Generic Name: misoprostol

Brand Names: Cytotec

Uses

Prevention of NSAIA-induced Ulcers

Treatment to reduce the risk of NSAIA-induced gastric ulcers in patients at high risk (e.g., concomitant debilitating disease, geriatric patients, history of upper GI ulcer) of developing complications (e.g., bleeding, perforation, death) from these ulcers.

Not recommended for use in women of childbearing potential unless the woman is at high risk of developing gastric ulcers or of complications resulting from NSAIA-induced gastric ulcers.

Gastric Ulcer

Short-term treatment of active, benign, gastric ulcer†; however, not considered a drug of choice.

Maintenance treatment following healing of active gastric ulcer to reduce ulcer recurrence†.

Duodenal Ulcer

Short-term treatment of endoscopically or radiographically confirmed active duodenal ulcer†; however, not considered a drug of choice.

Termination of Pregnancy

Use as an adjunct to mifepristone for medical termination of an intrauterine pregnancy. (See Pregnancy under Cautions.)

Labor Induction

Treatment to improve cervical inducibility (cervical “ripening”) in appropriately selected pregnant women with unfavorable cervices with a medical or obstetric need for labor induction†. However, avoid such use in women with prior uterine surgery or cesarean section because of the risk of possible uterine rupture.

Postpartum Hemorrhage

Prevention or treatment of serious postpartum hemorrhage† in the presence of uterine atony.

Dosage and Administration

Administration

Administer orally.

Also has been administered intravaginally†, using tablets formulated for oral administration.

Oral Administration

Administer in divided doses after meals and at bedtime.

Avoid concomitant administration with a magnesium-containing or other laxative antacid to minimize the incidence of misoprostol-induced diarrhea. (See GI Effects under Cautions and also see Interactions.)

Dosage

Available as mifoprostol; dosage expressed in terms of mifoprostol.

Adults

Prevention of NSAIA-Induced Ulcers

Oral

200 mcg 4 times daily. May reduce dosage to 100 mcg 4 times daily if higher dosage is not well tolerated; however, reduced dosage may be less effective. Alternatively, 200 mcg twice daily. Continue therapy for the duration of NSAIA therapy.

Gastric Ulcer

Oral

100 or 200 mcg 4 times daily for 8 weeks.†

Duodenal Ulcer

Oral

100 or 200 mcg 4 times daily or 400 mcg twice daily for 4–8 weeks.†

Termination of Pregnancy

Oral

400 mcg administered orally on day 3 (2 days after mifepristone administration) unless abortion has occurred and has been confirmed by clinical examination or ultrasonographic scan. See Mifepristone 76:00.

Induction of Labor

Intravaginal

Initially, 25 mcg (¼ of a 100-mcg oral tablet). Subsequently, 25-mcg every 3–6 hours.†

Prescribing Limits

Adults

Induction of Labor

Intravaginal

Maximum 25 mcg. Subsequently, maximum 25-mcg every 3–6 hours. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)†

Special Populations

Renal Impairment

Routine dosage reduction not required; however, dosage can be reduced if not tolerated.

Geriatric Patients

Routine dosage reduction not required; however, dosage can be reduced if not tolerated.

Cautions

Contraindications

• Pregnancy (for reducing the risk of NSAIA-induced gastric ulcers).
• Known hypersensitivity to prostaglandins.

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Possible teratogenic and abortifacient effects; possible serious fetal harm when administered to pregnant women. Possible uterine contractions and uterine bleeding and total or partial expulsion of the products of conception in pregnant women. Spontaneous abortions may result in dangerous uterine bleeding, premature birth, or birth defects. Possible congenital abnormalities (e.g., skull defects, cranial nerve palsies, facial malformations, and limb defects); sometimes associated with fetal death.

Do not use in pregnant women for reducing the risk of NSAIA-induced gastric ulcers. (See Contraindications under Cautions.) Do not initiate therapy in women of childbearing potential until pregnancy is excluded and other necessary precautions (effective contraception) are ensured. Initiate therapy only after determining that patient is reliable and able to comply with effective contraceptive measures. Perform a reliable, blood pregnancy test within 2 weeks prior to beginning therapy. Initiate therapy on the second or third day of the next normal menstrual cycle, after a negative pregnancy test is reported. (See Pregnancy and also see Lactation under Cautions.)

If inadvertently administered during pregnancy or if the patient becomes pregnant while receiving the drug, discontinue therapy and inform patient of the potential hazard to the fetus.

Intravaginal use may result in uterine hyperstimulation, uterine tetany, uterine rupture, amniotic fluid embolism, pelvic pain, retained placenta, severe genital bleeding, shock, fetal bradycardia, and fetal and maternal death, especially with dosages >25 mcg. (See Prescribing Limits under Dosage and Administration.) Risk of uterine rupture increases with advancing gestational age, prior uterine surgery (including cesarean delivery), and grand multiparity. Intravaginal use is not recommended in patients with a previous cesarean delivery or prior major uterine surgery.

Sensitivity Reactions

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, reported.

General Precautions

GI Effects

Possible diarrhea; usually apparent after about 2 weeks of therapy. Generally is self-limiting, resolving within about a week after onset. Possible increased risk of profound (e.g., voluminous, watery) and life-threatening diarrhea in patients with inflammatory bowel disease. Use with extreme caution in these patients; careful monitoring recommended. Careful monitoring recommended in patients prone to dehydration or in whom its consequences would be dangerous. Administer in divided doses after meals and at bedtime; avoid concomitant administration with a magnesium-containing or other laxative antacid to minimize diarrhea. (See Interactions.)

Cardiovascular Effects

Chest pain, edema, diaphoresis, hypotension, hypertension, arrhythmia, phlebitis, increased serum concentrations of cardiac enzymes, syncope, MI (some fatal), and thromboembolic events (e.g., pulmonary embolism, arterial thrombosis, cerebrovascular accident) reported; causal relationship to drug not established. Use with caution in patients with preexisting cardiovascular disease.

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category X. (See Fetal/Neonatal Morbidity and Mortality and also see Contraindications under Cautions.)

Ruptured ectopic pregnancy (rarely resulting in fatal hemorrhage); serious, rarely fatal, bacterial (e.g., Clostridium sordellii) infection and sepsis; or MI reported in a limited number of patients receiving intravaginal misoprostol with mifepristone for termination of pregnancy; causal relationship to regimen not established.

Lactation

Not known whether misoprostol is distributed into milk. Use not recommended.

Pediatric Use

Safety and efficacy not established in children <18 years of age.

Geriatric Use

No substantial differences in safety relative to younger adults.

Renal Impairment

Possible increased half-life, peak plasma misoprostol acid concentrations, and areas under the plasma concentration-time curves (AUCs). (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Diarrhea, abdominal pain.

Interactions

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interaction unlikely.

Specific Drugs and Foods

Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed from the GI tract; 88% of a dose is absorbed.

Onset

Following oral administration, inhibition of gastric acid secretion reaches a maximum within 60–90 minutes.

Duration

Following oral administration, inhibition of gastric acid secretion persists for at least 3 hours. Duration is directly related to dose.

Food

Food and antacids decrease the rate of absorption of misoprostol, resulting in delayed and decreased peak plasma concentrations.

Special Populations

Increased peak plasma misoprostol acid concentrations and AUCs in patients with renal impairment. In geriatric patients, possible increased AUCs; however, peak plasma concentrations are not affected.

Distribution

Extent

Distribution into human body tissues and fluids has not been fully characterized. Not known whether misoprostol and/or misoprostol acid cross the placenta or are distributed into milk in humans.

Plasma Protein Binding

Approximately 80–90%.

Elimination

Metabolism

Rapidly and extensively metabolized to misoprostol acid (the free acid), at least in part in the GI tract. Misoprostol acid undergoes extensive, rapid metabolism to form inactive metabolites.

Elimination Route

Excreted in urine (73%) mainly as metabolites and in feces (15%) via biliary excretion.

Half-life

Biphasic; half-life of free acid is 20–40 minutes.

Special Populations

In patients with renal impairment, possible increased half-life.

Stability

Storage

Oral

Tablets

Well-closed containers a≤25°C.

Actions

• Inhibits gastric acid secretion and protects the gastroduodenal mucosa.
• Exhibits substantial dose-related inhibitory effects on basal, nocturnal, and food- or histamine-stimulated gastric acid secretion via a direct action at the parietal cells.
• Protective effect may result from increased mucus secretion, increased bicarbonate secretion from nonparietal cells, enhancement or maintenance of blood flow of the mucosa (possibly via direct vasodilation), protection of submucosal cell proliferation, stabilization of mucosal membrane systems, prevention of mucosal barrier disruption, enhancement of transmucosal diffusion potential, and inhibition or reduction of back diffusion of hydrogen ions into the mucosa.
• Stimulates intestinal fluid secretion and effects motility.
• Increases the amplitude and frequency of uterine contractions and stimulates uterine bleeding and total or partial expulsion of uterine contents in pregnant women.

Advice to Patients

• Importance of providing patient a copy of manufacturer’s patient information. Patients should read the patient information before initiating misoprostol therapy and every time the prescription is refilled.
• Risk of serious fetal harm if administered in pregnant women. Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy and advise pregnant women of risk to the fetus. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
• Importance of informing patient that sharing the drug with another individual, particularly a woman of childbearing potential, could be hazardous.
• Importance of promptly informing clinicians if they have problems with or questions about misoprostol.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions July 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.