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Clomiphene

Aromatase Inhibitor · Treatment of infertility

Also known as Clomifene citrate, CLOMID, SEROPHENE, Milophene

Aromatase InhibitorTreatment of infertility
CDSCO approvedSchedule H
EXCRETION
not curated
INTERACTIONS
1 major
SEVERE in our sources
PREGNANCY
Possible effects on fetal development; exclude pregnancy before treatment.
FDA category + note
Top interactionssee all 7
  • Gonadotropins (e.g., Fsh, Lh)SevereDatabase

Mechanism

Clomiphene is classified as an anti-estrogen, acting as a pure antagonist at estrogen receptors in all tissues studied. This antagonism disrupts the negative feedback of estrogen on the hypothalamus and pituitary gland. Consequently, it leads to increased secretion of gonadotropins, which stimulates ovulation in anovulatory women.

Indications

Treatment of infertility in anovulatory womentreatment of infertility in anovulatory women (with functional hypothalamic-hypophyseal-ovarian system and adequate endogenous estrogen production)polycystic ovary syndrome (PCOS)dysfunctional bleeding with anovulatory cyclesinduction of superovulation (in women with unexplained infertility)

Dosing

Adult
gel | 15 unit dose P £30.83 DT = £30.83 Capsule EXCIPIENTS: May contain Arachis (peanut) oil ▶ Utrogestan (Besins Healthcare (UK) Ltd) Progesterone 100 mg Utrogestan 100mg capsules | 30 capsule P £5.13 DT = £5.13 Progesterone 200 mg Utrogestan 200mg vaginal capsules with applicators | 21 capsule P £21.00 DT = £21.00 8.1a Anti-oestrogens OVULATION STIMULANTS Clomifene citrate 20-Nov-2019 (Clomiphen…

Pharmacokinetics

Half-life
5–7 days (long plasma t1/2 due to plasma-protein binding, enterohepatic circulation, and accumulation in fatty tissues)
Excretion
primarily in the feces, to a lesser extent in the urine

Contraindications

  • Pregnancy
  • Liver disease or history of liver dysfunction
  • Uterine fibroids

Side effects

Common
Abdominal distensionAlopeciaAngioedemaAnxietyBreast tendernessDepressionDisorientationDizzinessFatigueHeadacheHot flushHypertriglyceridaemiaInsomniaMenstrual cycle irregularitiesMood alteredNauseaPalpitationsParaesthesiaSkin reactionsSpeech disorderSyncopeTachycardiaUterine disordersVertigoVomitingovarian hyperstimulationincreased incidence of multiple birthsovarian cystshot flashesblurred vision
Serious
  • Cataract
  • Cerebral thrombosis
  • Jaundice cholestatic
  • Neoplasms
  • Nervous system disorders
  • Optic neuritis
  • Ovarian and fallopian tube disorders
  • Pancreatitis
  • Psychosis
  • Seizure
  • Stroke
  • Vision disorders
  • Visual impairment (discontinue and initiate ophthalmological examination)
  • increased risk of ovarian cancer (with prolonged use, e.g., ≥12 cycles)

Pregnancy & lactation

Pregnancy

Possible effects on fetal development; exclude pregnancy before treatment.

Lactation

May inhibit lactation.

Drug interactions

Gonadotropins (e.g., Fsh, Lh)
Severe
Database

Significantly increased risk of severe ovarian hyperstimulation syndrome (OHSS) and multiple gestations due to additive or synergistic effects on ovarian stimulation.

Concurrent use is generally contraindicated or requires extreme caution and very close monitoring by a fertility specialist. Typically, these agents are used sequentially, not concurrently, to avoid overstimulation. If used sequentially, ensure careful monitoring of ovarian response before initiating the second agent.

Danazol
Moderate
Database

Danazol suppresses gonadotropin release, which could theoretically antagonize the ovulation-inducing effects of clomiphene, potentially reducing its efficacy.

Avoid concurrent use if possible. If danazol is required, consider discontinuing clomiphene or using alternative ovulation induction strategies. Monitor for reduced efficacy of clomiphene.

Letrozole
Moderate
Database

Increased risk of ovarian hyperstimulation syndrome (OHSS) and multiple gestations due to additive or synergistic effects on ovulation induction. Both drugs are used to stimulate ovulation.

Concurrent use is generally not recommended due to increased risk of OHSS and multiple gestations. If sequential use is considered, ensure adequate washout period and careful monitoring of ovarian response.

Oral Contraceptives
Moderate
Database

Oral contraceptives suppress ovulation, directly counteracting the intended effect of clomiphene. This would render clomiphene ineffective.

Clomiphene should not be used concurrently with oral contraceptives. Patients must discontinue oral contraceptives before starting clomiphene treatment for ovulation induction.

Tamoxifen
Moderate
Database

Increased risk of ovarian hyperstimulation syndrome (OHSS) and other estrogenic side effects due to additive or synergistic effects on estrogen receptors. Both drugs can stimulate ovulation.

Monitor closely for signs of OHSS and other estrogenic side effects. Consider lower doses of one or both drugs or separate administration if concurrent use is deemed necessary. Generally, concurrent use is avoided unless specifically indicated and carefully managed.

Corticosteroids (e.g., Prednisone)
Mild
Database

Both clomiphene and corticosteroids can potentially affect glucose metabolism. While not a direct interaction, in patients predisposed to diabetes or with existing diabetes, there might be an additive effect on blood glucose levels.

Monitor blood glucose levels more closely in diabetic patients or those at risk for diabetes if both drugs are used concurrently. Adjust antidiabetic medication if necessary.

Metformin
Mild
Database

In women with PCOS, metformin can improve insulin sensitivity and ovulation. When combined with clomiphene, there may be an additive or synergistic effect on ovulation induction, potentially increasing the risk of OHSS or multiple gestations, though often beneficial for efficacy.

Monitor ovarian response carefully. While often used together beneficially in PCOS, the risk of OHSS and multiple gestations should be considered. Dosing of clomiphene may need adjustment.

Related guidelines

Other Aromatase Inhibitor drugs

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Sources: Goodman & Gilman 14e, BNF·Verified: 2026-05-13 · House clinical team