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.

• Overview
• Side Effects
• Dosage
• Professional
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• Interactions
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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 HbA_1c 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

20–25°C.¹ Do not freeze.¹

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 HbA_1c 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.

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