CYTOTEC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CYTOTEC (CYTOTEC).
Misoprostol is a synthetic prostaglandin E1 analog that binds to prostanoid receptors, leading to inhibition of gastric acid secretion (both basal and stimulated) and increased mucus and bicarbonate secretion, providing mucosal protection. Additionally, it stimulates uterine contractions and cervical ripening.
| Metabolism | Misoprostol is rapidly de-esterified to its free acid (misoprostol acid), which is the active metabolite. Further metabolism occurs via beta-oxidation and reduction of the cyclopentane ring. The primary metabolic enzymes are not well-defined, but esterases are involved in the initial hydrolysis. |
| Excretion | Following oral administration, misoprostol is rapidly de-esterified to misoprostol acid, the active metabolite. Renal excretion of misoprostol acid is approximately 64-73% of the dose (with 11-17% as unchanged acid) over 24 hours. Fecal excretion accounts for about 15% of the dose, primarily as metabolites. Biliary excretion is minimal. The remainder is eliminated as unidentified metabolites. |
| Half-life | Terminal elimination half-life of misoprostol acid is approximately 20-40 minutes. Due to rapid de-esterification, the half-life of the prodrug is very short (<5 minutes). No accumulation occurs with repeated dosing. In patients with renal impairment, half-life may be prolonged (up to 80 minutes) and dose adjustment may be necessary. |
| Protein binding | Misoprostol acid is approximately 80-90% bound to plasma proteins, primarily albumin. The binding is concentration-independent over therapeutic range. |
| Volume of Distribution | The apparent volume of distribution of misoprostol acid after oral administration is approximately 3-5 L/kg, indicating extensive tissue distribution. The high Vd reflects rapid uptake into tissues such as gastric mucosa, uterus, and kidneys. |
| Bioavailability | Oral bioavailability of misoprostol acid is about 70-80% after oral administration due to extensive first-pass metabolism (de-esterification). Vaginal bioavailability is approximately 3 times higher than oral (area under the curve about 3-fold greater) with prolonged absorption. Sublingual and buccal routes also yield higher bioavailability than oral, with sublingual achieving the highest peak concentrations. |
| Onset of Action | Onset of action varies by route: Oral: gastric acid suppression begins within 30 minutes, with peak effect at 60-90 minutes. Vaginal: onset of uterine contractions typically within 30-60 minutes. Buccal/sublingual: onset within 15-30 minutes. Intramuscular: not commonly used; onset within 15-30 minutes. |
| Duration of Action | Duration after oral dosing: gastric acid suppression lasts approximately 3-6 hours. For cervical ripening and induction of labor, effects persist for 4-6 hours after vaginal administration. Misoprostol does not provide sustained protection against NSAID-induced ulcers beyond the dosing interval (typically 4 times daily). |
200 mcg orally four times daily with food for prevention of NSAID-induced gastric ulcers. For termination of pregnancy: 800 mcg vaginally every 12-24 hours or 600 mcg orally as a single dose.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended for renal impairment based on GFR; use with caution in patients with renal disease due to potential for increased adverse effects. |
| Liver impairment | No specific dosage adjustment based on Child-Pugh score; however, use with caution in hepatic impairment due to limited data. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no standard weight-based dosing available. |
| Geriatric use | Dose selection should be cautious, starting at the lower end of the dosing range (e.g., 200 mcg orally twice daily) due to increased sensitivity to gastrointestinal effects and potential for renal impairment in elderly patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CYTOTEC (CYTOTEC).
| Breastfeeding | Misoprostol is excreted into breast milk in small amounts (M/P ratio approximately 1.0). No adverse effects reported in breastfed infants with short-term maternal use. However, caution is advised with chronic or high-dose use due to potential for diarrhea in the infant. Generally considered compatible with breastfeeding. |
| Teratogenic Risk | Misoprostol (Cytotec) is contraindicated in pregnancy due to its ability to induce uterine contractions and cause fetal harm. First trimester: high risk of fetal death, congenital anomalies (e.g., Moebius sequence), and miscarriage. Second and third trimesters: risk of uterine hyperstimulation, fetal distress, preterm delivery, and fetal demise. Use only for medical termination of pregnancy under strict protocols. |
■ FDA Black Box Warning
Cytotec administration by any route is contraindicated in pregnant women because it can cause abortion or harm to the fetus. Cytotec should not be used for labor induction or cervical ripening outside of an approved clinical setting with strict adherence to recommended dosing and route of administration.
| Serious Effects |
["Pregnancy (for NSAID ulcer prevention indication)","Known hypersensitivity to misoprostol or other prostaglandins","Use for labor induction in patients with uterine scarring (relative contraindication)"]
| Precautions | ["Risk of uterine rupture when used for labor induction, especially in women with prior cesarean section or uterine surgery","May cause diarrhea (dose-dependent), which can be severe and require discontinuation","Hydration status should be monitored due to potential for dehydration from diarrhea","Use caution in patients with inflammatory bowel disease or those at risk for gastrointestinal bleeding"] |
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| Fetal Monitoring | During use for cervical ripening or labor induction (off-label in some countries): continuous fetal heart rate monitoring and uterine activity assessment (tocodynamometry) required. Monitor for uterine hyperstimulation, fetal distress, and maternal vital signs. In termination of pregnancy: monitor for excessive bleeding, incomplete abortion, and signs of infection. |
| Fertility Effects | No direct effects on fertility. However, misoprostol is used to induce abortion, which may lead to complications (e.g., infection, uterine scarring) that could impair future fertility. No known permanent impact on ovulation or implantation when used as indicated. |