Lansoprazole

Lansoprazole is a proton pump inhibitor (PPI) medication that decreases the amount of acid produced in the stomach by irreversibly inhibiting the gastric H+/K+ ATPase enzyme in parietal cells.^[1]^[2] It is indicated for the short-term treatment (up to 8 weeks) of active duodenal ulcers, gastric ulcers, and erosive esophagitis associated with gastroesophageal reflux disease (GERD), as well as for the long-term management of pathological hypersecretory conditions such as Zollinger-Ellison syndrome.^[3]^[4]^[5] First approved by the U.S. Food and Drug Administration (FDA) on May 10, 1995, under the brand name Prevacid, lansoprazole was developed by Takeda Pharmaceuticals and is now available as a generic drug in delayed-release oral capsules (15 mg and 30 mg) and orally disintegrating tablets.^[6]^[7] As part of the PPI class, lansoprazole provides superior acid suppression compared to H2-receptor antagonists, promoting ulcer healing and symptom relief while reducing the risk of complications like bleeding or perforation in acid-related disorders.^[8]^[9] Common side effects include headache, diarrhea, and abdominal pain, though long-term use has been associated with risks such as nutrient deficiencies, bone fractures, and increased susceptibility to infections; it is generally well-tolerated when used as directed.^[4]^[5]

Pharmacology

Mechanism of action

Lansoprazole is a substituted benzimidazole that functions as a proton pump inhibitor (PPI). It irreversibly inhibits the H⁺/K⁺-ATPase enzyme, commonly referred to as the proton pump, which is situated on the apical membrane of gastric parietal cells and catalyzes the final step in acid secretion by exchanging intracellular hydrogen ions for extracellular potassium ions.^[1]^[2] As a prodrug, lansoprazole is inactive until it reaches the acidic environment of the secretory canaliculi in activated parietal cells, where it becomes protonated and undergoes rearrangement to form a reactive sulfenamide intermediate. This sulfenamide then forms a stable covalent disulfide bond with one or more cysteine residues on the H⁺/K⁺-ATPase, primarily Cys813 and Cys321, thereby inactivating the enzyme and halting proton translocation into the gastric lumen.^[8]^[10] The irreversible nature of this binding leads to prolonged suppression of gastric acid production, lasting 24 to 48 hours or until new H⁺/K⁺-ATPase enzymes are synthesized by the parietal cells.^[2]^[8] In comparison to other PPIs, lansoprazole exhibits a distinct binding profile—targeting Cys813 and Cys321—while omeprazole binds Cys813 and Cys892, and pantoprazole binds Cys813 and Cys822; these differences may subtly affect recovery kinetics and potency, though lansoprazole provides comparable duration and efficacy in acid inhibition overall.^[8] By blocking the proton pump, lansoprazole reduces both basal and stimulated gastric acid output by up to 90%.^[11]^[12]

Pharmacokinetics

Lansoprazole is rapidly absorbed following oral administration, with an absolute bioavailability of approximately 80% to 90% after the initial dose, increasing to nearly 100% upon repeated dosing due to saturation of first-pass metabolism.^[13]^[14] Peak plasma concentrations are typically achieved within 1.7 hours for immediate-release formulations, though this may be delayed in delayed-release capsules due to enteric coating dissolution in the small intestine. Food intake can delay absorption and slightly reduce the extent of bioavailability by about 25%, but does not significantly alter overall exposure with multiple doses.^[13]^[15] The drug is highly protein-bound (approximately 97%) and widely distributed in the body. Metabolism occurs primarily in the liver through cytochrome P450 enzymes, with CYP2C19 responsible for the major pathway producing the active metabolite 5'-hydroxy lansoprazole, and CYP3A4 contributing to additional hydroxylation and sulfoxidation. These metabolites retain proton pump inhibitory activity, extending the pharmacological effect.^[13]^[8] The plasma elimination half-life of lansoprazole is 1.5 to 2 hours in healthy adults, though the duration of acid suppression exceeds this due to irreversible binding to proton pumps. Excretion is predominantly fecal via biliary secretion, accounting for about two-thirds of the dose as metabolites, with less than 1% of unchanged drug recovered in urine; renal clearance is minimal, and no dosage adjustment is required for mild to moderate renal impairment. In severe hepatic impairment, clearance is reduced, necessitating dose reductions to avoid accumulation.^[13]^[14] Pharmacokinetics vary by age, with elderly patients exhibiting approximately 40% lower clearance and prolonged half-life compared to younger adults, potentially requiring monitoring. Ethnic differences influence metabolism, particularly via CYP2C19 polymorphisms; individuals of Asian descent, who have a higher prevalence of poor metabolizer genotypes (up to 15-20%), experience greater plasma exposure and enhanced acid suppression from standard doses.^[13]^[16]

Medical uses

Indications

Lansoprazole is approved by the FDA and EMA for the short-term treatment and maintenance of duodenal ulcers, short-term treatment of active benign gastric ulcers, healing and maintenance of erosive esophagitis associated with gastroesophageal reflux disease (GERD), symptomatic GERD, reduction of the risk of NSAID-associated gastric ulcers in patients with a history of gastric ulcer who require continued NSAID treatment, and long-term management of pathological hypersecretory conditions such as Zollinger-Ellison syndrome.^[17] In combination with antibiotics such as amoxicillin and clarithromycin, lansoprazole is indicated for the eradication of Helicobacter pylori in patients with active or one-year history of duodenal ulcer disease, typically administered as triple therapy for 10 to 14 days.^[17] Pivotal clinical trials have demonstrated H. pylori eradication rates of 80% to 90% with this regimen.^[18] For erosive esophagitis, lansoprazole 30 mg once daily achieves endoscopic healing in 80% to 92% of patients after 8 weeks, depending on disease severity.^[17] Although not formally approved for these purposes, lansoprazole is used off-label with supporting evidence for the prevention of NSAID-induced ulcers in at-risk patients (e.g., those with multiple risk factors such as age >65 years or concurrent anticoagulant use) even without prior ulcer history, and for stress ulcer prophylaxis in critically ill patients, such as those being weaned from mechanical ventilation.^[19]^[20]^[21] Use of lansoprazole generally requires confirmation of acid-related etiology, such as through endoscopy for ulcers or pH monitoring for GERD when symptoms are atypical or diagnosis is uncertain.^[17]^[22]

Dosage and administration

Lansoprazole is available in oral formulations including delayed-release capsules, orally disintegrating tablets (ODTs), and oral suspension.^[23] Oral doses should be taken before meals to optimize acid suppression, and the capsules or tablets are enteric-coated to protect the drug from gastric acid; they should not be crushed or chewed unless using the ODT or suspension form, which can be mixed with water or soft foods for easier administration, including via nasogastric or enteral tubes.^[24]^[25] For adults, dosing varies by indication. Treatment of active duodenal ulcer typically involves 15 mg orally once daily for up to 4 weeks, while maintenance therapy to prevent recurrence is 15 mg once daily.^[25] For active benign gastric ulcer or NSAID-associated gastric ulcer, the dose is 30 mg orally once daily for up to 8 weeks.^[26] Erosive esophagitis associated with gastroesophageal reflux disease (GERD) is treated with 30 mg orally once daily for up to 8 weeks, followed by 15 mg once daily for maintenance if needed.^[25] In triple therapy for Helicobacter pylori eradication in patients with duodenal ulcer, lansoprazole is given at 30 mg orally twice daily for 10 to 14 days, combined with amoxicillin 1 g twice daily and clarithromycin 500 mg twice daily.^[27] For pathological hypersecretory conditions such as Zollinger-Ellison syndrome, the initial dose is 60 mg orally once daily, adjusted based on patient response up to a maximum of 180 mg per day (doses greater than 120 mg should be divided), often divided into multiple doses.^[23]^[17] Pediatric dosing is approved by the FDA for symptomatic GERD and erosive esophagitis in children aged 1 to 17 years and is weight-based. For children aged 1 to 11 years weighing less than 30 kg, the dose is 15 mg orally once daily for up to 12 weeks; those weighing 30 kg or more receive 30 mg once daily.^[17] For adolescents aged 12 to 17 years, the dose is 15 mg orally once daily for up to 8 weeks for non-erosive GERD or 30 mg once daily for up to 8 weeks for erosive esophagitis.^[17] Pediatric use is not recommended by the EMA due to limited clinical data.^[28] Dosing in children under 1 year is not established.^[29] Treatment duration is generally short-term for healing (4 to 8 weeks depending on the condition) and long-term for maintenance therapy in recurrent cases, with no routine need for tapering upon discontinuation.^[25] Monitoring involves assessing symptom resolution and, for non-responders, repeat endoscopy to evaluate healing; doses may be increased if inadequate response occurs.^[17] No dosage adjustment is required for renal impairment, but in severe hepatic impairment (Child-Pugh Class C), the dose should be reduced to 15 mg orally once daily.^[23]^[25]

Adverse effects

Common adverse effects

The common adverse effects of lansoprazole, defined as those occurring in more than 1% of patients during clinical trials, are predominantly mild gastrointestinal disturbances and neurological symptoms that typically resolve without intervention. These effects are generally self-limiting, often appearing within the first few weeks of treatment and subsiding as the body adjusts, with dose adjustment required only rarely.^[13]^[30] In short-term clinical trials involving thousands of patients, the most frequent adverse effects included headache, diarrhea, abdominal pain, nausea, and constipation, with incidences slightly higher than placebo for most but comparable or lower for headache. Other effects such as dizziness and rash occurred at rates less than 1%. Post-marketing surveillance data align with these trial findings, confirming their frequency without significant deviations.^[13]^[31]

Adverse Effect	Incidence with Lansoprazole (%)	Incidence with Placebo (%)
Headache	>1 (lower than placebo)	>1
Diarrhea	3.8	2.3
Abdominal Pain	2.1	1.2
Nausea	1.3	1.2
Constipation	1.0	0.4
Dizziness	<1	Not specified
Rash	<1	Not specified

Management of these effects focuses on symptomatic relief, such as over-the-counter remedies for headache or diarrhea, and monitoring; discontinuation is uncommon as the benefits for acid-related conditions often outweigh these transient issues. Meta-analyses of proton pump inhibitors, including lansoprazole, indicate no substantial increase in overall adverse event rates compared to placebo beyond these common ones in short-term use.^[30]

Serious adverse effects

Long-term use of lansoprazole, a proton pump inhibitor (PPI), has been associated with several serious adverse effects, primarily due to its impact on gastric acid suppression and nutrient absorption. These risks are generally rare but can be significant, particularly in patients using the drug for more than one year. Hypomagnesemia is a notable risk with prolonged lansoprazole therapy, typically emerging after one year of use, and may manifest as tetany, arrhythmias, seizures, or other symptoms of severe magnesium depletion. The U.S. Food and Drug Administration (FDA) has issued alerts on this issue for PPIs including lansoprazole, noting that most cases required discontinuation of the PPI and magnesium supplementation, with resolution occurring within weeks to months. Risk factors include advanced age, concurrent use of diuretics or other magnesium-depleting drugs, and high-dose or long-duration therapy. Periodic monitoring of serum magnesium levels is recommended for patients on long-term lansoprazole, especially those with predisposing factors. Lansoprazole use has also been linked to an increased risk of osteoporotic fractures, particularly of the hip, wrist, and spine, in a dose- and duration-dependent manner. A meta-analysis of observational studies found that PPI therapy, including lansoprazole, modestly elevates the overall fracture risk (odds ratio approximately 1.3), with stronger associations for long-term use. The FDA has required labeling updates for lansoprazole to warn of this potential, emphasizing risks in elderly patients or those on concurrent steroids or diuretics. Bone density monitoring is advised for at-risk patients on extended therapy. Vitamin B12 deficiency is another long-term concern with lansoprazole, resulting from reduced gastric acid-mediated release and absorption of the vitamin. This risk increases with treatment duration exceeding one year, potentially leading to megaloblastic anemia or neurological complications if untreated. Patients on prolonged lansoprazole should be monitored for B12 levels, with supplementation considered if deficiency is detected. Regarding infections, lansoprazole has been associated with a higher incidence of community-acquired pneumonia, with meta-analyses indicating a 1.5-fold increased risk, particularly in the initial months of therapy. Similarly, PPI use including lansoprazole elevates the risk of Clostridium difficile-associated diarrhea, with a meta-analysis reporting an odds ratio of approximately 2.0 based on pooled data from observational studies. These infections are thought to arise from altered gastric pH favoring bacterial overgrowth. Other serious effects include acute interstitial nephritis, a rare hypersensitivity reaction reported in case studies with lansoprazole, often presenting with renal dysfunction that resolves upon discontinuation. Cutaneous lupus erythematosus or lupus-like syndrome has also been documented in isolated cases linked to lansoprazole, featuring skin rashes and arthralgias that improve after stopping the drug. Fundic gland polyps, benign gastric lesions, have been associated with long-term PPI use in older studies, but recent evidence as of 2024 does not support a causal link with lansoprazole or other PPIs.^[32] Emerging research as of 2024-2025 suggests potential cardiovascular risks with long-term PPI use, including lansoprazole, such as increased incidence of ventricular arrhythmias (particularly when coadministered with ceftriaxone) or mixed findings on coronary heart disease risk compared to other PPIs. Evidence remains inconclusive, but monitoring is advised in at-risk patients.^[33] Lansoprazole carries no specific black box warnings, but FDA communications highlight the cumulative long-term risks of PPIs, urging judicious use and monitoring to balance benefits against these potential harms.

Interactions and contraindications

Drug interactions

Lansoprazole, primarily metabolized by the cytochrome P450 enzyme CYP2C19, acts as a competitive inhibitor of this enzyme, potentially elevating plasma concentrations of coadministered substrates such as diazepam, phenytoin, and warfarin.^[34] For diazepam, lansoprazole can decrease its metabolism, leading to prolonged effects and requiring dose adjustments in patients on long-term therapy.^[35] Similarly, phenytoin levels may increase, necessitating therapeutic drug monitoring to avoid toxicity.^[36] With warfarin, lansoprazole may enhance anticoagulant effects, increasing bleeding risk, so international normalized ratio (INR) monitoring is recommended during initiation or dose changes.^[37] Lansoprazole also impairs the activation of clopidogrel, a prodrug dependent on CYP2C19 for conversion to its active metabolite, thereby reducing its antiplatelet efficacy and potentially heightening cardiovascular event risk.^[38] Clinical studies indicate this interaction is more pronounced in CYP2C19 extensive metabolizers, advising avoidance of the combination when possible or consideration of alternative acid-suppressive therapy.^[39] By elevating gastric pH, lansoprazole reduces the absorption of acid-dependent drugs, including ketoconazole and itraconazole, which may result in subtherapeutic antifungal levels and treatment failure.^[40] Iron supplements exhibit decreased bioavailability, potentially exacerbating anemia in susceptible patients, while digoxin absorption can paradoxically increase, raising toxicity risk; administering these agents at least 2 hours before or after lansoprazole mitigates these effects.^[36] Compared to other proton pump inhibitors (PPIs), lansoprazole exhibits potent direct inhibition of CYP2C19 in vitro (IC50 0.73 μM), more so than esomeprazole (IC50 3.7 μM), though omeprazole and esomeprazole also show metabolism-dependent inhibition; clinical impacts vary by patient genotype and drug combination.^[41]^[42]^[43] Pharmacodynamically, lansoprazole contributes to hypomagnesemia, particularly with prolonged use, and this risk is amplified when combined with diuretics, which independently promote magnesium loss; serum magnesium monitoring is advised in at-risk patients.^[44] Additionally, by altering gut pH and microbiota, lansoprazole heightens infection susceptibility, with additive effects alongside antibiotics that disrupt flora, increasing Clostridioides difficile risk.^[45] Management strategies include timing doses to separate lansoprazole from interacting agents, regular monitoring of drug levels (e.g., phenytoin) or INR (for warfarin), and selecting alternative PPIs like pantoprazole for patients on clopidogrel to minimize CYP2C19 interference.^[46]

Contraindications and precautions

Lansoprazole is contraindicated in patients with known hypersensitivity to lansoprazole, any substituted benzimidazole, or any component of the formulation.^[47] Concomitant use with rilpivirine-containing products is also contraindicated due to decreased rilpivirine absorption, which may lead to loss of virologic response and development of resistance to rilpivirine or to the class of non-nucleoside reverse transcriptase inhibitors.^[47] In patients with severe hepatic impairment (Child-Pugh class C), the recommended dosage is reduced to 15 mg once daily to account for prolonged metabolism and potential accumulation.^[23] No dosage adjustment is required for mild to moderate hepatic impairment.^[13] For renal impairment, no dosage adjustment is necessary, though patients should be monitored for potential adverse effects such as hypomagnesemia or acute interstitial nephritis.^[28] Lansoprazole is classified as FDA pregnancy category B, with animal reproduction studies showing no evidence of fetal harm at doses up to 40 times the recommended human dose, but limited human data available; it should be used during pregnancy only if clearly needed and benefits outweigh risks.^[13] The drug is excreted in human milk, though in low amounts unlikely to cause adverse effects in breastfed infants; caution is advised, with monitoring of the infant for potential gastrointestinal effects, and a decision to discontinue nursing or the drug should consider the importance of treatment to the mother.^[48] In elderly patients, use caution due to increased risk of bone fractures (hip, wrist, or spine) with long-term or high-dose use, particularly in those with osteoporosis or other risk factors for bone loss.^[5] Elderly individuals are also at higher risk for Clostridioides difficile-associated diarrhea associated with proton pump inhibitor use.^[13] For patients presenting with undiagnosed and new-onset dyspepsia, particularly those over 60 years or with alarm symptoms (e.g., weight loss, anemia), gastric malignancy should be ruled out prior to initiating therapy, as symptomatic response to lansoprazole does not preclude underlying cancer.^[13] Abrupt discontinuation of long-term lansoprazole therapy may lead to rebound acid hypersecretion, manifesting as worsened dyspepsia or gastroesophageal reflux symptoms; gradual tapering is recommended to minimize this effect.^[49] The American Gastroenterological Association (AGA) recommends periodic review of proton pump inhibitor use and deprescribing in patients without ongoing indications, using strategies such as on-demand dosing or switching to less potent acid suppressants, with monitoring for symptom recurrence.^[49]

Chemistry

Chemical structure and properties

Lansoprazole has the chemical formula C₁₆H₁₄F₃N₃O₂S and a molecular weight of 369.36 g/mol.^[35]^[50] Its systematic name is 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole, featuring a benzimidazole core linked via a sulfinyl group to a substituted pyridine ring.^[1] The sulfoxide moiety is critical for its activation in acidic environments, while the trifluoroethoxy substituent enhances lipophilicity, contributing to membrane permeability.^[51] Lansoprazole appears as a white to brownish-white powder. It exhibits poor solubility in water (practically insoluble) but is freely soluble in dehydrated alcohol and somewhat soluble in chloroform and methanol.^[50] The compound has pKa values of approximately 3.9 for the pyridine nitrogen and 8.7 for the benzimidazole, influencing its ionization and solubility profile in physiological conditions.^[51]^[52] Lansoprazole is acid-labile, with a half-life of about 30 minutes at pH 5 in aqueous solution at room temperature, but extending to around 18 hours at pH 7, necessitating enteric coatings for oral formulations to prevent degradation in gastric acid.^[53] It remains stable under light exposure for up to two months but degrades in aqueous media, with the rate increasing at lower pH levels.^[12] For identification, lansoprazole shows characteristic infrared (IR) absorption bands at approximately 3400 cm^-1 (N-H stretch), 1600 cm^-1 (C=N stretch), and 1050 cm^-1 (S=O stretch), while ¹H NMR spectra feature peaks around 8.5 ppm (pyridine proton) and 2.3 ppm (methyl group).^[52]

Synthesis and formulation

The synthesis of lansoprazole is a multi-step process typically beginning with the condensation of 2-mercaptobenzimidazole and 2-chloromethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine to form the thioether intermediate, followed by selective oxidation of the sulfide to the sulfoxide using an oxidizing agent such as m-chloroperbenzoic acid (mCPBA) in a solvent like dichloromethane at low temperature to minimize over-oxidation to the sulfone.^[54] This route, originally described in the foundational patent for the compound, ensures high yield and purity of the racemic product. Alternative routes may involve starting from nitro-substituted pyridine derivatives, such as 3-methyl-4-nitropyridine N-oxide, which is converted to the trifluoroethoxy-substituted chloromethyl pyridine through a series of substitutions and reductions before coupling with the benzimidazole moiety.^[55] Key patents address stereoselective oxidation steps for producing the (R)-enantiomer (dexlansoprazole), employing chiral catalysts or resolving agents like (R)-mandelic acid to achieve enantiomeric excess greater than 99%, improving pharmacokinetic profiles over the racemate. Quality control in lansoprazole production focuses on controlling impurities arising from incomplete oxidation, side reactions, or residual solvents, with the United States Pharmacopeia (USP) monograph specifying that individual impurities, such as the sulfone or sulfide forms, must not exceed 0.5%, and total impurities limited to 1.0% relative to the main peak via HPLC analysis.^[56] The European Pharmacopoeia (EP) similarly mandates limits for specified impurities like lansoprazole sulfone (impurity A) at not more than 0.5 times the principal peak area (approximately 0.3%) and total impurities not exceeding 1.5%. These standards ensure the active pharmaceutical ingredient (API) meets pharmaceutical-grade purity, with analytical methods involving reverse-phase chromatography to detect and quantify trace levels of process-related impurities.^[57] Lansoprazole is formulated primarily as delayed-release oral dosage forms to protect the acid-labile drug from gastric degradation, including capsules containing 15 mg or 30 mg of enteric-coated granules, orally disintegrating tablets (15 mg, 30 mg) that dissolve rapidly in the mouth, oral suspensions (e.g., 3 mg/mL for pediatric use), and intravenous solutions supplied as 30 mg lyophilized powder in single-dose vials for reconstitution.^[13] These formulations employ multilayer coatings to achieve pH-dependent release, with the granules or pellets designed for uniform drug distribution and bioavailability equivalent to the innovator product. Common excipients in these formulations include hydroxypropyl cellulose as a binder in the granulation step and magnesium carbonate as a base to neutralize acidity during enteric coating with methacrylic acid copolymers, ensuring stability and controlled release in the intestine.^[12] Other inactive ingredients, such as sucrose-based sugar spheres for pellet cores, talc as a glidant, and hypromellose for capsule shells, support manufacturability and patient compliance without affecting efficacy. Formulated lansoprazole products exhibit good stability, with a typical shelf-life of 2 to 3 years when stored at controlled room temperature (15–30°C) in light-resistant containers, as degradation via dimerization or sulfoxide reduction is minimized under these conditions per stability studies in the product dossiers.^[13] Accelerated testing confirms retention of at least 95% potency over the labeled period, with no significant increase in impurities.

History

Development

Lansoprazole was developed by Takeda Pharmaceuticals during the 1980s as a second-generation proton pump inhibitor (PPI), building on the success of omeprazole, the first PPI introduced for acid-related disorders. Takeda's research focused on benzimidazole derivatives to enhance antisecretory potency for treating peptic ulcers and gastroesophageal reflux. The compound was first synthesized in 1984 through modifications to earlier prototypes like timoprazole, incorporating a trifluoroethoxy group on the pyridine ring to improve chemical stability under acidic conditions.^[58]^[59] Lead optimization efforts at Takeda emphasized enhancing bioavailability and gastric stability compared to initial analogs. These modifications resulted in superior oral absorption, with lansoprazole achieving approximately 80-90% bioavailability in early formulations, outperforming omeprazole's 30-40% due to reduced sensitivity to gastric acid degradation.^[60] Preclinical studies in animal models, including rats and dogs, demonstrated lansoprazole's potent and sustained inhibition of histamine-stimulated gastric acid secretion, surpassing that of H2-receptor antagonists like ranitidine by irreversibly binding to the H+/K+-ATPase proton pump.^[61] Toxicology assessments in rats and dogs revealed no genotoxicity in key assays, such as the Ames test or in vivo micronucleus test, and no carcinogenicity at clinically relevant doses, though high-dose chronic exposure in rats led to enterochromaffin-like cell hyperplasia.^[13] Takeda filed the US patent application for lansoprazole (US Patent No. 4,628,098) on July 29, 1985, claiming priority from 1984, covering the compound's structure and use as an antisecretory agent; it was issued on December 9, 1986.^[62] During development, the compound was designated AG-1749, later marketed as Prevacid upon regulatory approval.^[63]

Regulatory approvals

Lansoprazole received its initial marketing approval in Japan in 1991, developed and launched by Takeda Pharmaceutical Company as an anti-ulcer agent under the brand name Takepron.^[64] In Europe, the drug was first approved for marketing in 1991 through national authorizations, with centralized European Medicines Agency (EMA) procedures following later for specific formulations and indications.^[65] In the United States, the Food and Drug Administration (FDA) approved lansoprazole on May 10, 1995, for the short-term treatment of active duodenal ulcers, maintenance treatment of duodenal ulcers, and symptomatic gastroesophageal reflux disease (GERD) in adults.^[66] The approval was expanded on June 17, 1997, to include triple therapy with amoxicillin and clarithromycin for the eradication of Helicobacter pylori in patients with duodenal ulcers.^[67] Pediatric approval for children aged 1 to 17 years followed in 2002 for short-term treatment of GERD and erosive esophagitis.^[68] In 2009, the FDA granted over-the-counter (OTC) status to lansoprazole 15 mg delayed-release capsules for the short-term relief of frequent heartburn occurring two or more days per week.^[69] Health Canada approved lansoprazole in 1995 for the treatment of acid-related gastrointestinal disorders in adults.^[70] The EMA granted a pediatric indication extension in 2009, allowing use in children for conditions such as GERD and erosive esophagitis based on submitted data under the Pediatric Investigation Plan.^[71] In 2010, the FDA required label updates for all proton pump inhibitors, including lansoprazole, to include warnings about a possible increased risk of fractures of the hip, wrist, and spine with high-dose or long-term use (one year or longer). This was followed in 2012 by an FDA safety communication highlighting the potential association between proton pump inhibitors like lansoprazole and increased risk of Clostridium difficile-associated diarrhea.^[72] No major global withdrawals of lansoprazole have occurred, though quality issues led to voluntary recalls of certain generic formulations in 2012, including lots affected by dissolution failures or microbial contamination in the United States and Canada.^[73]^[74]

Society and culture

Availability and brand names

Lansoprazole is marketed under various brand names worldwide, including Prevacid in the United States, Zoton in the United Kingdom, Lanzor in several European countries, and Takepron in Japan.^[75]^[35] Over-the-counter formulations are available as Prevacid 24HR in the US for short-term heartburn relief.^[23] It is available in prescription delayed-release capsules of 15 mg and 30 mg strengths, as well as orally disintegrating tablets in 15 mg and 30 mg for those who have difficulty swallowing.^[13] Over-the-counter versions are typically limited to 15 mg capsules. Generic versions of lansoprazole are widely available in most markets, often in the same dosage forms.^[26] Lansoprazole has been approved for use in over 100 countries for treating acid-related disorders.^[76] It is commonly prescribed and dispensed globally, with significant market presence in North America, Europe, Asia, and other regions.^[77] In the United States, generic lansoprazole costs approximately $0.05 to $0.10 per 30 mg dose as of November 2025, depending on quantity and pharmacy, making it an affordable option for chronic use.^[78] In developing countries with established generic manufacturing, prices are often lower, around $0.03 to $0.15 per dose as of 2025, though availability can vary and costs may rise in areas lacking local production.^[79]^[80] Supply of lansoprazole has faced occasional disruptions due to manufacturing challenges, including active pharmaceutical ingredient shortages reported in 2020 and 2021 in North America and Europe.^[81]^[82] These issues were generally resolved by mid-2022 through alternative suppliers, but intermittent shortages persisted in regions like Canada into 2025 before resolution in November 2025, highlighting vulnerabilities in global production chains.^[83]^[84]

Patents and generic availability

The primary patent covering the lansoprazole compound, U.S. Patent No. 4,628,098 issued to Takeda Pharmaceutical Company, expired on May 10, 2009. Secondary patents related to formulations, such as U.S. Patent No. 6,328,994 for delayed-release orally disintegrating tablets, provided additional protection until its expiration on November 17, 2021. Pediatric exclusivity under the Best Pharmaceuticals for Children Act extended market exclusivity by six months beyond the core patent term, delaying full generic competition until November 10, 2009.^[85] Generic entry began shortly after patent expiration, with the U.S. Food and Drug Administration (FDA) approving the first abbreviated new drug applications (ANDAs) for lansoprazole delayed-release capsules on November 10, 2009, to Mylan Pharmaceuticals.^[86] Subsequent approvals, including for Teva Pharmaceuticals in October 2010, accelerated market penetration.^[87] By the mid-2010s, generics had captured over 90% of the U.S. market share for lansoprazole, reflecting the typical rapid shift following patent cliffs for proton pump inhibitors.^[88] Patent challenges by generic manufacturers against Takeda and Abbott Laboratories, the original co-marketers of Prevacid, were common. In a notable 2008 federal court ruling, Takeda and Abbott prevailed over Teva in an infringement suit on formulation patents, upholding the delay in generic launch until 2009.^[89] Similar litigations, including actions in Canada involving Apotex, focused on secondary patents and section 8 damages under the Patented Medicines (Notice of Compliance) Regulations, further shaping the timeline for generic availability.^[90] All generic lansoprazole products received FDA ANDA approvals, requiring demonstration of bioequivalence to the reference listed drug (Prevacid) through pharmacokinetic studies showing comparable absorption, typically with 80-125% confidence intervals for key parameters like AUC and Cmax.^[91] This ensured therapeutic equivalence, facilitating widespread substitution. The influx of generics resulted in an 74% average price decline in the second year post-entry, substantially lowering costs from branded levels and enhancing affordability.^[92] In low-income countries, such as South Africa and China, generic lansoprazole has improved access to treatment for acid-related disorders by reducing prices to 10-20% of originator costs through policy-driven generic promotion.^[93]

Research

Completed clinical trials

Lansoprazole's efficacy in treating gastroesophageal reflux disease (GERD) was established through several pivotal multicenter, double-blind, randomized controlled trials conducted in the 1990s. In U.S. and international studies involving patients with erosive esophagitis, lansoprazole at 30 mg once daily achieved endoscopic healing rates exceeding 90% after 8 weeks of treatment, significantly outperforming ranitidine at 150 mg twice daily, which yielded healing rates of 53% to 69%. These trials, enrolling hundreds of patients with moderate to severe disease, also demonstrated superior symptom relief, including reduced heartburn frequency and severity, with lansoprazole groups reporting up to 80% resolution compared to 50-60% with ranitidine.^[94]^[95] Maintenance therapy trials further supported lansoprazole's role in preventing relapse. In a 1-year double-blind study of patients with healed erosive esophagitis, lansoprazole 15 mg or 30 mg once daily maintained remission in 67% to 93% of participants, respectively, compared to only 13% with ranitidine 150 mg twice daily. Similar results were observed in extension studies, where lansoprazole reduced relapse rates by over 80% relative to H2-receptor antagonists (H2RAs), with sustained symptom control in the majority of patients.^[96]^[97] For Helicobacter pylori eradication, phase III trials evaluated triple therapy combining lansoprazole 30 mg twice daily with amoxicillin 1 g twice daily and clarithromycin 500 mg twice daily. A 14-day regimen achieved intention-to-treat eradication rates of 90% to 94% in patients with duodenal ulcers, surpassing dual therapy options and confirming lansoprazole's synergistic role in enhancing antibiotic efficacy through acid suppression. These studies, involving over 1,000 patients, also showed rapid ulcer healing in 85-95% of cases post-eradication.^[98]^[99] Long-term safety was assessed in extension studies for erosive esophagitis maintenance. A 2-year open-label trial in adults with healed esophagitis treated with lansoprazole 15 mg or 30 mg once daily reported low adverse event rates, with gastrointestinal symptoms in less than 5% of participants and no significant increases in serious events compared to shorter-term data; overall tolerability was comparable to placebo in controlled phases. Further extensions up to 6 years confirmed sustained safety, with remission maintained in 75% of patients and minimal withdrawals due to adverse effects.^[100]^[101] Meta-analyses have reinforced these findings. The Cochrane review on short-term treatments for GERD-like symptoms, originally published in 2006 and updated through 2020, analyzed over 50 trials and concluded that proton pump inhibitors (PPIs) like lansoprazole are superior to H2RAs for endoscopic healing (risk ratio 1.26, 95% CI 1.20-1.33) and heartburn relief (risk ratio 1.18, 95% CI 1.07-1.30), with number needed to treat of 9 for healing benefits. The 2017 update emphasized consistent superiority across PPIs, including lansoprazole, in endoscopy-negative reflux disease.^[102] Pediatric trials from 2001 to 2008 validated lansoprazole for GERD in children. A 2003 multicenter, double-blind trial in 204 children aged 1 to 11 years with endoscopically or histologically proven erosive esophagitis showed lansoprazole 15 mg or 30 mg once daily (weight-adjusted) provided significant symptom relief in 64-85% of patients after 8 weeks, compared to 50% with placebo, with endoscopic healing in 58% of those with erosive disease. A 2008 placebo-controlled study in infants aged 1 to 12 months (n=162) found no significant difference in overall symptom reduction but supported safety; combined data from earlier pediatric studies led to FDA approval in 2002 for short-term treatment of GERD in children aged 1 to 11 years and in 2004 for ages 12 to 17 years. Adverse events were mild and similar across groups, primarily respiratory or gastrointestinal.^[103]^[104]

Ongoing and future research

Recent studies have explored the potential repurposing of lansoprazole and other proton pump inhibitors (PPIs) for COVID-19 treatment, focusing on their ability to inhibit viral entry by altering endosomal acidification. A 2021 review highlighted mixed preliminary results from observational data suggesting PPIs like lansoprazole might reduce viral replication in vitro, but clinical trials from 2021-2023, including a phase 2/3 study on PPI prophylaxis in high-risk patients, showed no significant reduction in hospitalization rates or mortality, with some analyses indicating potential associations with worse outcomes in severe cases.^[105]^[106]^[107] Investigations into lansoprazole's effects on the gut microbiome have intensified post-2020, revealing alterations in microbial composition that could impact gut health. A 2023 meta-analysis of human microbiota studies found that PPI use, including lansoprazole, is associated with decreased bacterial diversity and increased abundance of potentially pathogenic species like Enterobacteriaceae, potentially contributing to dysbiosis and heightened risk of infections such as Clostridium difficile. In vitro models simulating gastroesophageal reflux demonstrated that lansoprazole exposure leads to shifts in beneficial bacteria growth, underscoring the need for longitudinal studies on long-term gut health implications.^[108]^[109]^[110] Emerging research is examining lansoprazole as an adjunct in cancer therapy, particularly for gastric cancer, where it may enhance chemotherapy efficacy by reversing multidrug resistance. Phase II trials and preclinical studies from 2021 onward have shown that high-dose lansoprazole combined with agents like cisplatin inhibits tumor growth more effectively than chemotherapy alone, potentially through modulation of ABC transporters. Conversely, observational data from 2023-2024 indicate that routine PPI use, including lansoprazole, might reduce the effectiveness of oral chemotherapeutics like capecitabine in various cancers, prompting calls for cautious co-administration. On neurodegenerative risks, multiple observational studies between 2022 and 2025 have reported conflicting associations with long-term lansoprazole use and dementia; a 2023 nationwide cohort found a 33% increased risk in users over 4.4 years, attributed to possible B12 deficiency or vascular effects, while a 2024 Mendelian randomization study refuted causality.^[111]^[112]^[113]^[114]^[115] To address rising H. pylori clarithromycin resistance, European trials in 2023 have evaluated higher-dose lansoprazole regimens in quadruple therapy. Data from the European Registry on H. pylori Management (2019-2023) support 14-day high-dose PPI protocols (e.g., esomeprazole 40 mg thrice daily, adaptable to lansoprazole equivalents) achieving eradication rates above 90% in resistant strains, particularly when combined with bismuth and antibiotics. Future directions include personalized dosing guided by pharmacogenomics, as CYP2C19 genotyping identifies ultrarapid metabolizers requiring 4-fold higher lansoprazole doses for optimal acid suppression and H. pylori eradication, per 2022 CPIC guidelines. Additionally, exploratory studies are assessing lansoprazole combinations with biologics for inflammatory bowel disease (IBD), though a 2024 analysis found concomitant PPI use may diminish biologic efficacy in Crohn's disease by altering pharmacokinetics.^[116]^[117]^[118] Ongoing gaps in knowledge are being addressed through large-scale cohorts, building on a 2024 meta-analysis linking PPIs to elevated myocardial infarction risk (HR 1.16-1.45). Environmental research on PPIs highlights potential persistence of transformation products in aquatic systems, though comprehensive lifecycle assessments remain needed; 2017 process improvements in lansoprazole production aimed to reduce solvent use and waste.^[119]^[120]