WARNINGS
See boxed WARNINGS.
PRECAUTIONS
Caution should be employed when administering misoprostol to patients with pre-existing cardiovascular disease.
Information for Patients
Women of childbearing potential using misoprostol to decrease the risk of NSAID-induced ulcers should be told that they must not be pregnant when misoprostol therapy is initiated, and that they must use an effective contraception method while taking misoprostol.
See boxed WARNINGS.
Misoprostol is intended for administration along with nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, to decrease the chance of developing an NSAID-induced gastric ulcer.
Misoprostol should be taken only according to the directions given by a physician.
If the patient has questions about or problems with misoprostol, the physician should be contacted promptly.
THE PATIENT SHOULD NOT GIVE MISOPROSTOL TO ANYONE ELSE. Misoprostol 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 misoprostol package the patient receives from the pharmacist will include a leaflet containing patient information. The patient should read the leaflet before taking misoprostol and each time the prescription is renewed because the leaflet may have been revised.
Keep misoprostol out of the reach of children.
SPECIAL NOTE FOR WOMEN: Misoprostol may cause abortion (sometimes incomplete), premature labor, or birth defects if given to pregnant women.
Misoprostol 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.
Drug interactions
See Clinical Pharmacology . Misoprostol has not been shown to interfere with the beneficial effects of aspirin on signs and symptoms of rheumatoid arthritis. Misoprostol does not exert clinically significant effects on the absorption, blood levels, and antiplatelet effects of therapeutic doses of aspirin. Misoprostol has no clinically significant effect on the kinetics of diclofenac or ibuprofen.
Animal toxicology
A reversible increase in the number of normal surface gastric epithelial cells occurred in the dog, rat, and mouse. No such increase has been observed in humans administered misoprostol for up to 1 year.
An apparent response of the female mouse to misoprostol in long-term studies at 100 to 1000 times the human dose was hyperostosis, mainly of the medulla of sternebrae. Hyperostosis did not occur in long-term studies in the dog and rat and has not been seen in humans treated with misoprostol.
Carcinogenesis, mutagenesis, impairment of fertility
There was no evidence of an effect of misoprostol on tumor occurrence or incidence in rats receiving daily doses up to 150 times the human dose for 24 months. Similarly, there was no effect of misoprostol on tumor occurrence or incidence in mice receiving daily doses up to 1000 times the human dose for 21 months. The mutagenic potential of misoprostol was tested in several in vitro assays, all of which were negative.
Misoprostol, when administered to breeding male and female rats at doses 6.25 times to 625 times the maximum recommended human therapeutic dose, produced dose-related pre- and post-implantation losses and a significant decrease in the number of live pups born at the highest dose. These findings suggest the possibility of a general adverse effect on fertility in males and females.
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.
Misoprostol is not fetotoxic or teratogenic in rats and rabbits at doses 625 and 63 times the human dose, respectively.
Nonteratogenic effects
See boxed WARNINGS. Misoprostol may endanger pregnancy (may cause abortion) and thereby cause harm to the fetus when administered to a pregnant woman. Misoprostol may produce uterine contractions, uterine bleeding, and expulsion of the products of conception. Abortions caused by misoprostol 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.
Labor and delivery
Misoprostol can induce or augment uterine contractions. Vaginal administration of misoprostol, outside of its approved indication, has been used as a cervical ripening agent, for the induction of labor and for treatment of serious postpartum hemorrhage in the presence of uterine atony. A major adverse effect of the obstetrical use of misoprostol is the hyperstimulation of the uterus which may progress to uterine tetany with marked impairment of uteroplacental blood flow, uterine rupture (requiring surgical repair, hysterectomy, and/or salpingo-oophorectomy), or amniotic fluid embolism. Pelvic pain, retained placenta, severe genital bleeding, shock, fetal bradycardia, and fetal and maternal death have been reported.
There may be an increased risk of uterine tachysystole, uterine rupture, meconium passage, meconium staining of amniotic fluid, and Cesarean delivery due to uterine hyperstimulation with the use of higher doses of misoprostol, including the manufactured 100 mcg tablet. The risk of uterine rupture increases with advancing gestational ages and with prior uterine surgery, including Cesarean delivery. Grand multiparity also appears to be a risk factor for uterine rupture.
The effect of misoprostol on later growth, development, and functional maturation of the child when misoprostol is used for cervical ripening or induction of labor has not been established. Information on misoprostol's effect on the need for forceps delivery or other intervention is unknown.
Nursing mothers
It is unlikely that misoprostol is excreted in human milk since it is rapidly metabolized throughout the body. However, it is not known if the active metabolite (misoprostol acid) is excreted in human milk. Therefore, misoprostol should not be administered to nursing mothers because the potential excretion of misoprostol acid could cause significant diarrhea in nursing infants.
Pediatric use
Safety and effectiveness of misoprostol in pediatric patients have not been established.
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