Introduction
Triptorelin is a synthetic decapeptide analog of gonadotropin-releasing hormone (GnRH) used primarily in oncology and endocrinology. As a long-acting GnRH agonist, it initially stimulates then suppresses pituitary gonadotropin secretion, leading to profound suppression of sex hormone production. This monograph provides comprehensive clinical information about triptorelin for healthcare professionals.
Mechanism of Action
Triptorelin acts as a potent agonist at pituitary GnRH receptors. Following initial stimulation (flare effect), continuous administration leads to downregulation of GnRH receptors and desensitization of pituitary gonadotrophs. This results in suppressed secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), ultimately causing profound reduction in testosterone production in males and estrogen production in females. The drug achieves medical castration through this pituitary-gonadal axis suppression.
Indications
FDA-Approved Indications:- Advanced prostate cancer
- Endometriosis management
- Central precocious puberty
- Uterine fibroid management prior to surgery
- Assisted reproductive technologies
- Breast cancer in premenopausal women (off-label)
- Gender-affirming hormone therapy (off-label)
Dosage and Administration
Prostate Cancer:- 3.75 mg IM every 4 weeks
- 11.25 mg IM every 12 weeks
- 22.5 mg IM every 24 weeks
- 3.75 mg IM every 4 weeks for up to 6 months
- 0.1 mg/kg IM every 4 weeks (maximum 3.75 mg)
- Renal impairment: Dose adjustment not typically required
- Hepatic impairment: Use with caution
- Elderly: Standard dosing recommended
- Pediatrics: Approved for precocious puberty only
Pharmacokinetics
Absorption: Complete after intramuscular administration Distribution: Volume of distribution: 30-35 L; plasma protein binding: 0% Metabolism: Proteolytic cleavage in tissues Elimination: Half-life: 2.8-7.7 hours; primarily renal excretion (40-50%) Onset of Action: Initial stimulation within hours, suppression within 1-2 weeks Duration: Dependent on depot formulation (1, 3, or 6 months)Contraindications
- Hypersensitivity to triptorelin or any component of formulation
- Pregnancy (Category X)
- Breastfeeding
- Undiagnosed abnormal vaginal bleeding
- Women with osteoporosis or risk factors for bone loss
- Use in children except for central precocious puberty
Warnings and Precautions
Initial Disease Flare: May cause temporary worsening of symptoms in prostate cancer patients during first weeks of therapy Bone Density Loss: Significant bone mineral density reduction may occur with prolonged use Cardiovascular Risk: Increased risk of myocardial infarction, sudden cardiac death, and stroke Metabolic Effects: May induce insulin resistance and lipid abnormalities Pituitary Apoplexy: Rare cases reported, particularly in patients with pituitary adenomas QT Prolongation: May prolong QT interval; use caution in patients with risk factors Hypersensitivity Reactions: Anaphylactoid reactions possibleDrug Interactions
Drugs that Prolong QT Interval: Increased risk of torsades de pointes (antiarrhythmics, antipsychotics, antibiotics) Corticosteroids: May alter metabolic effects Other Hormonal Therapies: Additive effects on hormone suppression Drugs Metabolized by CYP450: Minimal interaction potentialAdverse Effects
Very Common (>10%):- Hot flashes (70-80%)
- Injection site reactions
- Decreased libido
- Erectile dysfunction
- Headache
- Fatigue
- Nausea
- Arthralgia
- Weight changes
- Mood disturbances
- Anaphylaxis
- Pituitary apoplexy
- Severe bone pain
- Cardiovascular events
- Spinal cord compression
- Osteoporotic fractures
Monitoring Parameters
Baseline:- Complete blood count
- Comprehensive metabolic panel
- Testosterone/estradiol levels
- PSA (prostate cancer patients)
- Bone density scan (if long-term use anticipated)
- ECG (if risk factors for QT prolongation)
- Testosterone levels (target <50 ng/dL for prostate cancer)
- PSA every 3-6 months
- Bone mineral density annually
- Lipid profile annually
- Glucose tolerance annually
- Cardiovascular assessment regularly
Patient Education
- Expect initial worsening of symptoms during first 2-4 weeks
- Report any severe headache, visual changes, or neurological symptoms immediately
- Hot flashes are common but manageable
- Importance of calcium and vitamin D supplementation for bone health
- Use effective non-hormonal contraception during treatment
- Regular follow-up appointments essential
- Injection site reactions usually resolve within few days
- Report any chest pain, palpitations, or shortness of breath
- Maintain healthy lifestyle with weight-bearing exercise
References
1. FDA Prescribing Information: Triptorelin 2. NCCN Guidelines: Prostate Cancer (2023) 3. Schlegel PN. Medical treatment of prostate cancer. J Androl. 2011 4. Lamb HM, Goa KL. Leuprorelin. Drugs. 1998 5. European Association of Urology Guidelines (2023) 6. American Society of Clinical Oncology Guidelines 7. Manufacturer's clinical trial data 8. UpToDate: Triptorelin drug information 9. Micromedex Drug Information 10. Clinical Pharmacology database
Note: This monograph provides general information and should not replace clinical judgment. Always consult current prescribing information and clinical guidelines.