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 cis-isomer.
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 sucrose.
Clomifene (previously clomiphene) is an orally administered, non steroidal, ovulatory stimulant that acts as a selective estrogen receptor modulator. Clomifene can lead to multiple ovulation, and hence increase the risk of conceiving twins. In comparison to purified FSH, the rate of ovarian hyperstimulation syndrome is low. There may be an increased risk of ovarian cancer and weight gain. Clomifene 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. Clomifene 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 clomifene 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.
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.
Indications and usage:
CLOMID is indicated for the treatment of ovulatory dysfunction in women desiring pregnancy. Impediments to achieving pregnancy must be excluded or adequately treated before beginning clomid 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 CLOMID 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).
CLOMID is indicated only in patients with demonstrated ovulatory dysfunction who meet the conditions described below:
Patients who are not pregnant.
Patients without ovarian cysts. CLOMID 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 CLOMID 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.
Dosage and administration:
Treatment of the selected patient should begin with a low dose, 50 mg daily (1 tablet) for 5 days. The dose should be increased only in those patients who do not ovulate in response to cyclic 50 mg CLOMID. A low dosage or duration of treatment course is particularly recommended if unusual sensitivity to pituitary gonadotropin is suspected, such as in patients with polycystic ovary syndrome.
The patient should be evaluated carefully to exclude pregnancy, ovarian enlargement, or ovarian cyst formation between each treatment cycle.
If progestin-induced bleeding is planned, or if spontaneous uterine bleeding occurs prior to therapy, the regimen of 50 mg daily for 5 days should be started on or about the 5th day of the cycle. Therapy may be started at any time in the patient who has had no recent uterine bleeding. When ovulation occurs at this dosage, there is no advantage to increasing the dose in subsequent cycles of treatment.
If ovulation does not appear to occur after the first course of therapy, a second course of 100 mg daily (two 50 mg tablets given as a single daily dose) for 5 days should be given. This course may be started as early as 30 days after the previous one after precautions are taken to exclude the presence of pregnancy. Increasing the dosage or duration of therapy beyond 100 mg/day for 5 days is not recommended.
The majority of patients who are going to ovulate will do so after the first course of therapy. If ovulation does not occur after three courses of therapy, further treatment with CLOMID is not recommended and the patient should be reevaluated. If three ovulatory responses occur, but pregnancy has not been achieved, further treatment is not recommended. If menses does not occur after an ovulatory response, the patient should be reevaluated. Long-term cyclic therapy is not recommended beyond a total of about six cycles
Hypersensitivity, liver or kidney failure, metrorrhagia of unknown etiology, ovarian cysts, neoplasms of genital organs, tumor or hypofunction of the hypophysis, endometriosis, ovarian failure together with hyperprolactinaemia, pregnancy.
Warnings and precautions:
Before taking Clomid notify your doctor if you have ever had any allergic reaction to clomiphene, liver diseases, mental depression, thrombophlebitis. This drug may cause vision problems, dizziness, or lightheadedness, be especially attentive if you need driving or operating machinery which requires high concentration of attention.
Inform your doctor and laboratory operators about all medications and herbal products you are taking if you are treated with Clomid.
Pregnancy and lactation:
Clomid 50mg Tablets is not indicated during pregnancy. Although there is no evidence that Clomid 50mg Tablets has a harmful effect on the human foetus, there is evidence that Clomid 50mg Tablets has a deleterious effect on rat and rabbit foetuses when given in high doses to the pregnant animal. To avoid inadvertent Clomid 50mg Tablets administration during early pregnancy, appropriate tests should be utilised during each treatment cycle to determine whether ovulation occurs. The patient should have a pregnancy test before the next course of Clomid 50mg Tablets therapy.
It is not known whether Clomifene citrate is excreted in human milk. Clomifene may reduce lactation.
Together with allergy symptoms such as swelling of lips, tongue, or face or hives in some patients may appear the following conditions: ovarian enlargement presenting as abdominal or pelvic pain, flushing, nausea, vomiting, or diarrhea, blurred vision, headache, abnormal uterine bleeding.
There have been no reports of acute overdosage with anabolics.
Store in cool dry place below 30℃. Protect from light.