A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Clomid Pharmacology, Pharmacokinetics, Studies, Metabolism - Clomiphene
Clomid Pharmacology, Pharmacokinetics, Studies, Metabolism - Clomiphene
CLINICAL PHARMACOLOGY
Action
Clomiphene citrate
tablets USP is a drug of
considerable pharmacologic and proper management of the patient,
clomiphene citrate tablets
USP potency. With careful selection
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 crtrate 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 antrestrogenic effects, which may vary from one species
to another. Some data suggest that zuclomiphene has greater estrogenic
activity then enclomrphene.
Clomiphene citrate
has no apparent
progestational, androgenic, or antrandrogenic 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.
Pharmacokinetics
Based on early studies with 14 C-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.
CLINICAL STUDIES
During clinical investigations,
7578 patients received clomiphene citrate tablets USP 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, 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.
Table 1.
|
Outcome of Reported Pregnancies in Clinical
Trials
(n = 2369)
|
|
Outcome
|
Total Number
of Pregnancies
|
Survival
Rate
|
| Pregnancy
Wastage |
| Spontaneous
Abortions |
483-
|
|
| Stillbirths
|
23
|
|
| Live Births
|
| Single
Births |
1697
|
98.16%
|
| Multiple
Births |
165
|
83.26%+
|
| - Includes
28 ectopic pregnancies,
4 hydatiform
moles and 1 fetus
papyraceous.
+ Indicates percentage of surviving infants
from these pregnancies.
|
The overall survival
of infants from multiple pregnancies including spontaneous
abortions, stillbirths, and neonatal deaths is 73%.
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