Milophene (clomiphene citrate)

The usual initial dosage of clomiphene citrate used to induce ovulation is 50 mg daily for 5 days. It is important to carefully time the dosage schedule. Therapy may be started at any time in patients who have had no recent uterine bleeding. If progestin-induced bleeding is planned, or if spontaneous uterine bleeding occurs prior to therapy, the regimen should be started on the fifth day of the cycle. Once ovulation has been established, each subsequent course of therapy should be started on the fifth day of the cycle. Although ovulation is slightly more likely to occur with a dosage of 100 mg daily for 5 days, the adverse effects and incidence of multiple ovulations with resulting plural gestations may be expected to increase at this higher dosage.

The majority of the patients who are going to respond to clomiphene citrate will ovulate after the first course of therapy, generally within 5-14 days. If ovulation has not occurred at this time, 100 mg of clomiphene citrate may be administered daily for 5 days, starting as early as 30 days after previous therapy. Dosage should be increased only in those patients who do not respond to the first course of therapy, and dosage should never be increased or extended beyond 100 mg daily for 5 days. Prolonged amenorrhea may be less responsive to clomiphene and may require 2 or more cycles of therapy. Three courses of clomiphene should constitute an adequate therapeutic trial; if ovulatory menses or pregnancy has not occurred at this time, the diagnosis should be reevaluated. The likelihood of conception decreases with each succeeding course of therapy.

Since the relative safety of long-term cyclic therapy with clomiphene has not been conclusively demonstrated, and since the majority of patients will ovulate after 3 courses of therapy, long-term cyclic therapy is not recommended.

Clomiphene citrate is administered orally.

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Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Estrogen Receptor Blockers (Erbs)/Fluoroestradiol F-18

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Drugs that bind to the estrogen receptor (ER) may compete with the binding of radioactive diagnostic agent fluoroestradiol F-18.(1)

CLINICAL EFFECTS: Concurrent use of estrogen receptor blockers such as selective estrogen receptor modulators (SERMs) and selective estrogen receptor down-regulators (SERDs) may reduce the detection of ER-positive lesions with fluoroestradiol F-18.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Before administering fluoroestradiol F-18, discontinue drugs that bind to the ER, such as SERMs and SERDs, for at least 5 biological half-lives.(1) The following washout periods apply when discontinuing ERBs, prior to fluoroestradiol F-18 administration: - Bazedoxifene = 7 days - Clomiphene = 25 days - Elacestrant = 11 days - Enclomiphene = 25 days - Fulvestrant = 28 weeks - Imlunestrant = 7 days - Ospemifene = 5 days - Raloxifene = 7 days - Tamoxifen = 8 weeks - Toremifene = 5 weeks

DISCUSSION: The following ERBs are linked to this monograph: SERDs: elacestrant, imlunestrant, and fulvestrant. SERMs: bazedoxifene, clomiphene, enclomiphene, ospemifene, raloxifene, tamoxifen and toremifene.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

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• Abnormal uterine bleeding
• Disease of liver
• Ovarian cyst
• Pituitary neoplasm
• Thyrotoxicosis
• Untreated hypothyroidism

• Endometriosis
• Ovarian hyperstimulation syndrome

• Endometrial carcinoma
• Hypertriglyceridemia
• Reduced visual acuity
• Scotomata

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More Frequent

• Ovarian cyst
• Ovarian enlargement

Rare or Very Rare

• After image
• Carcinoma of breast
• Cardiac arrhythmia
• Cataracts
• Cerebrovascular accident
• Drug-induced psychosis
• Endometrial carcinoma
• Endometriosis
• Erythema multiforme
• Erythema nodosum
• Fibrocystic breast disease
• Hepatitis
• Hypertension
• Hypertriglyceridemia
• Leukocytosis
• Macular retinal edema
• Neoplasm
• Neoplasm of liver
• Optic neuritis
• Ovarian hemorrhage
• Ovarian hyperstimulation syndrome
• Pancreatitis
• Photophobia
• Pulmonary thromboembolism
• Retinal hemorrhage
• Retinal thrombosis
• Scotomata
• Seizure disorder
• Sudden visual loss
• Thromboembolic disorder
• Thrombophlebitis
• Vision impairment
• Vitreous detachment

More Frequent

• Flushing

Less Frequent

• Abdominal distension
• Nausea
• Vomiting

Rare or Very Rare

• Abnormal hair texture
• Abnormal vaginal bleeding
• Accommodation disorder
• Acne vulgaris
• Alopecia
• Arthralgia
• Back pain
• Blurred vision
• Chest pain
• Constipation
• Depression
• Diarrhea
• Diplopia
• Disorder of thyroid gland
• Dizziness
• Dyspnea
• Edema
• Endometrial hypoplasia
• Erythema
• Fatigue
• Fever
• General weakness
• Gynecomastia
• Hirsutism
• Increased appetite
• Increased urinary frequency
• Insomnia
• Irritability
• Mastalgia
• Menorrhagia
• Migraine
• Mood changes
• Multiple pregnancy
• Myalgia
• Nervousness
• Ocular pain
• Palpitations
• Paresthesia
• Phlebitis
• Phosphene
• Photopsia
• Pruritus of skin
• Skin rash
• Symptoms of anxiety
• Syncope
• Tachycardia
• Tinnitus
• Urticaria
• Vaginal dryness
• Vertigo
• Vitreous floater
• Weight gain
• Weight loss

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The incidence of multiple ovulations with resulting plural gestations (mostly twins) is increased when conception occurs during a cycle in which clomiphene citrate is administered. Prior to clomiphene citrate therapy, the patient and her male sexual partner should be informed of the possibility and potential risks associated with plural gestation. Simultaneous bilateral tubal pregnancy, an extremely rare form of twin pregnancy, has been reported following combined therapy with clomiphene citrate and chorionic gonadotropin.

Clomiphene citrate is contraindicated during pregnancy. The drug has been shown to be teratogenic in rats and rabbits. Congenital abnormalities (e.g., Down's syndrome, exstrophy, club foot, tibial torsion, blocked tear duct, hemangioma, neural tube defects) have been reported in infants conceived following clomiphene citrate therapy. These effects have not been directly attributed to the drug and the manufacturers state that the cumulative rate of congenital abnormalities does not exceed that reported in the general population. To avoid inadvertent clomiphene citrate administration during early pregnancy, the patient should be carefully observed to determine if ovulation occurs. The basal body temperature should be recorded throughout all treatment cycles, and clomiphene therapy should be discontinued if pregnancy is suspected. If the basal body temperature is biphasic and not followed by menses, the possibility of an ovarian cyst and/or pregnancy should be excluded and subsequent clomiphene therapy should be delayed until a correct diagnosis has been made.

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