Zuclomiphene

442.42

405.96

213-008-6

3JU1DU3652

DTXSID1022843

G - Genito urinary system and sex hormones

2922299090

12.5

7.2

1.104±0.06 g/cm3(Predicted)

50-52 °C

509.0±50.0 °C(Predicted)

261.6ºC

H2O: Slightly soluble

Store below 40 deg C (104 deg F), preferably between 15 and 30 deg C (59 and 86 deg F), unless otherwise specified by manufacturer. Store in a well-closed container. Protect from light.

APPRECIABLY HYGROSCOPIC; MELTS WITH DECOMP BETWEEN 117 AND 119 °C /CITRATE/|CRYSTALS /CLOMIPHENE CITRATE/|WHITE TO PALE YELLOW POWDER /CLOMIPHENE CITRATE/

UNSTABLE TO AIR AND LIGHT

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

There is little information on serum aminotransferase levels during clomiphene therapy which is typically given in low doses for a short time only. There have been a few reports of mild serum enzyme elevations in patients taking clomiphene, but no convincing instances of idiosyncratic, clinically apparent liver injury with its use.

Clomiphene is an oral agent used to treat infertility in women desiring pregnancy. Clomiphene has been linked to a low rate of transient serum aminotransferase elevations during therapy and to rare instances of clinically apparent liver injury, which can be severe and even fatal.

Infertility Agents

Fertility Agents, Female|MEDICATION (VET): TO INDUCE OVULATION IN ANOVULATORY FEMALES, & TO INDUCE NORMAL MENSTRUAL CYCLING IN AMENORRHEA OR OLIGOMENORRHEA.|THE INCIDENCE OF MULTIPLE GESTATIONS IS ABOUT 8% OR SIX TIMES NORMAL BUT IS LOWER THAN WITH /HUMAN MENOPAUSAL GONADOTROPIN/ HMG. MULTIPLE BIRTHS ARE ALMOST ALWAYS TWINS; LARGER MULTIPLE GESTATIONS HAVE BEEN REPORTED RARELY. SPONTANEOUS ABORTIONS (MOSTLY EARLY MISCARRIAGES) OCCUR IN APPROX 20% OF CLOMIPHENE-INDUCED PREGNANCIES, WHICH MAY BE ONLY SLIGHTLY HIGHER THAN NORMAL BUT IS NOT HIGHER THAN AN INFERTILE POPULATION. /CLOMIPHENE CITRATE/|CLOMIPHENE CITRATE HAS ALSO BEEN USED IN MEN TO TREAT OLIGOSPERMIA ... BUT THE VALUE OF THIS TREATMENT HAS NOT YET BEEN ESTABLISHED. /CLOMIPHENE CITRATE/|For more Therapeutic Uses (Complete) data for CLOMIPHENE (10 total), please visit the HSDB record page.

OBJECTIVE SIGNS ARE RARELY FOUND, ALTHOUGH MEASURABLE LOSS OF VISUAL ACUITY, DEFINABLE SCOTOMATA, & CHANGES IN RETINAL CELL FUNCTION HAVE BEEN REPORTED. /CLOMIPHENE CITRATE/|OTHER ADVERSE REACTIONS INCLUDE...HEADACHE, BREAST ENGORGEMENT, & ABDOMINAL BLOATING. SYMPTOMS DISAPPEAR WHEN THERAPY IS STOPPED. /CLOMIPHENE CITRATE/|SOME PHYSICIANS CONSIDER VISUAL ABNORMALITIES TO BE A CONTRAINDICATION TO FURTHER USE, WHILE OTHERS CONTINUE THERAPY WITH LOWER DOSES. ... CLOMIPHENE SHOULD NOT BE ADMIN TO PREGNANT WOMEN; THERE IS NO INDICATION FOR CLOMIPHENE THERAPY ONCE CONCEPTION HAS BEEN ACHIEVED. /CLOMIPHENE CITRATE/|SULFOBROMOPHTHALEIN RETENTION MAY BE INCR. DESMOSTEROL LEVELS ARE ELEVATED BY HIGH DOSES.|For more Drug Warnings (Complete) data for CLOMIPHENE (21 total), please visit the HSDB record page.

SC DOSE OF (14)C CLOMIPHENE CITRATE...WAS DISTRIBUTED IN TISSUES OF FEMALE GUINEA PIG NEONATES... ESTROGENIC-RESPONSIVE TISSUES SHOWED HIGH AFFINITY FOR (14)C. LEVELS OF (14)C...CONSTANT IN UTERUS...THOSE IN OVARIES & PLASMA DECLINED...IN ADRENALS INCR. /CLOMIPHENE CITRATE/|ABOUT ONE-HALF OF THE INGESTED DOSE IS EXCRETED IN FIVE DAYS; TRACES APPEAR IN THE FECES UP TO SIX WEEKS AFTER ADMIN. /CLOMIPHENE CITRATE/|Clomiphene is well absorbed following oral administration. The drug and its metabolites are eliminated primarily in the feces and to a lesser extent in the urine. The rather long plasma half-life (approximately 5 to 7 days) is due largely to plasma protein binding, enterophepatic circulation, and accumulation in fatty tissues. Active metabolites with long half-lives also may be produced.

INCUBATION OF THE NONSTEROIDAL ANTIESTROGEN CLOMIPHENE WITH RAT LIVER MICROSOMES RESULTED IN THE FORMATION OF THE 4-HYDROXY-, N-DESETHYL-, & N-OXIDE METABOLITES, IN QUALITATIVE CONTRAST TO RESULTS PREVIOUSLY OBTAINED ANALOGOUSLY WITH RABBIT MICROSOMES IN WHICH ONLY THE FIRST 2 METABOLITES WERE DETECTED. ORAL ADMIN OF CLOMIPHENE RESULTED IN NO DETECTABLE URINARY ELIMINATION OF THE DRUG OR ITS METABOLITES. 4-HYDROXYCLOMIPHENE WAS THE SOLE DETECTABLE ELIMINATION PRODUCT IN FECAL EXTRACTIONS.

CLOMIPHENE...AFFECTS SPERMIOGENESIS @ PRIMARY SPERMATOCYTE LEVEL. DOSE USED WAS 7.25 MG/DAY. EFFECT IS THOUGHT TO BE DUE TO ESTROGENICITY MEDIATED VIA HYPOTHALAMO-HYPOPHYSEAL AXIS...|The antiestrogens tamoxifen and clomiphene are used primarily for the treatment of breast cancer and female infertility, respectively. These agents are used therapeutically for their antiestrogenic actions, but they can produce estrogenic as well as antiestrogenic effects. Both agents competitively block estradiol binding to its receptor, but the specific pharmacological activity they produce depends upon the species, the tissue, and the cellular endpoint measured. Consequently, these agents act as antagonists, agonists, or partial agonists depending upon the context in which they are used.|Clomiphene and tamoxifen clearly bind to the estrogen receptor and can prevent the binding of estrogens. However, there are indications that the drugs and estradiol may interact with overlapping but slightly different regions of the ligand binding site of the estrogen receptor. Depending upon the specific cellular context and gene in question, antiestrogen binding may yield a receptor complex that has full, partial, or no intrinsic activity.|Clomiphene may stimulate ovulation in women with an intact hypothalamic-pituitary-ovarian axis and adequate endogenous estrogens who have failed to ovulate. In these cases, it is thought that the drug opposes the negative feedback of endogenous estrogens resulting in increased gonadotropin secretion and ovulation. Most studies indicate that clomiphene increases the amplitude of LH and FSH pulses, without a change in pulse frequency. This suggests the drug is acting largely at the pituitary level to block inhibitory actions of estrogen on gonadotropin release from the gland and/or is somehow causing the hypothalamus to release larger amounts of gonadotropin-releasing hormone per pulse.|Initial animal studies with clomiphene showed slight estrogenic activity and moderate antiestrogenic activity, but the most striking effect was the inhibition of the pituitary's gonadotropic function. In both male and female animals, the compound acted as a contraceptive.

...REPORTED A CASE OF GRANULOSA-CELL TUMOR OF THE OVARY IN A 28-YR OLD FEMALE WHO HAD RECEIVED CLOMIPHENE CITRATE THERAPY FOR TWO CYCLES (2 FIVE-DAY COURSES OF 100 MG PER DAY). TWO CASES OF BILATERAL BREAST CANCER WERE REPORTED IN WOMEN AGED 28 AND 29 WHO HAD RECEIVED SUCH THERAPY. MOLAR PREGNANCIES HAVE BEEN OBSERVED FOLLOWING INDUCTION OF OVULATION BY CLOMIPHENE CITRATE...AND RAPID ENLARGEMENT OF UTERINE FIBROIDS HAS ALSO BEEN REPORTED. /CLOMIPHENE CITRATE/|A 28-YEAR OLD MALE WHO HAD RECEIVED 1 MG 'CISCLOMIPHENE CITRATE' (ENCLOMIPHENE, THE TRANS ISOMER) DAILY FOR 10 WK DEVELOPED A GERM-CELL TUMOR WITH ELEMENTS OF SEMINOMA AND MATURE ADULT TERATOMA. /TRANS- ISOMER OF CLOMIPHENE CITRATE/|REPORTED IS A CASE OF BILATERAL OVARIAN DYSPLASIA WITH ONE LARGE OVARIAN CYST IN AN INFANT WHOSE MOTHER WAS GIVEN CLOMIPHENE IMMEDIATELY BEFORE CONCEPTION. IT WAS CONCLUDED THAT TRANSPLACENTAL PASSAGE OF CLOMIPHENE COULD BE ASSOCIATED WITH CYSTIC DYSPLASIA OF THE OVARIES IN THE NEWBORN.|In a study of fifty-eight patients taking clomiphene citrate, four developed visual symptoms of phosphenes, consisting of episodes of flashing lights, or complaints of blurred vision, and two of these patients were found to have reduced visual acuity with central scotomas. In one of these patients the scotomas disappeared while the drug was still being administered. In the other patient the scotomas disappeared when the drug was stopped and reappeared when it was readministered. /Chlomiphene citrate/|For more Human Toxicity Excerpts (Complete) data for CLOMIPHENE (12 total), please visit the HSDB record page.

ESSENTIALLY 100% AS A MEDICINAL (1976) /CITRATE/

...IN THE US, IT IS AVAIL AS A USP GRADE CONTAINING 98-101% (ON THE BASIS OF THE ANHYDROUS MATERIAL) OF CLOMIPHENE CITRATE AS A MIXT OF THE CIS AND TRANS ISOMERS, CONTAINING 1% MAX WATER, 0.002% MAX HEAVY METALS AND 30-50% OF THE TRANS ISOMER. IT IS ALSO AVAIL IN 50 MG TABLETS CONTAINING 93-107% OF THE STATED AMT OF CLOMIPHENE CITRATE. /CLOMIPHENE CITRATE/|TRADE NAMES: CLOMID; CLOMIFENO; CLOMIVID; CLOMPHID; CHLORAMIPHENE; DYNERIC; GENOZYM; IKACLOMIN; MER-41; MRL 41; MRL/41; NSC 35770; OMIFIN /CLOMIPHENE CITRATE/

DUE TO ETHYLENE MOIETY IN MOLECULE, CLOMIPHENE IS A MIXTURE OF TWO ISOMERS. CIS- FORM POSSESSES ANTIESTROGENIC ACTIVITY, WHILE TRANS- FORM IS ESTROGENIC. THEREFORE, MIXTURE POSSESSES LESS THAN ONE HALF OF EITHER ACTIVITY.|THIS NONSTEROIDAL AGENT IS A MIXT OF TWO ISOMERS IN APPROX A 1:1 RATIO AND IS RELATED CHEMICALLY TO CHLOROTRIANISENE. /CLOMIPHENE CITRATE/|CLOMIPHENE CITRATE CAN BE SEPARATED INTO ITS CIS AND TRANS ISOMERS, ZUCLOMIPHENE AND ENCLOMIPHENE. IN THE US, ZUCLOMIPHENE...WAS PREVIOUSLY CALLED 'TRANSCLOMIPHENE', AND ENCLOMIPHENE...WAS PREVIOUSLY CALLED 'CISCLOMIPHENE'. /CLOMIPHENE CITRATE/

BULK CHEMICAL: INFRA-RED SPECTROMETRY (13.16 AND 13.51 UM). TABLETS: ULTRAVIOLET SPECTROMETRY (292 NM). /FROM TABLE/

Simple and rapid determination of clomiphene cis and trans isomers in human plasma by high performance liquid chromatography using on line post column photochemical derivatization and fluorescence detection.