Ovajet

Approved Indications:

• Female Infertility due to Ovulatory Dysfunction, including:
• Polycystic ovary syndrome (PCOS)
• Anovulatory or oligo-ovulatory cycles
• Luteal Phase Deficiency (secondary to inadequate ovulation)
• Unexplained Infertility (in some cases, as part of empiric therapy)

Off-Label (Clinically Accepted) Uses:

• Male Infertility due to Hypogonadotropic Hypogonadism (to increase spermatogenesis)
• Secondary Hypogonadism in Males – used to increase endogenous testosterone
• Functional Amenorrhea – to stimulate ovulation where appropriate
• Prevention of Ovarian Hyperstimulation Syndrome (OHSS) – in selected ART cycles
• Diagnosis of Pituitary Function – as a test for hypothalamic-pituitary-ovarian axis integrity

Adult Females (Infertility Treatment):

• Initial Dose: 50 mg orally once daily for 5 consecutive days, starting on day 2, 3, 4, or 5 of the menstrual cycle.
• If ovulation does not occur: Increase to 100 mg/day for 5 days in subsequent cycles.
• Maximum dose: 150 mg/day; do not exceed 6 ovulatory cycles total.
• Ovulation usually occurs 5–10 days after the last dose.

Adult Males (Off-label for Hypogonadism/Infertility):

• Typical Dose: 25–50 mg orally once daily or on alternate days.
• Duration: Several months (3–6 months or longer), with monitoring of testosterone, LH, FSH, and semen parameters.

Elderly:

• Not routinely used; safety and efficacy not established in elderly populations.

Pediatrics:

• Not indicated for pediatric use.

Renal/Hepatic Impairment:

• Contraindicated in hepatic dysfunction. Use caution in renal impairment; no standard dose adjustment available.

Clomiphene citrate acts as a Selective Estrogen Receptor Modulator (SERM), primarily functioning as an estrogen antagonist at the hypothalamic level. It binds to estrogen receptors in the hypothalamus, blocking the negative feedback of circulating estrogens. This leads to increased secretion of gonadotropin-releasing hormone (GnRH), which stimulates the pituitary to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The resultant rise in FSH and LH promotes follicular development and ovulation in women, and stimulates testosterone production and spermatogenesis in men.

• Absorption: Well absorbed orally; peak plasma concentrations occur within 5–7 hours.
• Bioavailability: High, but precise values not fully established.
• Distribution: Widely distributed; accumulates in fatty tissues and may remain in the body for weeks.
• Metabolism: Hepatic metabolism via demethylation and glucuronidation.
• Half-life: Approximately 5–7 days (some isomers may persist for weeks).
• Excretion: Primarily through feces via biliary elimination; minor renal excretion.

• Pregnancy: Category X (contraindicated) – Clomiphene is not to be used in pregnancy due to its ovulation-inducing effects and potential for fetal harm.
• Lactation: Not recommended during breastfeeding. Clomiphene may reduce milk production and its excretion into breast milk is not well studied.

• Primary Class: Ovulation Inducing Agent
• Subclass: Selective Estrogen Receptor Modulator (SERM)

• Pregnancy (Category X)
• Hypersensitivity to clomiphene or any excipients
• Liver disease or history of hepatic dysfunction
• Ovarian cysts not due to PCOS
• Abnormal uterine bleeding of undiagnosed cause
• Pituitary or hypothalamic tumors
• Thyroid or adrenal dysfunction (unless corrected)
• Organic intracranial lesions

• Ovarian Enlargement: Risk of cyst formation and abdominal discomfort; monitor pelvic exam and ultrasound.
• Multiple Gestations: Increased risk, primarily twins.
• Visual Disturbances: Blurred vision, scotomas, photophobia may occur; discontinue immediately if visual symptoms appear.
• Ovarian Hyperstimulation Syndrome (OHSS): Though less common than with gonadotropins, cases have been reported.
• Endometrial/ovarian cancer risk: Long-term use (>6 cycles) may increase risk; restrict to recommended duration.
• Use caution in patients with fibroids, depression, or seizure disorders.

Common (≥5%):

• Hot flashes
• Abdominal/pelvic bloating or discomfort
• Breast tenderness
• Nausea
• Headache

Less Common:

• Visual disturbances (blurred vision, photophobia, scotomas)
• Mood swings or depression
• Dizziness
• Ovarian enlargement or cysts

Rare but Serious:

• Ovarian hyperstimulation syndrome (OHSS)
• Ectopic pregnancy
• Multiple gestations
• Hepatic dysfunction

• Drug-Drug:
• May reduce efficacy of estrogen-containing contraceptives or hormone therapy.
• Use with other fertility agents (e.g., gonadotropins) increases risk of OHSS.
• Drug-Food/Alcohol:
• No major food interactions reported.
• Alcohol should be avoided in women trying to conceive.
• Enzyme Interactions:
• Clomiphene is metabolized hepatically but not primarily via CYP450, so significant CYP-mediated interactions are uncommon.

• Clinical practice guidelines recommend limiting use to 6 ovulatory cycles due to risk of adverse events and reduced success beyond this point.
• Increasing use in male hypogonadism as an alternative to testosterone therapy to preserve fertility.
• Updated safety alerts emphasize prompt discontinuation if visual disturbances or OHSS signs appear.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Humidity & Light: Protect from moisture and excessive light.
• Handling: Keep out of reach of children; store in original container.