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:
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.
Clomiphene – Clinical Pharmacology
Clomiphene 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.
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 therapy.