Misoprostol

INDICATIONS AND USAGE Misoprostol is indicated for reducing the risk of NSAID (nonsteroidal anti-inflammatory drugs, including aspirin)–induced gastric ulcers in patients at high risk of complications from gastric ulcer, e.g., the elderly and patients with concomitant debilitating disease, as well as patients at high risk of developing gastric ulceration, such as patients with a history of ulcer. Misoprostol Tablet has not been shown to reduce the risk of duodenal ulcers in patients taking NSAIDs. Misoprostol Tablets should be taken for the duration of NSAID therapy. Misoprostol Tablets has been shown to reduce the risk of gastric ulcers in controlled studies of 3 months' duration. It had no effect, compared to placebo, on gastrointestinal pain or discomfort associated with NSAID use.

DOSAGE & ADMINISTRATION The recommended adult oral dose of misoprostol for reducing the risk of NSAID-induced gastric ulcers is 200 mcg four times daily with food. If this dose cannot be tolerated, a dose of 100 mcg can be used. (See Clinical Pharmacology: Clinical studies . ) Misoprostol should be taken for the duration of NSAID therapy as prescribed by the physician. Misoprostol should be taken with a meal, and the last dose of the day should be at bedtime. Renal impairment Adjustment of the dosing schedule in renally impaired patients is not routinely needed, but dosage can be reduced if the 200-mcg dose is not tolerated. (See Clinical Pharmacology . )

CONTRAINDICATIONS See boxed WARNINGS . Misoprostol Tablets should not be taken by pregnant women to reduce the risk of ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Misoprostol Tablets should not be taken by anyone with a history of allergy to prostaglandins.

ADVERSE REACTIONS The following have been reported as adverse events in subjects receiving Misoprostol Tablets: Gastrointestinal: In subjects receiving Misoprostol Tablets 400 or 800 mcg daily in clinical trials, the most frequent gastrointestinal adverse events were diarrhea and abdominal pain. The incidence of diarrhea at 800 mcg in controlled trials in patients on NSAIDs ranged from 14 to 40% and in all studies (over 5,000 patients) averaged 13%. Abdominal pain occurred in 13 to 20% of patients in NSAID trials and about 7% in all studies, but there was no consistent difference from placebo. Diarrhea was dose related and usually developed early in the course of therapy (after 13 days), usually was self-limiting (often resolving after 8 days), but sometimes required discontinuation of Misoprostol Tablets (2% of the patients). Rare instances of profound diarrhea leading to severe dehydration have been reported. Patients with an underlying condition such as inflammatory bowel disease, or those in whom dehydration, were it to occur, would be dangerous, should be monitored carefully if Misoprostol Tablets is prescribed. The incidence of diarrhea can be minimized by administering after meals and at bedtime, and by avoiding coadministration of Misoprostol Tablets with magnesium-containing antacids. Gynecological: Women who received Misoprostol Tablets during clinical trials reported the following gynecological disorders: spotting (0.7%), cramps (0.6%), hypermenorrhea (0.5%), menstrual disorder (0.3%) and dysmenorrhea (0.1%). Postmenopausal vaginal bleeding may be related to Misoprostol Tablets administration. If it occurs, diagnostic workup should be undertaken to rule out gynecological pathology. (See boxed WARNINGS .) Elderly: There were no significant differences in the safety profile of Misoprostol Tablets in approximately 500 ulcer patients who were 65 years of age or older compared with younger patients. Additional adverse events which were reported are categorized as follows: Incidence greater than 1%: In clinical trials, the following adverse reactions were reported by more than 1% of the subjects receiving Misoprostol Tablets and may be causally related to the drug: nausea (3.2%), flatulence (2.9%), headache (2.4%), dyspepsia (2.0%), vomiting (1.3%), and constipation (1.1%). However, there were no significant differences between the incidences of these events for Misoprostol Tablets and placebo. Causal relationship unknown: The following adverse events were infrequently reported. Causal relationships between Misoprostol Tablets and these events have not been established but cannot be excluded: Body as a whole: aches/pains, asthenia, fatigue, fever, chills, rigors, weight changes. Skin: rash, dermatitis, alopecia, pallor, breast pain. Special senses: abnormal taste, abnormal vision, conjunctivitis, deafness, tinnitus, earache. Respiratory: upper respiratory tract infection, bronchitis, bronchospasm, dyspnea, pneumonia, epistaxis. Cardiovascular: chest pain, edema, diaphoresis, hypotension, hypertension, arrhythmia, phlebitis, increased cardiac enzymes, syncope, myocardial infarction (some fatal), thromboembolic events (e.g., pulmonary embolism, arterial thrombosis, and CVA). Gastrointestinal: GI bleeding, GI inflammation/infection, rectal disorder, abnormal hepatobiliary function, gingivitis, reflux, dysphagia, amylase increase. Hypersensitivity: anaphylactic reaction Metabolic: glycosuria, gout, increased nitrogen, increased alkaline phosphatase. Genitourinary: polyuria, dysuria, hematuria, urinary tract infection. Nervous system/Psychiatric: anxiety, change in appetite, depression, drowsiness, dizziness, thirst, impotence, loss of libido, sweating increase, neuropathy, neurosis, confusion. Musculoskeletal: arthralgia, myalgia, muscle cramps, stiffness, back pain. Blood/Coagulation: anemia, abnormal differential, thrombocytopenia, purpura, ESR increased. To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticlas, …

Drug Interactions See Clinical Pharmacology . Misoprostol Tablets has not been shown to interfere with the beneficial effects of aspirin on signs and symptoms of rheumatoid arthritis. Misoprostol Tablets does not exert clinically significant effects on the absorption, blood levels, and antiplatelet effects of therapeutic doses of aspirin. Misoprostol Tablets has no clinically significant effect on the kinetics of diclofenac or ibuprofen. Prostaglandins such as Misoprostol Tablets may augment the activity of oxytocic agents, especially when given less than 4 hours prior to initiating oxytocin treatment. Concomitant use is not recommended.

DESCRIPTION Misoprostol oral tablets contain either 100 mcg or 200 mcg of misoprostol, a synthetic prostaglandin E 1 analog. Misoprostol contains approximately equal amounts of the two diastereomers presented below with their enantiomers indicated by (±): C 22 H 38 O 5 M.W. = 382.5 (±) methyl 11α, 16-dihydroxy-16-methyl-9-oxoprost-13E-en-1-oate Misoprostol is a water-soluble, viscous liquid. Inactive ingredients of tablets are hydrogenated castor oil, hypromellose, microcrystalline cellulose, and sodium starch glycolate. Chemical Structure

OVERDOSAGE The toxic dose of Misoprostol Tablets in humans has not been determined. Cumulative total daily doses of 1600 mcg have been tolerated, with only symptoms of gastrointestinal discomfort being reported. In animals, the acute toxic effects are diarrhea, gastrointestinal lesions, focal cardiac necrosis, hepatic necrosis, renal tubular necrosis, testicular atrophy, respiratory difficulties, and depression of the central nervous system. Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnea, abdominal pain, diarrhea, fever, palpitations, hypotension, or bradycardia. Symptoms should be treated with supportive therapy. It is not known if misoprostol acid is dialyzable. However, because misoprostol is metabolized like a fatty acid, it is unlikely that dialysis would be appropriate treatment for overdosage.

HOW SUPPLIED Misoprostol Tablets, 100 mcg are available as white, round, unscored, flat beveled-edged tablets, marked with “443” on one side and “N” on the reverse side. NDC Number Size 70954-443-10 unit-of-use bottle of 60 70954-443-20 unit-of-use bottle of 120 Misoprostol Tablets, 200 mcg are available as white, round, scored, flat beveled-edged tablets, marked with “N” above the score-line and “444” below the score-line and plain on the reverse side. NDC Number Size 70954-444-10 unit-of-use bottle of 60 70954-444-20 unit-of-use bottle of 100 Pharmacist: Dispense in this unit-of-use, child-resistant container as defined in the USP. Provide Patient Information Leaflet with each dispensing. Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Store in a dry area. All trademarks are the property of their respective owners. Distributed by: ANI Pharmaceuticals, Inc. Baudette, MN 56623 Issued: 04/2025 LB4429-03