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Misoprostol

Pronunciation

Pronunciation

(mye soe PROST ole)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Cytotec: 100 mcg

Cytotec: 200 mcg [scored]

Generic: 100 mcg, 200 mcg

Brand Names: U.S.

  • Cytotec

Pharmacologic Category

  • Prostaglandin

Pharmacology

Misoprostol is a synthetic prostaglandin E1 analog that replaces the protective prostaglandins consumed with prostaglandin-inhibiting therapies (eg, NSAIDs); has been shown to induce uterine contractions

Absorption

Rapid and extensive

Metabolism

Hepatic; rapidly de-esterified to misoprostol acid (active)

Excretion

Urine (80%)

Onset of Action

Inhibition of gastric acid secretion: 30 minutes; Peak effect: 60 to 90 minutes

Time to Peak

Serum: Misoprostol acid: Fasting: 14 ± 8 minutes

Duration of Action

Inhibition of gastric acid secretion: 3 hours

Half-Life Elimination

Misoprostol acid: 20 to 40 minutes

Protein Binding

Misoprostol acid: 80% to 90%

Special Populations: Renal Function Impairment

Cmax, AUC, and t½ are almost doubled, but no clear correlation between degree of impairment and AUC is shown. No dosage adjustment is recommended. However, dose reduction may be needed if patient does not tolerate.

Special Populations: Elderly

AUC is increased in patients >64 years of age. However, no dose adjustment is needed.

Use: Labeled Indications

NSAID-induced gastric ulcers: Prevention of NSAID-induced gastric ulcers

Termination of intrauterine pregnancy: Medical termination of intrauterine pregnancy through 70 days' gestation in combination with mifepristone (Mifeprex prescribing information March 2016)

Use: Unlabeled

Cervical ripening and labor induction (except in women with prior cesarean delivery or major uterine surgery); prevention of postpartum hemorrhage; treatment of postpartum hemorrhage; treatment of incomplete or missed abortion in women <12 weeks gestation

Contraindications

Hypersensitivity to misoprostol, other prostaglandins, or any component of the formulation

When used for NSAID-induced gastric ulcer prevention (additional contraindications): Pregnancy

When used for termination of intrauterine pregnancy (additional contraindications): Refer to Mifepristone monograph.

Dosing: Adult

NSAID-induced gastric ulcers, prevention: Oral: 200 mcg 4 times daily with food; if not tolerated, may decrease dose to 100 mcg 4 times daily with food; last dose of the day should be taken at bedtime

Termination of intrauterine pregnancy: Oral: Refer to Mifepristone monograph.

Early pregnancy loss (off-label use): Intravaginal (off-label route): Initial dose: 800 mcg. May repeat with one dose if needed, ≥3 hours after the first dose and typically within 7 days if no response to the initial dose is observed (ACOG 150, 2015).

Incomplete abortion (treatment) (off-label use): Oral: 600 mcg as a single dose (ACOG 427, 2009)

Labor induction or cervical ripening (off-label uses): Intravaginal (off-label route): 25 mcg (1/4of 100 mcg tablet); may repeat at intervals no more frequent than every 3 to 6 hours (ACOG 107, 2009).

Missed abortion (treatment) (off-label use):

Intravaginal (off-label route): 800 mcg; may repeat every 3 hours for 2 additional doses if needed (ACOG 427, 2009).

Sublingual (off-label route): 600 mcg; may repeat every 3 hours for 2 additional doses if needed (ACOG 427, 2009).

Postpartum hemorrhage (prevention) (off-label use): Oral: 600 mcg as a single dose administered immediately after delivery (FIGO, 2012a).

Postpartum hemorrhage (treatment) (off-label use):

Rectal (off-label route): 800 to 1000 mcg (ACOG 76, 2006).

Sublingual (off-label route): 800 mcg as a single dose. Use caution if a prophylactic dose was already given, especially if adverse events were observed (FIGO, 2012b).

Dosing: Geriatric

NSAID-induced gastric ulcers, prevention: Refer to adult dosing.

Dosing: Pediatric

Termination of intrauterine pregnancy: Oral: Refer to adult dosing.

Dosing: Renal Impairment

Dose adjustment is not routinely needed; however, the dose may be reduced if the recommended dose is not tolerated. It is not known if misoprostol is removed by dialysis.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer's labeling.

Administration

Incidence of diarrhea may be lessened by having patient take dose right after meals and avoiding magnesium-containing antacids. When used for the prevention of NSAID-induced ulcers, therapy is usually begun on the second or third day of the next normal menstrual period in women of childbearing potential.

Termination of intrauterine pregnancy: Refer to Mifepristone monograph.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Dietary Considerations

When used for the prevention of NSAID-induced ulcers, take with food.

Storage

Store at or below 25°C (77°F).

Drug Interactions

Antacids: May enhance the adverse/toxic effect of MiSOPROStol. More specifically, concomitant use with magnesium-containing antacids may increase the risk of diarrhea. Management: Avoid concomitant use of misoprostol and magnesium-containing antacids. In patients requiring antacid therapy, employ magnesium-free preparations. Monitor for increased adverse effects (e.g., diarrhea, dehydration). Exceptions: Aluminum Hydroxide; Calcium Carbonate; Sodium Bicarbonate. Avoid combination

Carbetocin: MiSOPROStol may enhance the adverse/toxic effect of Carbetocin. Specifically, Carbetocin oxytocic effects may be enhanced. Avoid combination

Oxytocin: MiSOPROStol may enhance the adverse/toxic effect of Oxytocin. Specifically, oxytocic effects may be enhanced. Management: The manufacturer of misoprostol recommends avoiding concomitant use with oxytocin. Misoprostol may augment effects of oxytocin, particularly when given within 4 hours of oxytocin initiation. Consider therapy modification

Adverse Reactions

>10%: Gastrointestinal: Diarrhea, abdominal pain

1% to 10%:

Central nervous system: Headache

Gastrointestinal: Constipation, dyspepsia, flatulence, nausea, vomiting

<1% (Limited to important or life-threatening): Abnormal taste, abnormal vision, alkaline phosphatase increased, alopecia, anaphylaxis, anemia, amylase increase, anxiety, arrhythmia, arterial thrombosis, arthralgia, cardiac enzymes increased, chest pain, chills, confusion, CVA, deafness, depression, diaphoresis, dizziness, drowsiness, dysphagia, dyspnea, dysuria, edema, epistaxis, ESR increased, fatigue, fever, GI bleeding, GI inflammation, gingivitis, glycosuria, gout; gynecological disorders, hematuria, hepatobiliary function abnormal, hyper-/hypotension, impotence, loss of libido, MI, muscle cramps, myalgia, neuropathy, neurosis, nitrogen increased, pallor, phlebitis, polyuria, pulmonary embolism, purpura, rash, reflux, rigors, stiffness, syncope, thirst, thrombocytopenia, tinnitus, uterine rupture, weakness, weight changes

ALERT: U.S. Boxed Warning

Women of childbearing potential:

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. Ensure misoprostol is not taken by pregnant women to reduce the risk of ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs).

Patients must be advised of the abortifacient property and warned not to give the drug to others.

Do not use misoprostol for reducing the risk of NSAID-induced ulcer 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 if the drug is taken by mistake; and will begin misoprostol only on the second or third day of the next normal menstrual period.

Warnings/Precautions

Concerns related to adverse effects:

• Abortifacient: [US Boxed Warning]: Due to the abortifacient property of this medication, patients must be warned not to give this drug to others.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease.

• Renal impairment: Use with caution in patients with renal impairment.

Special populations:

• Elderly: Use with caution in the elderly.

• Pregnancy: Adverse events have been reported when used outside of current product labeling (cervical ripening, induction of labor, postpartum hemorrhage). Uterine tachysystole may occur and progress to uterine tetany; uteroplacental blood flow may be impaired and uterine rupture or amniotic fluid embolism may occur. The risk of uterine rupture may be increased with advanced gestational age, grand multiparity, or prior uterine surgery. Uterine activity and fetal status should be monitored in a hospital setting. Misoprostol should not be used in situations where uterotonic drugs are otherwise contraindicated or inappropriate.

• Women of childbearing potential: [US Boxed Warning]: Use of misoprostol during pregnancy may cause abortion, birth defects, or premature birth. Uterine rupture has been reported when used to induce labor after the eighth week of pregnancy. Misoprostol is not to be used to reduce NSAID-induced ulcers in a woman of childbearing potential unless she is capable of complying with effective contraceptive measures and is at high risk of developing gastric ulcers and/or their complications. If needed, the patient must have a negative pregnancy test within 2 weeks of starting therapy, she must use effective contraception during treatment, and therapy should begin on the second or third day of next normal menstrual period. Written and verbal warnings concerning the hazards of misoprostol should be provided.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Other warnings/precautions:

• Appropriate use: Termination of pregnancy: Misoprostol is approved for use with mifepristone for termination of pregnancy. Refer to mifepristone warnings, precautions, and contraindications for appropriate use of misoprostol for this indication.

• Appropriate use: Ulcers: For use only in patients at high risk of complications from gastric ulcers (eg, elderly patients, patients with concomitant diseases) or patients at high risk for developing gastric ulcers (eg, those with a history of ulcers) taking NSAIDs. Misoprostol must be taken during the duration of NSAID therapy. It is not effective in preventing duodenal ulcers in patients taking NSAIDs.

Monitoring Parameters

Prevention of NSAID-induced gastric ulcers: Pregnancy test in women of reproductive potential prior to therapy; adequate diagnostic measures in all cases of undiagnosed abnormal vaginal bleeding

Off-label pregnancy-related uses: Uterine activity and fetal status. When used for incomplete or missed abortion, reevaluate 1 to 2 weeks after dosing (ACOG 427, 2009). When used for termination of pregnancy: Prior to procedure, confirm pregnancy and Rh status; assess hemoglobin and hematocrit if anemia is suspected (ACOG 2014). Following procedure: Clinical exam, human Chorionic Gonadotropin (hCG) testing, and/or ultrasound to confirm complete termination of pregnancy; hemoglobin, hematocrit, and red blood cell count in cases of heavy bleeding. Consider CBC in any patient who reports nausea, vomiting, or diarrhea and weakness with or without abdominal pain, and without fever or other signs of infection more than 24 hours after administration of misoprostol (Mifeprex prescribing information March 2016).

Pregnancy Risk Factor

X

Pregnancy Considerations

Use for the prevention of NSAID-induced gastric ulcers is contraindicated in pregnant women.

[US Boxed Warning]: Use of misoprostol during pregnancy may cause abortion, birth defects, or premature birth. Uterine rupture has been reported when used to induce labor after the eighth week of pregnancy. Misoprostol is not to be used to reduce NSAID-induced ulcers in a woman of childbearing potential unless she is capable of complying with effective contraceptive measures and is at high risk of developing gastric ulcers and/or their complications. If needed, the patient must have a negative pregnancy test within 2 weeks of starting therapy, she must use effective contraception during treatment, and therapy should begin on the second or third day of next normal menstrual period. Written and verbal warnings concerning the hazards of misoprostol should be provided. Due to the abortifacient property of this medication, patients must be warned not to give this drug to others.

Congenital anomalies following first trimester exposure have been reported, including skull defects, cranial nerve palsies, facial malformations, and limb defects. Misoprostol may produce uterine contractions; fetal death, uterine perforation, and abortion may occur.

Misoprostol is FDA approved for the medical termination of pregnancy of ≤70 days in conjunction with mifepristone.

Because misoprostol may induce or augment uterine contractions, it has been used off-label as a cervical-ripening agent for induction of labor. Misoprostol should not be used for this purpose during the third trimester in women who have had a prior cesarean delivery or major uterine surgery because the risk of uterine rupture is increased (ACOG 107, 2009; ACOG 115, 2010). It has also been used for the treatment of incomplete or missed abortion (ACOG 427, 2009), early pregnancy loss (ACOG 150, 2015), or severe postpartum hemorrhage (ACOG 76, 2006; FIGO, 2012a; FIGO, 2012b). Some guidelines recommend misoprostol for postpartum hemorrhage only secondary to oxytocin in situations where oxytocin is not available (Leduc, 2000; FIGO, 2012a; FIGO, 2012b). Various routes of administration have been used for postpartum hemorrhage. Sublingual administration has the most rapid onset, the oral route produces the most pronounced initial increase in tonus, and rectal and vaginal routes exhibit longer durations of action as compared to oral and sublingual routes (Leduc, 2009). Adverse events associated with off-label obstetric uses include uterine tachysystole (may impair placental blood flow), uterine rupture, amniotic fluid embolism, or adverse fetal heart changes.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience abdominal cramps. Have patient report immediately to prescriber severe nausea, vomiting, severe abdominal pain, or severe diarrhea (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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