İHALE DÜNYASI
İHALE DÜNYASI
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 (±): Misoprostol is a water-soluble, viscous liquid chemically described as (±) methyl 11?, 16-dihydroxy-16-methyl-9-oxoprost-13E-en-1-oate. Each misoprostol tablet for oral administration contains either 100 mcg or 200 mcg of misoprostol and has the following inactive ingredients: Hydrogenated caster oil, hypromellose, microcrystalline cellose, and sodium starch glycolate. image of formula
Misoprostol tablets are 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 has not been shown to reduce the risk of duodenal ulcers in patients taking NSAIDs. Misoprostol should be taken for the duration of NSAID therapy. Misoprostol 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.
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 ).
See boxed WARNINGS. Misoprostol should not be taken by pregnant women to reduce the risk of ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs). Misoprostol should not be taken by anyone with a history of allergy to prostaglandins.
The following have been reported as adverse events in subjects receiving Cytotec: Gastrointestinal In subjects receiving Cytotec 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 14-40% and in all studies (over 5,000 patients) averaged 13%. Abdominal pain occurred in 13-20% 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 Cytotec (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 Cytotec is prescribed. The incidence of diarrhea can be minimized by administering after meals and at bedtime, and by avoiding coadministration of Cytotec with magnesium-containing antacids. Gynecological Women who received Cytotec 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 Cytotec 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 Cytotec 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 Cytotec 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 Cytotec and placebo. Causal relationship unknown The following adverse events were infrequently reported. Causal relationships between misoprostol 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 Anaphylaxis 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 | Gynecological Women who received Cytotec 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 Cytotec 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 Cytotec 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 Cytotec 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 Cytotec and placebo. | Causal relationship unknown The following adverse events were infrequently reported. Causal relationships between misoprostol 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 Anaphylaxis 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
See boxed WARNINGS . --- BOXED WARNING: MISOPROSTOL ADMINISTRATION TO WOMEN WHO ARE PREGNANT CAN CAUSE ABORTION, PREMATURE BIRTH, OR BIRTH DEFECTS. UTERINE RUPTURE HAS BEEN REPORTED WHEN MISOPROSTOL WAS ADMINISTERED IN PREGNANT WOMEN TO INDUCE LABOR OR TO INDUCE ABORTION BEYOND THE EIGHTH WEEK OF PREGNANCY. (See also PRECAUTIONS , and LABOR AND DELIVERY ). MISOPROSTOL SHOULD NOT BE TAKEN BY PREGNANT WOMEN TO REDUCE THE RISK OF ULCERS INDUCED BY NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) (See CONTRAINDICATIONS , WARNINGS and PRECAUTIONS ). PATIENTS MUST BE ADVISED OF THE ABORTIFACIENT PROPERTY AND WARNED NOT TO GIVE THE DRUG TO OTHERS. Misoprostol should not be used for reducing the risk of NSAID-induced ulcers in women of childbearing potential unless the patient is at high risk of complications from gastric ulcers associated with use of the NSAID, or is at high risk of developing gastric ulceration. In such patients, misoprostol may be prescribed if the patient: has had a negative serum pregnancy test within 2 weeks prior to beginning therapy. is capable of complying with effective contraceptive measures. has received both oral and written warnings of the hazards of misoprostol, the risk of possible contraception failure, and the danger to other women of childbearing potential should the drug be taken by mistake. will begin misoprostol only on the second or third day of the next normal menstrual period.