Data from FDA - Curated by EPG Health - Last updated 17 March 2018

Indication(s)

1 INDICATIONS AND USAGE TRELSTAR is indicated for the palliative treatment of advanced prostate cancer [see Clinical Studies (14) ]. TRELSTAR is a gonadotropin releasing hormone (GnRH) agonist indicated for the palliative treatment of advanced prostate cancer. (1)

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

Acute and Advanced Heart Failure

Acute and Advanced Heart Failure

What are the most effective treatments for acute heart failure? Can you define advanced heart failure? Discover here...

+ 3 more

Allergic Rhinitis

Allergic Rhinitis

Allergic rhinitis causes great strain on the workforce. Help to reduce sick days and improve productivity with appropriate treatment options.

+ 4 more

Anticoagulation Therapy for Stroke Prevention

Anticoagulation Therapy for Stroke Prevention

Anticoagulation therapy for Stroke Prevention Learning Zone offers a deep-dive into atrial fibrillation causes, consequences, diagnosis and management to help you deliver optimal care and prevent strokes in patients living with this common arrhythmia.

Load more

Related Content

Advisory information

contraindications
4 CONTRAINDICATIONS Known hypersensitivity to triptorelin or any other component of the product, or other GnRH agonists or GnRH. (4) Pregnancy. (4.2 and 8.1) 4.1 Hypersensitivity TRELSTAR is contraindicated in individuals with a known hypersensitivity to triptorelin or any other component of the product, or other GnRH agonists or GnRH [see Warnings and Precautions (5.1 ) ]. 4.2 Pregnancy TRELSTAR may cause fetal harm when administered to a pregnant woman. Expected hormonal changes that occur with TRELSTAR treatment increase the risk for pregnancy loss and fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ]. TRELSTAR is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Adverse reactions
6 ADVERSE REACTIONS 3.75 mg: The most common adverse reactions (≥ 5%) during TRELSTAR 3.75 mg therapy included hot flushes, skeletal pain, impotence, and headache. (6.1) 11.25 mg: The most common adverse reactions (≥ 5%) during TRELSTAR 11.25 mg therapy included hot flushes, skeletal pain, headache, edema in legs, and leg pain. (6.1) 22.5 mg: The most common adverse reactions (≥ 5%) during TRELSTAR 22.5 mg therapy included hot flushes, erectile dysfunction, and testicular atrophy. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of the three TRELSTAR formulations was evaluated in clinical trials involving patients with advanced prostate cancer. Mean testosterone levels increased above baseline during the first week following the initial injection, declining thereafter to baseline levels or below by the end of the second week of treatment. The transient increase in testosterone levels may be associated with temporary worsening of disease signs and symptoms, including bone pain, neuropathy, hematuria, and urethral or bladder outlet obstruction. Isolated cases of spinal cord compression with weakness or paralysis of the lower extremities have occurred [see Warnings and Precautions (5.3) ]. Adverse reactions reported for each of the three TRELSTAR formulations in the clinical trials, are presented in Table 2, Table 3, and Table 4. Often, causality is difficult to assess in patients with metastatic prostate cancer. The majority of adverse reactions related to triptorelin are a result of its pharmacological action, i.e., the induced variation in serum testosterone levels, either an increase in testosterone at the initiation of treatment, or a decrease in testosterone once castration is achieved. Local reactions at the injection site or allergic reactions may occur. The following adverse reactions were reported to have a possible or probable relationship to therapy as ascribed by the treating physician in at least 1% of patients receiving TRELSTAR 3.75 mg. Table 2. TRELSTAR 3.75 mg: Treatment-Related Adverse Reactions Reported by 1% or More of Patients During Treatment Adverse Reactions* TRELSTAR 3.75 mg N = 140 N % Application Site Disorders Injection site pain 5 3.6 Body as a Whole Hot flush 82 58.6 Pain 3 2.1 Leg pain 3 2.1 Fatigue 3 2.1 Cardiovascular Disorders Hypertension 5 3.6 Central and Peripheral Nervous System Disorders Headache 7 5.0 Dizziness 2 1.4 Gastrointestinal Disorders Diarrhea 2 1.4 Vomiting 3 2.1 Musculoskeletal System Disorders Skeletal pain 17 12.1 Psychiatric Disorders Insomnia 3 2.1 Impotence 10 7.1 Emotional lability 2 1.4 Red Blood Cell Disorders Anemia 2 1.4 Skin and Appendages Disorders Pruritus 2 1.4 Urinary System Disorders Urinary tract infection 2 1.4 Urinary retention 2 1.4 * Adverse reactions for TRELSTAR 3.75 mg are coded using the WHO Adverse Reactions Terminology (WHOART) The following adverse reactions were reported to have a possible or probable relationship to therapy as ascribed by the treating physician in at least 1% of patients receiving TRELSTAR 11.25 mg. Table 3. TRELSTAR 11.25 mg: Treatment-Related Adverse Reactions Reported by 1% or More of Patients During Treatment Adverse Reactions * TRELSTAR 11.25 mg N = 174 N % Application Site Injection site pain 7 4.0 Body as a Whole Hot flush 127 73.0 Leg pain 9 5.2 Pain 6 3.4 Back pain 5 2.9 Fatigue 4 2.3 Chest pain 3 1.7 Asthenia 2 1.1 Peripheral edema 2 1.1 Cardiovascular Disorders Hypertension 7 4.0 Dependent edema 4 2.3 Central and Peripheral Nervous System Disorders Headache 12 6.9 Dizziness 5 2.9 Leg cramps 3 1.7 Endocrine Breast pain 4 2.3 Gynecomastia 3 1.7 Gastrointestinal Disorders Nausea 5 2.9 Constipation 3 1.7 Dyspepsia 3 1.7 Diarrhea 2 1.1 Abdominal pain 2 1.1 Liver and Biliary System Abnormal hepatic function 2 1.1 Metabolic and Nutritional Disorders Edema in legs 11 6.3 Increased alkaline phosphatase 3 1.7 Musculoskeletal System Disorders Skeletal pain 23 13.2 Arthralgia 4 2.3 Myalgia 2 1.1 Psychiatric Disorders Decreased libido 4 2.3 Impotence 4 2.3 Insomnia 3 1.7 Anorexia 3 1.7 Respiratory System Disorders Coughing 3 1.7 Dyspnea 2 1.1 Pharyngitis 2 1.1 Skin and Appendages Rash 3 1.7 Urinary System Disorders Dysuria 8 4.6 Urinary retention 2 1.1 Vision Disorders Eye pain 2 1.1 Conjunctivitis 2 1.1 * Adverse reactions for TRELSTAR 11.25 mg are coded using the WHO Adverse Reactions Terminology (WHOART) The following adverse reactions occurred in at least 5% of patients receiving TRELSTAR 22.5 mg. The table includes all reactions whether or not they were ascribed to TRELSTAR by the treating physician. The table also includes the incidence of these adverse reactions that were considered by the treating physician to have a reasonable causal relationship or for which the relationship could not be assessed. Table 4. TRELSTAR 22.5 mg: Adverse Reactions Reported by 5% or More of Patients During Treatment Adverse Reactions * TRELSTAR 22.5 mg N = 120 Treatment-Emergent Treatment-Related N % N % General Disorders and Administration Site Conditions Edema peripheral 6 5.0 0 0 Infections and Infestations Influenza 19 15.8 0 0 Bronchitis 6 5.0 0 0 Endocrine Diabetes Mellitus/Hyperglycemia 6 5.0 0 0 Musculoskeletal and Connective Tissue Disorders Back pain 13 10.8 1 0.8 Arthralgia 9 7.5 1 0.8 Pain in extremity 9 7.5 1 0.8 Nervous System Disorders Headache 9 7.5 2 1.7 Psychiatric Disorders Insomnia 6 5.0 1 0.8 Renal and Urinary Disorders Urinary tract infection 14 11.6 0 0 Urinary retention 6 5.0 0 0 Reproductive System and Breast Disorders Erectile dysfunction 12 10.0 12 10.0 Testicular atrophy 9 7.5 9 7.5 Vascular Disorders Hot flush 87 72.5 86 71.7 Hypertension 17 14.2 1 0.8 * Adverse reactions for TRELSTAR 22.5 mg are coded using the Medical Dictionary for Regulatory Activities (MedDRA) Changes in Laboratory Values During Treatment The following abnormalities in laboratory values not present at baseline were observed in 10% or more of patients: TRELSTAR 3.75 mg: There were no clinically meaningful changes in laboratory values detected during therapy. TRELSTAR 11.25 mg: Decreased hemoglobin and RBC count and increased glucose, BUN, SGOT, SGPT, and alkaline phosphatase at the Day 253 visit. TRELSTAR 22.5 mg: Decreased hemoglobin and increased glucose and hepatic transaminases were detected during the study. The majority of the changes were mild to moderate. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of gonadotropin releasing hormone agonists. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. During postmarketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required. During postmarketing experience, convulsions, and thromboembolic events including, but not limited to, pulmonary emboli, cerebrovascular accident, myocardial infarction, deep venous thrombosis, transient ischemic attack, and thrombophlebitis have been reported.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION TRELSTAR is administered as a single intramuscular injection in either buttock. Due to different release characteristics, the dosage strengths are not additive and must be selected based upon the desired dosing schedule. (2.1) 3.75 mg every 4 weeks. (2.1) 11.25 mg every 12 weeks. (2.1) 22.5 mg every 24 weeks. (2.1) MIXJECT Preparation Peel the cover away from the blister pack containing the vial adapter. Do not remove the vial adapter from the blister pack. Place the blister pack containing the vial adapter firmly on the vial top, piercing the vial. Push down gently until you feel it snap in place. Remove the blister pack from the vial adapter. MIXJECT_instructionshelv_v15_Step2_NEW MIXJECT_instructionshelv_v15_Step3_NEW MIXJECT_instructionshelv_v15_Step4_NEW MIXJECT_instructionshelv_v15_Step5_NEW MIXJECT_instructionshelv_v15_Step6_NEW MIXJECT_instructionshelv_v15_Step7_NEW 2.1 Dosing Information TRELSTAR must be administered under the supervision of a physician. TRELSTAR is administered by a single intramuscular injection in either buttock. Dosing schedule depends on the product strength selected (Table 1). The lyophilized microgranules are to be reconstituted in sterile water. No other diluent should be used. Table 1. TRELSTAR Recommended Dosing Dosage 3.75 mg 11.25 mg 22.5 mg Recommended dose 1 injection every 4 weeks 1 injection every 12 weeks 1 injection every 24 weeks Due to different release characteristics, the dosage strengths are not additive and must be selected based upon the desired dosing schedule. The suspension should be administered immediately after reconstitution. As with other drugs administered by intramuscular injection, the injection site should be alternated periodically. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. 2.2 Reconstitution Instructions for TRELSTAR Please read the instructions completely before you begin. Wash your hands with soap and hot water and put on gloves immediately prior to preparing the injection. Place the vial in a standing upright position on a clean, flat surface that is covered with a sterile pad or cloth. Remove the Flip-Off® button from the top of the vial, revealing the rubber stopper. Disinfect the rubber stopper with an alcohol wipe. Discard the alcohol wipe and allow the stopper to dry. Using a syringe fitted with a sterile 21-gauge needle, withdraw 2 mL sterile water for injection, and inject into the vial. Shake well to thoroughly disperse particles to obtain a uniform suspension. The suspension will appear milky. Slowly withdraw the entire contents of the reconstituted suspension into the syringe. The suspension should be administered immediately after reconstitution. Inject the patient in either buttock with the contents of the syringe. 2.3 Reconstitution Instructions for TRELSTAR with MIXJECT SYSTEM Please read the instructions completely before you begin. MIXJECT Preparation Wash your hands with soap and hot water and put on gloves immediately prior to preparing the injection. Place the sealed tray on a clean, flat surface that is covered with a sterile pad or cloth. Peel the cover away from the tray and remove the MIXJECT components and the TRELSTAR vial. Remove the Flip-Off button from the top of the vial, revealing the rubber stopper. Place the vial in a standing upright position on the prepared surface. Disinfect the rubber stopper with the alcohol wipe. Discard the alcohol wipe and allow the stopper to dry. Proceed to MIXJECT Activation. MIXJECT Activation Peel the cover away from the blister pack containing the vial adapter. Do not remove the vial adapter from the blister pack. Place the blister pack containing the vial adapter firmly on the vial top, piercing the vial. Push down gently until you feel it snap in place. Remove the blister pack from the vial adapter. (a) Screw the plunger rod into the barrel end of the syringe. Remove the cap from the syringe barrel. (b) Connect the syringe to the vial adapter by screwing it clockwise into the opening on the side of the vial adapter. Be sure to gently twist the syringe until it stops turning to ensure a tight connection. While holding the vial, place your thumb on the plunger rod and push the plunger rod in all the way to transfer the diluent from the pre-filled syringe into the vial. Do not release the plunger rod. Keeping the plunger rod depressed, gently swirl the vial so that the diluent rinses the sides of the vial. This will ensure complete mixing of TRELSTAR and the sterile water diluent. The suspension will now have a milky appearance. In order to avoid separation of the suspension, proceed to the next steps without delay. (a) Invert the MIXJECT system so that the vial is at the top. Grasp the MIXJECT system firmly by the syringe and pull back the plunger rod slowly to draw the reconstituted TRELSTAR into the syringe. (b) Return the vial to its upright position, and disconnect the vial adapter and vial from the MIXJECT syringe assembly by turning the plastic cap of the vial adapter clockwise. Grasp only the plastic cap when removing. Lift up the safety cover and remove the clear plastic needle shield by pulling it from the assembly. The safety cover should be perpendicular to the needle, with the needle facing away from you. The syringe containing the TRELSTAR suspension is now ready for administration. The suspension should be administered immediately after reconstitution. After administering the injection, immediately activate the safety mechanism by centering your thumb or forefinger on the textured finger pad area of the safety cover and pushing it forward over the needle until you hear or feel it lock. Use the one-handed technique and activate the mechanism away from yourself and others. Activation of the safety cover causes virtually no splatter. Immediately discard the syringe assembly after a single use into a suitable sharps container.
Use in special populations
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category X [see 'Contraindications' section ]. TRELSTAR is contraindicated in women who are or may become pregnant while receiving the drug. Expected hormonal changes that occur with TRELSTAR treatment increase the risk for pregnancy loss. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Studies in pregnant rats administered triptorelin at doses of 2, 10, and 100 mcg/kg/day (approximately equivalent to 0.2, 0.8, and 8 times the estimated human daily dose based on body surface area) during the period of organogenesis demonstrated maternal toxicity and embryo-fetal toxicities. Embryo-fetal toxicities consisted of pre-implantation loss, increased resorption, and reduced mean number of viable fetuses at the high dose. Teratogenic effects were not observed in viable fetuses in rats or mice. Doses administered to mice were 2, 20, and 200 mcg/kg/day (approximately equivalent to 0.1, 0.7, and 7 times the estimated human daily dose based on body surface area). 8.3 Nursing Mothers TRELSTAR is not indicated for use in women [see Indications and Usage (1) ]. It is not known if triptorelin is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from TRELSTAR, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Prostate cancer occurs primarily in an older population. Clinical studies with TRELSTAR have been conducted primarily in patients ≥ 65 years [see Clinical Pharmacology (12.3) and Clinical Studies (14) ]. 8.6 Renal Impairment Subjects with renal impairment had higher exposure than young healthy males [see Clinical Pharmacology (12.3) ]. 8.7 Hepatic Impairment Subjects with hepatic impairment had higher exposure than young healthy males [see Clinical Pharmacology (12.3) ].
Pregnancy and lactation
8.3 Nursing Mothers TRELSTAR is not indicated for use in women [see Indications and Usage (1) ]. It is not known if triptorelin is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from TRELSTAR, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother.

Interactions

7 DRUG INTERACTIONS No drug-drug interaction studies involving triptorelin have been conducted. Human pharmacokinetic data with triptorelin suggest that C-terminal fragments produced by tissue degradation are either degraded completely within tissues or are rapidly degraded further in plasma, or cleared by the kidneys. Therefore, hepatic microsomal enzymes are unlikely to be involved in triptorelin metabolism. However, in the absence of relevant data and as a precaution, hyperprolactinemic drugs should not be used concomitantly with triptorelin since hyperprolactinemia reduces the number of pituitary GnRH receptors. None. (7)

More information

Category Value
Authorisation number NDA020715
Orphan designation No
Product NDC 0023-5902,0023-5904,0023-5906
Date Last Revised 09-01-2018
Type HUMAN PRESCRIPTION DRUG
RXCUI 199821
Marketing authorisation holder Allergan, Inc.