CLOPHENE TABLETS

Indications

• Anovulation
• Infertility due to polycystic ovary syndrome (PCOS)
• Ovulatory dysfunction

Dosage

Adults: The usual adult dose is 50 mg orally once daily for 5 days, starting on day 2, 3, 4, or 5 of the menstrual cycle. If ovulation

Mechanism of action

Clomifene exhibits both estrogenic and anti-estrogenic properties. Its exact mechanism is not fully understood, but it is believed to stimulate the release of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This stimulation can occur through direct activation of the hypothalamic-pituitary axis or by competing with endogenous estrogens, thereby reducing their inhibitory influence. As a result, clomifene promotes the development and maturation of ovarian follicles and induces ovulation.

Pharmacodynamics

As a selective estrogen receptor modulator, clomifene interacts with estrogen-receptor-containing tissues, such as the hypothalamus, pituitary, and ovaries. This interaction leads to a series of endocrine events culminating in a preovulatory gonadotropin surge and follicular rupture. Clomifene can cause multiple ovulations, increasing the chances of conceiving twins. Although the risk of ovarian hyperstimulation syndrome is lower compared to purified FSH, there may be concerns regarding potential weight gain and an increased risk of ovarian cancer.

Pharmacokinetics

Clomifene is well-absorbed after oral administration and has a long half-life, which allows for once-daily dosing. It undergoes hepatic metabolism, and its metabolites may also possess estrogenic activity. The exact pharmacokinetic profile, including the distribution and elimination routes, remains under investigation, but it is known to interact with various tissues that have estrogen receptors.

Contra-indications

• Pregnancy
• Ovarian cysts or enlargement (non-functional)
• Unexplained uterine bleeding
• Active liver disease
• Hypersensitivity to clomifene or any of its components

Adverse effects

• Hot flashes
• Nausea
• Vomiting
• Abdominal discomfort
• Visual disturbances
• Ovarian hyperstimulation syndrome
• Multiple pregnancies
• Weight gain
• Risk of ovarian cancer

Interactions

• May interact with other medications that affect liver enzymes, potentially altering clomifene metabolism
• Use with caution in patients taking anticoagulants due to potential alterations in the coagulation profile

Precautions

• Monitor for signs of ovarian hyperstimulation syndrome
• Use with caution in patients with a history of liver disease or visual disturbances
• Consider the potential for multiple pregnancies
• Assess the risks versus benefits in patients with a history of breast cancer or other estrogen-sensitive tumors

Pregnancy

Clomifene is contraindicated in pregnancy and should not be used during this period.

Breast-feeding

Clomifene is not recommended during breastfeeding due to potential effects on milk production and infant development.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets: 50 mg, 100 mg

Mechanism of action

Clomifene has both estrogenic and anti-estrogenic properties, but its precise mechanism of action has not been determined. Clomifene appears to stumulate the release of gonadotropins, follicle-stimulating hormone (FSH), and leuteinizing hormone (LH), which leads to the development and maturation of ovarian follicle, ovulation, and subsequent development and function of the coprus luteum, thus resulting in pregnancy. Gonadotropin release may result from direct stimulation of the hypothalamic-pituitary axis or from a decreased inhibitory influence of estrogens on the hypothalamic-pituitary axis by competing with the endogenous estrogens of the uterus, pituitary, or hypothalamus. Clomifene has no apparent progestational, androgenic, or antrandrogenic effects and does not appear to interfere with pituitary-adrenal or pituitary-thyroid function.

Pharmacodynamics

Clomifene (previously clomiphene) is an orally administered, non steroidal, ovulatory stimulant that acts as a selective estrogen receptor modulator (SERM). 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.