Misoprostol (misoprostol 100 ug) Dailymed

Misoprostol is extensively absorbed, and undergoes rapid de-esterification to its free acid, which is responsible for its clinical activity and, unlike the parent compound, is detectable in plasma. The alpha side chain undergoes beta oxidation and the beta side chain undergoes omega oxidation followed by reduction of the ketone to give prostaglandin F analogs. In normal volunteers, misoprostol is rapidly absorbed after oral administration with a T max of misoprostol acid of 12 ± 3 minutes and a terminal half-life of 20 to 40 minutes. There is high variability of plasma levels of misoprostol acid between and within studies but mean values after single doses show a linear relationship with dose over the range of 200 to 400 mcg. No accumulation of misoprostol acid was noted in multiple dose studies; plasma steady state was achieved within two days. Maximum plasma concentrations of misoprostol acid are diminished when the dose is taken with food and total availability of misoprostol acid is reduced by use of concomitant antacid. Clinical trials were conducted with concomitant antacid, however, so this effect does not appear to be clinically important. Mean ± SD C max (pg/ml) AUC (0–4) (pg·hr/ml) T max (min) Fasting 811 ± 317 417 ± 135 14 ± 8 With Antacid 689 ± 315 349 ± 108 Comparisons with fasting results statistically significant, p<0.05. 20 ± 14 With High Fat Breakfast 303 ± 176 373 ± 111 64 ± 79 After oral administration of radiolabeled misoprostol, about 80% of detected radioactivity appears in urine. Pharmacokinetic studies in patients with varying degrees of renal impairment showed an approximate doubling of T 1/2, C max, and AUC compared to normals, but no clear correlation between the degree of impairment and AUC. In subjects over 64 years of age, the AUC for misoprostol acid is increased. No routine dosage adjustment is recommended in older patients or patients with renal impairment, but dosage may need to be reduced if the usual dose is not tolerated. Drug interaction studies between misoprostol and several nonsteroidal anti-inflammatory drugs showed no effect on the kinetics of ibuprofen or diclofenac, and a 20% decrease in aspirin AUC, not thought to be clinically significant. Pharmacokinetic studies also showed a lack of drug interaction with antipyrine and propranolol when these drugs were given with misoprostol. Misoprostol given for 1 week had no effect on the steady state pharmacokinetics of diazepam when the two drugs were administered 2 hours apart. The serum protein binding of misoprostol acid is less than 90% and is concentration-independent in the therapeutic range. After a single oral dose of misoprostol to nursing mothers, misoprostol acid was excreted in breast milk. The maximum concentration of misoprostol acid in expressed breast milk was achieved within 1 hour after dosing and was 7.6 pg/mL (CV 37%) and 20.9 pg/ml (CV 62%) after single 200 µg and 600 µg misoprostol administration, respectively. The misoprostol acid concentrations in breast milk declined to < 1 pg/ml at 5 hours post-dose.

Misoprostol Tablets has been shown to produce uterine contractions that may endanger pregnancy. (See boxed .)

Misoprostol Tablets has been shown to produce uterine contractions that may endanger pregnancy. (See boxed WARNINGS .)

Women of childbearing potential using Misoprostol Tablets to decrease the risk of NSAID-induced ulcers should be told that they must not be pregnant when Misoprostol Tablets therapy is initiated, and that they must use an effective contraception method while taking Misoprostol Tablets.

Women of childbearing potential using Misoprostol Tablets to decrease the risk of NSAID-induced ulcers should be told that they must not be pregnant when Misoprostol Tablets therapy is initiated, and that they must use an effective contraception method while taking Misoprostol Tablets. See boxed WARNINGS . Misoprostol Tablets 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 Tablets should be taken only according to the directions given by a physician. If the patient has questions about or problems with Misoprostol Tablets, the physician should be contacted promptly. THE PATIENT SHOULD NOT GIVE MISOPROSTOL TABLETS TO ANYONE ELSE. Misoprostol Tablets 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 Tablets package the patient receives from the pharmacist will include a leaflet containing patient information. The patient should read the leaflet before taking Misoprostol Tablets and each time the prescription is renewed because the leaflet may have been revised. Keep Misoprostol Tablets out of the reach of children. SPECIAL NOTE FOR WOMEN: Misoprostol Tablets may cause birth defects, abortion (sometimes incomplete), premature labor or rupture of the uterus if given to pregnant women. Misoprostol Tablets 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.



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 Tablets is not fetotoxic or teratogenic in rats and rabbits at doses 625 and 63 times the human dose, respectively.

See boxed WARNINGS . Misoprostol Tablets may endanger pregnancy (may cause abortion) and thereby cause harm to the fetus when administered to a pregnant woman. Misoprostol Tablets may produce uterine contractions, uterine bleeding, and expulsion of the products of conception. Abortions caused by Misoprostol Tablets 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.

Misoprostol Tablets can induce or augment uterine contractions. Vaginal administration of Misoprostol Tablets, 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 Tablets is uterine tachysystole 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 and lead to adverse fetal heart changes. Uterine activity and fetal status should be monitored by trained obstetrical personnel in a hospital setting. The risk of uterine rupture associated with misoprostol use in pregnancy increases with advancing gestational ages and prior uterine surgery, including Cesarean delivery. Grand multiparity also appears to be a risk factor for uterine rupture. The use of Misoprostol Tablets outside of its approved indication may also be associated with meconium passage, meconium staining of amniotic fluid, and Cesarean delivery. Maternal shock, maternal death, fetal bradycardia, and fetal death have also been reported with the use of misoprostol. Misoprostol Tablets should not be used in the third trimester in women with a history of Cesarean section or major uterine surgery because of an increased risk of uterine rupture. Misoprostol Tablets should not be used in cases where uterotonic drugs are generally contraindicated or where hyperstimulation of the uterus is considered inappropriate, such as cephalopelvic disproportion, grand multiparity, hypertonic or hyperactive uterine patterns, or fetal distress where delivery is not imminent, or when surgical intervention is more appropriate. The effect of Misoprostol Tablets on later growth, development, and functional maturation of the child when Misoprostol Tablets is used for cervical ripening or induction of labor has not been established. Information on Misoprostol Tablet’s effect on the need for forceps delivery or other intervention is unknown. The use of Misoprostol Tablets for the management of postpartum hemorrhage has been associated with reports of high fevers (greater than 40 degrees Celsius or 104 degrees Fahrenheit), accompanied by autonomic and central nervous system effects, such as tachycardia, disorientation, agitation, and convulsions. These fevers were transient in nature. Supportive therapy should be dictated by the patient’s clinical presentation.

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.