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  Clomiphene
 
Author: Donna Karasic, PharmD Last modified: March 31, 2002
 

  INDICATIONS

  • Male Infertility (non-FDA approved use) rarely used
  • Female Infertility
  • Lactation Suppression (non-FDA approved use)
  • Polycystic Ovary Disease (non-FDA approved use)
  • Dysfunctional uterine bleeding (non-FDA approved use)
  • Estrogen Replacement Therapy (non-FDA approved use)
  • Pubertal Gynecomastia (non-FDA approved use)
  • Hypogonadism (non-FDA approved use)

  DOSAGE

  • Male infertility: 50 to 400mg/day for 2 to 12 months has been used; however this use is controversial and further study is needed.
  • Female infertility: 1st course-50mg/day x5 days; begin any time if no history of recent uterine bleeding; if progestin-induced bleeding is intended or uterine bleeding occurs prior to treatment then
  • Female infertility, con't: start on 5th day of cycle. 2nd course of therapy: increase dose 100mg/day for 5 days. Start 2nd course as early as 30 days after previous course.
  • Female infertility, con't: Three courses are an adequate trial. If ovulatory menses has not yet occurred, re-evaluate diagnosis.

  PHARMACOKINETICS

  • Well absorbed from the GI tract.
  • Primarily excreted in the feces.
  • Drug appears in feces 6 weeks after administration suggesting remaining drug/metabolites are slowly excreted. Enterohepatic circulation occurs.
  • Peak response in male infertility: 2-3 months; female infertility: 11-12 days.
  • Elimination half-life: 5 days.

  ADVERSE EFFECTS

  • The frequency and severity of adverse reactions appear to be dose related and occur most frequently in patients receiving high doses and/or prolonged therapy.
  • Vasomotor symptoms (10.4%)- "hot flashes" are usually mild and disappear after therapy is discontinued.
  • Abdominal discomfort (5.5%)
  • Ovarian enlargement (14%)
  • Breast tenderness (2.1%)
  • Increased appetite and weight gain (0.4%)
  • Visual symptoms such as blurring of vision, diplopia, photophobia, decreased visual acuity

  CONTRAINDICATIONS

  • Pregnancy- this drug has been shown to be teratogenic in rats and rabbits.
  • Liver disease
  • Abnormal uterine bleeding
  • Emdometrial carcinoma
  • Organic intracranial lesion, such as pituitary tumor
  • Uncontrolled thyroid or adrenal dysfunction
  • Hypersensitivity to clomiphene

  DRUG INTERACTIONS

  • Danazol
  • Estradiol
  • Gonadorelin

  FORMS

  • 50mg tablets

  MECHANISM OF ACTION

  • Clomiphene is a racemic mixture of cis (zuclomiphene) and trans (enclomiphene) isomers of a synthetic nonsteroidal agent with weak estrogenic and moderate antiestrogenic properties
  • Clomiphene increases the output of pituitary gonadotropins
  • It binds competitively to estrogen receptors, decreasing the sites available to endogenous estrogen
  • The resulting decreased binding of endogenous estrogen to hypothalamic and pituitary estrogen receptors results in increased secretion of LH-RH and FSH-RH followed by the gonadotropins LH and FSH
  • This effect is seen in both males and females
 
IMPORTANT POINTS/RECOMMENDATIONS
  • Caution performing tasks requiring mental alertness or physical coordination (driving or operating heavy machinery).
  • Multiple ovulations with resulting plural gestations (mostly twins) is increased.
  • Do not take if pregnant; this drug is teratogenic in rats and rabbits.
 
REFERENCES
  1. Hutchinson TA & Shahan DR (Eds) ;  Clomiphene ;  MICROMEDEX Healthcare Series; MICROMEDEX, Greenwood Village, Colorado (edition expires 3-2002)

  2. McEvoy, Gerald K. (Ed) ;  Clomiphene Citrate ;  American Hospital Formulary Service 2001; Bethesda, MD

Copyright © 2002 The Johns Hopkins University School of Medicine. All rights reserved.