Triptorelin
Class: Gonadotropins
VA Class: AN500
Chemical Name: 6-d-Tryptophan luteinizing hormone-releasing factor (pig)
Molecular Formula: C64H82N18O13
CAS Number: 57773-63-4
Brands: Trelstar
Medically reviewed by Drugs.com. Last updated on Oct 6, 2020.
Introduction
Antineoplastic agent; synthetic decapeptide analog of gonadotropin-releasing hormone (GnRH, luteinizing hormone-releasing hormone, gonadorelin);1 7 structurally related to leuprolide and goserelin.1 2 3 4 6 7
Uses for Triptorelin
Prostate Cancer
Palliative treatment of advanced prostate cancer.1 8
Triptorelin Dosage and Administration
Administration
IM Administration
Administer by IM injection every 4 weeks (28 days) as the 3.75-mg formulation, every 12 weeks as the 11.25-mg formulation, or every 24 weeks as the 22.5-mg formulation.1
Inject IM into either buttock; alternate injection sites periodically.1
Administer under the supervision of a qualified clinician.1
Reconstitution
Reconstitute powder just prior to administration.1
Using a syringe with 21-gauge needle, add 2 mL of sterile water for injection to vial containing the powder (3.75-, 11.25-, or 22.5-mg formulation); do not reconstitute with other diluents.1 Shake well to disperse particles and obtain a uniform, milky suspension.1
If using the single-dose delivery system, add contents of the prefilled syringe (2 mL of sterile water for injection) to a vial containing the powder according to the manufacturer’s instructions.1 Mix well.1
Withdraw entire contents of vial and use immediately.1
Dosage
Available as triptorelin pamoate; dosage is expressed in terms of triptorelin.1
Adults
Prostate Cancer
IM
3.75 mg every 4 weeks (28 days) as the 3.75-mg formulation, 11.25 mg every 12 weeks as the 11.25-mg formulation, or 22.5 mg every 24 weeks as the 22.5-mg formulation.1 Dosage strengths are not additive; select dosage and formulation based on desired dosing schedule.1
Special Populations
Hepatic Impairment
No special population recommendation at this time.1
Renal Impairment
No special population recommendation at this time.1
Cautions for Triptorelin
Contraindications
-
Known hypersensitivity to triptorelin or any other ingredient in the formulation, other GnRH agonists, or GnRH.1
-
Known or suspected pregnancy.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Warnings/Precautions
Warnings
Fetal/Neonatal Morbidity and Mortality
Expected hormonal changes increase the risk for pregnancy loss and fetal harm when administered to a pregnant woman.1 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.1
Initial Worsening of Hormone-dependent Disease
Possible worsening of signs and/or symptoms of prostate cancer and/or development of new manifestations (e.g., bone pain, neuropathy, hematuria, urethral or bladder outlet obstruction) due to transient increase in serum testosterone concentrations during initial weeks of therapy.1 2 3 5
Possible spinal cord compression contributing to weakness or paralysis; possibly fatal.1 2 5
If spinal cord compression or renal impairment develops, institute standard treatment of these complications; consider immediate orchiectomy in extreme cases.1
Increased risk of neurologic and/or GU complications during initial therapy in patients with prostate cancer and metastatic vertebral lesions and/or urinary tract obstruction.1 Observe such patients closely during initial weeks of therapy.1 5
Hyperglycemia
Possible hyperglycemia and increased risk of diabetes in patients receiving GnRH agonists for treatment of prostate cancer.1 10 Studies evaluating risk of diabetes in women and children receiving GnRH agonists not performed to date.9
Evaluate patients for risk factors for diabetes and carefully weigh benefits and risks of GnRH agonist therapy before selecting treatment for prostate cancer.10
Periodically monitor blood glucose and/or HbA1c in patients receiving GnRH agonists for treatment of prostate cancer.1 10 Manage hyperglycemia or diabetes according to current standards of care.1 10
Cardiovascular Effects
Thromboembolic events (e.g., PE, cerebrovascular accidents, MI, DVT, TIA, thrombophlebitis) reported.1 Possible increased risk of cardiovascular disease (e.g., MI, sudden cardiac death, stroke) in patients receiving GnRH agonists for treatment of prostate cancer.1 10 Studies evaluating risk of cardiovascular disease in women and children receiving GnRH agonists not performed to date.9
Evaluate patients for cardiovascular risk factors and carefully weigh benefits and risks of GnRH agonist therapy before selecting treatment for prostate cancer.1 10
Monitor patients receiving GnRH agonists for manifestations of cardiovascular disease; manage cardiovascular disease according to current standards of care.1 10
Sensitivity Reactions
Hypersensitivity Reactions
Anaphylactic shock, hypersensitivity, and angioedema reported.1 If such reactions occur, discontinue the drug immediately and provide supportive and symptomatic care.1
Major Toxicities
Pituitary Apoplexy
Pituitary apoplexy, a clinical syndrome resulting from infarction of the pituitary gland, reported rarely.1 7 Most cases occur within 2 weeks of the first dose, sometimes within the first hour.1 7 If manifestations (e.g., sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, sometimes cardiovascular collapse) occur, immediate medical attention required.1 7 In most cases, pituitary adenoma diagnosed.1
General Precautions
Laboratory Monitoring
Periodically determine serum testosterone concentrations to monitor therapeutic response.1
Specific Populations
Pregnancy
Category X.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Lactation
Not known whether distributed into milk; not indicated for use in women.1 Discontinue nursing or the drug.1
Pediatric Use
Safety and efficacy not established in children.1
Geriatric Use
Studies conducted principally in patients ≥65 years of age, since prostate cancer occurs mainly in an older patient population.1
Common Adverse Effects
Hot flushes (flashes), skeletal pain, neuropathy, hematuria, urethral or bladder outlet obstruction, impotence, headache, pain at injection site, leg pain and edema, dysuria, hypertension.1
Also observed with 11.25-mg formulation: Decreased hemoglobin concentrations and erythrocyte counts, increased BUN, increased serum concentrations of glucose, AST, ALT, and alkaline phosphatase.1
Also observed with the 22.5-mg formulation: Decreased hemoglobin concentrations, increased serum glucose and hepatic aminotransferase (transaminase) concentrations.1
Interactions for Triptorelin
Metabolism unlikely to involve CYP enzymes; effect of triptorelin on other drug-metabolizing enzymes unknown.1
Drugs That Induce Hyperprolactinemia
Potential pharmacologic interaction (possible decrease in triptorelin efficacy due to decreased number of GnRH receptors) with drugs such as antipsychotic agents, methyldopa, metoclopramide, and reserpine.1 6 Concomitant use not recommended.1
Triptorelin Pharmacokinetics
Absorption
Bioavailability
Following IM administration, peak plasma concentrations usually are attained within 1–3 hours.1
Distribution
Extent
Not known whether triptorelin is distributed into milk.1
Plasma Protein Binding
No evidence that triptorelin binds to plasma proteins.1
Elimination
Metabolism
Metabolism is unknown; involvement of CYP enzymes is unlikely.1 No metabolites identified to date.1
Elimination Route
Hepatic and renal elimination.1
Half-life
Approximately 3 hours.1
Special Populations
In males with hepatic impairment or moderate or severe renal impairment, AUC increased 2- to 4-fold compared with healthy males.1
Stability
Storage
Parenteral
Powder for Injection
Actions
-
Potent inhibitor of gonadotropin secretion when given continuously in therapeutic doses; greater activity than naturally occurring GnRH.1
-
Transient surge in circulating levels of LH, FSH, testosterone, and estradiol observed after initial administration.1 Sustained decreases in LH and FSH secretion and reduced testicular and ovarian steroidogenesis observed following chronic, continuous administration (generally 2–4 weeks after initiation of therapy).1 4
-
Reduction of serum testosterone in males comparable to effects achieved after surgical castration; results in inactivation of physiologic functions and tissues dependent on testosterone.1 2 4 These effects usually are reversible after cessation of therapy.1
Advice to Patients
-
Importance of informing patients that serum testosterone concentrations may increase after the initial dose.1 Risk of worsening symptoms (e.g., bone pain, spinal cord injury, hematuria, urethral or bladder outlet obstruction) of prostate cancer during initial weeks of therapy.1 Increased serum testosterone concentrations and associated symptoms should decline 3–4 weeks later.1 Importance of promptly reporting weakness or paresthesia of the lower limbs and/or worsening of urinary symptoms to clinicians.6
-
Risk of anaphylactoid and other sensitivity reactions.1
-
Importance of promptly reporting sudden onset of headache, vomiting, or visual changes to clinicians.1
-
Risk of diabetes or loss of glycemic control in patients with preexisting diabetes.1 10 Importance of undergoing recommended monitoring of blood glucose or HbA1c concentrations.1 10
-
Possibility of increased risk of MI, sudden cardiac death, and stroke in men receiving GnRH agonists for the treatment of prostate cancer.1 10 Importance of being monitored for manifestations of cardiovascular disease.1 10
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1
-
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 7 If used during pregnancy, apprise of potential fetal hazard.1
-
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Parenteral |
For injection, for IM use only |
3.75 mg (of triptorelin) |
Trelstar |
Watson |
Trelstar (with Mixject) |
Watson |
|||
11.25 mg (of triptorelin) |
Trelstar |
Watson |
||
Trelstar (with Mixject) |
Watson |
|||
22.5 mg (of triptorelin) |
Trelstar |
Watson |
||
Trelstar (with Mixject) |
Watson |
AHFS DI Essentials™. © Copyright 2021, Selected Revisions October 16, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
References
1. Watson Pharma, Inc. Trelstar (triptorelin pamoate for injectable suspension) prescribing information. Parsippany, NJ; 2011 Apr. Available from website. Accessed 2011 May 26. http://pi.watson.com/data_stream.asp?product_group=1684&p=pi&language=E
2. Parmar H, Phillips RH, Lightman SL et al. Randomized controlled study of orchidectomy vs long-acting D-Trp-6-LHRH microcapsules in advanced prostatic carcinoma. Lancet. 1985; 2:1201-5. http://www.ncbi.nlm.nih.gov/pubmed/2866289?dopt=AbstractPlus
3. Mahler C. Is disease flare a problem? Cancer. 1993; 72:3799-802.
4. Rolandi E, Martorana G, Franceschini R et al. Treatment of prostatic cancer with a depot preparation of an LHRH analogue: endocrine effects. Curr Ther Res. 1985; 38:670-5.
5. Kahan A, Delrieu F, Amor B et al. Disease flare induced by D-Trp6-LHRH analogue in patients with metastatic prostatic cancer. Lancet. 1984; 1:971-2. http://www.ncbi.nlm.nih.gov/pubmed/6143912?dopt=AbstractPlus
6. Pharmacia & Upjohn, Kalomazoo, MI: Personal communication.
7. Watson Pharma. Trelstar LA 11.25 mg (triptorelin pamoate for injectable suspension) prescribing information. Corona, CA: 2006 Aug.
8. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52.
9. Food and Drug Administration. GnRH agonists: safety review of drug class used to treat prostate cancer (sold under the brand names Lupron, Zoladex, Trelstar, Viadur, Vantas, Eligard, Synarel, and generics). Rockville, MD; 2010 May 3. From FDA web site. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm210576.htm
10. Food and Drug Administration. GnRH agonists: label change--increased risk of diabetes and cardiovascular disease (update). Rockville, MD; 2010 Oct 20. From FDA web site. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm230359.htm
More about triptorelin
- Side Effects
- During Pregnancy
- Dosage Information
- Patient Tips
- Drug Interactions
- En Español
- 6 Reviews
- Drug class: gonadotropin releasing hormones
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Other brands: Trelstar, Triptodur, Trelstar Depot, Trelstar LA