Introduction
Trelstar (triptorelin pamoate) is a synthetic decapeptide agonist analog of gonadotropin-releasing hormone (GnRH) used primarily in oncology and endocrinology. It is available as a long-acting depot formulation that provides sustained release of the active compound. Trelstar is manufactured by Verity Pharmaceuticals and is approved for the palliative treatment of advanced prostate cancer.
Mechanism of Action
Triptorelin acts as a potent GnRH receptor agonist. Initially, it stimulates pituitary gonadotropin release, resulting in a transient increase in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. With continuous administration, it causes downregulation of GnRH receptors in the pituitary gland, leading to profound suppression of gonadotropin secretion and subsequent reduction in testosterone production to castrate levels (<50 ng/dL) in men. This creates a medical castration effect that is reversible upon discontinuation of therapy.
Indications
- Palliative treatment of advanced prostate cancer
- Management of central precocious puberty (off-label in some regions)
- Endometriosis management (off-label in some regions)
FDA-approved specifically for:
- Advanced prostate cancer requiring androgen deprivation therapy
Dosage and Administration
Available formulations:- Trelstar 3.75 mg: Monthly administration
- Trelstar 11.25 mg: 3-month formulation
- Trelstar 22.5 mg: 6-month formulation
- 3.75 mg intramuscularly every 4 weeks
- 11.25 mg intramuscularly every 12 weeks
- 22.5 mg intramuscularly every 24 weeks
- Administer by deep intramuscular injection in the buttock
- Rotate injection sites
- Reconstitute with provided diluent according to manufacturer instructions
- Renal impairment: Use with caution; no specific dosage adjustment recommended
- Hepatic impairment: No dosage adjustment required
- Elderly: No dosage adjustment required
Pharmacokinetics
Absorption: Following IM injection, triptorelin is slowly released from the depot formulation with peak concentrations reached within 1-3 hours initially, followed by sustained release. Distribution: Volume of distribution is approximately 30-33 L. Protein binding is minimal (0-15%). Metabolism: Undergoes extensive proteolytic degradation in tissues and plasma. No significant hepatic metabolism via cytochrome P450 system. Elimination: Terminal half-life is approximately 2.8-5.5 hours. Excreted primarily via urine (40-50%) and feces (5-20%). Steady state: Castrate testosterone levels achieved within 2-4 weeks of initiation and maintained throughout dosing interval.Contraindications
- Hypersensitivity to triptorelin, other GnRH agonists, or any component of the formulation
- Women who are or may become pregnant (Category X)
- Breastfeeding women
- Patients with unexplained vaginal bleeding
- Use in pediatric patients (except for approved precocious puberty indications)
Warnings and Precautions
Cardiovascular risk: Increased risk of myocardial infarction, sudden cardiac death, and stroke. Evaluate cardiovascular risk before initiation. Bone density loss: Significant bone mineral density loss may occur. Consider baseline bone density assessment and calcium/vitamin D supplementation. Metabolic effects: May cause hyperglycemia and diabetes. Monitor blood glucose regularly. Tumor flare phenomenon: Initial transient increase in testosterone during first week may cause worsening of symptoms (bone pain, urinary obstruction, neurological symptoms). Hypersensitivity reactions: Anaphylactic reactions and angioedema have been reported. Pituitary apoplexy: Rare cases reported, typically within first week of initiation. QT prolongation: May prolong QT interval. Use with caution in patients with risk factors for QT prolongation.Drug Interactions
Drugs that prolong QT interval: Concurrent use may increase risk of torsades de pointes (antiarrhythmics, antipsychotics, antibiotics) Corticosteroids: May alter metabolism and effects Androgens, estrogens: May counteract therapeutic effect Laboratory interactions: May interfere with pituitary function testsAdverse Effects
Very common (>10%):- Hot flashes (60-80%)
- Erectile dysfunction (40-60%)
- Decreased libido (30-50%)
- Injection site reactions (15-30%)
- Fatigue (10-20%)
- Headache
- Dizziness
- Arthralgia
- Myalgia
- Edema
- Gynecomastia
- Nausea
- Cardiovascular events
- Osteoporosis fractures
- Spinal cord compression
- Pituitary apoplexy
- Anaphylaxis
- Severe hyperglycemia
Monitoring Parameters
Baseline:- Testosterone levels
- PSA levels
- Bone density scan (DEXA)
- Cardiovascular risk assessment
- Renal and hepatic function
- Blood glucose and HbA1c
- Electrolytes including calcium
- Testosterone levels (q3-6 months)
- PSA (every 3-6 months)
- Bone mineral density (annually)
- Blood glucose (regularly)
- Cardiovascular assessment (regularly)
- Signs of tumor flare (first 2 weeks)
- Injection site reactions
- Cognitive function assessment
- Lipid profile
- Body composition changes
Patient Education
- Expect initial worsening of symptoms during first 1-2 weeks (tumor flare)
- Hot flashes are common and may persist throughout therapy
- Report any chest pain, shortness of breath, or neurological symptoms immediately
- Maintain adequate calcium and vitamin D intake
- Regular exercise may help maintain bone strength
- Injection site reactions are common but usually mild
- Use sun protection as photosensitivity may occur
- Inform all healthcare providers about Trelstar therapy
- Notify physician if diabetes symptoms develop (increased thirst, urination)
- Practice fall prevention strategies due to osteoporosis risk
- Understand that fertility may be affected during treatment
References
1. FDA Prescribing Information: Trelstar (triptorelin pamoate) 2. Schroder FH, et al. Eur Urol. 2018;73(2):178-188 3. Sharifi N, et al. J Clin Oncol. 2005;23(4):789-795 4. Perlmutter MA, et al. Rev Urol. 2007;9(1):1-8 5. NCCN Guidelines: Prostate Cancer Version 4.2023 6. Moghul S, et al. Ther Adv Urol. 2021;13:17562872211053160 7. Smith MR, et al. N Engl J Med. 2018;379(5):447-456 8. European Association of Urology Guidelines: Prostate Cancer 2023
This information is provided for educational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional for personalized medical guidance.