Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
CLOMID vs EVISTA
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Competitive antagonist of estrogen receptors (ER) in hypothalamus and pituitary, leading to increased gonadotropin-releasing hormone (Gn RH) and subsequent LH and FSH release, stimulating ovulation.
Selective estrogen receptor modulator (SERM) that binds to estrogen receptors, acting as an agonist in bone and antagonist in breast and uterine tissues.
Treatment of ovulatory dysfunction in women desiring pregnancy (FDA approved),Off-label: treatment of male infertility (oligospermia)
Treatment and prevention of osteoporosis in postmenopausal women,Reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis,Reduction in risk of invasive breast cancer in postmenopausal women at high risk for breast cancer
50 mg orally once daily for 5 days, starting on day 5 of the menstrual cycle. May increase to 100 mg daily if no response.
60 mg orally once daily.
Terminal half-life is 5–7 days for zuclomiphene (active isomer), with prolonged elimination due to enterohepatic recirculation.
Terminal elimination half-life is approximately 32.5 hours (range 27-39 hours) for raloxifene and its glucuronide conjugates; clinically relevant for once-daily dosing.
Hepatic via CYP3A4 and CYP2D6; undergoes enterohepatic circulation; terminal half-life ~5-7 days
Extensively metabolized in the liver via glucuronidation (UGT1A1, UGT1A8, UGT1A9) and CYP3A4-mediated oxidation.
Primarily hepatic metabolism; metabolites excreted in feces (42%) and urine (8% unchanged).
Raloxifene undergoes extensive glucuronidation; <0.1% excreted unchanged in urine. Approximately 95% is excreted in feces over 5 days (primarily as glucuronide conjugates). Renal elimination of unchanged drug is negligible (<0.1%).
Highly protein bound (>99%), primarily to albumin.
>95% bound to plasma proteins, primarily albumin and α1-acid glycoprotein.
Not well-characterized; limited data suggest a large Vd (>100 L) due to extensive tissue distribution.
Apparent Vd/F is approximately 1000-1500 L (not weight-based; extensive tissue distribution).
Oral bioavailability is approximately 50% due to first-pass metabolism.
Absolute oral bioavailability is approximately 2% due to extensive first-pass glucuronidation; systemic exposure is dose-proportional.
No specific adjustment required; use caution in severe impairment (Cr Cl <30 m L/min) as data limited.
No dose adjustment required for mild to moderate renal impairment (Cr Cl ≥30 m L/min). Not recommended in severe renal impairment (Cr Cl <30 m L/min) due to lack of data.
Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment, no adjustment recommended, but monitor liver function.
Contraindicated in patients with Child-Pugh Class B or C hepatic impairment. No specific dose adjustment recommended for Child-Pugh Class A, but use with caution.
Not indicated for use in children; safety and efficacy not established.
Safety and efficacy not established in pediatric patients; no recommended dose.
Not indicated for postmenopausal women. Use not recommended in elderly due to lack of efficacy in anovulation.
No specific dose adjustment required; use standard adult dosing. Consider increased risk of venous thromboembolism and stroke in elderly women.
None
Increased risk of venous thromboembolism (VTE) and death from stroke. Not for use in women with active or history of VTE, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. Not for use in women with atrial fibrillation or other conditions that increase risk of stroke.
Ovarian hyperstimulation syndrome (OHSS),Ovarian enlargement,Visual disturbances (especially with prolonged use),Multiple pregnancy (increased risk),Ectopic pregnancy,Ovarian cancer risk (theoretical, based on prolonged use)
Risk of VTE; discontinue if VTE occurs. Risk of stroke; discontinue if stroke occurs or for prolonged immobilization. May increase risk of endometrial cancer; monitor for abnormal bleeding. Not for premenopausal women. Use with caution in patients with hepatic impairment or cholestasis. May increase triglycerides; monitor in patients with history of hypertriglyceridemia.
Pregnancy (Category X),Liver disease or dysfunction,Undiagnosed abnormal vaginal bleeding,Ovarian cyst or enlargement not due to polycystic ovary syndrome,Hypersensitivity to clomiphene or components
Active or history of VTE, pregnancy, women who may become pregnant, lactation, hypersensitivity to raloxifene, or any component of the formulation.
No specific food interactions. Avoid grapefruit as it may alter metabolism (theoretical due to CYP3A4 involvement).
Avoid grapefruit and grapefruit juice as they may increase raloxifene levels. No other significant food interactions.
Clomiphene citrate is contraindicated in pregnancy. It is associated with an increased risk of fetal malformations, including neural tube defects, specifically when exposure occurs during the first trimester. Second and third trimester risks are not well studied due to contraindication, but theoretical risks include ovarian hyperstimulation syndrome (OHSS) effects on pregnancy.
Pregnancy Category X. Raloxifene is contraindicated in pregnancy. In animal studies, raloxifene caused fetal abnormalities including skeletal malformations and cardiovascular defects. Human data are unavailable due to contraindication; use in pregnancy may cause fetal harm.
Safety in breastfeeding is not established. Clomiphene may reduce milk production. The M/P ratio is unknown. It is generally not recommended during breastfeeding.
Raloxifene is excreted in rat milk; no human data available. The M/P ratio is unknown. Due to potential adverse effects on the infant, breastfeeding is not recommended during therapy.
No dose adjustments are relevant as clomiphene is contraindicated in pregnancy. Pharmacokinetic changes in pregnancy are not applicable due to contraindication.
No dosing adjustments are applicable as raloxifene is contraindicated in pregnancy. Pharmacokinetic changes in pregnancy do not inform dose modifications due to the contraindication.
Monitor ovarian size via ultrasound to reduce risk of ovarian hyperstimulation syndrome (OHSS). Limit course to 3-6 cycles due to increased risk of ovarian tumors. Check pregnancy test before each cycle. Use with caution in liver disease.
Monitor for venous thromboembolism; avoid in patients with active or history of VTE. May increase risk of stroke in postmenopausal women with coronary heart disease. No significant effect on breast cancer incidence. Administer with caution in hepatic impairment. Discontinue prior to prolonged immobilization or surgery.
Take exactly as prescribed, typically 50 mg daily for 5 days starting on day 5 of menstrual cycle.,Report abdominal pain, bloating, nausea, or weight gain (possible OHSS).,Avoid alcohol due to hepatotoxicity risk.,Most pregnancies occur within first 3 cycles; consider alternative after 6 cycles.,May cause visual disturbances; report blurred vision or spots.
Take once daily with or without food.,Report any signs of blood clots (leg pain/swelling, sudden chest pain, shortness of breath).,May cause hot flashes, leg cramps, or flu-like symptoms.,Avoid pregnancy; not indicated for premenopausal women.,Requires adequate calcium and vitamin D intake.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about CLOMID vs EVISTA, answered by our medical review team.
CLOMID is a Selective Estrogen Receptor Modulator that works by Competitive antagonist of estrogen receptors (ER) in hypothalamus and pituitary, leading to increased gonadotropin-releasing hormone (Gn RH) and subsequent LH and FSH release, stimulating ovulation.. EVISTA is a Selective Estrogen Receptor Modulator that works by Selective estrogen receptor modulator (SERM) that binds to estrogen receptors, acting as an agonist in bone and antagonist in breast and uterine tissues.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between CLOMID and EVISTA depend on the specific clinical indication. These are both Selective Estrogen Receptor Modulator agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of CLOMID is: 50 mg orally once daily for 5 days, starting on day 5 of the menstrual cycle. May increase to 100 mg daily if no response.. The standard adult dose of EVISTA is: 60 mg orally once daily.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between CLOMID and EVISTA in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. CLOMID is classified as Category C. Clomiphene citrate is contraindicated in pregnancy. It is associated with an increased risk of fetal malformations, including neural tube defects, specifically when exposure occurs. EVISTA is classified as Category C. Pregnancy Category X. Raloxifene is contraindicated in pregnancy. In animal studies, raloxifene caused fetal abnormalities including skeletal malformations and cardiovascular defec. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.