Lansoprazole

Lansoprazole is a Proton pump Inhibitor belonging to class Anti-ulcer agent.

Lansoprazole is a proton pump inhibitor used to help gastrointestinal ulcers heal, to treat symptoms of gastroesophageal reflux disease (GERD), to eradicate Helicobacter pylori, and to treat hypersecretory conditions such as Zollinger-Ellison Syndrome.

The oral bioavailability of lansoprazole is reported to be 80-90% and the peak plasma concentration (Cmax) is achieved about 1.7 hours after oral dosing. The apparent volume of distribution of lansoprazole is 0.4 L/kg and 97% of lansoprazole is plasma protein bound. Lansoprazole is predominantly metabolized in the liver by CYP3A4 and CYP2C19. The resulting major metabolites are 5-hydroxy lansoprazole and the sulfone derivative of lansoprazole and about 14-23% of a lansoprazole is eliminated in the urine with this percentage range including both conjugated and unconjugated hydroxylated metabolites

Lansoprazole shows common side effects like Diarrhoea, Skin rash, Severe stomach ache, Nausea and vomiting, Flu like symptoms, Muscle or joint pain, Headache, Excessive gas in stomach, Swelling of face, lips, eyelids, tongue, hands and feet, Irregular heartbeat, Decreased appetite, Pain at the injection site.

Lansoprazole is available in the form of Oral Capsule, Oral tablet, powder for injection, granules for reconstitution.

Lansoprazole is available in India, Europe, Japan, US.

Lansoprazole is an Anti-ulcer agent belonging to class Proton pump inhibitors.

As a PPI, lansoprazole is a prodrug and requires protonation via an acidic environment to become activated. Once protonated, lansoprazole is able to react with cysteine residues, specifically Cys813 and Cys321, on parietal H+,K+-ATPase resulting in stable disulfides. PPI's in general can provide prolonged inhibition of acid secretion due to their ability to bind covalently to their targets.

The Onset of action of Lansoprazole occurs within 1-3 hours (orally).

The Duration of action of Lansoprazole in the body is approximately>1 day via oral route.

The Tmax was found to be approximately 1.5-2 hours.

Lansoprazole is available in the form of Oral Capsule, Oral tablet, powder for injection, granules for reconstitution.

Lansoprazole Oral capsule, Oral tablet and granules are taken by mouth usually once a day.

As a PPI, lansoprazole is a prodrug and requires protonation via an acidic environment to become activated. Once protonated, lansoprazole is able to react with cysteine residues, specifically Cys813 and Cys321, on parietal H+, K+-ATPase resulting in stable disulfides. PPI's in general are able to provide prolonged inhibition of acid secretion due to their ability to bind covalently to their targets.

Lansoprazole is a Proton pump Inhibitor belonging to class Anti-ulcer agent.

Lansoprazole is an anti-ulcer medicine used to treat conditions where the stomach produces too much acid. Stomach and duodenal ulcers, gastroesophageal reflux disease (GERD), and Zollinger-Ellison syndrome are certain problems caused by high levels of stomach acid.

Lansoprazole is approved for use in the following clinical indications

Adult indication

• Eosinophilic esophagitis
• Gastroesophageal reflux disease, erosive or nonerosive
• Hypersecretory conditions
• Peptic ulcer disease
• NSAID-associated gastric ulcer
• Stress ulcer prophylaxis in critically-ill patients

Pediatric indication

• Gastroesophageal reflux disease, symptomatic
• Erosive esophagitis, treatment

Adult Dose

• Eosinophilic esophagitis

Oral: 30 mg twice daily for an 8-week trial. Once 8-week trial is complete and remission is achieved, the dose may be gradually lowered to an individualized maintenance level.

• Gastroesophageal reflux disease, erosive or nonerosive

Oral: 15 mg once daily; if symptoms persist after 4 to 8 weeks, increase to 30 mg once daily. Discontinue therapy after 8-week treatment course.

• Hypersecretory conditions

Oral: Initial: 60 mg once daily; adjust dose based upon patient response and to reduce acid secretion to <10 mEq/hour (5 mEq/hour in patients with prior gastric surgery); doses of 90 mg twice daily have been used; administer doses >120 mg/day in divided doses.

• Peptic ulcer disease

Duodenal ulcer: Oral: Short-term treatment: 15 mg once daily for 4 weeks; maintenance therapy: 15 mg once daily.

Gastric ulcer: Oral: Short-term treatment: 30 mg once daily for up to 8 weeks. Some clinical trial data suggests a dose of 15 mg once daily for up to 8 weeks may also be effective.

Helicobacter pylori eradication: Oral: 30 mg 3 times daily administered with amoxicillin 1,000 mg 3 times daily for 14 days or 30 mg twice daily administered with amoxicillin 1,000 mg and clarithromycin 500 mg twice daily for 10 to 14 days.

• NSAID-associated gastric ulcer

Prevention: Oral: 15 mg once daily for up to 12 weeks; controlled studies did not extend past 12 weeks.

Treatment: Oral: 30 mg once daily for 8 weeks; controlled studies did not extend past 8 weeks.

• Stress ulcer prophylaxis in critically-ill patients

Oral: 30 mg once daily.

Pediatric Dose

• Gastroesophageal reflux disease, symptomatic

Weight-based dosing:

Infants: Oral: 2 mg/kg/day; a dose of 1 mg/kg/day has also been shown to increase gastric pH in infants and decrease frequency of GERD symptoms (eg, regurgitation/vomiting, feeding refusal, crying, back arching) from baseline.

Children and Adolescents: Oral: 0.7 to 3 mg/kg/day; maximum daily dose: 30 mg/day.

Fixed dosing:

Infants ≥3 months: 7.5 mg twice daily or 15 mg once daily was shown to provide better symptom relief compared to dietary management in 68 patients.

Children ≤11 years:

≤30 kg: 15 mg once daily.

>30 kg: 30 mg once daily.

Children ≥12 years and Adolescents: Oral: 15 mg once daily.

• Erosive esophagitis, treatment

Children ≤11 years:

≤30 kg: 15 mg once daily.

>30 kg: 30 mg once daily.

Children ≥12 years and Adolescents: Oral: 30 mg once daily.

Lansoprazole is available in various strengths as 15 mg; 30 mg; 3 mg/mL.

Lansoprazole is available in the form of Oral Capsules, Oral tablets, powder for injection, and granules for reconstitution.

• Dosage Adjustment in Hepatic impairment Patient

Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): 15 mg once daily.

Lansoprazole is contraindicated in patients with

• Lansoprazole is contraindicated in patients with known severe hypersensitivity to any component of the formulations of Lansoprazole, NAPROSYN (naproxen), or over-the-counter products containing naproxen.
• Lansoprazole is contraindicated in patients who have experienced aspirin- or NSAID-related asthma, urticaria, or allergic-type reactions. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients.
• Lansoprazole is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.

• Clostridioides difficile-associated diarrhea (CDAD)

Use of proton pump inhibitors (PPIs) may increase risk of CDAD, especially in hospitalized patients; consider CDAD diagnosis in patients with persistent diarrhea that does not improve. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

• Cutaneous and systemic lupus erythematosus

Has been reported as new onset or exacerbation of existing autoimmune disease; most cases were cutaneous lupus erythematosus (CLE), most commonly, subacute CLE (occurring within weeks to years after continuous therapy). Systemic lupus erythematosus (SLE) is less common (typically occurs within days to years after initiating treatment) and occurred primarily in young and older adults. Discontinue therapy if signs or symptoms of CLE or SLE occur and refer to a specialist for evaluation; most patients improve 4 to 12 weeks after discontinuation of lansoprazole.

• Dermatologic reactions

Severe cutaneous adverse reactions, including acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported.

• Fractures

Increased incidence of osteoporosis-related bone fractures of the hip, spine, or wrist may occur with PPI therapy. Patients on high-dose or long-term therapy should be monitored. Use the lowest effective dose for the shortest duration of time, use vitamin D and calcium supplementation, and follow appropriate guidelines to reduce risk of fractures in patients at risk.

• Fundic gland polyp

Use of PPIs increases risk of fundic gland polyps, especially with long-term use >1 year. May occur without symptoms, but nausea, vomiting, or abdominal pain may occur; GI bleeding and/or anemia may occur with ulcerated polyps. Diagnosis of polyps may also increase risk for small intestinal blockage. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

• Hypomagnesemia

Reported rarely, usually with prolonged PPI use of ≥3 months (most cases >1 year of therapy). May be symptomatic or asymptomatic; severe cases may cause tetany, seizures, and cardiac arrhythmias. Hypomagnesemia may lead to or exacerbate hypocalcemia in patients at risk (eg, hypoparathyroidism). Hypomagnesemia may also lead to hypokalemia. Hypomagnesemia and hypocalcemia may be corrected by magnesium/calcium supplementation, although discontinuation of lansoprazole may be necessary.

• Tubulointerstitial nephritis

Acute tubulointerstitial nephritis has been observed in patients taking PPIs; may occur at any time during therapy. Patients may present with symptomatic hypersensitivity reaction to nonspecific symptoms of impaired kidney function (eg, anorexia, malaise, nausea); may be diagnosed with biopsy and in the absence of extra-kidney manifestations (eg, fever, rash, arthralgia). Discontinue and evaluate patients if acute tubulointerstitial nephritis is suspected.

• Vitamin B₁₂ deficiency

Prolonged treatment (≥2 years) may lead to vitamin B₁₂ malabsorption and subsequent vitamin B₁₂ deficiency. The magnitude of the deficiency is dose-related and the association is stronger in females and those younger in age (<30 years of age); prevalence is decreased after discontinuation of therapy

Lansoprazole or its metabolites are excreted in the milk of rats. It is not known whether lansoprazole is excreted in human milk. Because many drugs are excreted in human milk, because of the potential for serious adverse reactions in nursing infants from lansoprazole, and because of the potential for tumorigenicity shown for lansoprazole in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue lansoprazole, taking into account the importance of lansoprazole to the mother.

Reproduction studies have been performed in pregnant rats at oral doses up to 40 times the recommended human dose and in pregnant rabbits at oral doses up to 16 times the recommended human dose and have revealed no evidence of impaired fertility or harm to the fetus due to lansoprazole. There are, however, no adequate or well-controlled studies on pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

• Common

Clostridium difficile-associated diarrhea, gastrointestinal infections (e.g. Salmonella, Campylobacter), cutaneous lupus erythematosus (CLE), subacute CLE, SLE, severe cutaneous adverse reactions (e.g. acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis), osteoporosis-related bone fractures of the hip, spine, or wrist (long-term use or high doses), fundic gland polyps (prolonged use), acute tubulointerstitial nephritis, vitamin B₁₂ deficiency (long-term use), hypomagnesemia (prolonged use), which may lead to hypocalcemia and hypokalaemia, Leucopenia, eosinophilia, thrombocytopenia, vertigo, visual disturbances, Vomiting, nausea, diarrhea, abdominal pain, constipation, flatulence, dry mouth or throat. Fatigue, cholestatic jaundice, hepatitis. Increased liver enzymes, Arthralgia, myalgia, Headache, dizziness, somnolence, interstitial pneumonia, Urticaria, pruritus, rash.

• Drugs with pH-Dependent Absorption Kinetics

Lansoprazole causes long-lasting inhibition of gastric acid secretion. Lansoprazole and other PPIs are likely to substantially decrease the systemic concentrations of the HIV protease inhibitor atazanavir, which is dependent upon the presence of gastric acid for absorption, and may result in a loss of therapeutic effect of atazanavir and the development of HIV resistance. Therefore, Lansoprazole and other PPIs should not be co-administered with atazanavir. Lansoprazole and other PPIs may interfere with the absorption of other drugs where gastric pH is an important determinant of oral bioavailability (e.g., ampicillin esters, digoxin, iron salts, ketoconazole).

• Warfarin

In a study of healthy subjects, co-administration of single or multiple 60 mg doses of Lansoprazole and warfarin did not affect the pharmacokinetics of warfarin nor prothrombin time. However, there have been reports of increased INR and prothrombin time in patients receiving PPIs and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with PPIs and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.

• Tacrolimus

Concomitant administration of lansoprazole and tacrolimus may increase whole blood levels of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.

• Theophylline

A minor increase (10%) in the clearance of theophylline was observed following the administration of Lansoprazole concomitantly with theophylline. Although the magnitude of the effect on theophylline clearance is small, individual patients may require additional titration of their theophylline dosage when Lansoprazole is started or stopped to ensure clinically effective blood levels.

• Clopidogrel

Concomitant administration of lansoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition. No dose adjustment of clopidogrel is necessary when administered with an approved dose of Lansoprazole.

• Methotrexate

Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxy methotrexate. However, no formal drug interaction studies of high dose methotrexate with PPIs have been conducted.

The common side effects of Lansoprazole include the following

• Common side effects

Constipation, nausea, headache, dizziness, diarrhea.

• Rare side effects

Rash, hives, itching, swelling of the eyes, face, lips, mouth, throat, or tongue; difficulty breathing or swallowing, hoarseness, blistering, peeling, or bleeding skin; sores on the lips, nose, mouth, or genitals; swollen glands, shortness of breath, fever, flu-like symptoms, increased or decreased urination, blood in urine, fatigue, nausea, loss of appetite, fever, rash, or joint pain, irregular, fast, or pounding heartbeat; muscle spasms; uncontrollable shaking of a part of the body, excessive tiredness, lightheadedness, dizziness, or seizures, severe diarrhea with watery stools, stomach pain, or fever that does not go away, new or worsening joint pain, rash on cheeks or arms that is sensitive to sunlight.

• Pregnancy

Pregnancy Category B

Pregnancy Category B. Reproduction studies have been performed in pregnant rats at oral doses up to 40 times the recommended human dose and in pregnant rabbits at oral doses up to 16 times the recommended human dose and have revealed no evidence of impaired fertility or harm to the fetus due to lansoprazole. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

• Nursing Mothers

Lansoprazole or its metabolites are excreted in the milk of rats. It is not known whether lansoprazole is excreted in human milk. Because many drugs are excreted in human milk, because of the potential for serious adverse reactions in nursing infants from lansoprazole, and because of the potential for tumorigenicity shown for lansoprazole in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue lansoprazole, taking into account the importance of lansoprazole to the mother.

• Pediatric Use

The safety and effectiveness of Lansoprazole have been established in pediatric patients 1 to 17 years of age for short-term treatment of symptomatic GERD and erosive esophagitis, however, Lansoprazole was not effective in patients with symptomatic GERD 1 month to less than 1 year of age in a multicenter, double-blind, placebo controlled study.

• Geriatric Use

No dosage adjustment of Lansoprazole is necessary in geriatric patients. The incidence rates of Lansoprazole-associated adverse reactions and laboratory test abnormalities are similar to those seen in younger patients.

Pharmacodynamic

Lansoprazole decreases gastric acid secretion by targeting H+,K+-ATPase, which is the enzyme that catalyzes the final step in the acid secretion pathway in parietal cells. Conveniently, lansoprazole administered any time of day is able to inhibit both daytime and nocturnal acid secretion. The result is that lansoprazole is effective at healing duodenal ulcers, reduces ulcer-related pain, and offers relief from symptoms of heartburn Lansoprazole also reduces pepsin secretion, making it a useful treatment option for hypersecretory conditions such as Zollinger-Ellison syndrome.

Pharmacokinetics

• Absorption

The oral bioavailability of lansoprazole is reported to be 80-90% and the peak plasma concentration (Cmax) is achieved about 1.7 hours after oral dosing.

• Distribution

The apparent volume of distribution of lansoprazole is 0.4 L/kg and 97% of lansoprazole is plasma protein bound.

• Metabolism and Excretion

Lansoprazole is predominantly metabolized in the liver by CYP3A4 and CYP2C19. The resulting major metabolites are 5-hydroxy lansoprazole and the sulfone derivative of lansoprazole and about 14-23% of lansoprazole is eliminated in the urine with this percentage range including both conjugated and unconjugated hydroxylated metabolites

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• https://www.drugs.com/dosage/lansoprazole.html
• https://go.drugbank.com/drugs/DB00448
• https://www.drugs.com/lansoprazole.html
• https://medlineplus.gov/druginfo/meds/a695020.html#:~:text=Nonprescription (over-the-counter,acid made in the stomach.
• https://reference.medscape.com/drug/Lansoprazole-solu-tab-lansoprazole-341991