BUSERELIN INJECTION

Indications

• Moderate to severe endometriosis
• Uterine fibroids
• Hormone-sensitive prostate cancer

Dosage

Adults: For intranasal administration, the usual dose is 150 to 300 micrograms four times a day, starting in the early follicular phase or midluteal phase, depending on the clinical scenario. For subcutaneous injection, the typical dosage is 200 to 500 micrograms once daily, which can be increased if necessary, with a maximum of 500

Mechanism of action

Buserelin stimulates the pituitary gland's gonadotrophin-releasing hormone receptor (GnRHR), leading to a desensitization of the receptor and a subsequent reduction in gonadotropin secretion. This results in decreased testosterone synthesis in males and inhibition of estrogen secretion in females. Over time, chronic administration leads to sustained suppression of FSH and LH levels.

Pharmacodynamics

Buserelin exhibits enhanced potency compared to natural LHRH, with effects on FSH and LH release that are 20 to 170 times greater. Its pharmacological action lasts longer than that of natural LHRH, with sustained increases in plasma LH and FSH for up to 7 hours, and a return to baseline levels requiring approximately 24 hours post-administration. Chronic dosing leads to long-term suppression of gonadotropins and associated steroidogenesis.

Pharmacokinetics

Buserelin can be administered via subcutaneous injection or intranasal spray, with absorption characteristics dependent on the route of administration. After subcutaneous administration, peak plasma concentrations are typically reached within a few hours. The half-life of buserelin is relatively short, necessitating multiple doses for sustained therapeutic effect. It is metabolized primarily by proteolytic enzymes and eliminated through the kidneys.

Contra-indications

• Pregnancy
• Severe hypersensitivity to buserelin or any component of the formulation
• Active or suspected sex hormone-dependent tumors (e.g., prostate cancer, breast cancer) unless under expert supervision

Adverse effects

• Hot flushes
• Decreased libido
• Menstrual cycle irregularities
• Breast cysts
• Dyspepsia
• Alopecia
• Uterine haemorrhage
• Irritability
• Sweat changes
• Bone loss
• Embolism and thrombosis

Interactions

• Other hormonal contraceptives may interfere with the efficacy of buserelin
• Concurrent use with medications affecting hormonal pathways may result in altered effects

Precautions

• History of depression (discontinue if severe depression recurs)
• Risk factors for osteoporosis (dual X-ray absorptiometry scan recommended before starting treatment)
• Monitoring required in patients with conditions that may be exacerbated by hormone suppression

Pregnancy

Buserelin is contraindicated in pregnancy due to the risk of adverse effects on the developing fetus.

Breast-feeding

It is not known whether buserelin is excreted in human milk. Caution should be exercised when administering to nursing women.

Storage

Store in a cool, dry place, protected from light. Keep out of reach of children.

Formulations

• Intranasal spray: 150 micrograms per spray
• Subcutaneous injection: 200–500 micrograms

Mechanism of action

Buserelin stimulates the pituitary gland's gonadotrophin-releasing hormone receptor (GnRHR). Buserelin desensitizes the GnRH receptor, reducing the amount of gonadotropin. In males, this results in a reduction in the synthesis and release of testosterone. In females, estrogen secretion is inhibited. While initially, there is a rise in FSH and LH levels, chronic administration of Buserelin results in a sustained suppression of these hormones.

Pharmacodynamics

The substitution of glycine in position 6 by D-serine, and that of glycinamide in position 10 by ethylamide, leads to a nonapeptide with a greatly enhanced LHRH effect. The effects of buserelin on FSH and LH release are 20 to 170 times greater than those of LHRH. Buserelin also has a longer duration of action than natural LHRH. Investigations in healthy adult males and females have demonstrated that the increase in plasma LH and FSH levels persist for at least 7 hours and that a return to basal values requires about 24 hours. Clinical inhibition of gonadotropin release, and subsequent reduction of serum testosterone or estradiol to castration level, was found when large pharmacologic doses (50-500 mcg SC/day or 300-1200 mcg IN/day) were administered for periods greater than 1 to 3 months. Chronic administration of such doses of buserelin results in sustained inhibition of gonadotropin production, suppression of ovarian and testicular steroidogenesis and, ultimately, reduced circulating levels of gonadotropin and gonadal steroids. These effects form the basis for buserelin use in patients with hormone-dependent metastatic carcinoma of the prostate gland as well as in patients with endometriosis.