30 tablets 50 mg.
Each tablet contains:
Clomiphene citrate 50 mg.
Mechanism of Action and Pharmacokinetics
It is a non-steroidal agent for oral administration, which can induce ovulation in selected anovulatory women. It is a drug that has considerable pharmacological potency. It is essential to carefully evaluate and select the patient and pay close attention to dose coordination before treatment with clomiphene citrate. The conservative selection and management of the patient contribute to the success of anovulation treatment. Clomiphene citrate induces ovulation in most selected anovulatory patients. The different criteria for ovulation include: an ovulatory peak of estrogen excretion followed by biphasic basal levels of the body temperature curve; the urinary excretion of pregnandiol at postovulatory levels, and endometrial findings characteristic of the luteal phase. A review of the eleven publications that appeared between 1964 and 1978 showed that pregnancy occurred in 35% of the 5154 patients with ovulatory dysfunction who received clomiphene citrate. Pregnancies after administration of clomiphene citrate: Number of patients / 5154 / Range. Percentage of patients who ovulanb / 75 / 50-94%. Percentage of ovulatory cycles / 53 / 33-69%. Percentage of pregnant patients / 35 / 11-52%. Percentage of live births / 86 / 74-99.8%. Percentage of abortions / 14 / 0.2-26%. Percentage of single births / 90 / 67-100%. Survival percentage / 99 / 98.2-100%. Percentage of multiple births / 10 / 0-33%. Survival percentage / 96 / 82-100%. a Includes patients receiving a different dosage regimen than recommended. b Average of studies. Apparently, clomiphene citrate therapy mediates ovulation by increasing gonadotrophin production by the pituitary gland. These in turn stimulate the maturation and endocrine activity of the ovarian follicle, followed by the development and function of the corpus luteum. The increased urinary excretion of gonadotrophins and estrogen suggests involvement of the pituitary gland. Studies with clomiphene citrate with labeled C14 have shown that in humans it is easily absorbed orally, and that it is excreted mainly by feces. At 5 days an average of 51% of the administered dose is excreted. After intravenous administration, 37% is excreted in 5 days. The appearance of C14 in feces 6 weeks after administration suggests that the rest of the drug and / or its metabolites are slowly excreted from a pool of sequestered enterohepatic recirculation.
Clomiphene citrate is indicated for the treatment of ovulatory insufficiency in patients who wish to become pregnant, whose husbands are fertile and potent. Those cases in which there are impediments to this goal should be excluded or they should be treated appropriately before starting treatment. The administration of clomiphene citrate is indicated only in patients who have proven ovarian dysfunction and in whom the following conditions are met: 1. Normal liver function. 2. Physiological indications of normal endogenous estrogen (as estimated by vaginal smears, endometrial biopsy, determination of urinary estrogen levels, or for bleeding in response to progesterone). Reduced estrogen levels, while less favorable, do not prevent a successful treatment. 3. Clomiphene citrate treatment is not effective for those patients who present with ovarian or pituitary primary insufficiency. It cannot replace an appropriate treatment of other disorders that cause ovulatory dysfunction, for example thyroid or adrenal pathology. 4. A particularly careful evaluation should be performed before starting treatment with clomiphene citrate in those patients who present with abnormal uterine bleeding. It is very important to detect neoplastic lesions.
General considerations: Physicians experienced in the management of gynecological or endocrinological disorders should supervise the evaluation and treatment of patients who are candidates for treatment with clomiphene citrate. Patients should be chosen for treatment with clomiphene citrate only after having performed a careful diagnostic evaluation (see Indications). The treatment plan must be presented briefly before starting it. Before starting with clomiphene citrate, impediments to achieve the treatment goal should be discarded or properly treated beforehand. When determining the initial dose schedule, the efficacy against potential side effects should be weighed. For example, the data available to date suggest that ovulation and pregnancy are slightly easier to reach with 100 mg / day for 5 days than 50 mg / day for 5 days. However, as the dose increases, it is possible to expect ovarian overstimulation and other side effects to appear. Although the data have not yet established a relationship between dose level and multiple births, it is reasonable that there is such a correlation in the pharmacological field. For these reasons, the treatment of the usual patient should be started with a dose of 50 mg daily for 5 days.
Pregnancy: Even when no direct effect of clomiphene citrate therapy has been observed on the human fetus, clomiphene citrate should not be administered in cases where pregnancy is suspected, since these effects have been reported in animals . Basal body temperature should be recorded during all treatment cycles to avoid inadvertent administration of clomiphene citrate at the beginning of a pregnancy; and treatment should be discontinued if pregnancy is suspected. If after the administration of clomiphene citrate the basal body temperature is biphasic and is not followed by menstruation, the possibility of an ovarian cyst and / or pregnancy should be ruled out. The next cycle should be postponed until a correct diagnosis has been determined. Hepatic disease: Clomiphene citrate should not be used in patients with liver disease or a history of liver dysfunction. Abnormal uterine bleeding: The use of clomiphene citrate is contraindicated in patients with abnormal uterine bleeding.
Diagnosis prior to clomiphene citrate therapy: Careful evaluation of candidates for treatment with clomiphene citrate should be performed. A complete pelvic exam should be performed before starting treatment and should be repeated before each subsequent cycle. Clomiphene citrate should not be administered to patients with ovarian cyst, as a further increase in the ovaries may occur. Since the incidence of endometrial carcinoma and ovulatory disorders increases with age, endometrial biopsy should always be done to rule out the first of these causes in such patients. If abnormal uterine bleeding occurs, all diagnostic measures are necessary. Ovarian overstimulation during treatment with clomiphene citrate: To minimize the danger associated with the occasional abnormal increase in ovarian size during treatment with clomiphene citrate (see Side Effects), the lowest dose that produces good results should be chosen. Some patients with polycystic ovary syndrome are unusually sensitive to gonadotrophin and may have an exaggerated response to the usual doses of clomiphene citrate. The maximum enlargement of the ovaries, whether abnormal or physiological, does not occur until several days after the interruption of clomiphene citrate. The patient who complains of pelvic pain after receiving clomiphene citrate should be carefully examined. If an enlargement of the ovaries appears, the clomiphene treatment should be discontinued until the ovaries have returned to the size prior to the treatment, and the dose or duration of the next cycle should be reduced.
Enlargement of the ovaries and cyst formation after clomiphene citrate therapy return spontaneously within a few days or weeks after stopping treatment. Therefore, unless there is a strong indication for a laparotomy, a conservative management of this enlarged cyst should always be done. A cause-effect relationship between ovarian hyperstimulation and ovarian cancer has not been determined. However, as a correlation between ovarian cancer, nulliparity, infertility and age has been suggested, if the ovarian cyst does not return spontaneously, a full evaluation should be done to rule out the presence of ovarian cancer. Multiple pregnancy: In the reviewed publications, the incidence of multiple pregnancies was increased during those cycles in which clomiphene citrate was administered. Among the 1803 pregnancies in which the result was reported, 90% were single fetuses and 10% were twins. Less than 1% of reported deliveries resulted in triplets or more twins. Of these multiple pregnancies, 96-99% ended in the birth of live newborns. The patient and her husband should be advised on the frequency and potential dangers due to multiple pregnancies before beginning treatment. Ectopic pregnancy: There is a high probability of ectopic pregnancy in women who conceived, after a therapy with 50 mg of clomiphene.
Restrictions of Use
Do not use in case of hypersensitivity to some of its components; during pregnancy and breastfeeding period. Also, do not use in patients with hypertension, or in patients with cardiovascular problems, hepatic and renal dysfunction.
Treatment in case of overdose: There have been no reports of overdose with the product.