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Medication Safety Issues
Sound-alike/look-alike issues:
ClomiPHENE may be confused with clomiPRAMINE, clonidine
Clomid® may be confused with clonidine
Serophene® may be confused with Sarafem™
Pronunciation
(KLOE mi feen)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of ovulatory failure in patients desiring pregnancy
Pregnancy Risk Factor
X
Pregnancy Considerations
Embryotoxic effects were observed in animal 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.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
Clomiphene may decrease lactation.
Contraindications
Hypersensitivity to clomiphene citrate or any of its components; 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
Warnings/Precautions
Concerns related to adverse effects:
• Ovarian enlargement: May be accompanied by abdominal distention or abdominal pain and generally regresses without treatment within 2-3 weeks. Do not continue dosing until ovaries are of normal size.
• Ovarian hyperstimulation syndrome (OHSS): OHSS is characterized by severe ovarian enlargement, abdominal pain/distention, nausea, vomiting, diarrhea, dyspnea, and oliguria, and may be accompanied by ascites, pleural effusion, hypovolemia, electrolyte imbalance, hemoperitoneum, and thromboembolic events. If severe hyperstimulation occurs, stop treatment and hospitalize patient. This syndrome develops rapidly within 24 hours to several days and generally occurs during the 7-10 days immediately following treatment.
• Visual disturbances: Blurring or other visual symptoms can occur; patients with visual disturbances should discontinue therapy and have an eye exam.
Disease-related concerns:
• Polycystic ovarian syndrome (PCOS): Use with caution in patients unusually sensitive to pituitary gonadotropins (eg, POS).
Other warnings/precautions:
• Appropriate use: To minimize risks, use only at the lowest effective dose.
• Multiple births: May result from the use of these medications; advise patient of the potential risk of multiple births before starting the treatment.
Adverse Reactions
>10%: Endocrine & metabolic: Ovarian enlargement (14%)
1% to 10%:
Central nervous system: Headache (1%)
Endocrine & metabolic: Hot flashes (10%), breast discomfort (2%), abnormal uterine bleeding (1%)
Gastrointestinal: Distention/bloating/discomfort (6%), nausea (2%), vomiting (2%)
Ocular: Visual symptoms (2%, includes blurring of vision, diplopia, floaters, lights, phosphenes, photophobia, scotomata, waves)
<1%: Acute abdomen, alopecia, appetite increased, constipation, depression, dermatitis, diarrhea, dizziness, dry hair, fatigue, insomnia, lightheadedness, nervousness, rash, urinary frequency/volume increased, vaginal dryness, vertigo, weight gain/loss
Postmarketing/case reports (limited to important or life-threatening): Abnormal accommodation, acne, allergic reaction, arrhythmia, chest pain, edema, endometriosis, erythema multiforme, erythema nodosum, eye pain, fever, hypertension, hypertrichosis, macular edema, migraine, mood changes, neoplasms, optic neuritis, ovarian cyst, ovarian hemorrhage, palpitation, PE, pruritus, retinal hemorrhage, retinal thrombosis, seizure, stroke, syncope, tachycardia, temporary loss of vision, thrombophlebitis, thyroid disorder, tinnitus, transaminase increased, tubal pregnancy, uterine hemorrhage
Drug Interactions
There are no known significant interactions.
Storage
Store at room temperature of 15°C to 30°C (59°F to 86°F). Protect from light, heat, and excessive humidity.
Mechanism of Action
Clomiphene is a racemic mixture consisting of zuclomiphene (?38%) and enclomiphene (?62%), each with distinct pharmacologic properties. Enclomiphene is much less potent in inducing ovulation; however, it is more rapidly absorbed and metabolized, allowing the more potent activity of zuclomiphene to predominate. Zuclomiphene 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.
Pharmacodynamics/Kinetics
Onset of action: Ovulation: 5-10 days following course of treatment
Duration: Effects are cumulative; ovulation may occur in the cycle following the last treatment
Metabolism: Hepatic; undergoes enterohepatic recirculation
Half-life elimination: 5-7 days
Time to peak, plasma: ~6 hours
Excretion: Primarily feces; urine (small amounts)
Dosage
Oral: Adults: Ovulation induction: Females:
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.
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. A low dose or duration of course is recommended in patients where unusual sensitivity to pituitary gonadotropin is suspected (eg, PCOS).
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.
Maximum dose: 100 mg once daily for 5 days for 6 cycles. Discontinue if ovulation does not occur after 3 courses of treatment; or if 3 ovulatory responses occur but pregnancy is not achieved. Re-evaluate if menses does not occur following ovulatory response. Doses larger than 150 mg have been reported, however, pregnancy rates are low.
Administration: Oral
The total daily dose should be taken at one time to maximize effectiveness.
Monitoring Parameters
Basal body temperature, serum progesterone, urinary luteinizing hormone; follicular growth and endometrial thickness may be useful in some cases; pregnancy test prior to repeat courses
Reference Range
Serum progesterone: Ovulation generally occurs with levels ?3 ng/mL; best results with levels >10 ng/mL
Test Interactions
Clomiphene may increase levels of serum thyroxine and thyroxine-binding globulin (TBG)
Patient Education
Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. There may be a risk of multiple pregnancies with therapy. Do not take any new medication during therapy unless approved by prescriber. Follow recommended schedule of dosing exactly. May cause hot flashes (cool clothes and cool environment may help). Report acute sudden headache; respiratory difficulty; warmth, swelling, pain, or redness in calves; breast enlargement (male) or breast discomfort (female); abnormal menstrual bleeding; vision changes (blurring, diplopia, photophobia, floaters); acute abdominal discomfort; or fever. Breast-feeding precaution: Do not breast-feed.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause insomnia, fatigue, or depression
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess results of laboratory tests, therapeutic effectiveness (according to purpose for use), and adverse response regularly during therapy. Teach patient proper use (eg, measuring basal body temperature and timing intercourse), possible side effects/appropriate interventions, and adverse symptoms to report. Pregnancy risk factor X: Determine that patient is not pregnant before beginning treatment. Breast-feeding is contraindicated.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as citrate [scored]: 50 mg
Clomid®, Serophene®: 50 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Clomid)
50 mg (5): $75.94
Tablets (ClomiPHENE Citrate)
50 mg (30): $84.99
Tablets (Serophene)
50 mg (5): $57.32
References
ACOG Committee on Practice Bulletins-Gynecology. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists, Number 34, February 2002. “Management of Infertility Caused by Ovulatory Dysfunction. American College of Obstetricians and Gynecologists,” Obstet Gynecol, 2002, 99(2):347-58.
Dickey RP and Holtkamp DE, “Development, Pharmacology, and Clinical Experience With Clomiphene Citrate,” Hum Reprod Update, 1996, 2(6):483-506.
Goldstein SR, Siddhanti S, Ciaccia AV, et al. “A Pharmacological Review of Selective Oestrogen Receptor Modulators,” Hum Reprod Update, 2000, 6(3):212-24.
Practice Committee of the American Society for Reproductive Medicine, “Use of Clomiphene Citrate in Women,” Fertil Steril, 2006, 86(5 Suppl):187-93.
Purvin VA, “Visual Disturbance Secondary to Clomiphene Citrate,” Arch Ophthalmol, 1995, 113(4):482-4.
Sokol RZ, “Prevention and Management of Complications Occurring During Treatment With Clomiphene,” Drug Saf, 1990, 5(5):313-6.
Walker AB, Eldridge PR, and MacFarlane IA, “Clomiphene-Induced Pituitary Apoplexy in a Patient With Acromegaly,” J Endocrinol, 1995, 144:29.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2009
Content last modified March 2009
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