GONAPEPTYL DEPOT POWDER FOR INJECTION

Indications

• Advanced prostate cancer
• Endometriosis

Dosage

Adults: For advanced prostate cancer, the recommended dosage is 11.25 mg administered intramuscularly every 3 months, or 3 mg every 4 weeks for endometriosis, to be initiated within the first 5 days of the menstrual cycle.

Mechanism of action

Triptorelin acts as a potent agonist of GnRH receptors, exhibiting significantly higher release activity for LH and FSH compared to native GnRH. This agonistic activity leads to an initial surge in hormone levels, followed by receptor down-regulation and decreased hormone secretion.

Pharmacodynamics

After administration, triptorelin causes a transient increase in FSH, LH, estradiol, and testosterone. This initial surge can exacerbate symptoms of prostate cancer, such as urinary obstruction and bone pain. However, after 2-4 weeks of treatment, there is a sustained decrease in FSH and LH, resulting in significantly reduced serum testosterone levels, mimicking surgical castration effects, which leads to the inactivation of hormone-dependent tissues.

Pharmacokinetics

Triptorelin is administered via subcutaneous or intramuscular injection. Following administration, it is rapidly absorbed, with peak plasma concentrations occurring within a few hours. The half-life of triptorelin is approximately 3 hours, but its effects can last longer due to the down-regulation of hormone secretion. The drug is metabolized primarily in the liver and excreted via the kidneys.

Adverse effects

• anxiety
• asthenia
• depression
• diabetes mellitus
• dizziness
• dry mouth
• gastrointestinal discomfort
• gynaecomastia
• haemorrhage
• oedema
• sexual dysfunction
• painful sexual intercourse
• pelvic pain
• sleep disorders
• weight changes
• alopecia
• appetite abnormality
• asthma

Precautions

• History of depression
• Metabolic bone disease (risk of decreased bone mineral density)
• Risk factors for osteoporosis
• Risk of spinal cord compression in men
• Risk of ureteric obstruction in men
• Increased risk of sensitivity to restored testosterone if treatment is interrupted

Pregnancy

Triptorelin is not indicated during pregnancy and should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is unknown whether triptorelin is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

Store in a refrigerator (2-8°C). Do not freeze. Protect from light.

Formulations

• {'name': 'DECAPEPTYL SR 11.25 MG', 'route': 'intramuscular injection', 'indication': 'Advanced prostate cancer (specialist use only)', 'dose': '11.25 mg every 3 months'}
• {'name': 'DECAPEPTYL SR 3 MG', 'route': 'intramuscular injection', 'indication': 'Advanced prostate cancer (specialist use only)', 'dose': '3 mg every 4 weeks'}
• {'name': 'GONAPEPTYL DEPOT', 'route': 'subcutaneous or deep intramuscular injection', 'indication': 'Advanced prostate cancer (specialist use only)'}

Mechanism of action

Triptorelin is a synthetic agonist analog of gonadotropin releasing hormone (GnRH). Animal studies comparing triptorelin to native GnRH found that triptorelin had 13 fold higher releasing activity for luteinizing hormone, and 21-fold higher releasing activity for follicle-stimulating hormone.

Pharmacodynamics

The first administration of triptorelin is followed by a transient surge of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol,and testosterone. The time, peak and decline of testosterone in the body varies depending on the dose administered. This initial surge is often responsible for worsening of prostate cancer symptoms such as urethral or bladder outlet obstruction, bone pain, spinal cord injury and hematuria in the early stages. A sustained decrease in FSH and LH, and significant reduction of testicular steroidogenesis is usually seen 2-4 weeks post-initiation of therapy. This result is a reduction of serum testosterone to levels which are typically seen in surgically castrated men. Ultimately, tissues and functions that require these hormones become inactive. The effects of triptorelin can usually be reversed once the drug is discontinued.