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Clarithromycin

Clarithromycin is a semisynthetic derived from erythromycin, chemically known as 6-O-methylerythromycin with the molecular formula C₃₈H₆₉NO₁₃. It belongs to the class of antibiotics and is used to treat a variety of mild-to-moderate bacterial infections, including those of the , skin, and soft tissues. Clarithromycin exhibits a broader spectrum of activity and improved pharmacokinetic profile compared to its parent compound erythromycin, allowing for better oral absorption and tissue penetration. Developed in the 1970s by the Japanese pharmaceutical company as an enhancement over erythromycin's limitations, such as acid instability and gastrointestinal side effects, clarithromycin was approved for use in 1991. It quickly became a widely prescribed in the U.S., though its use has declined in recent years due to safety concerns. As a second-generation , it represents an evolution from the first-generation erythromycin introduced in the , offering enhanced efficacy against common respiratory pathogens. Clarithromycin exerts its antibacterial effect by binding to the 50S ribosomal subunit of susceptible , thereby inhibiting protein and leading to bacterial growth cessation. It is primarily metabolized by 3A isozymes, producing an , 14-hydroxyclarithromycin, which contributes to its therapeutic activity, particularly against . The drug achieves high concentrations in tissues such as the lungs and skin, making it suitable for treating localized infections. Common indications for clarithromycin include , , , , skin and soft tissue infections, and eradication in combination with other agents like amoxicillin and a . It is effective against major respiratory pathogens such as , , and . However, bacterial resistance, particularly via ribosomal methylation, has emerged as a concern, influencing its use in certain guidelines. Notable safety considerations include an increased risk of prolongation and , particularly in patients with cardiac risk factors, leading to FDA warnings and recommendations against its use in such populations. Gastrointestinal adverse effects like and are frequent, though less severe than with erythromycin. Clarithromycin is contraindicated with certain drugs like due to potential for serious arrhythmias.

Medical uses

Treatment of bacterial infections

Clarithromycin is approved for the treatment of mild to moderate bacterial infections caused by susceptible strains, including those of the upper and lower , and , and specific opportunistic infections. In upper respiratory tract infections, it is indicated for acute maxillary due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae; or due to Streptococcus pyogenes; and acute in children due to H. influenzae, M. catarrhalis, or S. pneumoniae. For lower respiratory tract infections, clarithromycin treats acute exacerbations of chronic due to H. influenzae, M. catarrhalis, or S. pneumoniae, as well as (CAP) caused by H. influenzae, Mycoplasma pneumoniae, S. pneumoniae, or Chlamydia pneumoniae. As per the 2025 American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) guidelines for , monotherapy such as a single 2 g dose of (preferred) or clarithromycin (500 mg twice daily for less than 5 days if clinically stable) is suggested for outpatient of healthy adults without comorbidities when bacterial is suspected and atypical pathogens may be involved, especially in penicillin-allergic patients; empiric antibiotics are suggested even if a respiratory is detected due to risk. For non-severe hospitalized cases, with a such as and a is recommended. For , the Centers for Disease Control and Prevention (CDC) endorses clarithromycin as an alternative to penicillin in allergic individuals, with a 10-day course to eradicate group A . Clarithromycin plays a key role in for Helicobacter pylori eradication in patients with , typically administered as 500 mg twice daily with amoxicillin (1 g twice daily) and a (e.g., omeprazole 20 mg twice daily) for 14 days; however, the 2024 American College of Gastroenterology (ACG) guidelines recommend this regimen only if prior antimicrobial susceptibility testing confirms clarithromycin sensitivity, due to rising resistance rates exceeding 15% in many regions, preferring bismuth quadruple therapy otherwise. For skin and soft tissue infections, clarithromycin is indicated for uncomplicated cases such as or due to or S. pyogenes, with the IDSA guidelines supporting its use in mild, non-purulent infections as an alternative for beta-lactam-intolerant patients, emphasizing a 5- to 10-day course after source control. In immunocompromised patients, particularly those with and counts below 50 cells/μL, clarithromycin is used for primary prophylaxis against disseminated * (MAC) disease, as per CDC recommendations, reducing incidence by over 90% in clinical trials; it serves as an alternative to preferred when the latter is not tolerated. Standard dosing regimens for most infections are 250-500 mg orally twice daily for adults (or 1,000 mg once daily extended-release for or ) and 15 mg/kg/day divided every 12 hours for children (maximum 1,000 mg/day), with durations typically ranging from 7 to 14 days to ensure bacterial eradication while minimizing risk; adjustments are required for renal impairment (creatinine clearance <30 mL/min: 50% dose reduction). For H. pylori eradication and MAC prophylaxis, the adult dose is 500 mg twice daily, with pediatric MAC prophylaxis at 7.5 mg/kg twice daily (up to 500 mg twice daily). The World Health Organization includes clarithromycin on its Model List of Essential Medicines for treating respiratory tract infections and as part of regimens for H. pylori in resource-limited settings where susceptibility allows.

Spectrum of activity

Clarithromycin exhibits a broad spectrum of antibacterial activity, primarily targeting Gram-positive aerobes, some Gram-negative aerobes, and several atypical and intracellular pathogens. Its efficacy stems from its semisynthetic modification of erythromycin, enhancing its stability and penetration properties. Against Gram-positive bacteria, clarithromycin demonstrates strong activity, particularly against Streptococcus pneumoniae, Streptococcus pyogenes, and methicillin-sensitive Staphylococcus aureus. For S. pneumoniae, the modal minimum inhibitory concentration (MIC) is approximately 0.03 mg/L, with MIC90 values typically ranging from 0.12 to 0.5 mg/L for susceptible strains. Clarithromycin provides effective coverage against atypical respiratory pathogens, including Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. MIC90 values for M. pneumoniae are notably low, around 0.004 mg/L, underscoring its potency in community-acquired pneumonia caused by these organisms. The antibiotic is also effective against Helicobacter pylori in combination regimens for peptic ulcer disease, with typical MIC90 values of 0.25 mg/L for susceptible isolates, though rising resistance impacts eradication rates. Additionally, clarithromycin shows significant activity against Mycobacterium avium complex (MAC), particularly in disseminated infections among immunocompromised patients, where it reduces bacteremia when used in multidrug therapy. Resistance to clarithromycin among streptococci has emerged as a concern, with macrolide resistance rates in S. pneumoniae reaching 30-40% in various regions, driven primarily by the , which encodes ribosomal and confers high-level resistance via the MLSB . Efflux-mediated resistance via mef(A) is another mechanism but typically results in lower-level resistance. Compared to erythromycin, clarithromycin offers improved acid stability due to a at the C-6 position, reducing gastric degradation, and superior tissue penetration, achieving higher concentrations in and tissues, which enhances its clinical utility against respiratory pathogens.

Use in

Idiopathic hypersomnia is a central disorder of hypersomnolence characterized by despite adequate sleep duration, without or other features typical of , often accompanied by prolonged and unrefreshing naps. Clarithromycin, a , has been investigated off-label for treating , primarily based on small-scale studies suggesting improvements in subjective sleepiness. In a of 53 patients with and suspected GABA-A receptor hyper-reactivity, 64% reported reduced daytime sleepiness after a 2-week of clarithromycin, with significant improvements in reaction times on vigilance testing among responders; 38% continued long-term use. A randomized, double-blind, -controlled crossover involving 22 adults with or without found that clarithromycin (500 mg twice daily for 2 weeks) led to modest reductions in (ESS) scores (mean decrease of 3.4 points versus 1.1 for placebo) and improved subjective alertness, though objective measures like maintenance of wakefulness test showed no significant change. The proposed mechanisms for clarithromycin's effects in involve negative allosteric modulation of GABA-A receptors, reducing inhibitory neurotransmission in the , as demonstrated in neuronal cultures where it decreased GABA-mediated signaling. Additional hypotheses include suppression of pro-inflammatory cytokines or alterations in that influence sleep-wake regulation, though these remain under investigation. Typical dosing in these studies is 500 mg orally twice daily (with meals), though lower doses such as 250 mg daily have been explored off-label for maintenance to minimize side effects. Long-term use requires monitoring for gastrointestinal upset, taste disturbances, and potential cardiac risks due to prolongation. Despite these findings, clarithromycin lacks FDA approval for , and evidence is limited by small sample sizes and study designs; a 2021 Cochrane review concluded insufficient data to confirm efficacy, based on one low-quality trial with only 10 participants showing no significant differences from . The issued a conditional recommendation for its use in adults, citing moderate-quality evidence from one randomized trial and one , but emphasized the need for larger randomized controlled trials. Ongoing research in the , including a 2019-initiated mechanistic study (NCT04026958), continues to evaluate its impact on sleepiness and in syndromes, with preliminary data supporting subjective benefits but highlighting variability in response.

Safety profile

Contraindications

Clarithromycin is contraindicated in patients with a known to clarithromycin, erythromycin, or any other , as well as to any component of the formulation, due to the risk of severe allergic reactions. Concomitant use of clarithromycin with certain drugs metabolized by , such as , , or ergotamine/, is prohibited because clarithromycin inhibits , leading to elevated plasma levels of these agents and an increased risk of prolongation, potentially resulting in and sudden cardiac death. Patients with a history of cholestatic or hepatic dysfunction associated with previous clarithromycin or other therapy should not receive clarithromycin, as rechallenge may precipitate recurrent severe . Clarithromycin is contraindicated in individuals with known prolongation of the , congenital , or a history of ventricular cardiac , including , owing to its potential to exacerbate these conditions and cause life-threatening arrhythmias. Coadministration of clarithromycin and is contraindicated in patients with renal or hepatic impairment, as this combination substantially increases exposure, heightening the risk of colchicine-induced and . For certain formulations, such as the oral suspension, clarithromycin should be avoided in infants under 6 months of age, as safety and effectiveness have not been established in this population.

Adverse effects

Clarithromycin is generally well tolerated, but adverse effects occur in a notable proportion of patients, with gastrointestinal disturbances being the most frequent, affecting up to 13% overall. Discontinuation due to adverse reactions occurs in approximately 1-3% of patients, similar to rates with comparators in clinical trials. Gastrointestinal effects are common, including (up to 10%), (5-8%), (2%), and disturbances such as a metallic taste (3-6%). These symptoms are typically mild to moderate and often resolve upon cessation of . Cardiac risks include prolongation, which is dose-dependent and more pronounced with intravenous administration than oral forms. Ventricular arrhythmias, such as , are rare, occurring in less than 1% of patients, though the increases in those with predisposing factors like imbalances. Meta-analyses from the 2010s indicate that clarithromycin use may elevate the short-term of cardiovascular events, including and cardiac mortality, with hazard ratios around 1.3-2.5 compared to non-use. Some meta-analyses indicate a short-term increased of cardiovascular events (hazard ratios around 1.2-2.5 during or shortly after ); however, recent studies (2023-2025) show mixed results with no consistent of long-term beyond the treatment period. A 2025 multicenter found clarithromycin associated with increased of major adverse cardiovascular events (MACE) in adults with , though other recent analyses report no consistent elevation in long-term outcomes. Hepatic effects involve elevated liver enzymes in 2-3% of patients, with rare instances of cholestatic that may require discontinuation. For renal considerations, dose adjustment is recommended in patients with creatinine clearance below 30 mL/min to prevent accumulation and potential toxicity. Central nervous system effects include (2%) and (1-2%), while hallucinations and seizures are rare, reported in isolated cases particularly in patients with renal . Other adverse effects encompass superinfections such as difficile-associated (1-2%) and allergic reactions, including (1%) and (less than 0.1%). Long-term use may lead to due to disruption of normal flora.

Drug interactions

Clarithromycin is a strong inhibitor of the 3A4 () enzyme, which can significantly increase plasma concentrations of co-administered metabolized by this pathway, potentially leading to enhanced toxicity or adverse effects. This inhibition also affects (P-gp), a transporter involved in drug efflux, further amplifying interactions with substrates of both and P-gp. Clinicians are advised to monitor drug levels, adjust doses, or select alternative antibiotics when possible to mitigate these risks. Concomitant use with statins metabolized by CYP3A4, such as and simvastatin, is contraindicated due to the risk of from markedly elevated exposure; clarithromycin can increase simvastatin area under the curve (AUC) by up to 10-fold. For , the dose should be limited to 20 mg daily, and for pravastatin, to 40 mg daily, with close monitoring for muscle toxicity. Similarly, interaction with like verapamil can elevate their levels, increasing the risk of ; dose reduction of the is recommended. With , clarithromycin can double or more its serum concentrations, heightening seizure risk, necessitating carbamazepine level monitoring and potential dose reduction. Life-threatening and fatal interactions have been reported with , as clarithromycin's dual inhibition of and P-gp substantially increases colchicine exposure, leading to and neuropathy; co-administration is contraindicated in patients with renal or hepatic impairment, and colchicine dose should be reduced by 75% in those with normal function. For protease inhibitors like , the interaction is bidirectional: ritonavir boosts clarithromycin by 77% while clarithromycin mildly increases ritonavir exposure by about 12%; clarithromycin doses exceeding 1 g daily should be avoided with ritonavir, with reduction to 500 mg twice daily otherwise. Clarithromycin can potentiate the anticoagulant effects of by increasing its levels, requiring close INR monitoring and possible dose adjustment. It also elevates concentrations via inhibition, potentially causing ; levels should be monitored, and doses reduced as needed. For , clarithromycin inhibits P-gp-mediated renal and intestinal efflux, increasing exposure by up to 70% or more, which may lead to ; serum levels must be monitored, and doses adjusted accordingly. Recent updates highlight interactions with novel antivirals, such as (Paxlovid), where ritonavir's inhibition further elevates clarithromycin levels, potentially exacerbating its own toxicities; alternative antibiotics are preferred, or clarithromycin dose reduction considered under close supervision. For immunomodulators like , clarithromycin may increase exposure via inhibition, warranting dose adjustments per product labeling.

Use during pregnancy and breastfeeding

Based on findings from , clarithromycin is not recommended for use in women except in clinical circumstances where no alternative is appropriate. There are no adequate and well-controlled studies in women. In , including rats and monkeys, high doses of clarithromycin resulted in embryofetal , such as decreased fetal weight, skeletal variations, and increased fetal loss, particularly at exposures exceeding therapeutic levels. data remain limited, with no large-scale randomized controlled trials available, leading to recommendations that clarithromycin be avoided in individuals except in cases where no suitable alternatives exist. Observational studies from the have raised concerns about potential risks, particularly when clarithromycin is used in the first . A large involving over 65,000 pregnancies found that exposure to clarithromycin was associated with an increased of 1.65 (95% 1.07 to 2.54) for any major congenital malformation and 2.80 (95% 1.50 to 5.24) specifically for cardiac malformations, such as conotruncal defects, compared to penicillin use. Other analyses of exposure, including clarithromycin, have reported a 1.5- to 2-fold increased risk of cardiovascular anomalies, though confounding factors like underlying infections may contribute. Due to these findings, alternatives such as , which has a more favorable safety profile in , are preferred for therapy needs during . Regarding breastfeeding, clarithromycin is excreted into human milk at low concentrations, with peak levels of approximately 0.25 mg/L and a relative infant dose estimated at 0.9% to 1.7% of the maternal weight-adjusted dose. It is generally considered compatible with by authoritative sources, as the amounts are unlikely to cause significant adverse effects in most , and the drug is safely administered directly to pediatric patients at higher doses. However, infants should be monitored for gastrointestinal disturbances, such as or , and a potential, though rare, risk of has been noted in association with exposure during breastfeeding based on epidemiologic data. Postpartum guidelines recommend continuing breastfeeding without interruption, but if concerns arise, timing feeds to coincide with trough drug levels (e.g., 4-6 hours post-dose, given clarithromycin's of 3-4 hours) may minimize exposure; recent registry data and cohort studies from the early 2020s, including follow-up on macrolide-exposed infants, show no significant long-term neurodevelopmental or growth impacts.

Pharmacology

Mechanism of action

Clarithromycin, a , exerts its primary antibacterial effect by reversibly binding to the 50S subunit of the bacterial , specifically at domain V of the 23S rRNA, which blocks the nascent peptide exit tunnel and prevents the elongation of the polypeptide chain during protein synthesis. This inhibition disrupts essential bacterial protein production, leading to bacteriostatic activity against most susceptible pathogens. At higher concentrations, such as four times the , clarithromycin demonstrates bactericidal effects against certain organisms, including , by accelerating bacterial killing within hours of exposure. Compared to its predecessor erythromycin, clarithromycin offers enhanced pharmacological properties, including greater resistance to hydrolysis in due to a methoxy substitution at the C-6 position of the erythronolide ring, and superior intracellular accumulation in tissues and , which improves its efficacy against intracellular pathogens. Beyond its antimicrobial action, clarithromycin exhibits effects by inhibiting the activation of in immune and epithelial cells, thereby suppressing the production of proinflammatory cytokines such as interleukin-6 and tumor factor-alpha. This mechanism contributes to its utility in non-infectious inflammatory conditions. Clarithromycin shows no significant activity against Gram-negative enteric bacteria primarily due to poor penetration across their outer membrane, compounded by efflux pumps that limit intracellular drug levels.

Pharmacokinetics

Clarithromycin is rapidly absorbed from the gastrointestinal tract following oral administration, with an absolute bioavailability of approximately 50-55%. The presence of food may enhance the extent of absorption, increasing bioavailability by up to 25% for certain tablet formulations, though the effect varies and is not always significant across studies. For immediate-release formulations, peak plasma concentrations (Cmax) of 1-2 mcg/mL are typically achieved 1-2 hours after a 250 mg dose. In contrast, extended-release formulations exhibit delayed absorption, with Cmax reached 4-6 hours post-dose, allowing for once-daily dosing while maintaining therapeutic levels. The drug demonstrates extensive distribution throughout the body, with high penetration into tissues such as the lungs, where concentrations can be 10-20 times higher than in , supporting its in respiratory infections. Clarithromycin exhibits low (around 40-70%, decreasing at higher concentrations) and readily crosses biological membranes due to its lipophilic nature. Its , 14-OH-clarithromycin, also distributes widely and contributes significantly to antimicrobial activity, particularly against , where it accounts for 20-40% of the combined effect due to its comparable or enhanced potency relative to the parent compound. Clarithromycin undergoes hepatic metabolism primarily via the enzyme , producing the active 14-OH-clarithromycin . The elimination of the parent drug is 3-4 hours following 250 mg doses every 12 hours, extending to 5-7 hours at higher doses like 500 mg due to slight nonlinearity in . The has a of 5-7 hours, contributing to prolonged activity. occurs mainly through hepatic and renal routes, with approximately 20% of the dose eliminated unchanged in the after 250 mg and 10-15% in , primarily as metabolites. The remainder is excreted as metabolites, with renal clearance accounting for about 15-20 mL/min in healthy individuals. In patients with renal impairment ( clearance <30 mL/min), clearance is reduced, necessitating dose adjustments to avoid accumulation. Hepatic impairment similarly prolongs and reduces clearance, requiring cautious dosing.

History and development

Discovery and approval

Clarithromycin was developed by researchers at Co., Ltd. in during the early as a semisynthetic derivative of erythromycin A. The key modification involved selective 6-O-methylation at the C-6 hydroxyl group of erythromycin, achieved through the use of 9-oxime intermediates to enable regioselective protection and methylation. This structural alteration was designed to address limitations of erythromycin, such as instability in acidic environments. Taisho launched the drug under the brand name Clarith in the market in 1991, following initial research efforts that began in the late 1970s. Preclinical evaluations highlighted clarithromycin's advantages over erythromycin, including markedly improved acid stability due to the 6-O-methyl group, which prevented rapid degradation in gastric conditions and resulted in higher oral of approximately 55% compared to erythromycin's 30-65%. Additionally, the modification reduced gastrointestinal side effects by minimizing the formation of inactive degradation products and lowering stimulation of motilin receptors, which are associated with erythromycin-induced and motility disturbances. These properties positioned clarithromycin as a more tolerable and effective oral for clinical use. The U.S. (FDA) granted initial approval for clarithromycin (as Biaxin) on October 31, 1991, for treating mild to moderate infections of the , skin, and skin structure caused by susceptible bacteria such as and . In December 1992, the FDA expanded its indications to include prophylaxis against disseminated (MAC) disease in patients with advanced infection, marking the first such approval for a in this context; treatment of active MAC infections followed shortly thereafter. In Europe, clarithromycin received marketing authorization in 1990 through , Taisho's international partner since 1985, for similar antibacterial indications. Clarithromycin was added to the World Health Organization's Model List of Essential Medicines in 1998, specifically noted for its role in combination regimens for eradication in , reflecting its global importance in treating common bacterial infections. The original patents for clarithromycin expired in the early 2000s—2004 in and May 2005 in the U.S.—paving the way for widespread generic production and increased accessibility.

Regulatory actions and warnings

In 2001, the U.S. Food and Drug Administration (FDA) added a warning to the labeling of clarithromycin regarding drug interactions that can cause QT interval prolongation, potentially leading to torsades de pointes and sudden cardiac death, particularly when coadministered with drugs like pimozide that also affect cardiac repolarization. This action followed post-marketing reports of serious cardiac events, including two cases of sudden death associated with the combination of clarithromycin and pimozide. The FDA has issued a black box warning for clarithromycin in the United States, contraindicating its use with certain substrates such as due to the risk of life-threatening cardiac arrhythmias from QT prolongation and elevated levels. In 2018, the FDA updated the labeling to include additional warnings on the risk of and when clarithromycin is used concomitantly with s like or simvastatin, stemming from inhibition that increases exposure. In 2018, the () recommended restricting clarithromycin use in patients with heart disease following a review of epidemiological studies, including meta-analyses, indicating an increased short-term risk of cardiovascular mortality compared to other antibiotics. This led to enhanced product information emphasizing avoidance in individuals with coronary heart disease, , or significant arrhythmias to mitigate short-term risks of and sudden cardiac death. Clarithromycin has faced restrictions or suspensions in certain countries, including limited pediatric use in the for children under 6 months of age due to insufficient safety data and potential for adverse effects in this population. In the 2020s, regulatory agencies have implemented further actions, such as the EMA's 2021 updates to labeling regarding prolongation risks, including recommendations for monitoring in patients with hypomagnesaemia and avoidance in high-risk cardiac patients. Similarly, the FDA reinforced warnings in 2018 and beyond, advising against clarithromycin in patients with preexisting cardiac conditions based on observational data showing elevated long-term mortality. These regulatory measures have influenced clinical guidelines, including the American Heart Association's reduced recommendation for clarithromycin in prophylaxis, favoring narrower indications and alternative agents to minimize cardiac risks in at-risk populations.

Society and culture

Available formulations

Clarithromycin is available in several pharmaceutical formulations for oral and intravenous administration, tailored to different patient needs and infection severities. The primary oral forms include immediate-release tablets in strengths of 250 mg and 500 mg, which are typically taken twice daily, and extended-release tablets of 500 mg designed for once-daily dosing. For pediatric patients or those unable to swallow tablets, clarithromycin is offered as an oral suspension in concentrations of 125 mg/5 mL and 250 mg/5 mL, reconstituted from granules prior to use. The reconstituted suspension should be stored at (15–30°C), shaken well before each dose, and discarded after 14 days or if unused, as it does not require but maintains under these conditions. In severe infections requiring management, an intravenous is available outside the (e.g., in the UK and ) as a 500 mg powder in a single-dose , reconstituted and diluted for over at least 60 minutes every 12 hours. The extended-release provides comparable to the immediate-release version but allows for simplified once-daily administration, potentially reducing gastrointestinal upset such as and compared to twice-daily dosing. Certain formulations include excipients that may pose risks for specific patients; for instance, some immediate-release tablets contain lactose monohydrate, which could affect those with , while oral suspensions often include as a , a concern for individuals with . Regulatory approvals show consistency in available strengths between the FDA and EMA, with both agencies endorsing the 250 mg and 500 mg immediate-release tablets, 500 mg extended-release tablets, and 125 mg/5 mL and 250 mg/5 mL oral suspensions, though minor differences may exist in excipient compositions across regions.

Brand names and manufacturers

Clarithromycin was originally marketed under the brand name Biaxin in the by , which is now part of following a corporate ; the Biaxin brand has been discontinued in the , but generic versions remain available. In and , it is primarily sold as Klacid, also developed and initially manufactured by . Regional variations include Klaricid in the , originally produced by , and Macladin in , manufactured by Laboratori Guidotti. Following the expiration of key patents in the United States on May 23, 2005, clarithromycin became widely available as a , leading to a significant shift in market dynamics with generics comprising the majority of prescriptions. Major generic manufacturers include , which produces extended-release tablets equivalent to Biaxin XL; (now part of ), offering film-coated tablets; , providing various formulations; and (now under ), which was among the first to gain FDA approval for generic clarithromycin tablets and oral suspensions in 2007. A notable combination product is Prevpac, which pairs clarithromycin with amoxicillin and for the treatment of infections associated with duodenal ulcers; this was originally approved by the FDA under . Generic versions of clarithromycin are available in tablet and suspension forms from these manufacturers, supporting broad accessibility for both immediate- and extended-release formulations. The post-patent era has seen occasional challenges, including recalls of certain products due to quality issues; for instance, in 2015, recalled batches of clarithromycin tablets classified as a Class II recall by the FDA, indicating potential temporary or reversible adverse health effects.

Research directions

Emerging antimicrobial applications

Clarithromycin is being investigated as an alternative for caused by in patients intolerant to first-line agents like . such as clarithromycin are recommended in clinical guidelines for individuals with allergies or contraindications to tetracyclines, offering a viable option despite potentially lower efficacy compared to standard treatments. A pilot study from 1991 demonstrated clarithromycin's effectiveness in resolving early symptoms, with resolving in most participants after 14-21 days of , supporting its role as a promising alternative that warrants further evaluation in modern trials. Although phase II data from the 2020s specifically for clarithromycin remain limited, its use aligns with broader applications in borrelial infections for intolerant patients. In the management of , clarithromycin has garnered attention for its anti-inflammatory properties, potentially reducing as an adjunct to standard care. Early observational studies indicated that initiating oral clarithromycin within the first few days of moderate hospitalization improved clinical outcomes, including shorter hospital stays and lower rates of , attributed to modulation of inflammatory pathways. A phase II trial (NCT04398004) further explored its addition to , showing enhanced early recovery in non-severe cases through reduced . However, randomized controlled trials have yielded mixed results, with some demonstrating modest benefits in viral respiratory infections while others reported no significant impact on progression to severe disease or mortality, highlighting the need for larger confirmatory studies. Beyond established use against Mycobacterium avium complex, clarithromycin plays a central role in combination regimens for nontuberculous mycobacterial infections, particularly M. abscessus in patients. Clinical guidelines from the Cystic Fibrosis Foundation endorse clarithromycin susceptibility testing alongside agents like and for M. abscessus complex, as it forms the backbone of multidrug therapy aimed at achieving sputum conversion and halting lung function decline. Retrospective analyses of treatment outcomes in cohorts reveal that clarithromycin-containing regimens, often paired with imipenem or , are associated with improved microbiological clearance rates, though cure rates remain below 50% due to intrinsic resistance mechanisms. Ongoing research emphasizes personalized dosing based on erm(41) gene status to optimize efficacy in this high-risk population. Efforts to combat antibiotic resistance have spotlighted clarithromycin's potential in disrupting biofilms, which contribute to chronic infections like . In pediatric cases of persistent middle ear inflammation following acute caused by , adjunctive clarithromycin therapy significantly reduced volumes and inflammatory markers compared to standard care alone, suggesting interference with biofilm-mediated persistence. In vitro models of chronic suppurative demonstrate that clarithromycin, particularly in combination with , enhances eradication of biofilms on mucosa by penetrating matrix barriers and inhibiting bacterial regrowth. The biofilm inhibition mechanism involves downregulation of quorum-sensing signals and disruption of extracellular polymeric substances, enabling better access to embedded pathogens. In vitro studies have elucidated clarithromycin's synergistic interactions with other agents, such as rifampin, against biofilm-associated bacteria. Combinations of clarithromycin and rifampin incorporated into polymer films prevented Staphylococcus aureus biofilm formation and achieved over 99.9% bacterial kill for up to 72 hours in MRSA models, outperforming single agents through complementary inhibition of adhesion and replication. Similarly, clarithromycin synergizes with fosfomycin to impair Staphylococcus pseudintermedius biofilm development, reducing minimum biofilm inhibitory concentrations by targeting multiple metabolic pathways. These findings underscore clarithromycin's utility in multidrug strategies for resistant chronic infections, with rifampin enhancing its penetration into staphylococcal biofilms. As of 2025, clinical trials continue to evaluate clarithromycin's expanded roles, including in respiratory infections. Broader investigations into adjunctive therapy for , such as the ongoing REACT trial (NCT06294600), explore clarithromycin's impact on progression, reflecting its evolving applications in viral-bacterial co-infections.

Investigations in sleep disorders

Recent small-scale clinical trials have examined clarithromycin's efficacy in without , a syndrome characterized by absent deficiency. A randomized crossover trial involving 23 adults with GABA-related hypersomnias, including those with without , demonstrated significant subjective reductions in scores after two weeks of clarithromycin (up to 1000 mg daily) compared to , though objective performance did not improve. No direct modulation of receptors was observed or hypothesized in this study, with benefits attributed instead to clarithromycin's negative allosteric modulation of GABA-A receptors. A retrospective clinical experience review of 53 patients with GABA-related hypersomnias, encompassing 12 with without , reported subjective daytime sleepiness improvements in 64% following clarithromycin treatment (500-1000 mg daily for two weeks), with significant enhancements in reaction times on vigilance testing among responders. Approximately 38% of participants elected to continue low-dose clarithromycin long-term for symptom management, suggesting potential tolerability in chronic use for hypersomnolence, though formal long-term safety data remain limited. Common adverse effects included gastrointestinal distress and altered taste in 19% of cases, with no serious events reported; however, risks such as resistance and P450-mediated drug interactions warrant monitoring. In comparison to approved agents like sodium oxybate, which targets cataplexy and sleepiness in narcolepsy type 1 through GABA-B agonism and consolidation of nighttime sleep, clarithromycin shows preliminary promise in non-cataplectic hypersomnias but lacks head-to-head trials or meta-analyses establishing equivalent efficacy. A completed multicenter mechanistic study (NCT04026958) assessed clarithromycin's effects on sleepiness in adults with narcolepsy (types 1 and 2) and idiopathic hypersomnia, incorporating neuroimaging and biomarker analyses to identify predictors of response, such as GABA-related cerebrospinal fluid modulators. Challenges in advancing clarithromycin for sleep disorders include the need for validated biomarkers to stratify responders, as current evidence derives from small cohorts with subjective endpoints predominating over objective measures. While exploratory pediatric applications in have been considered due to parallels with adult dysregulation, no dedicated trials exist as of 2025, raising ethical concerns regarding off-label use in children.