Brand name: Cytotec
Drug class: Prostaglandins
ATC class: A02BB01
VA class: GA309
Chemical name: 11α,13E)-(±)-11,16-Dihydroxy-16-methyl-9-oxo-prost-13-en-1-oic acid methyl ester
Molecular formula: C₂₂H₃₈O₅
CAS number: 59122-46-2

Medically reviewed by Drugs.com on Mar 28, 2023. Written by ASHP.

Introduction

Gastric antisecretory agent with protective effects on the gastroduodenal mucosa; a synthetic analog of prostaglandin E₁ (alprostadil).

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.

Contraindicated for this use in pregnant women.

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.

The American College of Gastroenterology (ACG) has published guidelines for the prevention of NSAIA-related ulcer complications. The guidelines state that misoprostol (administered in full doses of 800 mcg daily) is very effective in preventing ulcers and ulcer complications in patients taking NSAIDs, but use may be limited by adverse GI effects. There is evidence that lower doses (400–600 mcg daily) may also confer significant protection with a similar adverse effect profile to placebo.

Termination of Pregnancy

Used in conjunction with misoprostol for termination of intrauterine pregnancy through 70 days of gestation, dated from first day of last menstrual period; duration of pregnancy may be determined by menstrual history or clinical examination, or with an ultrasonographic scan if duration of pregnancy is uncertain or ectopic pregnancy is suspected.

The American College of Obstetricians and Gynecologists (ACOG) states that the medication abortion regimen supported by major medical organizations nationally and internationally includes mifepristone and misoprostol; if mifepristone is unavailable, then a misoprostol-only regimen is an acceptable alternative.

Gastric Ulcer

Short-term treatment of active, benign, gastric ulcer^{† [off-label]}; however, not considered a drug of choice.

Maintenance treatment following healing of active gastric ulcer to reduce ulcer recurrence^{† [off-label]}.

Duodenal Ulcer

Short-term treatment of endoscopically or radiographically confirmed active duodenal ulcer^{† [off-label]}; however, not considered a drug of choice.

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^{† [off-label]}. 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^{† [off-label]} in the presence of uterine atony.

Misoprostol Dosage and Administration

Administration

Administer orally.

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

Oral Administration

Prevention of NSAIA-induced ulcers: 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.

Termination of pregnancy: Administer misoprostol intrabuccally 24–48 hours following mifepristone administration. Place 2 misoprostol tablets in each side of the mouth between the cheek and gums for 30 minutes, then swallow any remnants with water or another liquid. Administer in an appropriate setting for the patient, taking into account that expulsion of uterine contents could begin within 2 hours following drug administration.

Dosage

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.

Termination of Pregnancy

Oral

800 mcg intrabuccally (two 200-mcg tablets placed in each cheek pouch) 24–48 hours following mifepristone administration. Administration of misoprostol <24 or >48 hours following mifepristone administration may result in reduced efficacy of the combined regimen.

Vaginal,†Sublingual†, or Buccal†

Alternatively, if mifepristone is unavailable, ACOG states misoprostol may be administered alone at a dose of 800 mcg vaginally, sublingually, or buccally. Repeat dose every 3 hours for up to 3 doses for the initial treatment regimen. The World Health Organization (WHO) does not specify a maximum number of misoprostol doses for this use.

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.

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.

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 for Misoprostol

Contraindications

• Pregnant women (when used to reduce 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. (See Boxed Warning.)

Possible uterine contractions and uterine bleeding and expulsion of the products of conception.

Uterine rupture reported when administered in pregnant women to induce labor or abortion.

Possible congenital abnormalities (e.g., skull defects, cranial nerve palsies, facial malformations, and limb defects); sometimes associated with fetal death.

Contraindicated in pregnant women for reducing the risk of NSAIA-induced gastric ulcers. 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.

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. 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.

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.

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.

Specific Populations

Pregnancy

Risk of serious fetal harm. (See Boxed Warning.)

Serious, sometimes fatal, bacterial (e.g., Clostridium sordellii) infection and sepsis or prolonged heavy vaginal bleeding reported following spontaneous, surgical, and medical abortions, including in patients receiving misoprostol with mifepristone for termination of pregnancy; causal relationship to regimen not established.

Lactation

Misoprostol is metabolized rapidly to the free acid following oral administration, which is biologically active and distributed into breast milk. No published reports of adverse effects associated with misoprostol in breast-fed infants. Caution is advised if used during breast-feeding.

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 AUC.

Common Adverse Effects

Diarrhea, abdominal pain.

Drug Interactions

Drugs Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interaction unlikely.

Specific Drugs and Foods

Misoprostol 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 AUC in patients with renal impairment. In geriatric patients, possible increased AUC; 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. Misoprostol acid distributes 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

Store in a dry place at ≤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.

• 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.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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