Clomifene

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Clomifene
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]

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Overview

Clomifene is a gonadotropin that is FDA approved for the treatment of ovulatory dysfunction in women desiring pregnancy. Common adverse reactions include flushing, abdominal bloating, abdominal discomfort, abdominal distension, nausea, vomiting, headache, visual disturbance, and breast pain.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Female Infertility due to Ovulatory Disorder
  • Treatment of the selected patient should begin with a low dose, 50 mg daily (1 tablet) for 5 days. The dose should be increased only in those patients who do not ovulate in response to cyclic 50 mg clomiphene citrate tablets USP. A low dosage or duration of treatment course is particularly recommended if unusual sensitivity to pituitary gonadotropin is suspected, such as in patients with polycystic ovary syndrome.
  • The patient should be evaluated carefully to exclude pregnancy, ovarian enlargement, or ovarian cyst formation between each treatment cycle.
  • If progestin-induced bleeding is planned, or if spontaneous uterine bleeding occurs prior to therapy, the regimen of 50 mg daily for 5 days should be started on or about the 5th day of the cycle. Therapy may be started at any time in the patient who has had no recent uterine bleeding. When ovulation occurs at this dosage, there is no advantage to increasing the dose in subsequent cycles of treatment.
  • If ovulation does not appear to occur after the first course of therapy, a second course of 100 mg daily (two 50 mg tablets given as a single daily dose) for 5 days should be given. This course may be started as early as 30 days after the previous one after precautions are taken to exclude the presence of pregnancy. Increasing the dosage or duration of therapy beyond 100 mg/day for 5 days is not recommended.
  • The majority of patients who are going to ovulate will do so after the first course of therapy. If ovulation does not occur after three courses of therapy, further treatment with clomiphene citrate tablets USP is not recommended and the patient should be reevaluated. If three ovulatory responses occur, but pregnancy has not been achieved, further treatment is not recommended. If menses does not occur after an ovulatory response, the patient should be reevaluated. Long-term cyclic therapy is not recommended beyond a total of about 6 cycles.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Clomifene in adult patients.

Non–Guideline-Supported Use

Clomiphene test
  • ClomiPHENE 100 mg daily given on days 5 through 9.[1]
Female infertility - Luteal phase defect
  • ClomiPHENE 100 mg daily for 5 days.[2]
In vitro fertilization
  • ClomiPHENE citrate 100 milligrams/day on cycle days 3 to 7.[3]

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Clomifene in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Clomifene in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Clomifene in pediatric patients.

Contraindications

  • Hypersensitivity
  • Clomiphene citrate tablets USP is contraindicated in patients with a known hypersensitivity or allergy to clomiphene citrate or to any of its ingredients.
  • Pregnancy
  • Pregnancy Category X. Clomiphene citrate tablets USP use in pregnant women is contraindicated, as clomiphene citrate does not offer benefit in this population.
  • Available human data do not suggest an increased risk for congenital anomalies above the background population risk when used as indicated. However, animal reproductive toxicology studies showed increased embryo-fetal loss and structural malformations in offspring. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risks to the fetus.
  • Liver Disease
  • Clomiphene citrate tablets USP therapy is contraindicated in patients with liver disease or a history of liver dysfunction.
  • Abnormal Uterine Bleeding
  • Ovarian Cysts
  • Other

Warnings

  • Visual Symptoms
  • Patients should be advised that blurring or other visual symptoms such as spots or flashes (scintillating scotomata) may occasionally occur during therapy with clomiphene citrate tablets USP. These visual symptoms increase in incidence with increasing total dose or therapy duration. These visual disturbances are usually reversible; however, cases of prolonged visual disturbance have been reported with some occurring after clomiphene citrate tablets USP discontinuation. The visual disturbances may be irreversible, especially with increased dosage or duration of therapy. Patients should be warned that these visual symptoms may render such activities as driving a car or operating machinery more hazardous than usual, particularly under conditions of variable lighting.
  • These visual symptoms appear to be due to intensification and prolongation of afterimages. Symptoms often first appear or are accentuated with exposure to a brightly lit environment. While measured visual acuity usually has not been affected, a study patient taking 200 mg clomiphene citrate tablets USP daily developed visual blurring on the 7th day of treatment, which progressed to severe diminution of visual acuity by the 10th day. No other abnormality was found, and the visual acuity returned to normal on the 3rd day after treatment was stopped.
  • Ophthalmologically definable scotomata and retinal cell function (electroretinographic) changes have also been reported. A patient treated during clinical studies developed phosphenes and scotomata during prolonged clomiphene citrate tablets USP administration, which disappeared by the 32nd day after stopping therapy.
  • Postmarketing surveillance of adverse events has also revealed other visual signs and symptoms during clomiphene citrate tablets USP therapy.
  • While the etiology of these visual symptoms is not yet understood, patients with any visual symptoms should discontinue treatment and have a complete ophthalmological evaluation carried out promptly.
  • Ovarian Hyperstimulation Syndrome
  • The ovarian hyperstimulation syndrome (OHSS) has been reported to occur in patients receiving clomiphene citrate therapy for ovulation induction. OHSS may progress rapidly (within 24 hours to several days) and become a serious medical disorder. In some cases, OHSS occurred following cyclic use of clomiphene citrate therapy or when clomiphene citrate was used in combination with gonadotropins. Transient liver function test abnormalities suggestive of hepatic dysfunction, which may be accompanied by morphologic changes on liver biopsy, have been reported in association with OHSS.
  • OHSS is a medical event distinct from uncomplicated ovarian enlargement. The clinical signs of this syndrome in severe cases can include gross ovarian enlargement, gastrointestinal symptoms, ascites, dyspnea, oliguria, and pleural effusion. In addition, the following symptoms have been reported in association with this syndrome: pericardial effusion, anasarca, hydrothorax, acute abdomen, hypotension, renal failure, pulmonary edema, intraperitoneal and ovarian hemorrhage, deep venous thrombosis, torsion of the ovary, and acute respiratory distress. The early warning signs of OHSS are abdominal pain and distention, nausea, vomiting, diarrhea, and weight gain. Elevated urinary steroid levels, varying degrees of electrolyte imbalance, hypovolemia, hemoconcentration, and hypoproteinemia may occur. Death due to hypovolemic shock, hemoconcentration, or thromboembolism has occurred. Due to fragility of enlarged ovaries in severe cases, abdominal and pelvic examination should be performed very cautiously. If conception results, rapid progression to the severe form of the syndrome may occur.
  • To minimize the hazard associated with occasional abnormal ovarian enlargement associated with clomiphene citrate tablets USP therapy, the lowest dose consistent with expected clinical results should be used. Maximal enlargement of the ovary, whether physiologic or abnormal, may not occur until several days after discontinuation of the recommended dose of clomiphene citrate tablets USP. Some patients with polycystic ovary syndrome who are unusually sensitive to gonadotropin may have an exaggerated response to usual doses of clomiphene citrate tablets USP. Therefore, patients with polycystic ovary syndrome should be started on the lowest recommended dose and shortest treatment duration for the first course of therapy
  • If enlargement of the ovary occurs, additional clomiphene citrate tablets USP therapy should not be given until the ovaries have returned to pretreatment size, and the dosage or duration of the next course should be reduced. Ovarian enlargement and cyst formation associated with clomiphene citrate tablets USP therapy usually regress spontaneously within a few days or weeks after discontinuing treatment. The potential benefit of subsequent clomiphene citrate tablets USP therapy in these cases should exceed the risk. Unless surgical indication for laparotomy exists, such cystic enlargement should always be managed conservatively.
  • A causal relationship between ovarian hyperstimulation and ovarian cancer has not been determined. However, because a correlation between ovarian cancer and nulliparity, infertility, and age has been suggested, if ovarian cysts do not regress spontaneously, a thorough evaluation should be performed to rule out the presence of ovarian neoplasia.

Precautions

  • General
  • Careful attention should be given to the selection of candidates for clomiphene citrate tablets USP therapy. Pelvic examination is necessary prior to clomiphene citrate tablets USP treatment and before each subsequent course.

Adverse Reactions

Clinical Trials Experience

  • Clomiphene citrate tablets USP, at recommended dosages, is generally well tolerated. Adverse reactions usually have been mild and transient and most have disappeared promptly after treatment has been discontinued. Adverse experiences reported in patients treated with clomiphene citrate during clinical studies are shown in Table 2.
This image is provided by the National Library of Medicine.
  • Patients on prolonged clomiphene citrate tablets USP therapy may show elevated serum levels of desmosterol. This is most likely due to a direct interference with cholesterol synthesis. However, the serum sterols in patients receiving the recommended dose of clomiphene citrate tablets USP are not significantly altered. Ovarian cancer has been infrequently reported in patients who have received fertility drugs. Infertility is a primary risk factor for ovarian cancer; however, epidemiology data suggest that prolonged use of clomiphene may increase the risk of a borderline or invasive ovarian tumor.

Postmarketing Experience

  • The following adverse reactions have been identified during post approval use of clomiphene citrate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Body as a Whole

Fever, tinnitus, weakness

Cardiovascular

Arrhythmia, chest pain, edema, hypertension, palpitation, phlebitis, pulmonary embolism, shortness of breath, tachycardia, thrombophlebitis

Central Nervous System

Migraine headache, paresthesia, seizure, stroke, syncope

Dermatologic

Acne, allergic reaction, erythema, erythema multiforme, erythema nodosum, hypertrichosis, pruritus, urticaria

Fetal/Neonatal Anomalies
  • Ear abnormalities and deafness
  • Lung tissue malformations
  • Malformations of the eye and lens (cataract)
Gastrointestinal

Pancreatitis

Genitourinary

Endometriosis, ovarian cyst (ovarian enlargement or cysts could, as such, be complicated by adnexal torsion), ovarian hemorrhage, tubal pregnancy, uterine hemorrhage, reduced endometrial thickness

Hepatic

Transaminases increased, hepatitis

Metabolism Disorders

Hypertriglyceridemia, in some cases with pancreatitis

Musculoskeletal

Arthralgia, back pain, myalgia

Neoplasms

Liver (hepatic hemangiosarcoma, liver cell adenoma, hepatocellular carcinoma); breast (fibrocystic disease, breast carcinoma); endometrium (endometrial carcinoma); nervous system (astrocytoma, pituitary tumor, prolactinoma, neurofibromatosis, glioblastoma multiforme, brain abcess); ovary (luteoma of pregnancy, dermoid cyst of the ovary, ovarian carcinoma); trophoblastic (hydatiform mole, choriocarcinoma); miscellaneous (melanoma, myeloma, perianal cysts, renal cell carcinoma, Hodgkin's lymphoma, tongue carcinoma, bladder carcinoma)

Psychiatric

Anxiety, irritability, mood changes, psychosis

Visual Disorders

Abnormal accommodation, cataract, eye pain, macular edema, optic neuritis, photopsia, posterior vitreous detachment, retinal hemorrhage, retinal thrombosis, retinal vascular spasm, temporary or prolonged loss of vision, possibly irreversible

Other

Leukocytosis, thyroid disorder

Drug Interactions

  • Drug interactions with clomiphene citrate tablets USP have not been documented.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category X
  • Clomiphene citrate use in pregnant women is contraindicated, as clomiphene citrate tablets USP treatment does not offer benefit in this population.
  • Available human data do not suggest an increased risk for congenital anomalies above the background population risk. However, animal reproductive toxicology studies showed increased embryo-fetal loss and structural malformations in offspring. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risks to the fetus.
  • Clinical Considerations
  • To avoid inadvertent clomiphene citrate tablets USP administration during early pregnancy, appropriate tests should be utilized during each treatment cycle to determine whether ovulation and/or pregnancy occurs. Patients should be evaluated carefully to exclude ovarian enlargement or ovarian cyst formation between each treatment cycle. The next course of clomiphene citrate tablets USP therapy should be delayed until these conditions have been excluded.
  • Human data
  • The available human data from epidemiologic studies do not show any apparent cause and effect relationship between clomiphene citrate periconceptual exposure and an increased risk of overall birth defects, or any specific anomaly. However, due to the small number of cases of congenital anomalies occurring in clomiphene citrate treated women, these epidemiologic studies were only able to rule out large differences in risk. The studies did not consider factors associated with female subfertility and were unable to adjust for other important confounders.
  • In addition, available data do not support an increased rate of spontaneous abortion among subfertile women treated with clomiphene citrate for ovulation induction.
  • Animal data
  • Oral administration of clomiphene citrate to pregnant rats during organogenesis at doses of 1 to 2 mg/kg/day resulted in hydramnion and weak, edematous fetuses with wavy ribs and other temporary bone changes. Doses of 8 mg/kg/day or more also caused increased resorptions and dead fetuses, dystocia, and delayed parturition, and 40 mg/kg/day resulted in increased maternal mortality. Single doses of 50 mg/kg caused fetal cataracts, while 200 mg/kg caused cleft palate. Following injection of clomiphene citrate 2 mg/kg to mice and rats during pregnancy, the offspring exhibited metaplastic changes of the reproductive tract. Newborn mice and rats injected during the first few days of life also developed metaplastic changes in uterine and vaginal mucosa, as well as premature vaginal opening and anovulatory ovaries. These findings are similar to the abnormal reproductive behavior and sterility described with other estrogens and antiestrogens.
  • In rabbits, some temporary bone alterations were seen in fetuses from dams given oral doses of 20 or 40 mg/kg/day during pregnancy, but not following 8 mg/kg/day. No permanent malformations were observed in those studies. Also, rhesus monkeys given oral doses of 1.5 to 4.5 mg/kg/day for various periods during pregnancy did not have any abnormal offspring.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Clomifene in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Clomifene during labor and delivery.

Nursing Mothers

  • It is not known whether clomiphene citrate tablets USP is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if clomiphene citrate tablets USP is administered to a nursing woman. In some patients, clomiphene citrate tablets USP may reduce lactation.

Pediatric Use

There is no FDA guidance on the use of Clomifene with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Clomifene with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Clomifene with respect to specific gender populations.

Race

There is no FDA guidance on the use of Clomifene with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Clomifene in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Clomifene in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Clomifene in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Clomifene in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral

Monitoring

There is limited information regarding Monitoring of Clomifene in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Clomifene in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Toxic effects accompanying acute overdosage of clomiphene citrate tablets USP have not been reported. Signs and symptoms of overdosage as a result of the use of more than the recommended dose during clomiphene citrate tablets USP therapy include nausea, vomiting, vasomotor flushes, blurred vision, spots or flashes, scotomata, ovarian enlargement with pelvic or abdominal pain.
  • Oral LD50. The acute oral LD50 of clomiphene citrate tablets USP is 1700 mg/kg in mice and 5750 mg/kg in rats. The toxic dose in humans is not known.

Management

  • In the event of overdose, appropriate supportive measures should be employed in addition to gastrointestinal decontamination. It is not known if clomiphene citrate tablets USP is dialyzable.

Chronic Overdose

There is limited information regarding Chronic Overdose of Clomifene in the drug label.

Pharmacology

Template:Px
Template:Px
Clomifene
Systematic (IUPAC) name
(E,Z)-2-(4-(2-chloro-1,2-diphenylethenyl)
phenoxy)-N,N-diethyl-ethanamine
Identifiers
CAS number 911-45-5
ATC code G03GB02
PubChem 2800
DrugBank DB00882
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 406 or 598.10 (with citrate)
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability High (>90%)
Metabolism Hepatic (with enterohepatic circulation)
Half life 5-7 days
Excretion Mainly renal, some biliary
Therapeutic considerations
Pregnancy cat.

B3 (Au), X (U.S.)

Legal status

S4 (Au), POM (UK), ℞-only (U.S.)

Routes per os

Mechanism of Action

  • Clomiphene citrate tablets USP is a drug of considerable pharmacologic potency. With careful selection and proper management of the patient, clomiphene citrate tablets USP has been demonstrated to be a useful therapy for the anovulatory patient desiring pregnancy.
  • Clomiphene citrate is capable of interacting with estrogen-receptor-containing tissues, including the hypothalamus, pituitary, ovary, endometrium, vagina, and cervix. It may compete with estrogen for estrogen-receptor-binding sites and may delay replenishment of intracellular estrogen receptors. Clomiphene citrate initiates a series of endocrine events culminating in a preovulatory gonadotropin surge and subsequent follicular rupture. The first endocrine event in response to a course of clomiphene therapy is an increase in the release of pituitary gonadotropins. This initiates steroidogenesis and folliculogenesis, resulting in growth of the ovarian follicle and an increase in the circulating level of estradiol. Following ovulation, plasma progesterone and estradiol rise and fall as they would in a normal ovulatory cycle.
  • Available data suggest that both the estrogenic and antiestrogenic properties of clomiphene may participate in the initiation of ovulation. The two clomiphene isomers have been found to have mixed estrogenic and antiestrogenic effects, which may vary from one species to another. Some data suggest that zuclomiphene has greater estrogenic activity than enclomiphene.
  • Clomiphene citrate has no apparent progestational, androgenic, or antiandrogenic effects and does not appear to interfere with pituitary-adrenal or pituitary-thyroid function.
  • Although there is no evidence of a "carryover effect" of clomiphene citrate tablets USP, spontaneous ovulatory menses have been noted in some patients after clomiphene citrate tablets USP therapy.

Structure

  • Clomiphene citrate tablets USP is an orally administered, nonsteroidal, ovulatory stimulant designated chemically as 2-[p-(2-chloro-1,2-diphenylvinyl)phenoxy] triethylamine citrate (1:1). It has the molecular formula of C26H28ClNO • C6H8O7 and a molecular weight of 598.09. It is represented structurally as:
This image is provided by the National Library of Medicine.
  • Clomiphene citrate is a white to pale yellow, essentially odorless, crystalline powder. It is freely soluble in methanol; soluble in ethanol; slightly soluble in acetone, water, and chloroform; and insoluble in ether.
  • Clomiphene citrate tablets USP is a mixture of two geometric isomers [cis (zuclomiphene) and trans (enclomiphene)] containing between 30% and 50% of the cis-isomer.
  • Each white scored tablet contains 50 mg clomiphene citrate USP. The tablet also contains the following inactive ingredients: corn starch, lactose, magnesium stearate, pregelatinized corn starch, and sucrose.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Clomifene in the drug label.

Pharmacokinetics

  • Based on early studies with 14C-labeled clomiphene citrate, the drug was shown to be readily absorbed orally in humans and excreted principally in the feces. Cumulative urinary and fecal excretion of the 14C averaged about 50% of the oral dose and 37% of an intravenous dose after 5 days. Mean urinary excretion was approximately 8% with fecal excretion of about 42%.
  • Some 14C label was still present in the feces 6 weeks after administration. Subsequent single-dose studies in normal volunteers showed that zuclomiphene (cis) has a longer half-life than enclomiphene (trans). Detectable levels of zuclomiphene persisted for longer than a month in these subjects. This may be suggestive of stereo-specific enterohepatic recycling or sequestering of the zuclomiphene. Thus, it is possible that some active drug may remain in the body during early pregnancy in women who conceive in the menstrual cycle during clomiphene citrate tablets USP therapy.

Nonclinical Toxicology

  • Long-term toxicity studies in animals have not been performed to evaluate the carcinogenic or mutagenic potential of clomiphene citrate.
  • Oral administration of clomiphene citrate tablets USP to male rats at doses of 0.3 or 1 mg/kg/day caused decreased fertility, while higher doses caused temporary infertility. Oral doses of 0.1 mg/kg/day in female rats temporarily interrupted the normal cyclic vaginal smear pattern and prevented conception. Doses of 0.3 mg/kg/day slightly reduced the number of ovulated ova and corpora lutea, while 3 mg/kg/day inhibited ovulation.

Clinical Studies

  • During clinical investigations, 7578 patients received clomiphene citrate tablets USP, some of whom had impediments to ovulation other than ovulatory dysfunction. In those clinical trials, successful therapy characterized by pregnancy occurred in approximately 30% of these patients.
  • There were a total of 2635 pregnancies reported during the clinical trial period. Of those pregnancies, information on outcome was only available for 2369 of the cases. Table 1 summarizes the outcome of these cases.
  • Of the reported pregnancies, the incidence of multiple pregnancies was 7.98%: 6.9% twin, 0.5% triplet, 0.3% quadruplet, and 0.1% quintuplet. Of the 165 twin pregnancies for which sufficient information was available, the ratio of monozygotic to dizygotic twins was about 1:5. Table 1 reports the survival rate of the live multiple births.
  • A sextuplet birth was reported after completion of original clinical studies; none of the sextuplets survived (each weighed less than 400 g), although each appeared grossly normal.
This image is provided by the National Library of Medicine.
  • In addition, reports of congenital anomalies have been received during postmarketing surveillance of clomiphene citrate.

How Supplied

  • NDC 0591-0781-30: 50 mg tablets in cartons of 30
  • Tablets are round, white, scored, and debossed Watson over 781.
  • Store tablets at controlled room temperature 59°-86°F (15°-30°C). Protect from heat, light, and excessive humidity, and store in closed containers.

Storage

There is limited information regarding Clomifene Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

  • The purpose and risks of clomiphene citrate tablets USP therapy should be presented to the patient before starting treatment. It should be emphasized that the goal of clomiphene citrate tablets USP therapy is ovulation for subsequent pregnancy. The physician should counsel the patient with special regard to the following potential risks:
  • Visual Symptoms
  • Advise that blurring or other visual symptoms occasionally may occur during or shortly after clomiphene citrate tablets USP therapy. It should be made clear to the patient that, in some instances, visual disturbances may be prolonged, and possibly irreversible, especially with increased dosage or duration of therapy. Warn that visual symptoms may render such activities as driving a car or operating machinery more hazardous than usual, particularly under conditions of variable lighting.
  • The patient should be instructed to inform the physician whenever any unusual visual symptoms occur. If the patient has any visual symptoms, treatment should be discontinued and complete ophthalmologic evaluation performed.
  • Abdominal/Pelvic Pain or Distention
  • Ovarian enlargement may occur during or shortly after therapy with clomiphene citrate tablets USP. To minimize the risks associated with ovarian enlargement, the patient should be instructed to inform the physician of any abdominal or pelvic pain, weight gain, discomfort, or distention after taking clomiphene citrate tablets USP.
  • Metabolism Disorders
  • Cases of hypertriglyceridemia have been reported. Preexisting or family history of hyperlipidemia and use of higher than recommended dose and/or longer duration of treatment with clomiphene citrate are associated with a risk of hypertriglyceridemia. Periodic monitoring of plasma triglycerides is recommended in patients with preexisting or family history of hyperlipidemia.
  • Multiple Pregnancy
  • Inform the patient that there is an increased chance of multiple pregnancy, including bilateral tubal pregnancy and coexisting tubal and intrauterine pregnancy, when conception occurs in relation to clomiphene citrate tablets USP therapy. The potential complications and hazards of multiple pregnancy should be explained.
  • Spontaneous Abortion and Congenital Anomalies
  • Inform the patient that the available data suggest no increase in the rates of spontaneous abortion (miscarriage) or congenital anomalies with maternal clomiphene citrate tablets USP use compared to rates in the general population.
  • During clinical investigation, the experience from patients with known pregnancy outcome (Table 1) shows a spontaneous abortion rate of 20.4% and stillbirth rate of 1.0%. Among the birth anomalies spontaneously reported as individual cases since commercial availability of clomiphene citrate tablets USP, the proportion of neural tube defects has been high among pregnancies associated with ovulation induced by clomiphene citrate tablets USP, but this has not been supported by data from population-based studies.

Precautions with Alcohol

  • Alcohol-Clomifene interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

  • CLOMIPHENE CITRATE®[4]

Look-Alike Drug Names

  • clomiPHENE® — clomiPRAMINE®[5]
  • Serophene® — Sarafem®[5]

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Loumaye E, Billion JM, Mine JM, Psalti I, Pensis M, Thomas K (1990). "Prediction of individual response to controlled ovarian hyperstimulation by means of a clomiphene citrate challenge test". Fertil Steril. 53 (2): 295–301. PMID 2105246.
  2. ↑ Brown J, Farquhar C, Beck J, Boothroyd C, Hughes E (2009). "Clomiphene and anti-oestrogens for ovulation induction in PCOS". Cochrane Database Syst Rev (4): CD002249. doi:10.1002/14651858.CD002249.pub4. PMID 19821295.
  3. ↑ Ingerslev HJ, Højgaard A, Hindkjaer J, Kesmodel U (2001). "A randomized study comparing IVF in the unstimulated cycle with IVF following clomiphene citrate". Hum Reprod. 16 (4): 696–702. PMID 11278221.
  4. ↑ "CLOMIPHENE CITRATE- clomiphene citrate tablet".
  5. ↑ 5.0 5.1 "http://www.ismp.org". External link in |title= (help)

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