CLOMID is contraindicated in patients with a known hypersensitivity or allergy to clomiphene citrate or to any of its ingredients.
CLOMID should not be administered during pregnancy. CLOMID may cause fetal harm in animals (see Animal Fetotoxicity). Although no causative evidence of a deleterious effect of CLOMID therapy on the human fetus has been established, there have been reports of birth anomalies which, during clinical studies, occurred at an incidence within the range reported for the general population (see Fetal/Neonatal Anomalies and Mortality; ADVERSE REACTIONS).
To avoid inadvertent CLOMID administration during early pregnancy, appropriate tests should be utilized during each treatment cycle to determine whether ovulation occurs. The patient should be evaluated carefully to exclude pregnancy, ovarian enlargement, or ovarian cyst formation between each treatment cycle. The next course of CLOMID therapy should be delayed until these conditions have been excluded.
Fetal/Neonatal Anomalies and Mortality
The following fetal abnormalities have been reported subsequent to pregnancies following ovulation induction therapy with CLOMID during clinical trials. Each of the following fetal abnormalities were reported at a rate of <1% (experiences are listed in order of decreasing frequency): Congenital heart lesions, Down syndrome, club foot, congenital gut lesions, hypospadias, microcephaly, harelip and cleft palate, congenital hip, hemangioma, undescended testicles, polydactyly, conjoined twins and teratomatous malformation, patent ductus arteriosus, amaurosis, arteriovenous fistula, inguinal hernia, umbilical hernia, syndactyly, pectus excavatum, myopathy, dermoid cyst of scalp, omphalocele, spina bifida occulta, ichthyosis, and persistent lingual frenulum. Neonatal death and fetal death/stillbirth in infants with birth defects have also been reported at a rate of <1%. The overall incidence of reported birth anomalies from pregnancies associated with maternal CLOMID ingestion during clinical studies was within the range of that reported for the general population.
In addition, reports of birth anomalies have been received during postmarketing surveillance of CLOMID (see ADVERSE REACTIONS).
Oral administration of clomiphene citrate to pregnant rats during organogenesis at doses of 1 to 2 mg/kg/day resulted in hydramnion and weak, edematous fetuses with wavy ribs and other temporary bone changes. Doses of 8 mg/kg/day or more also caused increased resorptions and dead fetuses, dystocia, and delayed parturition, and 40 mg/kg/day resulted in increased maternal mortality. Single doses of 50 mg/kg caused fetal cataracts, while 200 mg/kg caused cleft palate.
Following injection of clomiphene citrate 2 mg/kg to mice and rats during pregnancy, the offspring exhibited metaplastic changes of the reproductive tract. Newborn mice and rats injected during the first few days of life also developed metaplastic changes in uterine and vaginal mucosa, as well as premature vaginal opening and anovulatory ovaries. These findings are similar to the abnormal reproductive behavior and sterility described with other estrogens and antiestrogens.
In rabbits, some temporary bone alterations were seen in fetuses from dams given oral doses of 20 or 40 mg/kg/day during pregnancy, but not following 8 mg/kg/day. No permanent malformations were observed in those studies. Also, rhesus monkeys given oral doses of 1.5 to 4.5 mg/kg/day for various periods during pregnancy did not have any abnormal offspring.
CLOMID therapy is contraindicated in patients with liver disease or a history of liver dysfunction (see also INDICATIONS AND USAGE and ADVERSE REACTIONS).
Abnormal Uterine Bleeding
CLOMID is contraindicated in patients with abnormal uterine bleeding of undetermined origin (see INDICATIONS AND USAGE).
CLOMID is contraindicated in patients with ovarian cysts or enlargement not due to polycystic ovarian syndrome (see INDICATIONS AND USAGE and WARNINGS).
CLOMID is contraindicated in patients with uncontrolled thyroid or adrenal dysfunction or in the presence of an organic intracranial lesion such as pituitary tumor (see INDICATIONS AND USAGE).