Version July 2025
Dosage guidance:
Dosing: Time intercourse to coincide with the expected time of ovulation (usually 5 to 10 days after a clomiphene course).
Ovulation induction:
Initial course: Oral: 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 any time in patients with no recent uterine bleeding.
Dose adjustment: Oral: Subsequent doses may be increased to 100 mg once daily for 5 days only if ovulation does not occur at the initial dose. A lower dose of 25 mg may be used in patients sensitive to clomiphene or who consistently develop large ovarian cysts (Ref).
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/duration of therapy: Oral: 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 >100 mg once daily are not recommended by the manufacturer; however, some experienced clinicians use a maximum dose of 150 mg once daily. Higher doses (200 to 250 mg once daily) have been used in select patients but are generally not recommended due to limited data and experience (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
Use is contraindicated in patients with a history of liver disease or dysfunction.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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%)
<1%, postmarketing/case reports: Accommodation disturbance, acne vulgaris, alopecia, anxiety, arthralgia, back pain, cardiac arrhythmia, cataract, cerebrovascular accident, chest pain, constipation, depression, dermatitis, diarrhea, dizziness, dry hair, dyspnea, ectopic pregnancy, edema, endometriosis, endometrium disease (reduced thickness), erythema, erythema multiforme, erythema nodosum, eye pain, fatigue, fever, hepatitis, hypersensitivity reaction, hypertension, hypertrichosis, hypertriglyceridemia, increased appetite, increased serum transaminases, increased urine output, insomnia, irritability, leukocytosis, macular edema, migraine, mood changes, myalgia, neoplasm, nervousness, optic neuritis, ovarian cyst, ovarian hemorrhage, ovarian hyperstimulation syndrome, palpitations, pancreatitis, paresthesia, phlebitis, photopsia, pruritus, psychosis, pulmonary embolism, retinal hemorrhage, retinal thrombosis, retinal vascular spasm, seizure, severe abdominal pain, skin rash, syncope, tachycardia, thrombophlebitis, thyroid disease, tinnitus, urinary frequency, urticaria, uterine hemorrhage, vaginal dryness, vertigo, vision loss (temporary/prolonged), vitreous detachment (posterior), weakness, weight gain, weight loss
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 ovary syndrome); uncontrolled thyroid or adrenal dysfunction; presence of an organic intracranial lesion such as pituitary tumor; pregnancy.
Concerns related to adverse effects:
• Hyperlipidemia: Patients with, or a family history of, hyperlipidemia may be at increased risk of hypertriglyceridemia. High doses of clomiphene or long durations of therapy may increase risk this risk. Pancreatitis has been reported. Pretreatment screening of triglycerides is recommended.
• 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: Ovarian hyperstimulation syndrome (OHSS) is a rare, exaggerated response to ovulation induction therapy (Fiedler 2012; SOGC [Corbett 2014]). This syndrome may begin within 24 hours of human chorionic gonadotropin treatment but may become most severe 7 to 10 days after therapy (SOGC [Corbett 2014]). Mild/moderate OHSS signs/symptoms may include abdominal distention/discomfort, diarrhea, nausea, vomiting, and mild/moderate enlargement of ovaries/ovarian cysts. Severe OHSS signs/symptoms may include severe abdominal pain, anuria/oliguria, ascites, severe dyspnea, hypotension, hydrothorax, nausea/vomiting (intractable), pleural effusion, rapid weight gain, venous thrombosis, and large ovarian cysts. Decreased CrCl, hemoconcentration, hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte imbalances may also be present (ASRM 2024; Fiedler 2012; SOGC [Corbett 2014]). Treatment is primarily symptomatic and includes fluid and electrolyte management, analgesics, and prevention of thromboembolic complications (SOGC [Shmorgun 2017]).
• Visual disturbances: Blurring or other visual symptoms may occur; symptoms may increase with higher doses or duration of therapy and in some cases may be irreversible. These visual disturbances may render some activities more hazardous than normal (eg, operating machinery or driving). Discontinue therapy and promptly evaluate patients with visual disturbances.
Disease-related concerns:
• Ovarian cancer: Prolonged use may increase the risk of borderline or invasive ovarian cancer.
• Polycystic ovary syndrome: Use with caution in patients unusually sensitive to pituitary gonadotropins (eg, polycystic ovary syndrome); 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).
• Experienced physician: Use should be supervised by physicians who are thoroughly familiar with infertility problems and their management.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as citrate:
Clomid: 50 mg [scored; contains corn starch]
Generic: 50 mg
Yes
Tablets (Clomid Oral)
50 mg (per each): $11.31
Tablets (clomiPHENE Citrate Oral)
50 mg (per each): $9.43
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
The total daily dose should be taken at one time to maximize effectiveness (Ref).
Hazardous agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Ovulation induction: Treatment of ovulatory dysfunction in patients desiring to become pregnant.
ClomiPHENE may be confused with clomiPRAMINE, clonidine
Clomid may be confused with clonidine
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (contraindicated in pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
Serophene [multiple international markets] may be confused with Sarafem brand name for FLUoxetine [US and Puerto Rico]
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Fluoroestradiol F18: Coadministration of Selective Estrogen Receptor Modulators and Fluoroestradiol F18 may alter diagnostic results. Risk X: Avoid
Ospemifene: Selective Estrogen Receptor Modulators may increase adverse/toxic effects of Ospemifene. Ospemifene may also enhance adverse/toxic effects of other Selective Estrogen Receptor Modulators. Risk X: Avoid
Clomiphene is indicated for use in patients desiring to become pregnant. Patients with polycystic ovary syndrome (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. Advise patients of the potential risk for multiple births before starting treatment.
Clomiphene may be used for ovulation induction in patients diagnosed with PCOS and anovulatory infertility (and no other infertility factors) to improve ovulation and pregnancy rate. Exclude pregnancy prior to each treatment course. The risk of multiple pregnancy may be increased (Teede 2023).
Clomiphene has been evaluated for use in infertile males with low testosterone; however, additional studies are needed to determine efficacy and dosing (Al Wattar 2024; AUA/ASRM [Schlegel 2021]; Flores 2023; Huijben 2022; Jiang 2022; Puia 2022). Clomiphene is not approved for the treatment of male infertility; testicular tumors and gynecomastia have been observed following use of clomiphene in males.
Use is contraindicated in patients who are already pregnant.
Outcome data following clomiphene exposure close to conception and inadvertent exposure post conception are available (Auffret 2019; Nehard 2024; Reefhuis 2011; Scaparrotta 2017; Weller 2017). The incidences of adverse fetal effects or spontaneous abortion following maternal use of clomiphene for ovulation induction are similar to the general population.
Clomiphene is present in breast milk.
Data related to the presence of clomiphene in breast milk are available from a study evaluating a method for determining the presence of clomiphene and other medications in breast milk. Breast milk was sampled over 24 hours following the last dose of clomiphene to 1 patient. Using a mean milk concentration of 300 ng/mL, authors of the study calculated the estimated daily infant dose of clomiphene via breast milk to be 45 mcg/kg/day, providing a relative infant dose (RID) of 2.2% compared to a weight-adjusted maternal dose of 2,040.8 mcg/kg/day. The highest breast milk concentration reported was 582.5 ng/mL (Monfort 2021). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
The manufacturer recommends that caution be used if administered to patients who are breastfeeding. Clomiphene may decrease lactation.
Prior to therapy: serum estrogen. Rule out primary pituitary or ovarian failure, endometriosis/endometrial carcinoma, adrenal disorders, thyroid disorders, hyperprolactinemia, and male infertility. Serum triglycerides.
Pelvic exam prior to each course of therapy; pregnancy test prior to repeat courses; ovulation (may include serum progesterone; urinary luteinizing hormone; ultrasound) (SOGC [Smithson 2018]).
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) (SOGC [Shmorgun 2017]).
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, resulting in increased gonadotrophin-releasing hormone secretion from the hypothalamus and subsequent pituitary gonadotropin (follicle-stimulating hormone, luteinizing hormone) release, causing growth of the ovarian follicle, followed by follicular rupture (Dickey 1996).
Onset of action: Ovulation: 5 to 10 days following course of treatment
Duration: Effects are cumulative; ovulation may occur in the cycle following the last treatment (Dickey 1996)
Absorption: Readily absorbed
Metabolism: Hepatic; undergoes enterohepatic recirculation (Goldstein 2000)
Half-life elimination: ~5 days (Goldstein 2000)
Time to peak, plasma: ~6 hours (Goldstein 2000)
Excretion: Primarily feces (42%); urine (8%); some excretion may occur for up to 6 weeks after therapy is discontinued
