RiteMED Lansoprazole

Lansoprazole.

Each capsule contains: Lansoprazole, USP 30 mg.

Pharmacology: Pharmacodynamics: Lansoprazole, a benzimidazole derivative, belongs to a class of antisecretory compounds that suppress gastric acid secretion by specific inhibition of the (H⁺, K⁺)-ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the parietal cell, lansoprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated gastric acid secretion regardless of the stimulus. Lansoprazole does not exhibit anticholinergic or histamine type-2 antagonist activity.
Pharmacokinetics: Lansoprazole is rapidly absorbed after oral administration and peak plasma concentrations occur within 1.5 to 2 hours. Bioavailability is reported to be over 80%. Food reduces the peak concentration and the extent of absorption by 50 to 70%.
Lansoprazole is 97% bound to plasma proteins.
Lansoprazole is extensively metabolized in the liver, primarily by cytochrome P450 isoenzyme CYP2C19 to form 5-hydroxyl-lansoprazole and by CYP3A4 to form lansoprazole sulfone. Metabolites are excreted mainly in feces via the bile; only about 15 to 30% of a dose is excreted in urine.
The plasma elimination half-life of lansoprazole is approximately 1 to 2 hours.
Special Populations: Elderly: The clearance of lansoprazole is decreased in the elderly, with elimination half-life increased approximately 50 to 100%. Peak plasma levels were not increased.
Hepatic Impairment: The mean plasma half-life of lansoprazole was prolonged and the exposure is doubled in patients with hepatic impairment. However, a greater increase in exposure was observed in patients with moderate to severe hepatic impairment.
Renal Impairment: Patients with renal impairment had a shortened elimination half-life and decreased total area under the plasma concentration-time curve (AUC).

For the short-term and maintenance treatment of the following conditions: Duodenal ulcer; Gastric ulcer; Stomal ulcer; Reflux Esophagitis; Erosive Esophagitis (EE); Gastroesophageal reflux disease (GERD); Zollinger-Ellison syndrome (ZES); Nonsteroidal anti-inflammatory drug (NSAID)-induced gastric and duodenal ulcers; Helicobacter pylori (H. pylori) associated gastric and duodenal ulcers.

Lansoprazole capsule should be taken orally, preferably in the morning, 30 minutes before meals. (See table.)

Click on icon to see table/diagram/image

Dosage in Elderly: Dosage adjustment may be necessary due to reduced clearance of lansoprazole in the elderly. The daily dose should not exceed 30 mg.
Dosage in Patients with Hepatic Impairment: Dosage reduction is recommended.
The daily dose of lansoprazole should not exceed 30 mg.
Dosage in Patients with Renal Impairment: No dosage adjustment is necessary.

The effects of lansoprazole overdose in humans are not known. However, daily doses of up to 180 mg oral lansoprazole have been administered without significant adverse effects.
If overdose occurs, standard procedures (i.e., gastric emptying, administration of activated charcoal), symptomatic and supportive treatment is recommended.
Patients should be carefully monitored.
Lansoprazole is not significantly eliminated from the circulation by hemodialysis.

Patients who are hypersensitive to lansoprazole, other proton pump inhibitors (PPIs) or to any component of the product.
Patients who are receiving atazanavir sulfate.

Gastric Malignancy: Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric malignancy, thus the possibility of malignancy should be excluded prior to starting treatment with lansoprazole.
Acute Interstitial Nephritis: Acute interstitial nephritis has been observed in patients taking PPIs including lansoprazole. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Lansoprazole should be discontinued if acute interstitial nephritis develops.
Cyanocobalamin (vitamin B₁₂) Deficiency: The prolonged use of PPIs (e.g., longer than 3 years) may lead to malabsorption of protein bound vitamin B₁₂ caused by hypo- or achlorhydria and may contribute to the development of cyanocobalamin (vitamin B₁₂) deficiency. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported.
Clostridium difficile-Associated Diarrhea: Decreased gastric acidity due to any means, including PPIs, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with PPIs can lead to an increased risk of gastrointestinal infections such as Salmonella, Campylobacter, and Clostridium difficile.
PPI therapy, such as lansoprazole, may be associated with an increased risk of Clostridium difficile-associated diarrhea (CDAD), especially in hospitalized patients, the use of antibiotics, old age, and the presence of co-morbidities. This diagnosis should be considered for diarrhea that does not improve. Patients should use the lowest dose and the shortest duration of PPI therapy appropriate to the condition being treated.
Bone Fracture: PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines.
Hypomagnesemia: Symptomatic and asymptomatic hypomagnesemia has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), physicians may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically.
Helicobacter pylori (H. pylori) Eradication and Compliance: To avoid failure of the eradication treatment with a potential for developing antimicrobial resistance and a risk of failure with subsequent therapy, patients should be instructed to follow closely the prescribed regimen.
For the eradication of H. pylori, amoxicillin and clarithromycin should not be administered to patients with renal impairment since the appropriate dosage in this patient population has not yet been established.
Subacute Cutaneous Lupus Erythematosus (SCLE): PPIs, such as lansoprazole, are associated with very infrequent cases of SCLE. If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help immediately. Discontinuation of lansoprazole treatment should be considered.
Effects on Ability to Drive and Use Machine: Lansoprazole causes somnolence, dizziness, vertigo, and visual disturbances. Patients should be cautioned against engaging in activities requiring alertness such as operating machinery or driving a car.
Hepatic Impairment: Dose reduction should be considered in patients with moderate or severe hepatic impairment.
Renal Impairment: No dosage adjustment is necessary in patients with renal impairment.
Use in Children: The safety and efficacy of lansoprazole in children younger than 1 year old have not been established. However, the safety and efficacy of lansoprazole in children 1 to 17 years old have been established for short-term treatment of symptomatic GERD and erosive esophagitis.
Use in the Elderly: The frequency of adverse effects in elderly patients appears to be similar to that in younger patients. However, greater sensitivity of some older individuals cannot be ruled out. Clearance of lansoprazole may be decreased in elderly patients.

Pregnancy: Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Lansoprazole should only be used in pregnant women or women suspected of being pregnant if the potential benefits outweigh the potential risks of treatment.
Lactation: Lansoprazole or its metabolites are distributed into milk in rats; it is not known whether lansoprazole is distributed into human milk. A decision should be made whether to discontinue breastfeeding or to discontinue lansoprazole, taking into account the importance of the drug to the woman.

The most frequently reported adverse effects with lansoprazole include diarrhea, abdominal pain, nausea, constipation, headache, dizziness, vomiting, flatulence, dry mouth or throat, urticaria, itching, rash, and fatigue.
Infections and infestations: Bronchitis, Clostridium difficile-associated diarrhea, conjunctivitis, otitis media, pneumonia, pseudomembranous colitis, upper respiratory tract infection.
Neoplasms benign, malignant and unspecified (including cysts and polyps): Carcinoid, carcinoma, skin carcinoma.
Blood and lymphatic system disorders: Agranulocytosis, anemia, aplastic anemia, eosinophilia, hemolysis, hemolytic anemia, jaundice, leukopenia, lymph adenopathy, neutropenia, pancytopenia, thrombocytopenia.
Immune system disorders: Allergic reaction, anaphylactic reactions, asthma, erythema multiforme, ulcerative colitis.
Endocrine disorders: Abnormal menses, goiter, hypothyroidism.
Metabolism and nutrition disorders: Anorexia, avitaminosis, dehydration, diabetes mellitus, edema, hunger, hyperglycemia, hyperlipidemia, hypoglycemia, hypomagnesemia, hyponatremia, increased appetite, peripheral edema, thirst.
Psychiatric disorders: Abnormal dreams, aggression, agitation, anxiety, apathy, confusion, dementia, depersonalization, depression, emotional lability, hallucinations, hoarseness, hostility aggravated, insomnia, nervousness, neurosis, sleep disorder, somnolence.
Nervous system disorders: Amnesia, cerebrovascular accident, convulsion, diplopia, hemiplegia, hyperkinesia, hypoesthesia, migraine, myasthenia, numbness of tongue or lips, paresthesia, ptosis, speech disorders, taste loss, taste perversion, thinking abnormality, tremor, vertigo.
Eye disorders: Abnormal vision, amblyopia, blepharitis, blurred vision, cataract, dry eyes, eye pain, glaucoma, photophobia, retinal degeneration, visual disturbances, visual field defect.
Ear and labyrinth disorders: Deafness, tinnitus.
Cardiac disorders: Arrhythmia, bradycardia, chest pain, dyspnea, myocardial infarction, palpitations, tachycardia.
Vascular disorders: Epistaxis, hemoptysis, hypertension, hypotension, rectal hemorrhage, shock (circulatory failure), syncope, vasodilation.
Respiratory, thoracic and mediastinal disorders: Cough, flu syndrome, interstitial pneumonia, laryngeal neoplasia, lung fibrosis, parosmia, pharyngitis, pleural disorder, rhinitis, sinusitis, stridor, upper respiratory tract inflammation.
Gastrointestinal disorders: Abnormal stools, bezoar, candidiasis of the esophagus, cardiospasm, colitis, duodenitis, dyspepsia, dysphagia, enlarged abdomen, enteritis, epigastric discomfort, eructation, esophageal stenosis, esophageal ulcer, esophagitis, fecal discoloration, fundic gland polyps, gastritis, gastroenteritis, gastrointestinal anomaly, gastrointestinal hemorrhage, gastrointestinal moniliasis, glossitis, gum hemorrhage, halitosis, hematemesis, hiatal hernia, hiccup, impaired gastric emptying, increased salivation, melena, mouth ulceration, oral moniliasis, pancreatitis, rectal disorder, stomatitis, tongue disorder, tooth disorder, ulcerative stomatitis.
Hepatobiliary disorders: Cholelithiasis, hepatitis, hepatotoxicity.
Skin and subcutaneous tissue disorders: Acne, alopecia, dry skin, fixed eruption, hair disorder, maculopapular rash, nail disorder, petechiae, pruritus, Stevens-Johnson syndrome, subacute cutaneous lupus erythematosus, thrombotic thrombocytopenic purpura, toxic epidermal necrolysis.
Musculoskeletal and connective tissue disorders: Arthralgia, arthritis, back pain, bone disorder, chills, gout, hypertonia, joint disorder, leg cramps, musculoskeletal pain, myalgia, neck pain, neck rigidity, synovitis, tenesmus.
Renal and urinary disorders: Dysuria, interstitial nephritis, kidney calculus, kidney pain, polyuria, renal impairment, urethral pain, urinary frequency, urinary retention, urinary tract infection, urinary urgency.
Reproductive system and breast disorders: Breast enlargement, breast pain, breast tenderness, dysmenorrhea, gynecomastia, impotence, increased/decreased libido, leukorrhea, menorrhagia, menstrual disorder, pelvic pain, penis disorder, testis disorder, vaginitis.
General disorders and administration site conditions: Asthenia, crepitations, fever, general pain, malaise, metaplasia, sweating.
Investigations: Abnormal liver function tests, elevated alanine aminotransferase, weight gain/loss.
Injury, poisoning and procedural complications: Bone fracture, contact dermatitis, contusion.

Human Immunodeficiency Virus (HIV) Protease Inhibitors: Concomitant use of atazanavir and nelfinavir with PPIs is not recommended. Lansoprazole is expected to substantially decrease atazanavir or nelfinavir plasma concentrations and may result in a loss of therapeutic effect and the development of drug resistance. In contrast, coadministration of saquinavir and raltegravir with PPIs is expected to increase saquinavir or raltegravir concentrations, which may increase toxicity and require dose reduction.
Atazanavir: Gastric antisecretory effect of lansoprazole may reduce the solubility of atazanavir sulfate, resulting in a decrease in the blood concentration of atazanavir. Lansoprazole should not be coadministered with atazanavir.
pH-dependent Drugs: Lansoprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability. As with other drugs that decrease intragastric acidity, the absorption of drugs such as ampicillin esters, ketoconazole, atazanavir, nelfinavir, iron salts, erlotinib, and mycophenolate mofetil (MMF) can decrease, while the absorption of drugs such as digoxin can increase during treatment with lansoprazole. Increased monitoring is recommended during concomitant use with lansoprazole.
Digoxin: Coadministration of lansoprazole and digoxin may lead to increased digoxin plasma levels. The plasma levels of digoxin should be monitored and the dose of digoxin should be adjusted when initiating and discontinuing lansoprazole treatment.
Mycophenolate mofetil (MMF): Coadministration of lansoprazole in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure in organ rejection has not been established in transplant patients receiving lansoprazole and MMF.
Drugs Affecting/Metabolized by Hepatic Microsomal Enzymes: Lansoprazole is metabolized through the cytochrome P450 system, specifically through CYP3A4 and CYP2C19. Studies have shown that lansoprazole does not have clinically significant interactions with other drugs metabolized by the CYP450 system such as warfarin, antipyrine, indomethacin, acetylsalicylic acid, ibuprofen, phenytoin, prednisone, diazepam, clarithromycin, propranolol, amoxicillin or terfenadine. These compounds are metabolized through various CYP450 isoenzymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A.
Warfarin: Increased international normalized ratio (INR) and prothrombin time have been reported in patients receiving PPIs and warfarin concomitantly. Since such increases may lead to abnormal bleeding and even death, patients treated with PPIs and warfarin should be monitored for increases in INR and prothrombin time.
Tacrolimus and Fluvoxamine: Concomitant administration of lansoprazole and tacrolimus may increase the plasma concentrations of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. Inhibitors of CYP2C19 such as fluvoxamine would likely increase the systemic exposure to lansoprazole.
Drugs that Cause Hypomagnesemia: Possible increased risk of hypomagnesemia; For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., loop or thiazide diuretics), healthcare professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically thereafter.
Methotrexate: Concomitant administration of PPIs and methotrexate, primarily at high doses, may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate which may lead to methotrexate toxicity. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients.
Clopidogrel: Concomitant administration of lansoprazole and clopidogrel 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.
Sucralfate: Concomitant administration of lansoprazole with sucralfate resulted in delayed absorption and decreased bioavailability of lansoprazole by 17%. Lansoprazole should be administered at least 30 minutes before sucralfate.
Theophylline: Concomitant administration of theophylline and lansoprazole may result in a slight (10%) increase in theophylline clearance. The interaction is unlikely to be clinically important, although some patients may require adjustment of theophylline dosage when lansoprazole therapy is initiated or discontinued.
Laboratory Test Interactions: During treatment with antisecretory drugs, chromogranin (CgA) increases due to decreased gastric acidity. The increased CgA level may interfere with investigations for neuroendocrine tumors. Lansoprazole treatment should be temporarily stopped before CgA measurements to avoid this interference.

Store at temperatures not exceeding 30°C.

Antacids, Antireflux Agents & Antiulcerants

A02BC03 - lansoprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).

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