misoprostol 100 MCG Oral Tablet

WARNINGS

See boxed .

For hospital use only if misoprostol were to be used for cervical ripening, induction of labor, or for the treatment of serious post-partum hemorrhage, which are outside of the approved indication.

DRUG INTERACTIONS

Drug interactions See Clinical Pharmacology .

Cytotec has not been shown to interfere with the beneficial effects of aspirin on signs and symptoms of rheumatoid arthritis.

Cytotec does not exert clinically significant effects on the absorption, blood levels, and antiplatelet effects of therapeutic doses of aspirin.

Cytotec has no clinically significant effect on the kinetics of diclofenac or ibuprofen.

Prostaglandins such as Cytotec may augment the activity of oxytocic agents, especially when given less than 4 hours prior to initiating oxytocin treatment.

Concomitant use is not recommended .

OVERDOSAGE

The toxic dose of Cytotec 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.

DESCRIPTION

Cytotec 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.

Inactive ingredients of tablets are hydrogenated castor oil, hypromellose, microcrystalline cellulose, and sodium starch glycolate.

Chemical Structure

CLINICAL STUDIES

Clinical studies In a series of small short-term (about 1 week) placebo-controlled studies in healthy human volunteers, doses of misoprostol were evaluated for their ability to reduce the risk of NSAID-induced mucosal injury.

Studies of 200 mcg q.i.d.

of misoprostol with tolmetin and naproxen, and of 100 and 200 mcg q.i.d.

with ibuprofen, all showed reduction of the rate of significant endoscopic injury from about 70–75% on placebo to 10–30% on misoprostol.

Doses of 25–200 mcg q.i.d.

reduced aspirin-induced mucosal injury and bleeding.

HOW SUPPLIED

Cytotec 100-mcg tablets are white, round, with SEARLE debossed on one side and 1451 on the other side; supplied as: NDC Number Size 0025-1451-60 unit-of-use bottle of 60 0025-1451-20 unit-of-use bottle of 120 0025-1451-34 carton of 100 unit dose Cytotec 200-mcg tablets are white, hexagonal, with SEARLE debossed above and 1461 debossed below the line on one side and a double stomach debossed on the other side; supplied as: NDC Number Size 0025-1461-60 unit-of-use bottle of 60 0025-1461-31 unit-of-use bottle of 100 0025-1461-34 carton of 100 unit dose Store at or below 25°C (77°F), in a dry area.

INDICATIONS AND USAGE

Cytotec (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.

Cytotec has not been shown to reduce the risk of duodenal ulcers in patients taking NSAIDs.

Cytotec should be taken for the duration of NSAID therapy.

Cytotec 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.

PEDIATRIC USE

Pediatric use Safety and effectiveness of Cytotec in pediatric patients have not been established.

PREGNANCY

Pregnancy: Pregnancy Category X Teratogenic effects See boxed WARNINGS .

Congenital anomalies sometimes associated with fetal death have been reported subsequent to the unsuccessful use of misoprostol as an abortifacient, but the drug’s teratogenic mechanism has not been demonstrated.

Several reports in the literature associate the use of misoprostol during the first trimester of pregnancy with skull defects, cranial nerve palsies, facial malformations, and limb defects.

Cytotec is not fetotoxic or teratogenic in rats and rabbits at doses 625 and 63 times the human dose, respectively.

Nonteratogenic effects See boxed WARNINGS .

Cytotec may endanger pregnancy (may cause abortion) and thereby cause harm to the fetus when administered to a pregnant woman.

Cytotec may produce uterine contractions, uterine bleeding, and expulsion of the products of conception.

Abortions caused by Cytotec may be incomplete.

If a woman is or becomes pregnant while taking this drug to reduce the risk of NSAID-induced ulcers, the drug should be discontinued and the patient apprised of the potential hazard to the fetus.

NUSRING MOTHERS

Nursing mothers Misoprostol is rapidly metabolized in the mother to misoprostol acid, which is biologically active and is excreted in breast milk.

There are no published reports of adverse effects of misoprostol in breast-feeding infants of mothers taking misoprostol.

Caution should be exercised when misoprostol is administered to a nursing woman.

BOXED WARNING

WARNINGS CYTOTEC (MISOPROSTOL) ADMINISTRATION TO WOMEN WHO ARE PREGNANT CAN CAUSE BIRTH DEFECTS, ABORTION, OR PREMATURE BIRTH.

UTERINE RUPTURE HAS BEEN REPORTED WHEN CYTOTEC 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 ).

CYTOTEC SHOULD NOT BE TAKEN BY PREGNANT WOMEN TO REDUCE THE RISK OF ULCERS INDUCED BY NONSTEROIDAL 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.

Cytotec 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, Cytotec 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 Cytotec only on the second or third day of the next normal menstrual period.

INFORMATION FOR PATIENTS

Information for patients Women of childbearing potential using Cytotec to decrease the risk of NSAID-induced ulcers should be told that they must not be pregnant when Cytotec therapy is initiated, and that they must use an effective contraception method while taking Cytotec.

See boxed WARNINGS .

Cytotec is intended for administration along with nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, to decrease the chance of developing an NSAID-induced gastric ulcer.

Cytotec should be taken only according to the directions given by a physician.

If the patient has questions about or problems with Cytotec, the physician should be contacted promptly.

THE PATIENT SHOULD NOT GIVE CYTOTEC TO ANYONE ELSE.

Cytotec has been prescribed for the patient’s specific condition, may not be the correct treatment for another person, and may be dangerous to the other person if she were to become pregnant.

The Cytotec package the patient receives from the pharmacist will include a leaflet containing patient information.

The patient should read the leaflet before taking Cytotec and each time the prescription is renewed because the leaflet may have been revised.

Keep Cytotec out of the reach of children.

SPECIAL NOTE FOR WOMEN: Cytotec may cause birth defects, abortion (sometimes incomplete), or premature labor if given to pregnant women.

Cytotec is available only as a unit-of-use package that includes a leaflet containing patient information.

See Patient Information at the end of this labeling.

DOSAGE AND ADMINISTRATION

The recommended adult oral dose of Cytotec 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 .) Cytotec should be taken for the duration of NSAID therapy as prescribed by the physician.

Cytotec 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 .)