Overview
DESCRIPTION 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 C 26 H 28 ClNO.C 6 H 8 O 7 and a molecular weight of 598.08. It is represented structurally as Clomiphene citrate is a white to off-white crystalline powder.
Mechanism of Action
CLINICAL PHARMACOLOGY Action 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.
Indications
- INDICATIONS & USAGE Clomiphene citrate is indicated for the treatment of ovulatory dysfunction in women desiring pregnancy. Impediments to achieving pregnancy must be excluded or adequately treated before beginning clomiphene citrate 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.
Common Doses
- 50 mg
- 100 mg
Dosage
DOSAGE & ADMINISTRATION General Considerations The workup and treatment of candidates for clomiphene citrate therapy should be supervised by physicians experienced in management of gynecologic or endocrine disorders. Patients should be chosen for therapy with clomiphene citrate only after careful diagnostic evaluation (see INDICATIONS AND USAGE ). The plan of therapy should be outlined in advance. Impediments to achieving the goal of therapy must be excluded or adequately treated before beginning clomiphene citrate.
Contraindications
- CONTRAINDICATIONS Hypersensitivity Clomiphene citrate is contraindicated in patients with a known hypersensitivity or allergy to clomiphene citrate or to any of its ingredients. Pregnancy Clomiphene citrate use in pregnant women is contraindicated, as clomiphene citrate does not offer benefit in this population. Available human data do not suggest an increased risk for congenital anomalies above the background population risk when used as indicated. However, animal reproductive toxicology studies showed increased embryo-fetal loss and structural malformations in offspring.
Side Effects
- ADVERSE REACTIONS Clinical Trial Adverse Events. Clomiphene citrate, at recommended dosages, is generally well tolerated. Adverse reactions usually have been mild and transient and most have disappeared promptly after treatment has been discontinued. Adverse experiences reported in patients treated with clomiphene citrate during clinical studies are shown in Table 2. Table 2. Incidence of Adverse Events in Clinical Studies (Events Greater than 1%) (n = 8029*) Adverse Event % Ovarian Enlargement 13.6 Vasomotor Flushes 10.4 Abdominal-Pelvic Discomfort/Distention/Bloating 5.
Interactions
- DRUG INTERACTIONS Drug Interactions Drug interactions with clomiphene citrate have not been documented. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term toxicity studies in animals have not been performed to evaluate the carcinogenic or mutagenic potential of clomiphene citrate. Oral administration of clomiphene citrate to male rats at doses of 0.3 or 1 mg/kg/day caused decreased fertility, while higher doses caused temporary infertility. Oral doses of 0.1 mg/kg/day in female rats temporarily interrupted the normal cyclic vaginal smear pattern and prevented conception.