Clomiphene Citrate

Clomiphene Citrate is a medication used for the treatment of infertility by inducing ovulation in females. It inhibits the negative feedback mechanisms of estrogens in the hypothalamus and pituitary which stimulates the secretion of pituitary gonadotrophic hormones resulting in stimulation of ovulation. Clomiphene Citrate is used in the treatment of anovulation or oligo-ovulation in patients desiring pregnancy, whose sexual partners have adequate sperm, and who have potentially functional hypothalamic-hypophyseal-ovarian systems and adequate endogenous estrogen. It is also indicated in lactational amenorrhoea, psychogenic amenorrhoea, post oral contraceptive amenorrhoea and some cases of secondary amenorrhoea of unknown origin. For males, it is used in the treatment of infertility with oligospermia and poor sperm motility.

• Anovulation or oligo-ovulation in females (desiring pregnancy)
• Lactational amenorrhoea
• Psychogenic amenorrhoea
• Post oral contraceptive amenorrhoea
• Secondary amenorrhoea of unknown origin
• Oligospermia and poor sperm motility in males

Clomiphene has mainly antiestrogenic effects and some estrogenic effects. The mechanism in stimulating ovulation is unknown but is believed to be related to its antiestrogenic properties. By clomiphene competing with estrogen for binding sites at the hypothalamic level, the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), secretion is increased, which results in ovarian follicle maturation, followed by the preovulatory LH surge, ovulation, and the subsequent development of the corpus luteum. Usefulness in male infertility is also likely related to the increases in FSH and LH secretion.

Clomiphene inhibits the negative feedback mechanisms of estrogens in the hypothalamus and pituitary which stimulates the secretion of pituitary gonadotrophic hormones resulting in stimulation of ovulation.

Female Dose (Oral): 50 mg once daily for 5 days starting on the 2nd-5th day of menstrual cycle. If ovulation does not occur, the dose may be increased to 75-100 mg daily for 5 days (next course starting 30 days after previous course). Generally, 3 courses are adequate to assess whether ovulation is obtainable. If ovulation without conception occurs, repeat for 3-4 cycles. If pregnancy has not occurred after about 6 cycles, further therapy is not recommended.

Male Dose (Oral): 25 mg once daily for up to 90 days. A break of 5 days after every 25 days is recommended.

Hemodialysis patients: Loading dose of 250 mg-1 g prior to dialysis.

May be taken with or without food. Take in the dose and duration as advised by your doctor.

If you miss a dose of Clomiphene Citrate, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose. Do not double the dose.

Common Side Effects (>10%): Ovarian enlargement (14%), Vasomotor flushing (10%)

Less Common Side Effects (1-10%): Abdominal discomfort (6%), Blurred vision (1.5%), Breast discomfort (2%), Nausea/vomiting (2%)

Other Side Effects: Ovarian hyperstimulation, hot flushes, headache, depression, insomnia, intermenstrual spotting, menorrhagia, endometriosis, convulsions, weight gain, rash, dizziness, hair loss.

• Use only under medical supervision and after careful selection of patients.
• Complete pelvic examination is essential prior to start of treatment and should be repeated before each subsequent course to exclude pregnancy, ovarian enlargement or ovarian cyst formation.
• Use with caution in polycystic ovaries, uterine fibroids.
• Visual disturbances may develop which will impair ability to drive or operate machinery.
• There is a minimal chance of multiple pregnancies (patients should be warned).
• May reduce lactation.
• Contraindicated during pregnancy.

• Pregnancy
• Liver diseases
• Ovarian cysts
• Bleeding of undetermined origin
• Neoplasm of endometrium
• Hypersensitivity
• Abnormal bleeding
• Lactation
• Uncontrolled thyroid or adrenal dysfunction
• Organic intracranial lesions such as pituitary tumor

Decreased response with danazol.

May be taken with or without food. Caution with alcoholic drinks.

Use in pregnant women is contraindicated. To avoid inadvertent administration during early pregnancy, appropriate tests should be utilized during each treatment cycle to determine whether ovulation and/or pregnancy occurs. Pregnancy Category X.

It is not known whether clomiphene is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if administered to a nursing woman. Therapy may reduce lactation.

Limited information is available regarding use in children.

Elderly: As adults.

Contraindicated in liver disease. Should not be used in hepatic impairment.

Information on overdosage is not available. Consult a physician if overdose is suspected.

Keep below 30°C temperature, away from light & moisture. Keep out of reach of children.

Clomiphene Citrate