NDC 61919-375 Clomiphene Citrate

Clomiphene Citrate

NDC Product Code 61919-375

NDC Code: 61919-375

Proprietary Name: Clomiphene Citrate What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Clomiphene Citrate What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Product Characteristics

Color(s):
WHITE (C48325 - OFF WHITE)
Shape: ROUND (C48348)
Size(s):
9 MM
Imprint(s):
PAR;701
Score: 2

NDC Code Structure

  • 61919 - Directrx
    • 61919-375 - Clomiphene Citrate

NDC 61919-375-30

Package Description: 30 TABLET in 1 CARTON

NDC Product Information

Clomiphene Citrate with NDC 61919-375 is a a human prescription drug product labeled by Directrx. The generic name of Clomiphene Citrate is clomiphene citrate. The product's dosage form is tablet and is administered via oral form.

Labeler Name: Directrx

Dosage Form: Tablet - A solid dosage form containing medicinal substances with or without suitable diluents.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Clomiphene Citrate Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • CLOMIPHENE CITRATE 50 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • STARCH, CORN (UNII: O8232NY3SJ)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)
  • SUCROSE (UNII: C151H8M554)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Selective Estrogen Receptor Modulators - [MoA] (Mechanism of Action)
  • Estrogen Agonist/Antagonist - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Directrx
Labeler Code: 61919
FDA Application Number: ANDA075528 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 03-04-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Information for Patients

Clomiphene

Clomiphene is pronounced as (kloe' mi feen)

Why is clomiphene medication prescribed?
Clomiphene is used to induce ovulation (egg production) in women who do not produce ova (eggs) but wish to become pregnant (infertility). Clomiphene is in a class of medi...
[Read More]

* Please review the disclaimer below.

Clomiphene Citrate Product Label Images

Clomiphene Citrate Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Description

Clomiphene citrate tablets, USP is an orally administered, nonsteroidal, ovulatory stimulant designated chemically as 2-[p-(2chloro-1,2-diphenylvinyl)phenoxy] triethylamine citrate (1:1). It has the molecular formula of C26H28CINO • C6H8O7 and a molecular weight of 598.10. It is represented structurally as:[This is the structural formula]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 is a mixture of two geometric isomers [cis (zuclomiphene) and trans (enclomiphene)] containing between 30% and 50% of the cis-isomer.Each off-white debossed tablet contains 50 mg clomiphene citrate USP. The tablet also contains the following inactive ingredients: corn starch, lactose monohydrate, magnesium stearate, pregelatinized corn starch, and sucrose.

Clinical Pharmacology

ActionClomiphene citrate is a drug of considerable pharmacologic potency. With careful selection and proper management of the patient, clomiphene citrate 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, spontaneous ovulatory menses have been noted in some patients after clomiphene citrate therapy.PharmacokineticsBased 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 therapy.

Clinical Studies

During clinical investigations, 7578 patients received clomiphene citrate, some of whom had impediments to ovulation other than ovulatory dysfunction (see INDICATIONS AND USAGE). 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, 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.Table 1. Outcome of Reported Pregnancies in Clinical Trials (n = 2369)

* Includes 28 ectopic pregnancies, 4 hydatiform moles, and 1 fetus papyraceous.

† Indicates percentage of surviving infants from these pregnancies.
OutcomeTotal Number of PregnanciesSurvival RatePregnancy WastageSpontaneous Abortions483*Stillbirths24Live BirthsSingle Births169798.16%†Multiple Births16583.26%†The overall survival of infants from multiple pregnancies including spontaneous abortions, stillbirths, and neonatal deaths is 73%.Fetal/Neonatal Anomalies and Mortality The following fetal abnormalities have been reported subsequent to pregnancies following ovulation induction therapy with clomiphene citrate during clinical trials. Each of the following fetal abnormalities were reported at a rate of <1% (experiences are listed in order of decreasing frequency): Congenital heart lesions, Down syndrome, club foot, congenital gut lesions, hypospadias, microcephaly, harelip, and cleft palate, congenital hip, hemangioma, undescended testicles, polydactyly, conjoined twins and teratomatous malformation, patent ductus arteriosus, amaurosis, arteriovenous fistula, inguinal hernia, umbilical hernia, syndactyly, pectus excavatum, myopathy, dermoid cyst of scalp, omphalocele, spina bifida occulta, ichthyosis, and persistent lingual frenulum. Neonatal death and fetal death/stillbirth in infants with birth defects have also been reported at a rate of <1%. The overall incidence of reported congenital anomalies from pregnancies associated with maternal clomiphene citrate ingestion during clinical studies was within the range of that reported for the general population.In addition, reports of congenital anomalies have been received during postmarketing surveillance of clomiphene citrate (see ADVERSE REACTIONS).

Indications & Usage

Clomiphene citrate is indicated for the treatment of ovulatory dysfunction in women desiring pregnancy. Impediments to achieving pregnancy must be excluded or adequately treated before beginning clomiphene citrate therapy. Those patients most likely to achieve success with clomiphene therapy include patients with polycystic ovary syndrome (see WARNINGS: Ovarian Hyperstimulation Syndrome), amenorrhea-galactorrhea syndrome, psychogenic amenorrhea, post-oral-contraceptive amenorrhea, and certain cases of secondary amenorrhea of undetermined etiology.Properly timed coitus in relationship to ovulation is important. A basal body temperature graph or other appropriate tests may help the patient and her physician determine if ovulation occurred. Once ovulation has been established, each course of clomiphene citrate should be started on or about the 5th day of the cycle. Long-term cyclic therapy is not recommended beyond a total of about six cycles (including three ovulatory cycles). (See DOSAGE AND ADMINISTRATION and PRECAUTIONS.)Clomiphene citrate is indicated only in patients with demonstrated ovulatory dysfunction who meet the conditions described below (see CONTRAINDICATIONS):Patients who are not pregnant.

Patients without ovarian cysts. Clomiphene citrate should not be used in patients with ovarian enlargement except those with polycystic ovary syndrome. Pelvic examination is necessary prior to the first and each subsequent course of clomiphene citrate treatment.

Patients without abnormal vaginal bleeding. If abnormal vaginal bleeding is present, the patient should be carefully evaluated to ensure that neoplastic lesions are not present.

Patients with normal liver function.
In addition, patients selected for clomiphene citrate therapy should be evaluated in regard to the following:Estrogen Levels. Patients should have adequate levels of endogenous estrogen (as estimated from vaginal smears, endometrial biopsy, assay of urinary estrogen, or from bleeding in response to progesterone). Reduced estrogen levels, while less favorable, do not preclude successful therapy.

Primary Pituitary or Ovarian Failure. Clomiphene citrate therapy cannot be expected to substitute for specific treatment of other causes of ovulatory failure.

Endometriosis and Endometrial Carcinoma. The incidence of endometriosis and endometrial carcinoma increases with age as does the incidence of ovulatory disorders. Endometrial biopsy should always be performed prior to clomiphene citrate therapy in this population.

Other Impediments to Pregnancy. Impediments to pregnancy can include thyroid disorders, adrenal disorders, hyperprolactinemia, and male factor infertility.

Uterine Fibroids. Caution should be exercised when using clomiphene citrate in patients with uterine fibroids due to the potential for further enlargement of the fibroids.
There are no adequate or well-controlled studies that demonstrate the effectiveness of clomiphene citrate in the treatment of male infertility. In addition, testicular tumors and gynecomastia have been reported in males using clomiphene. The cause and effect relationship between reports of testicular tumors and the administration of clomiphene citrate is not known.Although the medical literature suggests various methods, there is no universally accepted standard regimen for combined therapy (i.e., clomiphene citrate in conjunction with other ovulation-inducing drugs). Similarly, there is no standard clomiphene citrate regimen for ovulation induction in vitro fertilization programs to produce ova for fertilization and reintroduction. Therefore, clomiphene citrate is not recommended for these uses.

Contraindications

HypersensitivityClomiphene citrate is contraindicated in patients with a known hypersensitivity or allergy to clomiphene citrate or to any of its ingredients.PregnancyPregnancy Category X. Clomiphene citrate 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. (See PRECAUTIONS: Pregnancy).Liver Disease. Clomiphene citrate therapy is contraindicated in patients with liver disease or a history of liver dysfunction (see also INDICATIONS AND USAGE and ADVERSE REACTIONS).Abnormal Uterine Bleeding. Clomiphene citrate is contraindicated in patients with abnormal uterine bleeding of undetermined origin (see INDICATIONS AND USAGE).Ovarian Cysts. Clomiphene citrate is contraindicated in patients with ovarian cysts or enlargement not due to polycystic ovarian syndrome (see INDICATIONS AND USAGE and WARNINGS).Other. Clomiphene citrate is contraindicated in patients with uncontrolled thyroid or adrenal dysfunction or in the presence of an organic intracranial lesion such as pituitary tumor (see INDICATIONS AND USAGE).

Warnings

Visual SymptonsPatients should be advised that blurring or other visual symptoms such as spots or flashes (scintillating scotomata) may occasionally occur during therapy with clomiphene citrate. 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 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 after-images. 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 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 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 therapy (see ADVERSE REACTIONS).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.OvarianHyperstimulationSyndromeThe 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 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. Some patients with polycystic ovary syndrome who are unusually sensitive to gonadotropin may have an exaggerated response to usual doses of clomiphene citrate. Therefore, patients with polycystic ovary syndrome should be started on the lowest recommended dose and shortest treatment duration for the first course of therapy (see DOSAGE AND ADMINISTRATION).If enlargement of the ovary occurs, additional clomiphene citrate 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 therapy usually regress spontaneously within a few days or weeks after discontinuing treatment. The potential benefit of subsequent clomiphene citrate 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

GeneralCareful attention should be given to the selection of candidates for clomiphene citrate therapy. Pelvic examination is necessary prior to clomiphene citrate treatment and before each subsequent course (see CONTRAINDICATIONS and WARNINGS).Information for PatientsThe purpose and risks of clomiphene citrate therapy should be presented to the patient before starting treatment. It should be emphasized that the goal of clomiphene citrate 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 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 (see WARNINGS).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. 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 (see WARNINGS).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 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 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%. (See CLINICAL STUDIES). Among the birth anomalies spontaneously reported as individual cases since commercial availability of clomiphene citrate, the proportion of neural tube defects has been high among pregnancies associated with ovulation induced by clomiphene citrate, but this has not been supported by data from population-based studies.Drug InteractionsDrug interactions with clomiphene citrate have not been documented.Carcinogenesisand Mutagenesis andImpairment of FertilityLong-term toxicity studies in animals have not been performed to evaluate the carcinogenic or mutagenic potential of clomiphene citrate.Oral administration of clomiphene citrate 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.PregnancyFetal Risk SummaryPregnancy Category X. (See CONTRAINDICATIONS.) Clomiphene citrate use in pregnant women is contraindicated, as clomiphene citrate 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 ConsiderationsTo avoid inadvertent clomiphene citrate 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 therapy should be delayed until these conditions have been excluded.Human DataThe 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 increase rate of spontaneous abortion among subfertile women treated with clomiphene for ovulation induction.Animal DataOral 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.Nursing MothersIt is not known whether clomiphene citrate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if clomiphene citrate is administered to a nursing woman. In some patients, clomiphene citrate may reduce lactation.Ovarian CancerProlonged use of clomiphene citrate tablets USP may increase the risk of a borderline or invasive ovarian tumor (see ADVERSE REACTIONS).

Adverse Reactions

Clinical Trial Adverse Events. Clomiphene citrate, 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.Table 2. Incidence of Adverse Events in Clinical Studies (Events Greater than 1%) (n = 8029*)

*Includes 498 patients whose reports may have been duplicated in the event totals and could not be distinguished as such. Also, excludes 47 patients who did not report symptom data.
Adverse Event%Ovarian Enlargement13.6Vasomotor Flushes10.4Abdominal-Pelvic Discomfort/Distention/Bloating5.5Nausea and Vomiting2.2Breast Discomfort2.1Visual Symptoms1.5Blurred vision, lights, floaters, waves, unspecified visualcomplaints, photophobia, diplopia, scotomata, phosphenesHeadache1.3Abnormal Uterine Bleeding1.3Intermenstrual spotting, menorrhagiaThe following adverse events have been reported in fewer than 1% of patients in clinical trials: Acute abdomen, appetite increase, constipation, dermatitis or rash, depression, diarrhea, dizziness, fatigue, hair loss/dry hair, increased urinary frequency/volume, insomnia, light-headedness, nervous tension, vaginal dryness, vertigo, weight gain/loss.Patients on prolonged clomiphene citrate 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 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.POST MARKETING ADVERSE EVENTSPostmarketing Adverse EventsThe following adverse reactions have been identified during the 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, weaknessCardiovascular: Arrhythmia, chest pain, edema, hypertension, palpitation, phlebitis, pulmonary embolism, shortness of breath, tachycardia, thrombophlebitisCentral Nervous System: Migraine headache, paresthesia, seizure, stroke, syncopeDermatologic: Acne, allergic reaction, erythema, erythema multiforme, erythema nodosum, hypertrichosis, pruritus, urticariaFetal/Neonatal Anomalies:Abnormal bone development: skeletal malformations of the skull, face, nasal passages, jaw, hand, limb (ectromelia including amelia, hemimelia, and phocomelia),foot (clubfoot), spine and joints

Cardiac abnormalities: septal heart defects, muscular ventricular septal defect, patent ductus arteriosus, tetralogy of Fallot, and coarctation of the aorta

Chromosomal disorders:Downs syndrome

Ear abnormalities and deafness

Gastrointestinal tract abnormalities: cleft lip and palate, imperforate anus, tracheoesophageal fistula, diaphragmatic hernia, omphalocele

Genitalia abnormalities: hypospadias, cloacal exstrophy

Lung tissue malformations

Malformations of the eye and lens (cataract)

Neoplasms: neuroectodermal tumor, thyroid tumor, hepatoblastoma, lymphocytic, leukemia

Nervous system abnormalities: neural tube defects (anencephaly, meningomyelocele),microcephaly, and hydrocephalus

Renal abnormalities: renal agenesis and renal dysgenesis

Others: dwarfism, mental retardation
Genitourinary: Endometriosis, ovarian cyst (ovarian enlargement or cysts could, as such, be complicated by adnexal torsion), ovarian hemorrhage, tubal pregnancy, uterine hemorrhage.Hepatic: Transaminases increased, hepatitis.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.DRUGABUSE AND DEPENDENCETolerance, abuse, or dependence with clomiphene citrate has not been reported.

Dosage & Administration

Signs and SymptomsToxic effects accompanying acute overdosage of clomiphene citrate have not been reported. Signs and symptoms of overdosage as a result of the use of more than the recommended dose during clomiphene citrate therapy include nausea, vomiting, vasomotor flushes, visual blurring, spots or flashes, scotomata, ovarian enlargement with pelvic or abdominal pain. (See CONTRAINDICATIONS: Ovarian Cyst.)Oral LD50. The acute oral LD50 of clomiphene citrate is 1700 mg/kg in mice and 5750 mg/kg in rats. The toxic dose in humans is not known.Dialysis. It is not known if clomiphene citrate is dialyzable.TreatmentIn the event of overdose, appropriate supportive measures should be employed in addition to gastrointestinal decontamination.

How Supplied

Clomiphene citrate tablets, USP, 50 mg are round, off-white, debossed “Par 701” with bisect on one side and plain on the other. They are supplied in cartons of 10 (NDC 49884-701-54) and cartons of 30 (NDC 49884-701-55).Storage - Store at controlled room temperature 15°-30°C (59°-86°F). Protect from heat, light, and excessive humidity, and store in closed containers.Manufactured by:PAR PHARMACEUTICALChestnut Ridge, N Y 10977Revised: 06/2016

* Please review the disclaimer below.

Previous Code
61919-374
Next Code
61919-376