WARNINGS
See boxed WARNINGS.
PRECAUTIONS
Caution should be employed when administering Cytotec
(misoprostol) to patients with pre-existing cardiovascular disease.
THE PATIENT SHOULD NOT GIVE CYTOTEC TO ANYONE ELSE.
Cytotec 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 Cytotec package the patient receives from the pharmacist will include a
leaflet containing patient information. The patient should read the leaflet
before taking Cytotec and each time the prescription is renewed because the
leaflet may have been revised.
Keep Cytotec out of the reach of children.
SPECIAL NOTE FOR WOMEN: Cytotec may cause abortion
(sometimes incomplete), premature labor, or birth defects if given to pregnant
women.
Cytotec 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. Cytotec has not been shown to interfere with the
beneficial effects of aspirin on signs and symptoms of rheumatoid arthritis.
Cytotec does not exert clinically significant effects on the absorption, blood
levels, and antiplatelet effects of therapeutic doses of aspirin. Cytotec 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 Cytotec for up to 1 year.
An apparent response of the female mouse to Cytotec 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 Cytotec.
Carcinogenesis, mutagenesis, impairment of fertility
There was no evidence of an effect of Cytotec 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 Cytotec on tumor occurrence or
incidence in mice receiving daily doses up to 1000 times the human dose for 21
months. The mutagenic potential of Cytotec 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.
Cytotec is not fetotoxic or teratogenic in rats and rabbits at doses 625 and
63 times the human dose, respectively.
WARNINGS. Cytotec may endanger pregnancy (may
cause abortion) and thereby cause harm to the fetus when administered to a
pregnant woman. Cytotec may produce uterine contractions, uterine bleeding, and
expulsion of the products of conception. Abortions caused by Cytotec 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
Cytotec can induce or augment uterine contractions. Vaginal
administration of Cytotec, 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 Cytotec 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 Cytotec, 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 Cytotec on later growth, development, and functional maturation
of the child when Cytotec is used for cervical ripening or induction of labor
has not been established. Information on Cytotec's effect on the need for
forceps delivery or other intervention is unknown.
Nursing mothers
Misoprostol is rapidly metabolized in the mother to misoprostol acid, which is
biologically active and is excreted in breast milk. There are no published
reports of adverse effects of misoprostol in breast-feeding infants of mothers
taking misoprostol. Caution should be exercised when misoprostol is administered
to a nursing woman.
Pediatric use
Safety and effectiveness of Cytotec in pediatric patients have not been
established.
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