Antiestrogen Steroid Hormones Powder 50-41-9 Clomifene Citrate
Clomid (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:
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.
Clomid is a mixture of two geometric isomers [cis (zuclomiphene)
and trans (enclomiphene)] containing between 30% and 50% of the
Each white scored tablet contains 50 mg clomiphene citrate USP. The
tablet also contains the following inactive ingredients: corn
starch, lactose, magnesium stearate, pregelatinized cornstarch, and
Clomid - Clinical Pharmacology
Clomid is a drug of considerable pharmacologic potency. With
careful selection and proper management of the patient, Clomid 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 Clomid,
spontaneous ovulatory menses have been noted in some patients after
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 Clomid therapy.
Clomiphene citrate Specifications:
|Test Items||Specification||Test Results|
|Appearance||White or off-white powder||white powder|
|Water||Not more than 1.0%||0.35%|
|Heavy water||Not more than 0.002%||Conforms|
|Related impuries||Related compound A:Not more than 2.0%||0.84%|
|Individual:Not more than 0.5%||0.36%|
During clinical investigations, 7578 patients received Clomid, 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
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
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
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 =
Includes 28 ectopic pregnancies, 4 hydatiform moles, and 1 fetus
Indicates percentage of surviving infants from these pregnancies.