liquid: 200 mg/5 mL; 100 mg/5 mL; Oral solid tablet: 200 mg; 400 mg; 600 mg |
| Paracetamol | Oral liquid: 125 mg/5 mL; 120 mg/5 mL; 250 mg/5 mL; Rectal suppository: 100 mg; 250 mg; Dispersible tablet: 100 mg; 250 mg; Tablet: 250 mg; 325 mg; 500 mg |
| Medicine | Forms |
|---|---|
| Codeine | Oral solid tablet: 30 mg (phosphate) |
| Fentanyl | Transdermal patch: 12 µg/hour; 25 µg/hour; 50 µg/hour; 75 µg/hour; 100 µg/hour |
| Methadone | Oral liquid: 5 mg/5 mL; 10 mg/5 mL; 5 mg/mL; 10 mg/mL (hydrochloride); Oral solid: 5 mg; 10 mg (hydrochloride) |
| Morphine | Oral liquid: 10 mg/5 mL (hydrochloride or sulfate); Oral solid immediate release: 10 mg; slow release: 10–200 mg (hydrochloride or sulfate); Granules slow release: 20–200 mg (sulfate); Parenteral injection: 10 mg in 1 mL ampoule (hydrochloride or sulfate) |
Symptom management in advanced disease
The World Health Organization Model List of Essential Medicines identifies a targeted set of pharmaceuticals for addressing non-pain symptoms in patients with advanced, life-limiting illnesses, emphasizing relief from distressing conditions such as nausea, vomiting, delirium, anxiety, excessive respiratory secretions, and gastrointestinal stasis. These medicines, grouped under "Medicines for other common symptoms in palliative care," prioritize oral and parenteral formulations suitable for varying levels of care, with selections driven by clinical evidence of symptom alleviation, pharmacokinetic suitability for frail patients, and global accessibility.[21][48] The approach underscores multimodal symptom control, integrating pharmacological interventions with non-drug measures, while acknowledging potential adverse effects like sedation or extrapyramidal symptoms that necessitate dose titration and monitoring.[54] Key medicines encompass antiemetics, antipsychotics, benzodiazepines, corticosteroids, anticholinergics, and prokinetics, each applied based on symptom etiology—for instance, centrally acting agents for chemoreceptor trigger zone stimulation versus peripherally acting ones for delayed gastric emptying. Amitriptyline, a tricyclic antidepressant (oral solid: 10–75 mg), aids in managing insomnia and depressive symptoms exacerbating overall distress, though its anticholinergic properties limit use in elderly patients prone to confusion.[21] Cyclizine (oral solid: 50 mg; parenteral: 50 mg/mL), an antihistamine, targets vestibular or opioid-induced nausea via H1 receptor blockade, with evidence from randomized trials showing superior efficacy over placebo in postoperative and chemotherapy contexts adaptable to palliative scenarios.[21][55] Dexamethasone (various forms including oral and injectable) serves multiple roles, including antiemetic effects through prostaglandin inhibition, appetite stimulation via cytokine modulation, and reduction of edema in conditions like hepatic or cerebral involvement, supported by systematic reviews demonstrating short-term benefits in advanced cancer without long-term survival impact.[21][55] Diazepam (various forms) addresses anxiety and myoclonus via GABA enhancement, with low-dose use for dyspnea providing subjective relief by reducing breathlessness perception, as evidenced in observational studies of terminal respiratory distress.[21] Haloperidol (oral, parenteral) controls delirium and agitation through dopamine D2 antagonism, also effective against refractory nausea, with meta-analyses confirming its utility in hyperactive delirium subtypes common in advanced disease, albeit with risks of QT prolongation requiring ECG oversight in vulnerable populations.[21][55] Hyoscine hydrobromide (parenteral, transdermal) diminishes terminal "death rattle" by inhibiting salivary and bronchial secretions, with clinical guidelines endorsing its use in the final hours based on expert consensus and small trials showing reduced caregiver distress despite limited patient-reported outcomes.[21] Metoclopramide (oral, parenteral) promotes gastric motility to alleviate opioid- or disease-related nausea, backed by Cochrane reviews indicating moderate efficacy for gastroparesis-like symptoms, though contraindicated in bowel obstruction due to perforation risk.[21] These agents collectively enable proportional palliation, with WHO advocating integration into national formularies to bridge evidence-practice gaps, as global surveys reveal undertreatment in low-resource settings despite proven cost-effectiveness.[55][54]| Symptom | Example Medicines | Primary Mechanism and Indication |
|---|---|---|
| Nausea/Vomiting | Cyclizine, Dexamethasone, Haloperidol, Metoclopramide | Antihistamine/H1 blockade; Steroid anti-inflammatory; Dopamine antagonism; Prokinetic/dopamine blockade for motility disorders |
| Delirium/Agitation | Haloperidol, Diazepam (adjunct) | D2 receptor blockade; GABA potentiation for calming |
| Anxiety/Dyspnea | Diazepam | Sedation and perceptual modulation of breathlessness |
| Excessive Secretions | Hyoscine hydrobromide | Antimuscarinic drying of airways |
| Anorexia/Depression | Dexamethasone, Amitriptyline | Cytokine suppression; Serotonin/norepinephrine reuptake inhibition |
Antiallergics, Antidotes, and Poisoning Treatments
Antiallergics for anaphylaxis
Epinephrine (adrenaline) injection, at a concentration of 1 mg/mL (as hydrochloride or hydrogen tartrate) in a 1 mL ampoule, is the cornerstone medicine for anaphylaxis on the WHO Model List of Essential Medicines.[56] Administered intramuscularly at doses of 0.01 mg/kg (maximum 0.5 mg per dose) for adults and children, it acts via alpha- and beta-adrenergic stimulation to reverse hypotension, bronchospasm, and mucosal edema characteristic of anaphylaxis, a severe, potentially fatal systemic allergic reaction triggered by allergens such as foods, insect stings, or medications.[56] Clinical evidence from randomized controlled trials and observational studies demonstrates that prompt epinephrine administration reduces mortality rates from over 20% in untreated cases to under 1% when given early, underscoring its essential status based on pharmacokinetic data showing peak effects within 5-10 minutes post-injection. Corticosteroids complement epinephrine in anaphylaxis management to mitigate late-phase inflammation and prevent biphasic reactions, which occur in up to 20% of cases hours after initial resolution.[56] Hydrocortisone powder for injection (100 mg as sodium succinate per vial) and dexamethasone injection (4 mg/mL in 1 mL ampoule as disodium phosphate salt) are listed, with hydrocortisone preferred for its mineralocorticoid activity in hypotensive patients and dexamethasone for its longer duration in outpatient settings.[56] Systematic reviews indicate corticosteroids reduce recurrence risk by 50-70% when added to epinephrine, though they lack acute bronchodilatory effects and are not substitutes for immediate adrenergic therapy. Antihistamines such as loratadine (tablet 10 mg or oral liquid 1 mg/mL) serve adjunctive roles in mild allergic symptoms but are not primary for anaphylaxis, as H1-blockers fail to address cardiovascular or respiratory compromise.[56] Prednisolone (tablet 5 mg or 25 mg; oral liquid 5 mg/mL for children) supports post-acute management to taper inflammation, with evidence from cohort studies showing equivalence to intravenous alternatives in preventing relapse.[56] These selections reflect WHO criteria prioritizing medicines with proven causal efficacy in resource-limited settings, where anaphylaxis incidence reaches 1-2% annually in high-risk populations, emphasizing availability of auto-injectors or ampoules for rapid deployment.[56]Non-specific and specific antidotes
The non-specific and specific antidotes section of the WHO Model List of Essential Medicines (24th list, 2025) addresses treatments for acute poisoning, emphasizing agents that either broadly mitigate toxin absorption or specifically neutralize particular xenobiotics.[20] Non-specific antidotes operate via universal mechanisms, such as gastrointestinal decontamination, independent of the toxin's identity, and are prioritized for their versatility in resource-limited settings where rapid toxin identification may be delayed.[20] Specific antidotes, conversely, target defined toxicological pathways, such as chelation of heavy metals or reversal of opioid receptor agonism, often requiring precise diagnosis to maximize efficacy and minimize risks like adverse reactions.[20] These selections reflect evidence from clinical toxicology data prioritizing cost-effective interventions that reduce mortality in high-burden poisoning scenarios, including pesticide and pharmaceutical overdoses prevalent in low- and middle-income countries.[20] Under non-specific antidotes, the list includes only activated charcoal, formulated as granules for oral suspension (50 mg).[20] This agent adsorbs a wide array of organic compounds, including many pharmaceuticals like theophylline and carbamazepine, preventing their systemic absorption when administered early in ingestion cases; alternative powder or liquid forms may substitute if granules are unavailable.[20] Its inclusion stems from randomized trials demonstrating reduced drug bioavailability, though it lacks efficacy against metals, alcohols, or caustics, and multiple-dose regimens enhance elimination for select toxins via enterohepatic recirculation. Specific antidotes comprise a core list of nine agents for frontline use, supplemented by five on the complementary list for specialized facilities with advanced diagnostics:- Acetylcysteine (injection: 200 mg/mL in 10-mL ampoule): Restores glutathione to detoxify the metabolite NAPQI in paracetamol overdose, reducing hepatotoxicity if given within 8-10 hours; oral solutions (10-20%) provide alternatives where IV access is limited.[20]
- Atropine (injection: 1 mg (sulfate) per mL in 1-mL ampoule): Competitively antagonizes muscarinic effects in organophosphate or carbamate pesticide poisoning, titrated to control secretions and bradycardia in cholinergic crisis.[20]
- Calcium gluconate (injection: 100 mg/mL (10%) in 10-mL ampoule): Neutralizes fluoride or calcium channel blocker toxicity by providing exogenous calcium, and treats hydrofluoric acid burns via local infiltration to bind fluoride ions.[20]
- Methylthioninium chloride (methylene blue) (injection: 10 mg/mL in 10-mL ampoule): Reduces methemoglobin to hemoglobin in cases from oxidants like dapsone or nitrites, though contraindicated in G6PD deficiency due to hemolysis risk.[20]
- Naloxone (injection: 400 micrograms (hydrochloride) in 1-mL ampoule): Reverses opioid-induced respiratory depression by mu-receptor antagonism, with repeat dosing for long-acting agents like methadone.[20]
- Penicillamine (solid oral: 250 mg): Chelates copper in Wilson's disease or lead/mercury in chronic poisoning, promoting urinary excretion despite potential hypersensitivity reactions.[20]
- Potassium ferric hexacyanoferrate(II)·2H₂O (Prussian blue) (powder for oral administration): Exchanges ions to bind thallium or radiocesium in the gut, accelerating fecal elimination in rare but severe exposures.[20]
- Sodium nitrite (injection: 30 mg/mL in 10-mL ampoule): Induces methemoglobinemia to sequester cyanide, used in combination with sodium thiosulfate for enhanced detoxification.[20]
- Sodium thiosulfate (injection: 250 mg/mL in 50-mL ampoule): Donates sulfur to convert cyanide to thiocyanate for renal excretion, often paired with sodium nitrite or as standalone in smoke inhalation.[20]
- Deferoxamine (powder for injection: 500 mg (mesilate) in vial): Binds ferric iron in acute overload, preventing organ damage via IV infusion.[20]
- Dimercaprol (BAL) (injection in oil: 50 mg/mL in 2-mL ampoule; 100 mg/mL in 3-mL ampoule): Chelates arsenic, gold, or mercury, administered intramuscularly despite pain and hypertension side effects.[20]
- Fomepizole (injection: 5 mg/mL (sulfate) in 20-mL ampoule or equivalents): Inhibits alcohol dehydrogenase to block toxic metabolite formation in ethylene glycol or methanol poisoning, preferred over ethanol due to fewer adverse effects.[20]
- Sodium calcium edetate (injection: 200 mg/mL in 5-mL ampoule): Chelates lead for urinary excretion in confirmed plumbism, monitored for nephrotoxicity.[20]
- Succimer (DMSA) (solid oral: 100 mg): Orally chelates lead or mercury with higher tolerability than parenteral agents, used in pediatric cases.[20]
Medicines for Nervous System Disorders
Antiseizure and antiepileptic agents
The World Health Organization's 24th Model List of Essential Medicines (2025) includes a core set of antiseizure medicines in section 5.1.1 to address epilepsy, status epilepticus, and related convulsive conditions, prioritizing agents with established efficacy, pharmacokinetic stability in diverse settings, and cost-effectiveness for global health systems.[20] These selections emphasize broad-spectrum options like phenobarbital and valproic acid for initial therapy in resource-constrained areas, where access to monitoring for adverse effects may be limited, alongside benzodiazepines for acute seizure termination.[57] Empirical data from randomized controlled trials demonstrate that first-line agents such as carbamazepine and phenytoin achieve seizure freedom in 60-70% of newly diagnosed patients when adhered to, though long-term retention varies due to side effects like cognitive impairment with phenobarbital.[58] Carbamazepine is listed in oral liquid (100 mg/5 mL), chewable tablet (100 mg; 200 mg), and scored tablet (100 mg; 200 mg; 400 mg) forms for focal and generalized tonic-clonic seizures, supported by its voltage-gated sodium channel blockade mechanism, which reduces neuronal hyperexcitability as evidenced by EEG normalization in clinical studies.[20] Phenytoin, available as injection (50 mg/mL sodium salt), oral liquid (30 mg/5 mL), solid oral dosage (25 mg; 50 mg; 100 mg sodium salt), and chewable tablet (50 mg), shares a similar mechanism but requires dose adjustments for nonlinear kinetics to avoid toxicity, with intravenous loading effective in 80-90% of status epilepticus cases per observational data.[20] [59] Phenobarbital, in injection (30 mg/mL or 60 mg/mL; 200 mg/mL sodium), oral liquid (15 mg/5 mL), and tablet (15 mg; 30 mg; 60 mg; 100 mg) forms, serves as a first-line option in low-income settings due to its low cost (under $0.01 per daily dose) and broad efficacy via GABA enhancement and sodium channel modulation, though randomized trials show higher discontinuation rates from sedation and behavioral effects compared to newer agents.[20] [60] Valproic acid (sodium valproate) is provided as oral liquid (200 mg/5 mL), crushable tablet (100 mg), and enteric-coated tablet (200 mg; 500 mg); it inhibits T-type calcium channels and boosts GABA, effective for generalized seizures, but carries a black-box warning against use in women of childbearing potential owing to teratogenic risks, with cohort studies reporting neural tube defect rates up to 10% in exposed pregnancies versus 0.1% baseline.[20] [58] Lamotrigine (tablet: 25 mg; 50 mg; 100 mg; 200 mg; chewable/dispersible: 2 mg; 5 mg; 25 mg; 50 mg; 100 mg; 200 mg) and levetiracetam (oral liquid: 100 mg/mL; tablet: 250 mg; 500 mg; 750 mg; 1000 mg) represent adjunctive therapies for refractory cases, added to the list in 2017 and 2023 respectively based on meta-analyses showing superior tolerability—lamotrigine with sodium channel and glutamate modulation, levetiracetam via synaptic vesicle protein binding—yielding 20-30% additional responders in treatment-resistant epilepsy without enzyme induction interactions.[20] [61] For acute management, diazepam (rectal gel: 5 mg/mL in 0.5 mL, 2 mL, 4 mL; rectal solution: 2 mg/mL or 4 mg/mL variants) and midazolam (oromucosal solution: 5 mg/mL or 10 mg/mL pre-filled; injection: 1 mg/mL or 5 mg/mL) provide rapid GABA-mediated seizure cessation, with rectal/buccal routes enabling community administration; trials indicate midazolam noninferiority to diazepam in pediatric status epilepticus, with onset within 3 minutes.[20] Lorazepam injection (2 mg/mL or 4 mg/mL in 1 mL ampoules) serves as an alternative, though intravenous access limits prehospital use.[20] Magnesium sulfate injection (0.5 g/mL in 2 mL or 10 mL ampoules) is restricted to eclampsia prevention, where it reduces recurrent seizures by 50% via NMDA antagonism per landmark trials, but lacks evidence for primary epilepsy.[20] Prednisolone, on the complementary list (oral liquid: 1 mg/mL; tablet: 1 mg; 5 mg; 10 mg), supports infantile spasms via anti-inflammatory effects, with short-term efficacy in 70% of cases from controlled studies, though long-term neurodevelopmental outcomes remain variable.[20] Overall, the list balances accessibility with evidence from systematic reviews, favoring generics over proprietary formulations to minimize costs, which average $5-20 annually per patient for maintenance therapy in essential regimens.[60]Treatments for multiple sclerosis and parkinsonism
The World Health Organization Model List of Essential Medicines identifies specific pharmaceuticals for managing multiple sclerosis, an inflammatory demyelinating disorder of the central nervous system that leads to progressive neurological impairment, and parkinsonism, a syndrome involving bradykinesia, rigidity, and tremor due to nigrostriatal dopamine depletion. These selections emphasize therapies with demonstrated efficacy in symptom control or disease modification, prioritizing availability, affordability, and evidence from clinical trials showing reductions in relapse rates, disability accumulation, or motor fluctuations.[20][62] For multiple sclerosis, the complementary list comprises cladribine (tablet: 10 mg), glatiramer acetate (subcutaneous injection: 20 mg/mL or 40 mg/mL in pre-filled syringe), and rituximab (intravenous injection: 500 mg/50 mL vial, including quality-assured biosimilars). Cladribine, a selective immune reconstitution therapy, depletes pathogenic lymphocytes to reduce annualized relapse rates by approximately 50% in relapsing-remitting MS over 96 weeks, as evidenced by phase 3 trials.[20] Glatiramer acetate modulates T-cell responses to promote anti-inflammatory shifts, yielding a 29% relative risk reduction in relapses compared to placebo in pivotal studies.[20] Rituximab, a monoclonal antibody targeting B cells, has shown sustained efficacy in reducing gadolinium-enhancing lesions and clinical relapses in open-label extensions of randomized trials, particularly in resource-constrained settings where biosimilars enhance accessibility.[20]00505-7/fulltext) These agents were incorporated in the 23rd list (2023) following expert review of comparative effectiveness, safety data from over 10,000 patients, and potential for generic production to address global disparities in MS care, where prior to inclusion, no specific disease-modifying therapies appeared on the list.[62] For parkinsonism, the core list includes levodopa + carbidopa (tablets: 100 mg + 10 mg; 100 mg + 25 mg; 250 mg + 25 mg; therapeutic alternative: benserazide substitution for carbidopa) and biperiden (tablet: 2 mg (hydrochloride); injection: 5 mg lactate in 1 mL ampoule; therapeutic alternative: trihexyphenidyl). Levodopa + carbidopa restores striatal dopamine levels, with carbidopa inhibiting peripheral metabolism to allow lower doses and mitigate nausea; long-term use improves Unified Parkinson's Disease Rating Scale motor scores by 30-50% initially, though motor complications emerge after 5-10 years in 50% of patients per longitudinal cohorts.[20] Biperiden or trihexyphenidyl, anticholinergic agents, competitively block muscarinic receptors to alleviate tremor and dystonia, offering adjunctive benefits in up to 60% of early-stage patients unresponsive to levodopa alone, based on randomized controlled trials.[20] These treatments, longstanding on the list since earlier editions, reflect causal prioritization of dopamine replacement as first-line therapy, supported by histopathological evidence linking substantia nigra loss to symptoms and pharmacokinetic data confirming central penetration.[63] Inclusion criteria emphasize square-wave stability for formulations to ensure bioavailability in low-resource supply chains.[20]Anti-Infective Medicines
Anthelminthics, including intestinal, filarial, and schistosomal
The World Health Organization (WHO) Model List of Essential Medicines designates specific anthelmintics for treating intestinal helminths, filarial parasites, and schistosomes, prioritizing agents with proven efficacy, safety, and cost-effectiveness for global public health needs.[21] These medicines target neglected tropical diseases prevalent in low-resource settings, where soil-transmitted helminths affect over 1.5 billion people annually and filarial infections like lymphatic filariasis impact 50 million. Schistosomiasis, caused by trematodes, burdens 250 million individuals, primarily in sub-Saharan Africa.[64] For intestinal anthelmintics, the list includes albendazole (tablet, chewable 400 mg; oral liquid 200 mg/5 mL), effective against soil-transmitted helminths including ascariasis, trichuriasis, and hookworm infections via microtubule disruption in parasites.[21] Mebendazole (tablet, chewable 100 mg or 500 mg) serves as an alternative benzimidazole for similar indications, particularly in children, with comparable efficacy in mass deworming programs reducing worm burdens by 70-90%.[21] Levamisole (tablet 50 mg or 150 mg as hydrochloride) targets nematodes like Ascaris and hookworms through neuromuscular paralysis. Niclosamide (tablet, chewable 500 mg) addresses cestode infections such as taeniasis, while praziquantel (tablet 150 mg, 500 mg, or scored 600 mg) treats intestinal flukes and cestodes by increasing parasite permeability to calcium.[21] These agents support preventive chemotherapy strategies, with single-dose albendazole recommended for preschool and school-aged children in endemic areas.[21] Antifilarials on the list comprise ivermectin (tablet 3 mg or 6 mg), which paralyzes microfilariae via glutamate-gated chloride channels, indicated for strongyloidiasis and onchocerciasis (river blindness).[21] Diethylcarbamazine (tablet 50 mg or 100 mg as dihydrogen citrate) targets lymphatic filariasis by immobilizing microfilariae and altering parasite membranes, often combined with albendazole for enhanced macrofilaricidal effects in mass drug administration programs aiming for elimination by 2030.[21] Ivermectin-albendazole co-administration reduces microfilarial loads by over 90% in treated populations, though caution is advised in loiasis co-endemic areas due to encephalopathy risks from rapid parasite death.[65] For schistosomal infections, praziquantel remains the cornerstone, dosed at 40-60 mg/kg in split doses for Schistosoma haematobium and S. mansoni, achieving cure rates of 60-90% by inducing tegumental damage and exposure to host immunity.[21] Complementary listing includes oxamniquine (capsule 250 mg; oral liquid 250 mg/5 mL), reserved for praziquantel failures in S. mansoni cases, interfering with parasite nucleic acid synthesis.[21] Annual or biannual mass treatment with praziquantel in endemic communities has reduced prevalence by up to 60%, though challenges persist with reinfection and suboptimal efficacy against juvenile worms.[64] Recent pediatric formulations, like crushed praziquantel tablets, address dosing gaps in children under 4 years, who comprise 40% of cases in high-burden areas.[21]Antibacterials by access, watch, and reserve groups, plus antituberculosis and antileprosy
The World Health Organization (WHO) classifies essential antibacterials into Access, Watch, and Reserve groups as part of its AWaRe framework, introduced in 2017 and updated periodically to promote rational antibiotic use, monitor consumption, and combat antimicrobial resistance. Access group antibiotics are first- or second-line options for common infections with lower resistance potential, intended to comprise at least 60% of total antibiotic consumption globally. Watch group agents have higher resistance risks and are recommended for specific indications or when Access options fail. Reserve group drugs are last-resort treatments for multidrug-resistant infections, reserved to preserve efficacy. This classification applies to antibacterials on the WHO Model List of Essential Medicines (EML), with the 24th adult list and 10th children's list updated in September 2025.[66][48] Key Access group antibacterials on the EML include amoxicillin (oral and parenteral forms), ampicillin (parenteral), benzylpenicillin and benzathine benzylpenicillin (parenteral), cefalexin (oral), cefazolin (parenteral), chloramphenicol (parenteral), clindamycin (oral and parenteral), cloxacillin (oral and parenteral), and combinations like amoxicillin + clavulanic acid (oral and parenteral). These are prioritized for empirical treatment of conditions such as community-acquired pneumonia, urinary tract infections, and sepsis in resource-limited settings due to their efficacy, safety profiles, and availability.[48][67]| Watch Group Antibacterials | Forms and Strengths |
|---|---|
| Azithromycin | Oral liquid (200 mg/5 mL); tablets (250 mg, 500 mg) |
| Cefixime | Oral liquid (100 mg/5 mL); tablets (200 mg, 400 mg) |
| Cefotaxime | Parenteral vials (250 mg to 2 g) |
| Ceftazidime | Parenteral vials (250 mg, 1 g) |
| Ceftriaxone | Parenteral vials (250 mg to 2 g) |
| Cefuroxime | Parenteral vials (250 mg to 1.5 g) |
| Clarithromycin | Oral liquid (125–250 mg/5 mL); tablets (250–500 mg); parenteral (500 mg) |
| Ciprofloxacin | Oral liquid (250 mg/5 mL); tablets (100–500 mg); parenteral (2 mg/mL IV) |
Ethambutol, a key first-line agent, inhibits mycobacterial cell wall synthesis but requires vision monitoring due to optic neuritis risk at doses above 15 mg/kg daily.[48] Antileprosy medicines consist of a multidrug regimen combining rifampicin, dapsone, and clofazimine, essential to prevent resistance in Mycobacterium leprae, which has no spontaneous mutations conferring resistance to this trio at therapeutic levels. Rifampicin (monthly supervised doses) targets DNA-dependent RNA polymerase, dapsone inhibits folate synthesis, and clofazimine provides bactericidal activity with anti-inflammatory effects for erythema nodosum leprosum reactions. The WHO recommends 6-month treatment for paucibacillary leprosy and 12 months for multibacillary, achieving cure rates over 95% when adhered to, though global case detection fell to 127,000 new diagnoses in 2023 amid underreporting concerns.[70][71][72]
Antifungals and antivirals for herpes, retrovirals, and hepatitis
The World Health Organization Model List of Essential Medicines identifies antifungal agents critical for managing invasive fungal infections, which cause over 1.5 million deaths annually, predominantly in immunocompromised individuals in low- and middle-income countries.[21] Selections prioritize broad-spectrum efficacy, oral availability where possible, and cost-effectiveness against pathogens like Cryptococcus neoformans, Candida species, and dermatophytes. Fluconazole, a triazole with high oral bioavailability, forms the core for treating cryptococcal meningitis and mucosal candidiasis, typically dosed at 200–800 mg daily for 2–8 weeks depending on severity.[73] Griseofulvin, on the core list for oral suspension or tablets (125–500 mg), targets dermatophyte infections of skin and nails, requiring 4–8 weeks of therapy due to its fungistatic action via microtubule disruption.[21] Complementary list antifungals address severe or resistant cases requiring specialized care. Amphotericin B, administered intravenously as deoxycholate (50 mg vial) or liposomal formulations, serves as first-line for induction therapy in disseminated histoplasmosis, mucormycosis, and visceral leishmaniasis co-infection, despite nephrotoxicity risks mitigated by lipid formulations in resource-permitted settings.[74] Flucytosine, combined with amphotericin B for cryptococcal meningitis, provides synergistic fungicidal activity at 100 mg/kg daily orally or IV, though monitoring for bone marrow suppression is essential. Itraconazole capsules (100 mg) treat systemic mycoses like histoplasmosis, while terbinafine tablets (250 mg) or cream (1%) handle refractory dermatophytoses. Echinocandins such as caspofungin and anidulafungin, added in 2021 for invasive candidiasis, inhibit cell wall synthesis and are reserved for azole-resistant strains.[74] Aciclovir, the sole essential antiherpes antiviral, inhibits herpes simplex virus (HSV) and varicella-zoster virus (VZV) DNA polymerase after phosphorylation by viral thymidine kinase, reducing lesion duration and viral shedding by 1–2 days in primary genital herpes. Available as intravenous (250 mg vial for encephalitis or neonatal infection), oral tablets (200 mg for 5–10 days in zoster), and 3% ophthalmic ointment, it underpins WHO guidelines for episodic or suppressive therapy in HIV co-infection.[75] Antiretrovirals target HIV replication across multiple classes to form combination regimens achieving undetectable viral loads in over 90% of adherent patients, per WHO-recommended dolutegravir-based first-line therapy initiated regardless of CD4 count. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) like lamivudine (150 mg tablet), emtricitabine (200 mg), tenofovir disoproxil fumarate (300 mg), and abacavir (300 mg) backbone regimens, often in fixed-dose combinations such as tenofovir/lamivudine/dolutegravir (TLD) for adults. Non-nucleoside RTIs include efavirenz (600 mg) for second-line in children. Protease inhibitors like atazanavir boosted with ritonavir (300/100 mg fixed-dose) or lopinavir/ritonavir inhibit gag-pol cleavage, used in pregnancy or resistance cases. Integrase strand transfer inhibitors, led by dolutegravir (50 mg), offer high potency and once-daily dosing with minimal drug interactions. Complementary agents include enfuvirtide for salvage therapy. These selections, updated to favor integrase inhibitors over efavirenz due to superior tolerability and resistance barriers, support scale-up in 2023 guidelines treating 30 million people globally.[21] For hepatitis, essential antivirals focus on chronic HBV and HCV, where untreated HBV affects 296 million and HCV 58 million carriers, driving liver cancer and cirrhosis. HBV nucleoside analogs entecavir (0.5–1 mg oral daily) and tenofovir disoproxil fumarate suppress replication in >95% of patients, preventing progression with indefinite therapy in cirrhotics. HCV direct-acting antivirals (DAAs) enable cure rates exceeding 95% in 8–12 weeks: sofosbuvir (400 mg), a nucleotide NS5B inhibitor, combined with daclatasvir (60 mg NS5A inhibitor) as pangenotypic oral fixed-dose (sofosbuvir/daclatasvir 400/60 mg), prioritize simplicity and affordability over genotype testing. These replaced interferon-based regimens, reflecting evidence from trials showing sustained virologic response without ribavirin in most cases, though monitoring for resistance remains key in high-burden areas.Antiprotozoals for amoebiasis, leishmaniasis, malaria, pneumocystosis, toxoplasmosis, and trypanosomiasis
The World Health Organization Model List of Essential Medicines designates specific antiprotozoal agents for treating infections caused by protozoa, prioritizing those with demonstrated efficacy, safety profiles, and cost-effectiveness based on global disease burden and clinical evidence.[21] In the 23rd edition (2023), section 6.5 outlines medicines for amoebiasis, leishmaniasis, malaria, pneumocystosis, toxoplasmosis, and trypanosomiasis, reflecting updates from expert committee reviews incorporating randomized controlled trials, pharmacokinetic data, and resistance patterns.[21] For amoebiasis and giardiasis, diloxanide furoate (tablet: 500 mg) targets luminal forms in asymptomatic carriers and mild intestinal cases in patients over 25 kg, while metronidazole (injection: 500 mg in 100 mL vial; oral liquid: 200 mg/5 mL; tablet: 200–500 mg) addresses invasive extraintestinal disease, with tinidazole as a therapeutic alternative; combination therapy is standard to eradicate both trophozoites and cysts.[21] Leishmaniasis treatments include amphotericin B (powder for injection: 50 mg liposomal or deoxycholate complex), the preferred parenteral option for visceral forms due to lower toxicity in liposomal formulations; meglumine antimoniate (injection: 1.5 g/5 mL); miltefosine (solid oral: 10 mg, 50 mg) for oral monotherapy in visceral and cutaneous cases; paromomycin (intramuscular solution: 750 mg base); and sodium stibogluconate (injection: 100 mg/mL in 30 mL vial), selected based on regional efficacy against Leishmania species and monitoring for antimony resistance.[21] Malaria management emphasizes artemisinin-based combination therapies (ACTs) for uncomplicated Plasmodium falciparum cases, such as artemether + lumefantrine (tablet: 20 mg + 120 mg; dispersible for children), artesunate + amodiaquine (tablet: 25 mg + 67.5 mg to 100 mg + 270 mg), artesunate + mefloquine (tablet: 25 mg + 55 mg to 100 mg + 220 mg), and dihydroartemisinin + piperaquine (tablet: 20 mg + 160 mg to 40 mg + 320 mg); severe malaria requires parenteral artesunate (injection: 60 mg) or artemether (oily injection: 80 mg/mL), followed by oral ACTs.[21] For P. vivax or ovale, chloroquine (oral liquid: 50 mg/5 mL; tablet: 100–150 mg) provides blood schizontocidal action, with primaquine (tablet: 7.5–15 mg) for 14-day radical cure of hypnozoites, contraindicated in G6PD deficiency; chemoprevention options include sulfadoxine + pyrimethamine, mefloquine (tablet: 250 mg), and doxycycline (100 mg oral) for at-risk groups, tailored to transmission intensity and resistance surveillance.[21] Pneumocystosis (Pneumocystis jirovecii pneumonia) and toxoplasmosis rely on sulfamethoxazole + trimethoprim (injection: 80 mg + 16 mg/mL; oral liquid: 200 mg + 40 mg/5 mL; tablet: 100 mg + 20 mg to 800 mg + 160 mg; dispersible: 100 mg + 20 mg) as first-line for prophylaxis and treatment, due to synergistic folate inhibition; pyrimethamine (tablet: 25 mg) combined with sulfadiazine (tablet: 500 mg) serves as alternative for toxoplasmosis encephalitis, with folinic acid rescue to mitigate bone marrow suppression, supported by outcomes in immunocompromised patients.[21] Complementary pentamidine (tablet: 200–300 mg isethionate) addresses refractory cases.[21] Trypanosomiasis treatments differentiate African (HAT) from American (Chagas) forms; for gambiense HAT, fexinidazole (tablet: 600 mg) is first-line oral for both stages, simplifying field administration over prior regimens.[21] First-stage HAT uses pentamidine (powder for injection: 300 mg isethionate) or suramin sodium (powder: 1 g); second-stage includes eflornithine (injection: 200 mg/mL) monotherapy or with nifurtimox (tablet: 30–120 mg scored), avoiding melarsoprol (injection: 180 mg/5 mL) due to encephalopathy risks; rhodesiense prioritizes suramin initially.[21] For Chagas, benznidazole (tablet: 12.5 mg, scored 50–100 mg) and nifurtimox treat acute and chronic phases, with efficacy highest in children and early infection, per parasitological clearance data.[21] Selections account for staging via CSF analysis and declining incidence from vector control.[21]Ectoparasiticides, Ebola, and COVID-19 specifics
The WHO Model List of Essential Medicines designates ivermectin (3 mg scored tablet) as the primary ectoparasiticide for treating scabies, an infestation caused by the mite Sarcoptes scabiei, which affects over 200 million people annually, predominantly in low-resource settings.[76][77] Ivermectin, an oral avermectin derivative, works by paralyzing and killing parasites through glutamate-gated chloride channel modulation, with clinical trials showing cure rates of 70-95% after one or two doses, superior to topical alternatives in mass treatment scenarios due to ease of administration and compliance.[21] This inclusion prioritizes ivermectin over topical agents like permethrin or benzyl benzoate, which, while effective, are not listed, reflecting WHO's emphasis on cost-effective, scalable options for endemic areas where scabies contributes to secondary bacterial infections like impetigo.[77] Section 6.7 of the list includes two monoclonal antibody therapies for Ebola virus disease: ansuvimab (mAb114, 400 mg IV powder for injection) and REGN-EB3 (atoltivimab + odesivimab + mazutivimab, IV infusions).[78] These were added in the 23rd list (2023) based on the PALM trial results from 2018-2019, which demonstrated 90% and 71% mortality reductions, respectively, for Zaire ebolavirus infections when administered within days of symptom onset compared to the investigational ZMapp antibody (71% mortality). Ansuvimab targets the Ebola glycoprotein to neutralize viral entry, while REGN-EB3 combines three antibodies for broader epitope coverage, reducing escape mutations; both outperform remdesivir or ZMapp in randomized controlled trials involving over 700 patients during the 2018-2020 Democratic Republic of Congo outbreak.[79] Their essential status addresses high case-fatality rates (up to 90% untreated) in resource-limited outbreaks, though cold-chain requirements limit accessibility. For COVID-19, section 6.8 recommends baricitinib (oral tablet) with a strong endorsement for severe or critical cases, as a Janus kinase inhibitor that reduces inflammation and cytokine storm, supported by meta-analyses of trials like ACTT-2 and RECOVERY showing 20-30% mortality reductions when added to dexamethasone and oxygen.[80] Nirmatrelvir with ritonavir (oral, complementary list) receives conditional recommendation for non-severe high-risk outpatients, based on the EPIC-HR trial (2021) demonstrating 89% reduction in hospitalization or death versus placebo in unvaccinated adults, though efficacy wanes against later variants and requires renal/hepatic monitoring.[21] Molnupiravir is conditionally approved for similar outpatients despite mixed trial data, including MOVe-OUT (2021) showing 30% hospitalization reduction but concerns over mutagenic risks and limited variant coverage; remdesivir applications were rejected due to insufficient survival benefits in WHO Solidarity trial (2020, n=11,000+).[80] These listings, derived from living guidelines updated through 2023, prioritize therapies with robust randomized evidence amid evolving epidemiology, excluding prophylactics or vaccines listed elsewhere. No substantive changes to this section occurred in the 24th list (September 2025).[26]Antimigraine Medicines
Acute treatment and prophylactic options
The WHO Model List of Essential Medicines designates acetylsalicylic acid (aspirin), paracetamol (acetaminophen), ibuprofen, and sumatriptan as key options for acute treatment of migraine attacks in adults. Acetylsalicylic acid is recommended in oral solid form at 300–500 mg doses as needed, up to a maximum of 4 g daily, based on its established efficacy in relieving pain and associated symptoms when administered early in an attack.[81] Paracetamol, available as 300–500 mg tablets or 10 mg/ml oral liquid, serves as an alternative analgesic for mild to moderate attacks, particularly where non-steroidal anti-inflammatory drugs are contraindicated.[82] Ibuprofen, at 400 mg oral doses as needed up to 1.2 g daily, provides anti-inflammatory and analgesic effects suitable for acute migraine management, reflecting additions in recent updates to expand accessible non-opioid options.[83] Sumatriptan, a triptan-class serotonin (5-HT1B/1D) receptor agonist, is included as 50 mg or 100 mg tablets (up to 200 mg daily) or 6 mg subcutaneous injection for moderate to severe attacks unresponsive to simpler analgesics, targeting vascular and neurogenic components of migraine pathophysiology.[84] For prophylaxis in patients experiencing frequent or debilitating migraines (typically more than four headache days per month), the list specifies propranolol, a non-selective beta-adrenergic blocker, in oral form at 40–240 mg daily in divided doses. This selection prioritizes its evidence-based reduction in attack frequency by 50% or more in responsive patients, with mechanisms involving decreased cerebral blood flow excitability and catecholamine effects, while balancing availability and safety profile over alternatives like antiepileptics or antidepressants not explicitly listed for this indication. Proposals for additional prophylactic agents such as amitriptyline or bisoprolol have been submitted but not yet incorporated, underscoring the list's conservative approach favoring generics with broad therapeutic utility.[85] These options emphasize cost-effective, first-line interventions supported by clinical trials demonstrating superiority over placebo in reducing migraine burden in resource-limited settings.Immunomodulators and Antineoplastics
Non-malignant immunomodulators
The WHO Model List of Essential Medicines designates a subset of immunomodulators under section 8.1 for non-malignant conditions, focusing on immunosuppressive agents critical for preventing organ transplant rejection and managing autoimmune and inflammatory disorders such as rheumatoid arthritis, Crohn's disease, and spondyloarthritis.[86] These selections prioritize drugs with established efficacy in reducing immune-mediated tissue damage, favorable risk-benefit profiles in resource-limited settings, and potential for oral or subcutaneous administration to enhance accessibility.[21] The 24th edition, released on September 5, 2025, retains the established core and complementary lists in this category, emphasizing cost-effective options amid global health system constraints.[3] Core list medicines include azathioprine, ciclosporin, tacrolimus, and adalimumab. Azathioprine, available as 50 mg or 100 mg intravenous powder for injection and oral tablets (25 mg, 50 mg) or 10 mg/mL liquid, functions as a purine analog that inhibits DNA synthesis in lymphocytes, serving as maintenance therapy post-transplant and for steroid-refractory rheumatoid arthritis.[86] Ciclosporin, in 25 mg capsules, 100 mg/mL oral liquid, and 50 mg/mL intravenous concentrate, and tacrolimus, with intravenous 5 mg/mL solution alongside oral granules (0.2 mg, 1 mg) and tablets (0.5–5 mg), act as calcineurin inhibitors to block T-cell signal transduction, primarily for prophylaxis against acute rejection in kidney, liver, and heart transplants, with evidence from randomized trials showing reduced graft loss rates by 20–40% compared to placebo.[86] Adalimumab, a recombinant human IgG1 monoclonal antibody, is formulated for subcutaneous injection (10 mg/0.2 mL, 20 mg/0.4 mL, 40 mg/0.4 mL, 40 mg/0.8 mL) and targets soluble and membrane-bound TNF-alpha to alleviate symptoms in moderate-to-severe rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease, and ulcerative colitis, with clinical data indicating ACR20 response rates of 50–60% in biologic-naïve patients.[86]| Medicine | List Status | Key Formulations | Primary Mechanism and Uses |
|---|---|---|---|
| Azathioprine | Core | IV powder (50 mg, 100 mg); oral liquid (10 mg/mL); tablets (25 mg, 50 mg) | Purine synthesis inhibition; transplant maintenance, autoimmune diseases like rheumatoid arthritis |
| Ciclosporin | Core | IV concentrate (50 mg/mL); oral liquid (100 mg/mL); capsules (25 mg) | Calcineurin inhibition; prevention of solid organ transplant rejection |
| Tacrolimus | Core | IV solution (5 mg/mL); oral granules (0.2 mg, 1 mg); tablets (0.5 mg, 0.75 mg, 1 mg, 2 mg, 5 mg) | Calcineurin inhibition; prophylaxis against acute transplant rejection |
| Adalimumab | Core | SC injection (10 mg/0.2 mL, 20 mg/0.4 mL, 40 mg/0.4 mL, 40 mg/0.8 mL) | TNF-alpha blockade; rheumatoid arthritis, inflammatory bowel disease, spondyloarthritis |
Cytotoxic, targeted, hormonal, and supportive cancer therapies
The cytotoxic medicines on the WHO Model List of Essential Medicines primarily comprise alkylating agents, antimetabolites, anthracyclines, antitumor antibiotics, and plant alkaloids that disrupt DNA replication, RNA synthesis, or microtubule function in rapidly dividing cancer cells.[21] These agents form the backbone of curative regimens for common malignancies such as acute leukemias, Hodgkin's and non-Hodgkin's lymphomas, testicular cancer, and childhood cancers, where randomized controlled trials demonstrate survival benefits exceeding those of best supportive care alone, particularly when combined in protocols like CHOP for lymphoma or ABVD for Hodgkin's disease.[87] Key examples include:- Cyclophosphamide: Oral or IV; indicated for breast cancer, lymphomas, and multiple myeloma; bioavailability approaches 100% orally, with evidence from meta-analyses showing hazard ratios for overall survival of 0.80-0.85 in adjuvant breast cancer settings.
- Methotrexate: Oral, IM, or IV; core for acute lymphoblastic leukemia (ALL) and trophoblastic diseases; high-dose regimens with leucovorin rescue yield cure rates over 80% in pediatric ALL per long-term cohort studies.
- Cisplatin: IV; essential for germ cell tumors (cure rates >90% in good-prognosis cases) and head/neck cancers; supported by phase III trials confirming 5-year survival improvements of 10-20% over non-platinum regimens.
- Doxorubicin: IV; used in sarcomas, breast cancer, and leukemias; cardiotoxicity limits cumulative dose to 450-550 mg/m², balanced against response rates of 50-70% in acute myeloid leukemia induction.
- Imatinib: Oral; first-line for CML, with 10-year overall survival rates exceeding 80% versus 15% historically with interferon; resistance via T315I mutation addressed by alternatives.
- Dasatinib or nilotinib: Oral alternatives for imatinib-resistant CML or Philadelphia-positive ALL; dasatinib shows faster responses in phase II trials, with complete cytogenetic response rates of 90% at 12 months.[89]
- Trastuzumab: IV; for HER2-positive breast cancer, reducing recurrence by 46% in adjuvant settings per meta-analyses of over 30,000 patients.[90]
- Tamoxifen: Oral; adjuvant therapy for estrogen receptor-positive breast cancer, extending disease-free survival by 10-15 years in postmenopausal women based on 20-year follow-up data from randomized trials.
- Anastrozole: Oral aromatase inhibitor; superior to tamoxifen in postmenopausal early breast cancer for preventing recurrence (hazard ratio 0.83).
- Dexamethasone: Oral or IV; for multiple myeloma and prostate cancer palliation, enhancing response to chemotherapy with minimal added toxicity in combination regimens.
- Allopurinol: Oral; prevents tumor lysis syndrome in high-burden leukemias, lowering uric acid by 70-80% and acute kidney injury incidence from 20% to <5% in prophylactic trials.
- Filgrastim (G-CSF): SC; shortens neutropenia duration by 2-3 days post-chemotherapy, reducing febrile neutropenia risk by 45% in meta-analyses of solid tumor regimens.
- Metoclopramide or ondansetron: For chemotherapy-induced nausea; ondansetron, a 5-HT3 antagonist, achieves complete response in 60-80% of highly emetogenic settings per guideline-derived evidence.
Medicines Affecting Blood and Coagulation
Antianaemia preparations
The antianaemia preparations in the WHO Model List of Essential Medicines target nutritional and other treatable causes of anemia, including iron deficiency (the predominant form worldwide, affecting approximately 1.74 billion people as of 2019 estimates), folate deficiency, and vitamin B12 deficiency, as well as anemia of chronic disease such as in renal failure or malignancy.[20] These medicines prioritize cost-effective oral therapies suitable for primary health care in resource-limited settings, where anemia contributes to 8.4% of all years lived with disability globally.[21] Oral iron supplementation reduces anemia prevalence by 50-70% in deficient populations when adhered to, though gastrointestinal side effects limit compliance in up to 40% of cases.[20] Core list medicines emphasize prophylaxis and treatment of deficiency anemias. Ferrous salts (such as sulfate, fumarate, or gluconate), providing elemental iron, are recommended for routine supplementation, with tablets equivalent to 60 mg iron for adults and oral liquids at 25 mg iron per mL for children or those unable to swallow solids; these forms enhance absorption when taken with vitamin C but require caution in malaria-endemic areas due to potential increased infection risk without antimalarials.[20] Folic acid tablets (1 mg for prevention, 5 mg for therapeutic correction of megaloblastic anemia) address folate shortages common in pregnancy and malnutrition, reducing neural tube defects by up to 70% when used prophylactically.[21] Hydroxocobalamin injection (1 mg per 1-mL ampoule) treats pernicious or dietary vitamin B12 deficiency, with cyanocobalamin as an equally efficacious alternative for intramuscular administration in cases of malabsorption.[20] The complementary list includes erythropoiesis-stimulating agents for specialized care. Epoetin alfa (erythropoietin injection, 1000 IU vial) stimulates red blood cell production in chronic kidney disease patients on dialysis or those with chemotherapy-induced anemia, improving hemoglobin levels by 1-2 g/dL but requiring monitoring for thrombosis risk, which occurs in 5-10% of users.[21] The 24th list (2025) added darbepoetin alfa as an extended-duration alternative, administered subcutaneously or intravenously, offering dosing intervals up to every three weeks with comparable efficacy to epoetin in maintaining hemoglobin targets above 10 g/dL.[20] Fixed-dose combinations of ferrous salt with folic acid are also endorsed for pregnant women to combat concurrent deficiencies, preventing maternal anemia and low birth weight.[48]| Medicine | Formulation | Primary Use |
|---|---|---|
| Ferrous salt | Oral liquid: equiv. 25 mg iron/mL; Tablet: equiv. 60 mg iron | Iron deficiency anemia prophylaxis and treatment |
| Folic acid | Tablet: 1 mg (prophylaxis); 5 mg (therapeutic) | Folate deficiency anemia |
| Hydroxocobalamin (or cyanocobalamin) | Injection: 1 mg/1 mL | Vitamin B12 deficiency anemia |
| Epoetin alfa (complementary) | Injection: 1000 IU/vial | Anemia of chronic renal failure or chemotherapy |
| Darbepoetin alfa (complementary, added 2025) | Injection: various doses per guidelines | Anemia of chronic disease, alternative to epoetin |
Coagulation modifiers and haemoglobinopathy treatments
The World Health Organization Model List of Essential Medicines designates specific coagulation factors and related agents for treating hereditary bleeding disorders, primarily hemophilia A and B, which affect approximately 1 in 5,000 males globally and result from deficiencies in clotting factors VIII or IX, leading to spontaneous or trauma-induced hemorrhages. Coagulation factor VIII (plasma-derived or recombinant) and coagulation factor IX (plasma-derived or recombinant) are included on the core list in powder for injection forms (e.g., 250–2000 IU vials), enabling replacement therapy to restore hemostasis; recombinant forms, added to the core in the 24th list (2025), minimize risks of pathogen transmission compared to plasma-derived products, with clinical equivalence demonstrated in prophylaxis reducing annual bleeding rates by over 80% in severe cases.[91][92] Emicizumab, a recombinant bispecific monoclonal antibody mimicking factor VIII activity, was added in 2025 for hemophilia A (with or without inhibitors), administered subcutaneously at doses like 1.5 mg/kg weekly, offering prophylaxis with bleeding rate reductions of 87% versus no prophylaxis in pivotal trials.[93][48] Haemoglobinopathies, including sickle cell disease (prevalence up to 2% in sub-Saharan Africa) and thalassemia, involve abnormal hemoglobin leading to hemolytic anemia, vaso-occlusion, and organ damage; treatments target symptom management and complications like iron overload from transfusions. Hydroxyurea (hydroxycarbamide), listed under cytotoxic medicines but indicated for sickle cell disease, increases fetal hemoglobin levels, decreasing painful crises by 50% and acute chest syndrome by 44% in randomized trials across age groups, with oral capsules (100 mg, 500 mg) recommended at maximum tolerated doses around 20–30 mg/kg/day after monitoring for myelosuppression.[94][95] Iron chelating agents address transfusion-induced overload, which causes cardiac and hepatic morbidity if ferritin exceeds 1000 μg/L; deferoxamine (core list, intramuscular/subcutaneous infusion 40–50 mg/kg/day) binds iron effectively but requires prolonged administration, while complementary deferiprone (oral 75–100 mg/kg/day) and deferasirox (oral 20–40 mg/kg/day) offer better compliance, with deferasirox reducing liver iron by 3–5 mg/g dry weight annually in thalassemia patients per phase III data.[56]| Medicine | Type | Primary Indication | Key Forms and Doses |
|---|---|---|---|
| Coagulation factor VIII (recombinant or plasma-derived) | Clotting factor | Hemophilia A | Powder for injection: 250–2000 IU/vial; prophylactic dosing 20–40 IU/kg 3x/week |
| Coagulation factor IX (recombinant or plasma-derived) | Clotting factor | Hemophilia B | Powder for injection: 250–2000 IU/vial; prophylactic 25–40 IU/kg 1–2x/week |
| Emicizumab | Monoclonal antibody | Hemophilia A prophylaxis | Subcutaneous: loading 3 mg/kg x4 weeks, maintenance 1.5 mg/kg weekly |
| Hydroxyurea | Cytoreductive | Sickle cell disease | Capsules: 100 mg, 500 mg; max tolerated ~25 mg/kg/day oral |
| Deferoxamine | Iron chelator | Iron overload in haemoglobinopathies | Powder for injection: 500 mg/vial; 40–50 mg/kg/day subcutaneous |
| Deferiprone (complementary) | Iron chelator | Iron overload in haemoglobinopathies | Tablets: 250 mg; 75–100 mg/kg/day oral |
| Deferasirox (complementary) | Iron chelator | Iron overload in haemoglobinopathies | Tablets: 250 mg; 20–40 mg/kg/day oral |
Blood products, plasma derivatives, and substitutes
The blood products, plasma derivatives, and substitutes category in the WHO Model List of Essential Medicines encompasses components derived from human blood, recombinant alternatives, and synthetic substitutes vital for transfusion medicine, management of coagulopathies, and volume resuscitation. These items address acute needs in hemorrhage, surgery, trauma, and inherited bleeding disorders, with selection prioritizing efficacy, safety profiles, and accessibility in diverse healthcare settings. The World Health Assembly resolution WHA63.12 underscores the importance of safe blood products, advocating national programs for voluntary donation and screening to mitigate transfusion-transmitted infections like HIV, hepatitis B, and syphilis.[97][20] Key blood components include whole blood for oxygen-carrying capacity in massive hemorrhage, fresh frozen plasma for replenishing clotting factors and proteins in disseminated intravascular coagulation or warfarin reversal, red blood cell concentrates for anemia correction, platelet concentrates for thrombocytopenia-induced bleeding, and cryoprecipitate—now specified as pathogen-reduced—for fibrinogen and Factor VIII replacement in hypofibrinogenemia or hemophilia when concentrates are unavailable. Pathogen reduction technologies, such as those using amotosalen/UVA for platelets or solvent-detergent treatment for plasma, enhance safety by inactivating viruses, bacteria, and parasites, though their adoption varies due to cost and infrastructure requirements in low-income countries.[98][20] Plasma derivatives feature human normal immunoglobulin for passive immunity in primary immunodeficiencies or post-exposure prophylaxis, and specific immunoglobulins like anti-D for Rh incompatibility prevention in pregnancies. Coagulation factors comprise plasma-derived Factor VIII and Factor IX concentrates for hemophilia A and B treatment, respectively, alongside recombinant versions to circumvent viral transmission risks inherent in plasma sourcing—historical outbreaks of HIV and hepatitis C via plasma products prompted this shift. The 2025 update incorporated emicizumab, a recombinant bispecific antibody mimicking Factor VIII activity for routine hemophilia A prophylaxis in patients with or without inhibitors, supported by clinical trials demonstrating 87% reduction in treated bleeds compared to prior therapies, thereby improving quality of life and reducing infusion frequency. Recombinant Factor VIII and IX further align with evidence favoring pathogen-free options, with cost-effectiveness analyses indicating long-term savings despite higher upfront costs in high-burden settings.[91][99][93] Synthetic plasma substitutes, such as dextran 70, provide temporary intravascular volume expansion in hypovolemic shock when blood products are scarce, though limited to short-term use due to risks of coagulopathy and renal impairment; their inclusion reflects pragmatic needs in emergencies without compromising overall reliance on biological products. WHO emphasizes rigorous pharmacovigilance and national regulatory oversight for these items, given variability in manufacturing standards and potential for adverse events like allergic reactions or thrombosis.[56][20]| Medicine | Indication | Form |
|---|---|---|
| Whole blood | Acute blood loss | Transfusion unit |
| Fresh frozen plasma | Coagulation factor deficiency | Frozen bag |
| Cryoprecipitate (pathogen-reduced) | Fibrinogen deficiency, hemophilia | Frozen liquid or lyophilized powder (>50 IU Factor VIII per unit)[98] |
| Coagulation Factor VIII (plasma-derived or recombinant) | Hemophilia A | Powder for injection (250-1000 IU/vial)[91] |
| Coagulation Factor IX (plasma-derived or recombinant) | Hemophilia B | Powder for injection (500-1000 IU/vial)[99] |
| Emicizumab | Hemophilia A prophylaxis | Subcutaneous injection |
| Dextran 70 | Hypovolemia substitute | Injectable solution |
Cardiovascular Medicines
Antianginals, antiarrhythmics, antihypertensives, and heart failure agents
The World Health Organization's Model List of Essential Medicines designates specific agents for antianginal, antiarrhythmic, antihypertensive, and heart failure management to address prevalent cardiovascular conditions in resource-limited settings, prioritizing therapies with established efficacy, safety profiles, and availability.[2] These selections, from the 24th list updated in September 2025, emphasize beta-blockers, nitrates, calcium channel blockers, and diuretics, reflecting evidence from clinical trials demonstrating reductions in mortality and symptoms, such as beta-blockers lowering angina episodes by 20-30% in stable coronary disease.[20] Complementary list items indicate needs for specialized facilities or monitoring due to risks like toxicity.[20] Antianginal medicines target angina pectoris by reducing myocardial oxygen demand or improving supply. The list includes:| Medicine | Dosage Forms and Strengths |
|---|---|
| Bisoprolol | Tablet: 1.25 mg; 5 mg (therapeutic alternatives: carvedilol, metoprolol)[20] |
| Glyceryl trinitrate | Tablet (sublingual): 500 micrograms[20] |
| Isosorbide dinitrate | Tablet (sublingual): 5 mg[20] |
| Verapamil | Tablet: 40 mg; 80 mg (hydrochloride)[20] |
| Medicine | Dosage Forms and Strengths |
|---|---|
| Bisoprolol | Tablet: 1.25 mg; 5 mg (therapeutic alternatives: carvedilol, metoprolol)[20] |
| Digoxin | Injection: 250 micrograms/mL in 2 mL ampoule; Oral liquid: 50 micrograms/mL; Tablet: 62.5 micrograms; 250 micrograms[20] |
| Epinephrine (adrenaline) | Injection: 100 micrograms/mL in 10 mL ampoule (as acid tartrate or hydrochloride)[20] |
| Lidocaine | Injection: 20 mg/mL (hydrochloride) in 5 mL ampoule[20] |
| Verapamil | Injection: 2.5 mg/mL (hydrochloride) in 2 mL ampoule; Tablet: 40 mg; 80 mg (hydrochloride)[20] |
| Amiodarone (complementary) | Injection: 50 mg/mL (hydrochloride) in 3 mL ampoule; Tablet: 100 mg; 200 mg; 400 mg (hydrochloride)[20] |
| Medicine | Dosage Forms and Strengths |
|---|---|
| Amlodipine | Tablet: 5 mg (as maleate, mesylate, or besylate; therapeutic alternatives: dihydropyridine derivatives)[20] |
| Bisoprolol | Tablet: 1.25 mg; 5 mg (therapeutic alternatives: atenolol, carvedilol, metoprolol; atenolol not first-line for uncomplicated hypertension in patients >60 years)[20] |
| Enalapril | Oral liquid: 1 mg/mL (as hydrogen maleate) [children]; Tablet: 2.5 mg; 5 mg; 10 mg (as hydrogen maleate; therapeutic alternatives: ACE inhibitors)[20] |
| Hydralazine | Powder for injection: 20 mg (hydrochloride) in ampoule; Tablet: 25 mg; 50 mg (hydrochloride; for severe pregnancy-induced hypertension only)[20] |
| Hydrochlorothiazide | Oral liquid: 50 mg/5 mL; Solid oral: 12.5 mg; 25 mg (therapeutic alternatives: chlorothiazide, chlorthalidone, indapamide)[20] |
| Lisinopril + Amlodipine | Tablet: 10 mg + 5 mg; 20 mg + 5 mg; 20 mg + 10 mg (therapeutic alternatives: ACE inhibitors, dihydropyridine derivatives)[20] |
| Lisinopril + Hydrochlorothiazide | Tablet: 10 mg + 12.5 mg; 20 mg + 12.5 mg; 20 mg + 25 mg (therapeutic alternatives: ACE inhibitors, thiazides)[20] |
| Losartan | Tablet: 25 mg; 50 mg; 100 mg (therapeutic alternatives: ARBs)[20] |
| Methyldopa | Tablet: 250 mg (for pregnancy-induced hypertension only)[20] |
| Perindopril + Amlodipine + Indapamide | Solid oral: 5 mg + 5 mg + 1.25 mg; 5 mg + 10 mg + 2.5 mg; 10 mg + 5 mg + 1.25 mg; 10 mg + 10 mg + 2.5 mg (therapeutic alternatives: ACE inhibitors, dihydropyridine derivatives, thiazides)[20] |
| Telmisartan + Amlodipine | Tablet: 40 mg + 5 mg; 80 mg + 5 mg; 80 mg + 10 mg (therapeutic alternatives: ARBs, dihydropyridine derivatives)[20] |
| Telmisartan + Hydrochlorothiazide | Tablet: 40 mg + 12.5 mg; 80 mg + 12.5 mg; 80 mg + 25 mg (therapeutic alternatives: ARBs, thiazides)[20] |
| Valsartan + Amlodipine + Hydrochlorothiazide | Solid oral: 5 mg + 160 mg + 12.5 mg; 5 mg + 160 mg + 25 mg; 10 mg + 160 mg + 12.5 mg; 10 mg + 160 mg + 25 mg; 10 mg + 320 mg + 25 mg (therapeutic alternatives: ARBs, dihydropyridine derivatives, thiazides)[20] |
| Sodium nitroprusside (complementary) | Powder for infusion: 50 mg in ampoule[20] |
| Medicine | Dosage Forms and Strengths |
|---|---|
| Bisoprolol | Tablet: 1.25 mg; 5 mg (therapeutic alternatives: carvedilol, metoprolol)[20] |
| Digoxin | Injection: 250 micrograms/mL in 2 mL ampoule; Oral liquid: 50 micrograms/mL; Tablet: 62.5 micrograms; 250 micrograms[20] |
| Enalapril | Tablet: 2.5 mg; 5 mg; 10 mg (as hydrogen maleate; therapeutic alternatives: ACE inhibitors)[20] |
| Furosemide | Injection: 10 mg/mL in 2 mL or 5 mL ampoule; Oral liquid: 20 mg/5 mL; 50 mg/5 mL [children]; Tablet: 20 mg; 40 mg (therapeutic alternatives: bumetanide, torasemide)[20] |
| Hydrochlorothiazide | Oral liquid: 50 mg/5 mL; Solid oral: 25 mg (therapeutic alternatives: chlorothiazide, chlorthalidone, indapamide)[20] |
| Losartan | Tablet: 25 mg; 50 mg; 100 mg (therapeutic alternatives: ARBs)[20] |
| Spironolactone | Tablet: 25 mg[20] |
| Digoxin (complementary) | Injection: 100 micrograms/mL in 1 mL ampoule; 250 micrograms/mL in 2 mL ampoule; Oral liquid: 50 micrograms/mL; Tablet: 62.5 micrograms; 125 micrograms; 250 micrograms[20] |
| Dopamine (complementary) | Injection: 40 mg/mL (hydrochloride) in 5 mL vial[20] |
Antithrombotics, lipid-lowering drugs, and fixed-dose combinations for CVD prevention
![A line drawing of a hexagon with two attachments representing the chemical structure of acetylsalicylic acid][float-right] The World Health Organization (WHO) Model List of Essential Medicines (EML), in its 24th edition published in September 2025, includes antithrombotic agents primarily for secondary prevention of atherosclerotic cardiovascular disease (CVD) by inhibiting platelet aggregation and thrombus formation. Acetylsalicylic acid (aspirin), available as 100 mg tablets, serves as the core antiplatelet medicine, reducing the risk of recurrent myocardial infarction, stroke, and vascular death in patients with prior CVD events, based on meta-analyses of randomized trials demonstrating approximately 20-25% relative risk reduction in serious vascular events. Clopidogrel, in 75 mg and 300 mg tablet forms, is listed as a core alternative or adjunct for patients intolerant to aspirin or those with acute coronary syndromes, supported by trials like CURE showing additive benefits when combined with aspirin. On the complementary list, direct oral anticoagulants (DOACs) such as apixaban and dabigatran etexilate (110 mg and 150 mg doses) are recommended for stroke prevention in non-valvular atrial fibrillation, reflecting evidence from RE-LY and ARISTOTLE trials indicating superior efficacy and safety over warfarin in reducing stroke risk by 20-30% with lower intracranial hemorrhage rates. Thrombolytics like alteplase (powder for injection: 10 mg, 20 mg, 50 mg) and streptokinase (1.5 million IU) are included complementarily for acute thrombotic events such as STEMI, where they restore coronary perfusion, though limited by bleeding risks and availability of percutaneous interventions in resource-constrained settings. Lipid-lowering agents target hypercholesterolemia to prevent atherosclerotic plaque progression. Atorvastatin, as the core statin, is recommended in tablet form for high-risk patients, with randomized controlled trials like TNT demonstrating dose-dependent LDL-C reductions of 20-50% and corresponding decreases in major coronary events by up to 22%. Simvastatin appears on the complementary list as a therapeutic equivalent, historically validated in the 4S trial for reducing CVD mortality by 30% in secondary prevention.90566-8/fulltext) These selections prioritize generics with established safety profiles over newer agents like PCSK9 inhibitors, which lack proportional cost-effectiveness data for essential status in low-income settings. Fixed-dose combinations (FDCs) for CVD prevention aim to enhance adherence in primary and secondary prophylaxis, particularly in populations with low health literacy or access barriers. Core listings include acetylsalicylic acid + atorvastatin + ramipril in various strengths (e.g., 100 mg + 20 mg + 2.5 mg tablets), combining antiplatelet, lipid-lowering, and antihypertensive effects; atorvastatin + perindopril + amlodipine (e.g., 20 mg + 5 mg + 5 mg); and a five-component polypill with acetylsalicylic acid + simvastatin + ramipril + atenolol + hydrochlorothiazide (100 mg + 20 mg + 5 mg + 50 mg + 12.5 mg). These were added following modeling and trials like the polypill studies, which project 75% adherence improvements and potential 50-80% CVD event reductions in high-burden regions, though real-world efficacy hinges on component dosing matching individual needs and monitoring for side effects like gastrointestinal bleeding from aspirin or myopathy from statins.[100]61061-4/fulltext)| Category | Medicine(s) | Dosage Forms | Status |
|---|---|---|---|
| Antiplatelets | Acetylsalicylic acid | Tablet: 100 mg | Core |
| Clopidogrel | Tablet: 75 mg; 300 mg | Core | |
| Anticoagulants/Thrombolytics (Complementary) | Apixaban; Dabigatran | Oral solid | Complementary |
| Alteplase; Streptokinase | Injection/powder | Complementary | |
| Lipid-lowering | Atorvastatin | Tablet | Core |
| Simvastatin | Tablet | Complementary | |
| FDCs | ASA + Atorva + Ramipril; Atorva + Perindopril + Amlodipine; ASA + Simva + Ramipril + Atenolol + HCTZ | Various fixed tablets | Core |
Dermatological, Diagnostic, and Antiseptic Medicines
Topical antifungals, anti-infectives, anti-inflammatories, and scabicides
The World Health Organization's Model List of Essential Medicines designates a select group of topical agents under dermatological medicines to address common skin conditions, prioritizing those with demonstrated efficacy, safety, and cost-effectiveness for resource-limited settings.[20] These include formulations for fungal infections, bacterial skin infections and wound care, inflammatory and pruritic dermatoses, and ectoparasitic infestations such as scabies.[20] Selection criteria emphasize public health relevance, with core list items representing minimum needs for basic health systems.[20] Updates to the 24th list, published in September 2025, maintain these topical options without major changes from prior editions, reflecting stable evidence on their utility for prevalent conditions like dermatophytosis, impetigo, eczema, and scabies.[20]Antifungal Medicines
Topical antifungals target superficial mycoses, such as those caused by dermatophytes or yeasts. The list includes:- Miconazole (cream or ointment: 2% nitrate), effective against a range of cutaneous fungi via inhibition of ergosterol synthesis.[20]
- Selenium sulfide (detergent-based suspension: 2%), used primarily for pityriasis versicolor and seborrheic dermatitis through antifungal and keratolytic actions.[20]
- Sodium thiosulfate (solution: 15%), applied for tinea versicolor by altering fungal cell environment.[20]
- Terbinafine (cream or ointment: 1% hydrochloride), a squalene epoxidase inhibitor for dermatophyte infections, noted for rapid fungicidal activity.[20]
Anti-infective Medicines
Topical anti-infectives address localized bacterial infections and aid wound healing, reducing reliance on systemic antibiotics to curb resistance. Included are:- Mupirocin (cream: 2% as calcium; ointment: 2%), targeting staphylococcal and streptococcal skin infections by inhibiting bacterial protein synthesis.[20]
- Potassium permanganate (aqueous solution: 1:10,000), serving as an antiseptic for wet dressings in exudative lesions or ulcers.[20]
- Silver sulfadiazine (cream: 1%), applied to burns for broad-spectrum antibacterial coverage, particularly against Pseudomonas, though restricted to patients over 2 months due to kernicterus risk in neonates.[20]
Anti-inflammatory and Antipruritic Medicines
These mitigate inflammation and itching in non-infectious dermatoses, with milder agents preferred for children and neonates. The list features:- Betamethasone (cream or ointment: 0.1% as valerate), a potent corticosteroid for severe inflammatory conditions, with caution for prolonged use due to atrophy risk.[20]
- Calamine (lotion), providing soothing relief via astringent and protective effects on irritated skin.[20]
- Hydrocortisone (cream or ointment: 1% acetate), the preferred mild glucocorticoid for neonates and sensitive areas to suppress local immune responses.[20]
Scabicides and Pediculicides
For ectoparasites, the list prioritizes agents effective against Sarcoptes scabiei and lice:- Benzyl benzoate (lotion: 25%), a scabicide for topical application, restricted to children over 2 years due to potential irritation.[20]
- Permethrin (cream: 5%; lotion: 1%), a pyrethroid neurotoxin targeting scabies mites and head lice, with high efficacy in single or repeat doses.[20]
Ophthalmic diagnostics and radiocontrast media
The World Health Organization's Model List of Essential Medicines, in its 24th edition updated in September 2025, designates specific ophthalmic diagnostic agents and radiocontrast media as essential for enabling key diagnostic procedures in primary and secondary health care settings, prioritizing efficacy, safety, and cost-effectiveness for prevalent conditions requiring imaging or ocular assessment.[20] These agents facilitate visualization of ocular surfaces and internal body structures, supporting diagnoses of trauma, infections, and structural abnormalities where advanced equipment may be unavailable.[48] Ophthalmic medicines on the list comprise fluorescein eye drops (1% sodium salt) and tropicamide eye drops (0.5%), with atropine and cyclopentolate as therapeutic alternatives to tropicamide. Fluorescein is applied topically to stain damaged corneal or conjunctival epithelium, revealing abrasions, foreign bodies, or defects under cobalt blue light illumination, aiding rapid evaluation of ocular trauma or dry eye-related issues.[102][103] Tropicamide, an anticholinergic agent, produces short-acting mydriasis (pupil dilation) and cycloplegia (paralysis of accommodation) to enable funduscopy, refraction, and examination of the retina and optic nerve, with effects onset within 20-40 minutes and duration of 4-6 hours.[104][105] Atropine offers longer-lasting cycloplegia for pediatric or refractory cases, while cyclopentolate provides intermediate duration, selected based on procedure needs and patient age to minimize systemic absorption risks like blurred vision or photophobia.[20] Radiocontrast media include amidotrizoate injection (140-420 mg iodine/ml as sodium or meglumine salt), barium sulfate aqueous suspension, and iohexol injection (140-350 mg iodine/ml). Amidotrizoate, a high-osmolar ionic agent, is administered intravenously or orally for excretory urography, angiography, venography, or gastrointestinal opacification, enhancing radiographic contrast despite higher nephrotoxicity risks compared to non-ionic alternatives.[106] Barium sulfate, an inert insoluble suspension, is given orally or rectally to delineate the esophagus, stomach, small bowel, and colon during fluoroscopy or CT, essential for detecting obstructions, perforations, or motility disorders without systemic absorption.[107][108] Iohexol, a low-osmolar non-ionic monomer, is favored for intravascular applications in CT angiography, myelography, or urography due to reduced osmolality and incidence of adverse reactions such as anaphylaxis or renal impairment, particularly in high-risk patients.[109][20] These media are restricted to supervised radiographic facilities, underscoring their role in bridging diagnostic gaps in essential health systems.[110]Antiseptics and disinfectants
The antiseptics and disinfectants category in the WHO Model List of Essential Medicines (EML) comprises agents selected for their roles in reducing microbial contamination on skin, mucous membranes, wounds, and environmental surfaces, thereby mitigating infection risks in healthcare facilities and communities. These selections prioritize broad-spectrum activity against bacteria, fungi, and viruses; stability under varying conditions; and affordability, with evidence from clinical trials demonstrating reductions in healthcare-associated infections (HAIs) such as surgical site infections (SSIs) by up to 40% in some settings when used for preoperative skin preparation.[21] The 24th EML, updated in September 2025, retains core agents from prior editions due to consistent efficacy data and lack of superior alternatives at scale.[3]| Medicine | Dosage Form and Strength | Primary Indications |
|---|---|---|
| Chlorhexidine (digluconate) | Solution: 5% for equipment disinfection; 0.5% for skin and umbilical cord care | Preoperative skin antisepsis, hand hygiene, neonatal umbilical cord cleansing to prevent omphalitis; reduces SSIs by 29-55% in meta-analyses of randomized trials.[21] |
| Ethanol (denatured) | Solution: 70-90% | Skin antisepsis before injections or surgery, hand rubs; effective against enveloped viruses and bacteria, with faster evaporation than water-based alternatives aiding compliance.[21] |
| Povidone iodine | Solution: 10% (diluted to 1% available iodine for topical use) | Wound irrigation, mucous membrane disinfection, preoperative preparation; broad-spectrum but inactivated by organic matter, limiting use in heavily contaminated sites.[21][111] |
Diuretics and Gastrointestinal Medicines
Diuretic agents
Diuretic agents in the WHO Model List of Essential Medicines promote diuresis to manage fluid overload in conditions such as heart failure, hypertension, and edema from renal or hepatic causes, with selections emphasizing cost-effective options suitable for primary health care systems.[21] The 23rd list (2023), with no substantive changes to this section in the 24th list (2025), includes seven agents across loop, thiazide, osmotic, and potassium-sparing classes, balancing potency, duration of action, and electrolyte effects to minimize risks like hypokalemia.[113] These medicines are prioritized for their evidence-based utility in reducing morbidity from cardiovascular and renal diseases, where empirical data from clinical trials demonstrate reductions in hospitalization rates and blood pressure.[114]| Medicine | Formulations | Notes/Indications |
|---|---|---|
| Amiloride (hydrochloride) | Tablet: 5 mg | Potassium-sparing diuretic; adjunct to thiazides or loop diuretics to prevent hypokalemia in edema or hypertension.[115] |
| Bumetanide | Parenteral forms (equivalent to furosemide) | Loop diuretic; alternative for severe edema, anuria, or oliguria when furosemide is unavailable.[113] |
| Furosemide | Injection: 10 mg/mL in 2 mL or 5 mL ampoules; Oral liquid: 20 mg/5 mL or 50 mg/5 mL; Tablet: 20 mg or 40 mg | Loop diuretic of first choice for acute and chronic edema in heart failure, renal impairment, or hypertension; rapid onset IV for emergencies.[116] |
| Hydrochlorothiazide | Tablet: 25 mg | Thiazide diuretic; for mild hypertension or edema, often combined with potassium-sparing agents.[113] |
| Mannitol | Injection: 10% or 20% solution | Osmotic diuretic; for cerebral edema, oliguric phase of acute renal failure, or to promote diuresis pre/post renal transplant. Complementary list item for specialized use.[21] |
| Spironolactone | Oral liquid: 5 mg/5 mL, 10 mg/5 mL, or 25 mg/5 mL; Tablet: 25 mg | Potassium-sparing aldosterone antagonist; for resistant edema in heart failure or cirrhosis, and primary hyperaldosteronism.[113] |
| Torasemide | Parenteral/oral forms (equivalent to furosemide) | Loop diuretic; alternative for edema, anuria, or oliguria with potentially longer duration than furosemide.[113] |
Antiulcer, antiemetic, anti-inflammatory, laxative, and antidiarrhoeal treatments
The World Health Organization Model List of Essential Medicines designates specific agents for gastrointestinal conditions involving excessive acid production, nausea, inflammation, bowel inertia, and fluid loss from diarrhea, prioritizing those with proven efficacy in reducing morbidity, particularly in low-resource settings where dehydration and ulcers contribute significantly to mortality.[20] These selections emphasize oral rehydration and acid suppression over symptomatic antidiarrheals, reflecting evidence from clinical trials showing rehydration prevents 90% of diarrhea-related deaths in children under five, while proton pump inhibitors outperform H2 antagonists in healing ulcers.[20] Updates in the 24th list (2025) maintain focus on cost-effective generics, though ranitidine's inclusion persists despite regulatory withdrawals in high-income countries due to nitrosamine impurities forming under storage, highlighting WHO's adaptation for global access where alternatives are limited.[20] Antiulcer treatments target peptic ulcers and reflux by inhibiting acid secretion; omeprazole, a proton pump inhibitor, is listed in oral (10–40 mg tablets), powder for oral liquid, and injectable forms, demonstrating superior healing rates (over 90% at 4–8 weeks) compared to placebo in randomized trials for Helicobacter pylori-associated ulcers.[20] Ranitidine, an H2-receptor antagonist, complements in oral liquid, tablets (150 mg), and injection, offering rapid symptom relief but lower long-term efficacy and noted risks of degradation into probable carcinogens like NDMA, prompting alternatives in some national lists.[20] Antiemetic medicines address nausea from chemotherapy, surgery, or gastroenteritis; metoclopramide (injection 5 mg/mL, oral 10 mg tablets) promotes gastric motility via dopamine antagonism, effective in postoperative nausea per meta-analyses. Ondansetron (injection 2 mg/mL, oral 4–24 mg) blocks 5-HT3 receptors, reducing chemotherapy-induced vomiting by 70–80% in trials, while dexamethasone (various oral and injectable doses) provides broad antiemetic synergy through glucocorticoid effects. Aprepitant, on the complementary list for highly emetogenic regimens, inhibits substance P/neurokinin-1, enhancing control when combined with 5-HT3 antagonists.[20] Anti-inflammatory agents for bowel diseases like ulcerative colitis include sulfasalazine (tablets 500 mg, suppositories, enemas), which delivers 5-aminosalicylic acid locally to reduce inflammation via inhibition of prostaglandin synthesis, with remission rates of 60–80% in mild-moderate cases per systematic reviews. Complementary options hydrocortisone and prednisolone (retention enemas) offer rapid steroid-mediated suppression for flares, reserved for severe disease due to systemic risks like osteoporosis.[20] Laxatives address constipation with senna (7.5 mg tablets), a stimulant anthraquinone that increases peristalsis and fluid secretion, supported by evidence of efficacy in opioid-induced constipation without dependency risks at short-term use.[20] Antidiarrhoeal treatments prioritize prevention of dehydration over motility inhibition; oral rehydration salts (ORS powder for 200–1000 mL solutions, with glucose 75 mmol/L, sodium 75 mmol/L, and electrolytes) restore fluid balance, averting shock in 93% of acute cases based on global trials. Zinc sulfate (20 mg dispersible tablets) adjunctively shortens diarrhea duration by 25% and reduces severity in children, per WHO-recommended supplementation for under-fives in endemic areas, avoiding opioids like loperamide due to risks of ileus in infectious etiologies.[20]| Category | Medicines | Key Forms | Primary Indications |
|---|---|---|---|
| Antiulcer | Omeprazole Ranitidine | Oral/injectable powders, tablets, liquids | Peptic ulcers, reflux esophagitis |
| Antiemetic | Metoclopramide Ondansetron Dexamethasone (Complementary: Aprepitant) | Tablets, injections, oral liquids | Nausea/vomiting from chemo, post-op, gastroenteritis |
| Anti-inflammatory | Sulfasalazine (Complementary: Hydrocortisone, Prednisolone) | Tablets, enemas, suppositories | Inflammatory bowel disease |
| Laxative | Senna | Tablets | Constipation |
| Antidiarrhoeal | ORS Zinc sulfate | Powders, dispersible tablets | Acute diarrhea, dehydration prevention |
Endocrine and Reproductive Medicines
Hormones for adrenal, thyroid, pituitary, diabetes, and hypoglycaemia
The World Health Organization (WHO) Model List of Essential Medicines designates certain hormones and therapeutic equivalents as essential for treating endocrine disorders involving the adrenal glands, thyroid, pituitary, diabetes mellitus, and hypoglycaemia, emphasizing agents that replace deficient hormones or counteract acute imbalances to prevent mortality and morbidity.[20] These inclusions are based on expert committee evaluations of clinical trial data demonstrating superior outcomes in preventing crises, such as adrenal insufficiency or diabetic ketoacidosis, particularly in low-resource contexts where access to diagnostics and alternatives is limited.[117] For adrenal disorders, hydrocortisone (powder for injection: 100 mg as sodium succinate; complementary list: granules 0.5–5 mg, tablets 5–20 mg) and fludrocortisone (complementary list: oral liquid 100 micrograms/mL acetate, tablet 100 micrograms acetate) are prioritized for replacement therapy in conditions like congenital adrenal hyperplasia and primary adrenal insufficiency, where glucocorticoid and mineralocorticoid deficits cause electrolyte imbalances, hypotension, and shock if untreated; evidence from cohort studies shows hydrocortisone reduces hospitalization rates by mimicking physiological cortisol rhythms, outperforming synthetic alternatives in long-term growth and metabolic stability.[20][117] Synthetic glucocorticoids like dexamethasone (injection 4 mg/mL, oral liquid 0.5–2 mg/5 mL, tablet 0.5–4 mg) and prednisolone (oral liquid 5 mg/mL, tablet 5–25 mg) supplement for acute management, with pharmacokinetic data indicating dexamethasone's longer half-life suits stress dosing during infections or surgery.[20] For thyroid disorders, levothyroxine (tablet: 25–100 micrograms sodium salt; complementary oral liquid formulations) serves as first-line replacement for hypothyroidism, restoring euthyroid states and preventing myxedema coma, as randomized controlled trials confirm normalized TSH levels and reduced cardiovascular risks with once-daily dosing.[20] Liothyronine (tablet: 5–20 micrograms) addresses rare cases of myxedema or conversion defects, though evidence limits its routine use due to arrhythmia risks without superior outcomes over levothyroxine monotherapy.[20] Antithyroid agents like propylthiouracil (tablet 50 mg) control hyperthyroidism, preferred in pregnancy for blocking peripheral T4-to-T3 conversion, with meta-analyses showing remission rates of 30–50% versus surgery.[20] Methimazole (complementary tablet 5–10 mg) offers longer duration, reducing dosing frequency, though hepatotoxicity data necessitate monitoring.[20] Pituitary hormone therapies include desmopressin (injection 4 micrograms/mL acetate, nasal spray 150 micrograms/actuation) for central diabetes insipidus, where vasopressin deficiency causes polyuria; intranasal administration achieves rapid antidiuresis, with studies reporting 90% efficacy in volume control without systemic effects.[20] Cabergoline (tablet 0.5–1 mg) treats hyperprolactinemia, dopamine agonist action shrinking prolactinomas, supported by trials showing 70–90% normalization of prolactin levels and tumor reduction over bromocriptine alternatives.[20] Somatropin (complementary powder for injection 5–10 mg human growth hormone) and octreotide (complementary injections) address growth hormone deficiency and acromegaly, respectively, with longitudinal data linking somatropin to improved height velocity in children (4–10 cm/year gains) and octreotide to IGF-1 suppression in 60–70% of cases.[20] In diabetes mellitus, insulin formulations are core hormones: human soluble insulin (injection 40–100 IU/mL), rapid-acting analogues (e.g., lispro/aspart/glulisine, 100 IU/mL), and intermediate-acting (e.g., NPH, 40–100 IU/mL) enable glycemic control, preventing complications; pivotal trials like DCCT demonstrate 76% relative risk reduction in retinopathy with intensive insulin therapy versus conventional.[20] Long-acting analogues (e.g., glargine/degludec, complementary) offer basal coverage with lower nocturnal hypoglycemia rates (odds ratio 0.68 in meta-analyses).[20] For hypoglycaemia, glucagon (powder for injection 1 mg) reverses insulin overdose or fasting states by hepatic glycogenolysis, with emergency data showing restored consciousness in 80–90% of severe cases within 10 minutes, essential where IV glucose is unavailable.[20] Diazoxide (complementary oral liquid 50 mg/mL, tablet 50 mg) manages hyperinsulinism in neonates, inhibiting insulin release, though monitoring for fluid retention is required per pharmacovigilance reports.[20]| Subsection | Key Medicines | Primary Indications | Evidence Basis |
|---|---|---|---|
| Adrenal | Hydrocortisone, Fludrocortisone | Insufficiency, electrolyte imbalance | Replacement prevents shock; cohort studies show metabolic stability[117] |
| Thyroid | Levothyroxine, Propylthiouracil | Hypo/hyperthyroidism | TSH normalization; remission rates 30–50%[20] |
| Pituitary | Desmopressin, Cabergoline | Diabetes insipidus, prolactinoma | 90% antidiuresis; 70–90% prolactin normalization[20] |
| Diabetes | Various Insulins | Glycemic control | 76% complication reduction in RCTs[20] |
| Hypoglycaemia | Glucagon | Acute reversal | 80–90% efficacy in emergencies[20] |
Contraceptives, ovulation inducers, uterotonics, and perinatal care agents
The World Health Organization (WHO) Model List of Essential Medicines designates a range of pharmaceuticals in the category of contraceptives, ovulation inducers, uterotonics, and perinatal care agents to prioritize interventions that prevent unintended pregnancies, facilitate fertility treatments, promote safe labor and delivery, and mitigate maternal and neonatal risks in resource-limited settings.[21] These selections emphasize agents with established efficacy, cost-effectiveness, and broad applicability, based on epidemiological data showing that inadequate access contributes to high rates of maternal mortality—estimated at 287,000 deaths annually worldwide, predominantly from hemorrhage and hypertensive disorders—and unintended pregnancies affecting over 120 million women yearly. The 23rd list (2023), with updates reflected in the 24th edition (2025), includes both core (minimum needs) and complementary (specialized facilities) items, prioritizing heat-stable formulations for low-resource environments where cold chains are unreliable.[20] Contraceptives comprise hormonal, mechanical, and barrier methods to inhibit ovulation, fertilization, or implantation, selected for their ability to reduce fertility rates by up to 99% with consistent use, as evidenced by clinical trials demonstrating failure rates below 1% for long-acting reversible options versus 9% for short-acting ones.[21] Key inclusions are:| Medicine | Dosage Form | Status |
|---|---|---|
| Ethinylestradiol + levonorgestrel | Tablet: 30 µg + 150 µg | Core |
| Ethinylestradiol + norethisterone | Tablet: 35 µg + 1 mg | Core |
| Levonorgestrel (emergency) | Tablet: 1.5 mg | Core |
| Medroxyprogesterone acetate (depot) | Injection: 150 mg/mL in 1-mL vial | Core |
| Etonogestrel-releasing implant | Single-rod: 68 mg | Core |
| Levonorgestrel-releasing IUD | Intrauterine system: 52 mg | Core |
| Copper-containing IUD | Device | Core |
| Condoms and diaphragms | Barrier devices | Core |
Immunologicals and Vaccines
Diagnostic immunologicals
Tuberculin, purified protein derivative (PPD), is the sole diagnostic immunological listed in the WHO Model List of Essential Medicines, categorized under immunologicals for intradermal injection to support tuberculosis diagnosis. This standardized extract from heat-killed, concentrated, and filtered cultures of Mycobacterium tuberculosis or an equivalent strain induces a delayed-type hypersensitivity reaction in sensitized individuals, manifesting as cutaneous induration measurable after 48–72 hours.[119] The preparation is essential in resource-limited settings for identifying latent tuberculosis infection (LTBI), particularly in children under 5 years and contacts of active cases, where it guides preventive therapy decisions amid global TB burdens exceeding 10 million incident cases annually as of 2023. Administered as 0.1 mL intradermally (typically 2–5 tuberculin units depending on age and protocol), PPD's inclusion on the core list reflects its cost-effectiveness and accessibility for primary screening, despite limitations such as reduced specificity in populations with prior BCG vaccination or nontuberculous mycobacterial exposure, which can yield false positives. WHO guidelines endorse its use alongside clinical evaluation and, where available, confirmatory molecular tests like Xpert MTB/RIF for active disease, emphasizing that positive reactions (≥5–15 mm induration, varying by risk group) indicate infection but not active disease. First added to the list in earlier editions and retained through the 23rd list (2023), PPD remains prioritized for essential health systems lacking advanced diagnostics, supporting the End TB Strategy's targets for incidence reduction. No complementary list items specify specialized formulations, underscoring its broad applicability in basic care.[2]Sera, immunoglobulins, monoclonal antibodies, and vaccines
The sera, immunoglobulins, and monoclonal antibodies in the WHO Model List of Essential Medicines deliver passive immunity by providing exogenous antibodies to neutralize toxins or pathogens immediately after exposure, which is vital for conditions with high mortality like tetanus, diphtheria, and envenomations where vaccine-induced immunity cannot act in time.[120] These products, often derived from human or animal plasma, carry risks of hypersensitivity reactions, particularly with equine sources, necessitating careful administration and compliance with WHO specifications for pathogen inactivation and purity to minimize transmission of blood-borne infections. Antivenom immunoglobulin targets venomous bites and stings from snakes, spiders, and scorpions prevalent in tropical regions, with species-specific formulations recommended based on local epidemiology to optimize efficacy and reduce adverse events.[121] Diphtheria antitoxin, typically equine-derived at doses of 10,000–20,000 IU intramuscularly, neutralizes circulating toxin in suspected cases, underscoring the need for rapid diagnosis given the disease's resurgence in under-vaccinated populations.[122] Tetanus immunoglobulin (human or equine) at 500 IU doses provides antitoxin for wound management in unvaccinated individuals, complementing active immunization to prevent the 30,000–50,000 annual neonatal deaths reported in low-resource settings prior to expanded programs. Anti-D immunoglobulin (human), administered at 300 mcg doses to Rh-negative mothers post-delivery or after potential sensitization events, prevents hemolytic disease of the newborn by targeting fetal Rh-positive cells, with evidence showing near-elimination of this condition in screened populations since its introduction in the 1960s. For rabies, both equine rabies immunoglobulin (150–400 IU/mL) and human rabies immunoglobulin are listed for post-exposure prophylaxis alongside vaccine, but shortages of human-derived products have prompted inclusion of anti-rabies virus monoclonal antibodies (e.g., 40–600 IU/mL formulations, human or murine), which offer consistent potency, lower impurity risks, and equivalence in animal models, as validated in clinical trials from 2018 onward.[123] [124] Vaccines in the list promote active, long-lasting immunity through antigens targeting priority pathogens, prioritized by global burden, transmissibility, and feasibility of delivery in primary care, with formulations like combination DTP-hepatitis B-Hib vaccines enhancing efficiency in expanded immunization programs that averted an estimated 154 million deaths since 1974.[125] Core vaccines include BCG for tuberculosis prevention in high-burden areas (efficacious against severe childhood forms but variable against pulmonary disease in adults), diphtheria-pertussis-tetanus (DTP) combinations, Haemophilus influenzae type b (Hib) to reduce meningitis and pneumonia (with 90% efficacy in trials), hepatitis B (reducing chronic carrier rates by over 95% when given neonatally), measles-rubella (preventing 56 million deaths since 2000 per WHO estimates), and poliomyelitis (oral or inactivated, contributing to wild poliovirus eradication in all but two countries as of 2023). Additional listings cover pneumococcal conjugate vaccine (PCV) for invasive disease reduction (up to 80% in children), rotavirus for diarrheal mortality (40–50% prevention in low-income settings), and human papillomavirus (HPV) for cervical cancer prevention (near-100% efficacy against vaccine-type infections).[125] Region-specific vaccines like cholera (oral, for outbreak control), Japanese encephalitis, meningococcal, rabies (for pre- or post-exposure), typhoid (Vi polysaccharide or conjugate), and yellow fever address endemic threats, with all required to meet WHO prequalification standards for stability and immunogenicity. Influenza (seasonal trivalent or quadrivalent) and HPV reflect updates for broader coverage, though implementation varies by cost and infrastructure, with evidence from modeling showing high return on investment for scaling in low- and middle-income countries.| Category | Key Examples | Primary Indications |
|---|---|---|
| Sera/Immunoglobulins | Antivenom immunoglobulin; Diphtheria antitoxin; Tetanus immunoglobulin; Anti-D immunoglobulin; Equine/human rabies immunoglobulin | Envenomation neutralization; Toxin-mediated diseases (diphtheria, tetanus); Rh sensitization prevention; Rabies post-exposure |
| Monoclonal Antibodies | Anti-rabies virus mAbs (e.g., Zabdeno, Clarity) | Rabies post-exposure prophylaxis (alternative to immunoglobulins) |
| Vaccines | BCG, DTP-Hib-HepB combo, measles-rubella, PCV, rotavirus, HPV | Tuberculosis (childhood), routine childhood immunization, pneumonia/meningitis, diarrhea, cervical cancer |
Mental and Behavioural Disorder Medicines
Antipsychotics and mood stabilizers for psychosis and bipolar
The World Health Organization Model List of Essential Medicines includes a selection of antipsychotics for the treatment of psychotic disorders, such as schizophrenia, characterized by hallucinations, delusions, and disorganized thinking. These medications primarily target dopamine D2 receptors to alleviate positive symptoms, with evidence from randomized controlled trials demonstrating moderate to high efficacy in reducing acute episodes and preventing relapse when used long-term. Chlorpromazine, the first antipsychotic, has been on the list since 1977, available as tablets (25–100 mg) and injections (25 mg/ml), effective in doses of 300–800 mg daily for adults but associated with sedation and anticholinergic effects. Haloperidol, a typical antipsychotic, follows with oral (2–10 mg) and injectable forms (5 mg/ml), showing superior efficacy over placebo in meta-analyses of over 20 trials involving thousands of patients with schizophrenia, though it carries risks of extrapyramidal symptoms like tardive dyskinesia in 20–30% of long-term users. Fluphenazine, often in depot injection form for maintenance (25 mg every 2–4 weeks), extends adherence in non-compliant patients, supported by Cochrane reviews confirming relapse reduction by up to 50% compared to placebo.[126][127] Second-generation antipsychotics, added progressively since the 2010s, offer improved tolerability profiles with lower extrapyramidal risks but higher metabolic adverse effects like weight gain and diabetes. Olanzapine (5–20 mg oral) demonstrates robust efficacy in acute psychosis, with network meta-analyses ranking it among the top for symptom reduction, though it increases obesity risk by 2–3 times versus typical agents. Risperidone (2–8 mg oral or long-acting injection) balances efficacy and side effects, effective in 70–80% of responders per clinical trials, while clozapine (100–300 mg) remains reserved for treatment-resistant cases due to agranulocytosis risk (1–2% incidence, requiring monitoring). Aripiprazole, quetiapine, and paliperidone were incorporated in the 23rd list (2023) for broader access, with quetiapine (50–800 mg) favored for its sedative properties in agitated psychosis, backed by head-to-head trials showing equivalence to haloperidol but better retention rates. These selections prioritize cost-effective generics in low-resource settings, where first-generation agents dominate due to affordability, despite evidence favoring atypicals for quality-of-life outcomes in high-income contexts.[128][127][21] For bipolar disorder, involving manic, depressive, and mixed episodes, mood stabilizers form the cornerstone, with lithium carbonate (300 mg solid oral form, serum levels 0.6–1.2 mmol/L) listed since 1977 for mania prophylaxis and suicide prevention, reducing relapse by 40–60% in maintenance trials spanning decades, though renal and thyroid monitoring is essential due to toxicity risks at levels above 1.5 mmol/L. Sodium valproate (200–500 mg enteric-coated tablets) and carbamazepine (100–200 mg scored tablets) provide alternatives, with valproate showing rapid antimanic effects in acute phases (efficacy odds ratio 1.8 vs. placebo in meta-analyses) but flagged for hepatotoxicity and severe teratogenicity (neural tube defects in 1–2% of pregnancies, prompting cautionary notes on the complementary list). Antipsychotics overlap for acute mania with psychosis, as second-generation agents like olanzapine and quetiapine demonstrate combined mood-stabilizing properties, preventing mood cycling in 50–70% of patients per longitudinal studies. The 2023 updates expanded these for bipolar to address evidence gaps in resource-limited areas, emphasizing combinations over monotherapy for refractory cases, while underscoring causal links between untreated episodes and functional decline, without overreliance on inflated efficacy claims from industry-sponsored trials.[129][130]Antidepressants, anxiolytics, OCD treatments, and substance use disorder agents
The World Health Organization's Model List of Essential Medicines, in its 24th edition published on September 5, 2025, designates a limited selection of pharmacological agents for managing depressive disorders, anxiety disorders, obsessive-compulsive disorder (OCD), and disorders due to psychoactive substance use, prioritizing those with established efficacy, safety profiles, and cost-effectiveness in resource-limited settings.[20] These medicines are selected based on systematic reviews of clinical trial data, pharmacokinetic properties, and global disease burden, emphasizing agents that demonstrate superior outcomes in reducing symptom severity compared to placebo or no treatment, while minimizing adverse effects and dependency risks.[20] For depressive disorders, tricyclic antidepressants (TCAs) like amitriptyline and selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are included, reflecting meta-analyses showing response rates of 50-60% in moderate to severe major depressive disorder, though with amitriptyline's broader utility for neuropathic pain complicating mood disorders.[20] Amitriptyline, a TCA available in tablet form (25 mg, 75 mg), is recommended for depressive disorders due to its potent inhibition of serotonin and norepinephrine reuptake, supported by randomized controlled trials (RCTs) demonstrating comparable efficacy to SSRIs in acute treatment phases, with remission rates around 30-40% at standard doses of 75-150 mg daily.[20] Its inclusion persists despite anticholinergic side effects like dry mouth and constipation, which occur in up to 50% of users, because of its low cost (often under $0.01 per dose in generic form) and versatility in primary care settings where electrocardiogram monitoring can mitigate cardiac risks. Fluoxetine, an SSRI in solid oral form (20 mg), serves as the representative for both depressive and anxiety-related conditions, backed by large-scale RCTs like the STAR*D trial showing sustained response in 30% of treatment-resistant cases after sequential therapy, with a favorable tolerability profile including lower sedation than TCAs.[20] Its long half-life (4-6 days) reduces withdrawal risks, making it suitable for adherence-challenged populations, though sexual dysfunction affects 20-30% of users per meta-analyses. For anxiety disorders, diazepam (tablet: 2 mg, 5 mg) is listed exclusively for short-term emergency management of acute or severe episodes, as benzodiazepines like it provide rapid gamma-aminobutyric acid (GABA) enhancement for symptom relief within hours, with RCTs confirming 70-80% reduction in acute panic symptoms versus placebo, but chronic use is discouraged due to tolerance development in 30-50% of patients within weeks and overdose risks.[20] Fluoxetine extends to anxiety, leveraging SSRIs' evidence from trials showing 40-60% response rates in generalized anxiety disorder over 8-12 weeks, superior to benzodiazepines for long-term prevention of relapse.[20] OCD treatments emphasize serotonergic agents, with clomipramine (capsule: 10 mg, 25 mg) as a TCA specifically potent for obsessions and compulsions via strong serotonin reuptake inhibition, evidenced by meta-analyses of 20+ RCTs yielding Yale-Brown Obsessive Compulsive Scale reductions of 20-40% at doses of 100-250 mg daily, outperforming placebo by effect sizes of 0.5-0.7, though cardiac monitoring is required due to QT prolongation risks in 5-10% of cases.[20] Fluoxetine complements this for OCD, with pediatric and adult trials demonstrating similar efficacy to clomipramine but fewer side effects, achieving 25-35% symptom improvement in first-line use.[20] Substance use disorder agents target alcohol, nicotine, and opioid dependence with pharmacotherapies proven to enhance abstinence rates in controlled settings. For alcohol use disorders, acamprosate calcium (tablet: 333 mg) modulates glutamate to reduce cravings, supported by RCTs showing 15-20% higher abstinence rates over 6 months versus placebo, particularly in detoxified patients.[20] Naltrexone (tablet: 50 mg; extended-release injection: 380 mg) blocks opioid receptors to curb relapse, with meta-analyses indicating 17% absolute risk reduction in heavy drinking days.[20] Nicotine replacement therapies (NRT: gum 2-4 mg, lozenge 2-4 mg, spray 1 mg/actuation, patches 5-30 mg/16-24 hrs) double quit rates (to 20-25%) per Cochrane reviews, by alleviating withdrawal via steady nicotine delivery without combustion toxins.[20] Varenicline (tablet: 0.5 mg, 1 mg) and bupropion (sustained-release tablet: 150 mg) further boost efficacy, with varenicline yielding 25-30% abstinence at 6 months via partial nicotinic agonism, and bupropion aiding via dopamine/norepinephrine modulation, though seizure risks limit its use in epileptics (0.1% incidence).[20] Cytisine (tablet: 1.5 mg), a plant-derived partial agonist, offers comparable quit rates to varenicline at lower cost, per RCTs in Eastern Europe showing 8-10% higher success.[20] For opioid use disorders, methadone (oral liquid: 5-10 mg/5 mL; complementary list) is restricted to supervised programs, reducing illicit use by 50-70% and mortality by 59% in cohort studies, via mu-opioid agonism stabilizing withdrawal without euphoria at maintenance doses of 60-100 mg daily.[20]| Category | Medicine | Form and Strength | Key Evidence for Inclusion |
|---|---|---|---|
| Depressive Disorders | Amitriptyline | Tablet: 25 mg, 75 mg | RCTs show 50-60% response; low cost for primary care. |
| Depressive Disorders | Fluoxetine | Solid oral: 20 mg | STAR*D trial: 30% remission in resistant cases; long half-life aids adherence. |
| Anxiety Disorders (acute) | Diazepam | Tablet: 2 mg, 5 mg | Rapid GABA relief; 70-80% acute symptom reduction, short-term only. |
| OCD | Clomipramine | Capsule: 10 mg, 25 mg | Meta-analyses: 20-40% Y-BOCS reduction; serotonin-specific. |
| Substance Use (Alcohol) | Naltrexone | Tablet: 50 mg; Injection: 380 mg | 17% reduction in heavy drinking; opioid blockade. |
| Substance Use (Nicotine) | Varenicline | Tablet: 0.5 mg, 1 mg | 25-30% abstinence; partial agonist superior to NRT. |
| Substance Use (Opioid) | Methadone (complementary) | Oral liquid: 5-10 mg/5 mL | 50-70% illicit use reduction in programs; mortality drop 59%. |
Musculoskeletal and Respiratory Medicines
Muscle relaxants, cholinesterase inhibitors, and joint disease treatments including gout and DMARDs
The World Health Organization's Model List of Essential Medicines (EML) designates peripherally-acting muscle relaxants and cholinesterase inhibitors for facilitating endotracheal intubation and providing muscle relaxation during surgical procedures, as well as for reversing neuromuscular blockade. These agents are critical in anaesthesia where controlled paralysis improves surgical conditions and patient safety, with selections based on pharmacokinetic profiles allowing rapid onset and offset to minimize residual effects post-operation. The 24th EML, published in September 2025, includes atracurium (injection: 10 mg/ml), suxamethonium (injection: 50 mg/ml), vecuronium (injection: 10 mg powder for reconstitution), and the cholinesterase inhibitor neostigmine (injection: 500 micrograms in 1-ml ampoule; tablet: 15 mg) as core medicines.[20] Atracurium and vecuronium are non-depolarizing agents preferred for their intermediate duration and spontaneous degradation independent of hepatic or renal function, reducing risks in patients with organ impairment, while suxamethonium offers rapid depolarization for emergency intubation despite risks like malignant hyperthermia in susceptible individuals.[131] Neostigmine reverses non-depolarizing blockade by inhibiting acetylcholinesterase to increase acetylcholine availability at neuromuscular junctions, often co-administered with atropine to counter muscarinic side effects; its inclusion extends to treating myasthenia gravis reversals in resource-limited settings where monitoring equipment may be absent.[132] Empirical data from perioperative studies confirm these agents' efficacy in reducing intubation failure rates to under 1% when used appropriately, though source credibility in anaesthesia literature favors peer-reviewed trials over anecdotal reports due to potential underreporting of adverse events in low-resource contexts.[133] For joint diseases, the EML prioritizes treatments targeting hyperuricemia in gout and disease-modifying agents for rheumatoid arthritis (RA), emphasizing cost-effective options that address inflammatory cascades and prevent joint destruction in populations with high disease burdens. Gout management centers on allopurinol (tablet: 100 mg), a xanthine oxidase inhibitor that lowers serum urate levels by inhibiting uric acid production, recommended for long-term prophylaxis after acute flares subside to reduce recurrence rates by up to 80% in clinical trials.[20] Its inclusion reflects evidence from randomized controlled trials showing sustained urate reduction below 6 mg/dL, correlating with fewer tophi and erosions, though monitoring for hypersensitivity syndrome—occurring in 0.1-0.4% of users, higher in HLA-B*5801 carriers—is essential, particularly in Southeast Asian populations where genetic prevalence elevates risks. Acute gout attacks may require adjunctive non-steroidal anti-inflammatory drugs or colchicine, but allopurinol remains core for chronic control due to its oral bioavailability and generic availability, averting renal complications from recurrent crystals.[72] Disease-modifying antirheumatic drugs (DMARDs) on the EML include methotrexate (tablet: 2.5 mg; injection: 50 mg/ml in 2-ml vial; complementary list: higher doses), sulfasalazine (tablet: 500 mg), chloroquine (tablet: 100-150 mg base; complementary), and azathioprine (tablet: 50 mg; complementary), selected for suppressing synovial inflammation and halting radiographic progression in RA. Methotrexate, the anchor therapy, inhibits dihydrofolate reductase to impair DNA synthesis in proliferating immune cells, achieving American College of Rheumatology 20% response criteria in 40-60% of patients within months when dosed at 7.5-25 mg weekly, with meta-analyses confirming delayed joint damage versus placebo.[134] Sulfasalazine, via 5-aminosalicylic acid metabolites, modulates cytokine production and neutrophil function, effective as monotherapy or combination for early RA, reducing disease activity scores by 30-50% in trials; chloroquine and azathioprine provide alternatives for milder cases or intolerance, though hepatic toxicity and myelosuppression necessitate baseline monitoring.[135] These DMARDs' prioritization stems from first-line status in guidelines, with real-world data from low-income settings showing improved functional outcomes and reduced disability-adjusted life years, despite academia's occasional overemphasis on biologics—unsupported by EML due to higher costs and access barriers—highlighting the list's focus on equitable, evidence-based interventions over emerging therapies lacking broad causal validation in diverse populations.[136]Antiasthmatics and COPD therapies
The WHO Model List of Essential Medicines designates specific inhaled bronchodilators and corticosteroids under the category of antiasthmatic medicines and those for chronic obstructive pulmonary disease (COPD), prioritizing agents with proven efficacy in relieving bronchospasm and controlling inflammation in resource-constrained settings.[21] These selections reflect clinical evidence from randomized trials showing short-acting beta-2 agonists like salbutamol improve forced expiratory volume in one second (FEV1) by 12-15% within minutes during acute attacks, while inhaled corticosteroids such as budesonide reduce exacerbation rates by 20-30% compared to placebo in moderate-to-severe asthma.[137] For COPD, long-acting muscarinic antagonists like tiotropium sustain bronchodilation, decreasing breathlessness and hospitalization risk by 14% over 12 months versus shorter-acting options.[138] Inclusion criteria emphasize cost-effectiveness, with generics enabling affordability where availability exceeds 80% in surveyed low- and middle-income countries (LMICs), though inhaler devices pose technique barriers reducing real-world efficacy.00330-8/fulltext) Key medicines include salbutamol for rapid symptom relief in both conditions, ipratropium bromide as an adjunct anticholinergic for additive bronchodilation (enhancing FEV1 by 10% beyond beta-agonists alone in acute COPD exacerbations), and combination budesonide-formoterol for dual anti-inflammatory and long-acting beta-agonist effects, supporting maintenance-and-reliever regimens that lower daily dosing needs.[139] Tiotropium addresses persistent airflow limitation in COPD, with trials confirming sustained FEV1 gains of 100-150 mL over baseline without tolerance development.[140] Epinephrine injection serves acute severe asthma unresponsive to inhalers, reversing anaphylactic components via alpha- and beta-adrenergic stimulation, though its use requires monitoring for cardiac risks.[21]| Medicine | Dosage Form(s) | Primary Use(s) |
|---|---|---|
| budesonide | Inhalation (aerosol): 100 mcg/dose; 200 mcg/dose | Asthma controller; COPD adjunct in frequent exacerbators |
| budesonide + formoterol | Dry powder inhaler: 100 mcg + 6 mcg/dose; 200 mcg + 6 mcg/dose | Asthma/COPD maintenance and reliever therapy |
| epinephrine (adrenaline) | Injection: 1 mg/mL in 1-mL ampoule | Acute severe asthma with anaphylaxis |
| ipratropium bromide | Inhalation (aerosol): 20 mcg/metered dose | Acute asthma/COPD exacerbations |
| salbutamol | Inhalation (aerosol/metered dose): 100 mcg/dose; Respirator solution: 5 mg/mL; Injection: 50 mcg/mL in 5-mL ampoule | Acute reliever for asthma/COPD |
| tiotropium | Powder for inhalation (capsule): 18 mcg; Inhalation solution: 1.25-2.5 mcg/actuation | COPD maintenance bronchodilator |
Ophthalmological and Ear/Nose/Throat Preparations
Anti-infectives, anti-inflammatories, anaesthetics, miotics, mydriatics, and anti-VEGF
The World Health Organization Model List of Essential Medicines designates specific ophthalmological preparations in the categories of anti-infectives, anti-inflammatories, local anaesthetics, miotics, mydriatics, and anti-vascular endothelial growth factor (anti-VEGF) agents to address prevalent eye conditions in resource-limited settings, prioritizing agents with proven efficacy against common pathogens, inflammation, and glaucoma while emphasizing affordability and availability.[21] These selections are based on epidemiological data showing high burdens of bacterial conjunctivitis, keratitis, viral infections like herpes simplex, fungal keratitis, uveitis, and angle-closure glaucoma in low- and middle-income countries, where access to specialized care is limited.[48] Evidence from clinical trials supports their use, such as randomized controlled studies demonstrating cure rates exceeding 80% for topical antibiotics in acute bacterial conjunctivitis.[143] Anti-infective agents target bacterial, viral, and fungal ocular infections, including trachoma and keratitis, which affect millions annually in endemic areas. The core list includes aciclovir 3% ointment for herpes simplex keratitis; azithromycin 1.5% eye drops for trachoma and chlamydial conjunctivitis; erythromycin 0.5% ointment for neonatal gonococcal ophthalmia and chlamydial infections; gentamicin solution (eye drops) for bacterial infections; ofloxacin 0.3% solution (eye drops) for bacterial corneal ulcers; and tetracycline 1% eye ointment for trachoma and other infections.[48] Natamycin 5% suspension (eye drops) is listed for fungal keratitis, supported by trials showing superior outcomes over voriconazole in reducing scarring.[21] A complementary listing includes povidone iodine 5% solution for preoperative disinfection, reducing endophthalmitis risk by up to 50% in surgical settings per meta-analyses.[48] Anti-inflammatory agents consist primarily of prednisolone 0.5% or 1% solution (eye drops) for anterior uveitis and scleritis, where it reduces inflammation and prevents vision loss; usage is cautioned with anti-infectives to avoid exacerbating infections, as evidenced by cohort studies linking steroid monotherapy to worsened keratitis outcomes.[48] Local anaesthetics feature tetracaine 0.5% solution (eye drops) for procedures like tonometry, foreign body removal, and suture adjustment, selected for rapid onset and short duration minimizing corneal toxicity risks observed in prolonged exposure studies.[21] Miotics and antiglaucoma medicines address acute and chronic glaucoma, a leading cause of irreversible blindness. Core agents include pilocarpine 2% or 4% solution (eye drops) for pupillary constriction in acute angle-closure glaucoma; and timolol 0.25% or 0.5% solution (eye drops), a beta-blocker reducing intraocular pressure by 20-25% in trials for open-angle glaucoma.[48] Acetazolamide tablet 250 mg or injection is complementary for refractory cases, inhibiting carbonic anhydrase to lower pressure, though systemic side effects like metabolic acidosis limit its use.[21] Mydriatics facilitate pupil dilation for refraction, examination, or uveitis treatment: atropine 0.1%, 0.5%, or 1% solution (eye drops) provides prolonged mydriasis, effective in cycloplegia as per pediatric refraction studies showing accurate measurements.[48] Anti-VEGF agents, on the complementary list for neovascular age-related macular degeneration and diabetic macular edema, include bevacizumab intravitreal injection (repurposed from oncology at lower cost), which inhibits vascular proliferation; real-world data from over 100,000 injections indicate visual acuity gains comparable to branded ranibizumab but at 1-2% of the price, justifying inclusion despite off-label status amid debates on regulatory approval for ocular use.[144] [21]ENT-specific medicines
The WHO Model List of Essential Medicines designates a limited set of topical preparations for ear, nose, and throat (ENT) conditions, emphasizing treatments for prevalent issues such as otitis externa and allergic rhinitis in settings with constrained resources. These complementary list items—acetic acid solution, budesonide nasal spray, and ciprofloxacin otic drops—target localized symptoms rather than systemic infections, which are addressed elsewhere in the list. Selection prioritizes agents with established efficacy against common bacterial and inflammatory pathologies, low cost, and minimal resistance risks when used topically.[21][48] Acetic acid 2% in alcohol ear drops serves as a first-line antiseptic for infectious diseases of the external ear, including acute otitis externa caused by Pseudomonas aeruginosa or fungal elements; its acidic pH disrupts microbial growth and biofilms without promoting antibiotic resistance. Clinical trials demonstrate resolution rates exceeding 80% in mild cases within 7-10 days, outperforming placebo in reducing pain and discharge, particularly in humid climates where swimmer's ear is endemic.[145][21] Budesonide nasal spray, at 100 micrograms per dose, is indicated for symptomatic relief of seasonal or perennial allergic rhinitis and adjunctive management of nasal polyps, reducing inflammation via glucocorticoid receptor agonism. Randomized controlled trials, including meta-analyses of over 5,000 patients, show significant improvements in nasal congestion, sneezing, and quality-of-life scores compared to placebo, with onset within 10 hours and sustained effects over 4-6 weeks; its inclusion reflects high prevalence of allergic ENT disorders in low-income populations, where oral alternatives pose greater systemic risks.[146][21] Ciprofloxacin 0.3% otic drops, or therapeutic equivalents, treat bacterial otitis externa refractory to acetic acid, leveraging fluoroquinolone bactericidal activity against gram-negative pathogens; guidelines recommend it for cases with perforation risk or prior treatment failure. Observational data from pediatric cohorts report cure rates of 70-90% after twice-daily application for 7 days, with low ototoxicity due to topical formulation, justifying its essential status amid rising community-acquired resistance to older agents like neomycin.[147][21]Other Supportive Medicines
Therapeutic foods, vitamins, minerals, and electrolyte solutions
The WHO Model List of Essential Medicines designates therapeutic foods, vitamins, minerals, and electrolyte solutions to combat malnutrition, micronutrient deficiencies, and dehydration, conditions that account for over 45% of deaths in children under 5 in low- and middle-income countries according to UNICEF estimates from 2023 data. These entries prioritize interventions with proven efficacy in reducing mortality, such as ready-to-use therapeutic food (RUTF) for severe acute malnutrition (SAM) and oral rehydration salts (ORS) for diarrheal dehydration, based on randomized controlled trials showing recovery rates exceeding 75% for outpatient RUTF use and a 93% reduction in diarrhea-related deaths attributable to ORS scale-up since the 1970s.[148][149] Therapeutic foods include RUTF, specified as a biscuit or paste with nutritional composition aligned to United Nations standards, providing high-energy (500 kcal per 92g sachet), micronutrient-enriched support for uncomplicated SAM in children over 6 months without medical complications. Developed in the 1990s and validated through cluster-randomized trials in Malawi and India, RUTF enables community-based treatment, achieving weight gain of 15-20g/kg/day and cure rates of 75-95% versus 50-60% for inpatient f-75 formulas, with minimal adverse events beyond mild gastrointestinal upset in under 5% of cases.[150] Its inclusion reflects cost-effectiveness, at $40-60 per child course, averting hospitalization costs and enabling scale-up to treat 5 million cases annually by 2023 per WHO reports.[21] Electrolyte solutions feature ORS, a glucose-sodium-potassium-citrate mixture in powder form for reconstitution (osmolarity ≤250 mOsm/L since 2003), targeting dehydration from acute diarrhea. Physiological studies confirm ORS exploits sodium-glucose cotransport in the small intestine, restoring fluid absorption at rates 20-25 times plasma levels, reducing stool output by 25% and vomiting incidence by 30% over prior hyperosmolar versions in meta-analyses of 18 trials involving 2,000+ children.[151] Potassium chloride and sodium chloride injections complement for severe cases requiring IV administration, while compound sodium lactate (Ringer's lactate) corrects acidosis and hypovolemia, with evidence from sepsis trials showing 15-20% mortality reductions versus saline alone.[21] Vitamins listed encompass retinol (vitamin A, oral 50,000-200,000 IU doses) to prevent xerophthalmia and reduce all-cause mortality by 24% in deficient populations per nine randomized trials; ascorbic acid (50mg tablets) for scurvy prevention; ergocalciferol or colecalciferol (400-1,000 IU) for rickets and hypocalcemia; and B-vitamins like thiamine (oral/parenteral for beriberi), riboflavin, nicotinamide, pyridoxine, folic acid (5mg for megaloblastic anemia), and hydroxocobalamin (IM for pernicious anemia). Multiple micronutrient powders for complementary feeding address overlapping deficiencies, with cluster trials in Asia showing 10-15% anemia reductions. Efficacy stems from supplementation trials in endemic areas, though over-supplementation risks like hypervitaminosis A (elevated intracranial pressure in 1-2% at high doses) necessitate targeted use.[21] Minerals include ferrous salts (e.g., sulfate 60mg elemental iron) for iron-deficiency anemia, increasing hemoglobin by 1-2g/dL in 12-week trials; zinc sulfate (10-20mg elemental) as ORS adjunct, shortening diarrhea duration by 25% and reducing incidence by 15% in Cochrane-reviewed studies of 24 trials; calcium (500mg elemental oral) for hypocalcemia and osteoporosis prevention; iodine for goiter prophylaxis; and potassium chloride for hypokalemia correction. These selections prioritize bioavailability and safety, with ferrous salts' absorption enhanced by vitamin C but limited by gastrointestinal side effects in 10-20% of users, underscoring need for fortified foods over supplements where feasible. Empirical data from demographic health surveys link their provision to 20-30% declines in deficiency-related morbidity since 2000.[48]| Category | Key Items | Forms and Strengths | Primary Indications |
|---|---|---|---|
| Therapeutic Foods | Ready-to-use therapeutic food | Biscuit or paste (UN-specified composition) | Severe acute malnutrition without complications |
| Electrolyte Solutions | Oral rehydration salts; Potassium chloride; Sodium chloride; Compound sodium lactate | Powder for ORS (low-osmolarity); Injectable solutions (e.g., 10-15% KCl, 0.9% NaCl) | Dehydration from diarrhea; Hypokalemia; Hyponatremia; Acid-base disturbances |
| Vitamins | Retinol; Ascorbic acid; Ergocalciferol/Cholecalciferol; Thiamine; etc. | Oral liquids/solids (e.g., 50mg ascorbic; 400 IU vitamin D); Parenteral where noted | Deficiency prevention (e.g., night blindness, scurvy, rickets, beriberi) |
| Minerals | Ferrous salt; Zinc sulfate; Calcium; Iodine | Oral solids (e.g., 60mg Fe; 20mg Zn); IV calcium gluconate (100mg/mL) | Anemia; Diarrhea adjunct; Hypocalcemia; Goiter |