Posted in Clinician Information

Clomiphene (Clomid) to Induce Ovulation

Adapted (partially verbatim) from LexiComp.

How to take it:

50 mg once daily for 5 days. Begin on or about the fifth day of cycle if progestin-induced bleeding is scheduled or spontaneous uterine bleeding occurs prior to therapy. Therapy may be initiated at anytime in patients with no recent uterine bleeding.

Contraindications

Hypersensitivity to clomiphene citrate or any of its components; liver disease or history of liver disease; abnormal uterine bleeding; enlargement or development of ovarian cyst (not due to polycystic ovarian syndrome); uncontrolled thyroid or adrenal dysfunction; presence of an organic intracranial lesion such as pituitary tumor; pregnancy

Canadian labeling: Additional contraindications (not in the US labeling): Hormone-dependent tumors, thrombophlebitis, uterine fibroids, mental depression.

Warnings/Precautions

Concerns related to adverse effects:

  • Ovarian enlargement: May be accompanied by abdominal distention or abdominal pain and generally regresses without treatment within a few days or weeks after therapy discontinuation. If ovaries are abnormally enlarged, withhold therapy until ovaries return to pretreatment size; reduce clomiphene dose and duration of future cycles.
  • Ovarian hyperstimulation syndrome (OHSS): OHSS is a rare exaggerated response to ovulation induction therapy (Corbett 2014; Fiedler 2012). This syndrome may begin within 24 hours of treatment but may become most severe 7 to 10 days after therapy (Corbett 2014). Symptoms of mild/moderate OHSS may include abdominal distention/discomfort, diarrhea, nausea, and/or vomiting. Severe OHSS symptoms may include severe abdominal pain, anuria/oliguria, ascites, severe dyspnea, hypotension, or nausea/vomiting (intractable). Decreased creatinine clearance, hemoconcentration, hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte imbalances may also be present (ASRM 2016; Corbett 2014; Fiedler 2012). Treatment is primarily symptomatic and includes fluid and electrolyte management, analgesics, and prevention of thromboembolic complications (ASRM 2016; SOGC-CFAS 2011).
  • Visual disturbances: Blurring or other visual symptoms can occur; symptoms may increase with higher doses or duration of therapy and in some cases may be irreversible. Patients with visual disturbances should discontinue therapy and receive prompt ophthalmic evaluation.

Disease-related concerns:

  • Ovarian cancer: Prolonged use may increase the risk of borderline or invasive ovarian cancer.
  • Polycystic ovarian syndrome (PCOS): Use with caution in patients unusually sensitive to pituitary gonadotropins (eg, PCOS); a lower dose may be necessary.
  • Uterine fibroids: Use caution in patients with uterine fibroids, may cause further enlargement.

Other warnings/precautions:

  • Appropriate use: To minimize risks, use only at the lowest effective dose for the shortest duration of therapy (especially for the first course of therapy). Women with PCOS, amenorrhea-galactorrhea syndrome, psychogenic amenorrhea, post oral contraceptive amenorrhea, and some cases of secondary amenorrhea of undetermined cause may most likely benefit from clomiphene therapy.
  • Experienced physician: Use should be supervised by physicians who are thoroughly familiar with infertility problems and their management.
  • Multiple births: May result from the use of this medication; advise patient of the potential risk of multiple births before starting the treatment.