Skip to Content




(KLOE mi feen)

Index Terms

  • Clomiphene Citrate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral, as citrate:

Serophene: 50 mg [DSC] [scored]

Generic: 50 mg

Brand Names: U.S.

  • Serophene [DSC]

Pharmacologic Category

  • Ovulation Stimulator
  • Selective Estrogen Receptor Modulator (SERM)


Clomiphene is a racemic mixture consisting of zuclomiphene (~38%) and enclomiphene (~62%), each with distinct pharmacologic properties. Clomiphene acts at the level of the hypothalamus, occupying cell surface and intracellular estrogen receptors (ERs) for longer durations than estrogen. This interferes with receptor recycling, effectively depleting hypothalamic ERs and inhibiting normal estrogenic negative feedback. Impairment of the feedback signal results in increased pulsatile GnRH secretion from the hypothalamus and subsequent pituitary gonadotropin (FSH, LH) release, causing growth of the ovarian follicle, followed by follicular rupture (ASRM 2013; Dickey, 1996).


Readily absorbed


Hepatic; undergoes enterohepatic recirculation (Goldstein 2000)


Primarily feces (42%); urine (8%); some excretion may occur for up to 6 weeks after therapy is discontinued

Onset of Action

Ovulation: 5 to 10 days following course of treatment

Time to Peak

~6 hours (Goldstein 2000)

Duration of Action

Effects are cumulative; ovulation may occur in the cycle following the last treatment (Dickey, 1996)

Half-Life Elimination

~5 days (Goldstein 2000)

Use: Labeled Indications

Treatment of ovulatory dysfunction in women desiring pregnancy


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

Dosing: Adult

Ovulation induction: Oral: Females: Note: Intercourse should be timed to coincide with the expected time of ovulation (usually 5 to 10 days after a clomiphene course).

Initial course: 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.

Dose adjustment: Subsequent doses may be increased to 100 mg once daily for 5 days only if ovulation does not occur at the initial dose. Lower doses (12.5 to 25 mg daily) may be used in women sensitive to clomiphene or who consistently develop large ovarian cysts (ASRM 2013).

Repeat courses: If needed, the 5-day cycle may be repeated as early as 30 days after the previous one. Exclude the presence of pregnancy. The lowest effective dose should be used.

Maximum dose: 100 mg once daily for 5 days for up to 6 cycles. Discontinue if ovulation does not occur after 3 courses of treatment; or if 3 ovulatory responses occur but pregnancy is not achieved. Long-term therapy (>6 cycles) is not recommended. Re-evaluate if menses does not occur following ovulatory response. Doses have ranged from 50 to 250 mg daily, although doses >100 mg daily have not been shown to increase pregnancy rates (ASRM 2013). The maximum recommended dose in women with PCOS is 150 mg daily (ESHRE/ASRM 2008).

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment

Use is contraindicated in patients with a history of liver disease or dysfunction.


The total daily dose should be taken at one time to maximize effectiveness (Dickey, 1996).


Store at room temperature of 15°C to 30°C (59°F to 86°F). Protect from light, heat, and excessive humidity.

Drug Interactions

Ospemifene: Selective Estrogen Receptor Modulators may enhance the adverse/toxic effect of Ospemifene. Ospemifene may also enhance adverse/toxic effects of other Selective Estrogen Receptor Modulators. Selective Estrogen Receptor Modulators may diminish the therapeutic effect of Ospemifene. Ospemifene may also diminish the therapeutic effects of other Selective Estrogen Receptor Modulators. Avoid combination

Adverse Reactions

>10%: Endocrine & metabolic: Ovary enlargement (14%)

1% to 10%:

Central nervous system: Headache (1%)

Endocrine & metabolic: Hot flash (10%)

Gastrointestinal: Abdominal distention (≤6%), abdominal distress (≤6%), bloating (≤6%), nausea (2%), vomiting (2%)

Genitourinary: Breast disease (discomfort: 2%), abnormal uterine bleeding (1%)

Ophthalmic: Visual disturbance (2%, includes blurred vision, diplopia, phosphene, photophobia, photopsia, scotomata, seeing visual waves, vitreous opacity)

<1% (Limited to important or life-threatening): Accommodation disturbance, acne vulgaris, cardiac arrhythmia, cerebrovascular accident, chest pain, depression, dizziness, dyspnea, ectopic pregnancy, edema, endometriosis, erythema multiforme, erythema nodosum, eye pain, fatigue, fever, hepatitis, hypersensitivity reaction, hypertension, hypertrichosis, increased serum transaminases, leukocytosis, macular edema, migraine, mood changes, neoplasm, optic neuritis, ovarian cyst, ovarian hemorrhage, palpitations, phlebitis, pruritus, psychosis, pulmonary embolism, retinal hemorrhage, retinal thrombosis, retinal vascular spasm, seizure, syncope, tachycardia, thrombophlebitis, thyroid disease, tinnitus, uterine hemorrhage, vision loss (temporary/prolonged), vitreous detachment (posterior)


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, an exaggerated response to ovulation induction therapy, is characterized by an increase in vascular permeability which causes a fluid shift from intravascular space to third space compartments (eg, peritoneal cavity, thoracic cavity) (ASRM 2008; SOGC-CFAS 2011). This syndrome may begin within 24 hours of treatment, but may become most severe 7 to 10 days after therapy (SOGC-CFAS 2011). OHSS is typically self-limiting with spontaneous resolution, although it may be more severe and protracted if pregnancy occurs (ASRM 2008). Symptoms of mild/moderate OHSS may include abdominal distention/discomfort, diarrhea, nausea, and/or vomiting. Severe OHSS symptoms may include abdominal pain that is severe, acute respiratory distress syndrome, anuria/oliguria, ascites, dyspnea, hypotension, nausea/vomiting (intractable), pericardial effusions, tachycardia, or thromboembolism. Decreased creatinine clearance, hemoconcentration, hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte imbalances may also be present (ASRM 2008; Fiedler 2012; SOGC-CFAS 2011). If severe OHSS occurs, stop treatment and consider hospitalizing the patient (ASRM 2008; SOGC-CFAS 2011). Treatment is primarily symptomatic and includes fluid and electrolyte management, analgesics, and prevention of thromboembolic complications (ASRM 2008; SOGC-CFAS 2011). The ascitic, pleural, and pericardial fluids may be removed if needed to relieve symptoms (eg, pulmonary distress or cardiac tamponade) (ASRM 2008; SOGC-CFAS 2011). Women with OHSS should avoid pelvic examination and/or intercourse (ASRM 2008; 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.

Monitoring Parameters

Prior to therapy: serum estrogen. Rule out primary pituitary or ovarian failure, endometriosis/endometrial carcinoma, adrenal disorders, thyroid disorders, hyperprolactinemia, and male infertility.

Pelvic exam prior to each course of therapy; pregnancy test prior to repeat courses; ovulation (may include serum estradiol, progesterone, urinary luteinizing hormone; ultrasound) (ASRM 2013).

OHSS: Monitoring of hospitalized patients should include abdominal circumference, albumin, cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin, serum creatinine, urine output, urine specific gravity, vital signs, weight (daily or as necessary) and liver enzymes (weekly) (ASRM 2008; SOGC-CFAS 2011).

Pregnancy Risk Factor


Pregnancy Considerations

Adverse events were observed in animal reproduction studies. The incidence of adverse fetal effects following maternal use of clomiphene for ovulation induction is similar to those seen in the general population. Clomiphene is not indicated for use in women who are already pregnant.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience hot flashes. Have patient report immediately to prescriber signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), difficulty breathing, angina, coughing up blood, severe headache, depression, mood changes, vaginal bleeding, menstrual changes, severe back pain, vision changes, or signs of ovarian hyperstimulation syndrome (severe abdominal pain or bloating; severe nausea, vomiting, or diarrhea; excessive weight gain; shortness of breath; or change in amount of urine passed) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.