Label: TRELSTAR- triptorelin pamoate kit

  • NDC Code(s): 0023-5902-04, 0023-5904-12, 0023-5906-23
  • Packager: Allergan, Inc.
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: New Drug Application

Drug Label Information

Updated December 15, 2018

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  • HIGHLIGHTS OF PRESCRIBING INFORMATION
    These highlights do not include all the information needed to use TRELSTAR safely and effectively. See full prescribing information for TRELSTAR.
         
    TRELSTAR® (triptorelin pamoate for injectable suspension), for intramuscular use
    Initial U.S. Approval: 2000

    RECENT MAJOR CHANGES

    Warnings and Precautions, Embryo-Fetal Toxicity (5.9)                12/2018

    INDICATIONS AND USAGE

    TRELSTAR is a gonadotropin releasing hormone (GnRH) agonist indicated for the palliative treatment of advanced prostate cancer.  (1)

    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)

    DOSAGE FORMS AND STRENGTHS

    Injectable suspension: 3.75 mg, 11.25 mg, 22.5 mg.  (3)

    CONTRAINDICATIONS

    • Known hypersensitivity to triptorelin or any other component of the product, or other GnRH agonists or GnRH.  (4)

    WARNINGS AND PRECAUTIONS

    • Hypersensitivity: Anaphylactic shock, hypersensitivity, and angioedema have been reported.  In the event of a reaction, discontinue TRELSTAR and initiate appropriate medical management.  (5.1)
    • Tumor Flare: Transient increase in serum testosterone levels can occur within the first few weeks of treatment.  This may worsen prostate cancer and result in spinal cord compression and urinary tract obstruction. Monitor patients at risk and manage as appropriate.  (5.2 and 5.3)
    • Effect on QT/QTc Interval: Androgen deprivation therapy may prolong the QT interval.  Consider risks and benefits. (5.4)
    • Hyperglycemia and Diabetes: Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH analogs. Monitor blood glucose level and manage according to current clinical practice. (5.5)
    • Cardiovascular Diseases: Increased risk of myocardial infarction, sudden cardiac death and stroke has been reported in men. Monitor for cardiovascular disease and manage according to current clinical practice. (5.6)

    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.

    DRUG INTERACTIONS

    None. (7)

          

    USE IN SPECIFIC POPULATIONS

    Pregnancy: TRELSTAR can cause fetal harm. (5.9, 8.1)

    Females and males of reproductive potential: TRELSTAR may impair fertility. (8.3)

    See 17 for PATIENT COUNSELING INFORMATION.

    Revised: 12/2018

  • Table of Contents

    FULL PRESCRIBING INFORMATION: CONTENTS*

    1       INDICATIONS AND USAGE

    2       DOSAGE AND ADMINISTRATION

    2.1       Dosing Information

    2.2        Reconstitution Instructions for TRELSTAR with MIXJECT SYSTEM

    3       DOSAGE FORMS AND STRENGTHS

    4       CONTRAINDICATIONS

    4.1       Hypersensitivity

    5       WARNINGS AND PRECAUTIONS

    5.1       Hypersensitivity Reactions

    5.2       Transient Increase in Serum Testosterone

    5.3       Metastatic Vertebral Lesions and Urinary Tract Obstruction

    5.4       Effect on QT/QTc Interval

    5.5       Hyperglycemia and Diabetes

    5.6       Cardiovascular Diseases

    5.7       Laboratory Tests

    5.8       Laboratory Test Interactions

    5.9       Embryo-Fetal Toxicity

    6       ADVERSE REACTIONS

    6.1       Clinical Trials Experience

    6.2       Postmarketing Experience

    7       DRUG INTERACTIONS

    8       USE IN SPECIFIC POPULATIONS

    8.1       Pregnancy

    8.2       Lactation

    8.3       Females and Males of Reproductive Potential

    8.4       Pediatric Use

    8.5       Geriatric Use

    8.6       Renal Impairment

    8.7       Hepatic Impairment

    10       OVERDOSAGE

    11       DESCRIPTION

    12       CLINICAL PHARMACOLOGY

    12.1       Mechanism of Action

    12.2       Pharmacodynamics

    12.3       Pharmacokinetics

    13       NONCLINICAL TOXICOLOGY

    13.1       Carcinogenesis, Mutagenesis, Impairment of Fertility

    14       CLINICAL STUDIES

    16       HOW SUPPLIED/STORAGE AND HANDLING

    17       PATIENT COUNSELING INFORMATION

    *
    Sections or subsections omitted from the full prescribing information are not listed.
  • 1       INDICATIONS AND USAGE

    TRELSTAR is indicated for the palliative treatment of advanced prostate cancer [see Clinical Studies (14)].

  • 2       DOSAGE AND ADMINISTRATION

    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 waterNo 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 with MIXJECT SYSTEM

    Please read the instructions completely before you begin.

    MIXJECT Preparation

    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.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(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.
    MIXJECT_instructionshelv_v15_Step3_NEWWhile 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.
    MIXJECT_instructionshelv_v15_Step4_NEWKeeping 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.
    MIXJECT_instructionshelv_v15_Step5_NEW(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.
    MIXJECT_instructionshelv_v15_Step6_NEWLift 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.
    MIXJECT_instructionshelv_v15_Step7_NEWAfter 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.
  • 3       DOSAGE FORMS AND STRENGTHS

    Injectable suspension: 3.75 mg, 11.25 mg, 22.5 mg.

  • 4       CONTRAINDICATIONS

    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)].

  • 5       WARNINGS AND PRECAUTIONS

    5.1       Hypersensitivity Reactions

    Anaphylactic shock, hypersensitivity, and angioedema related to triptorelin administration have been reported.  In the event of a hypersensitivity reaction, therapy with TRELSTAR should be discontinued immediately and the appropriate supportive and symptomatic care should be administered. 

    5.2       Transient Increase in Serum Testosterone

    Initially, triptorelin, like other GnRH agonists, causes a transient increase in serum testosterone levels.  As a result, isolated cases of worsening of signs and symptoms of prostate cancer during the first weeks of treatment have been reported with GnRH agonists.  Patients may experience worsening of symptoms or onset of new symptoms, including bone pain, neuropathy, hematuria, or urethral or bladder outlet obstruction [see Clinical Pharmacology  (12.2)].

    5.3       Metastatic Vertebral Lesions and Urinary Tract Obstruction

    Cases of spinal cord compression, which may contribute to weakness or paralysis with or without fatal complications, have been reported with GnRH agonists.  If spinal cord compression or renal impairment develops, standard treatment of these complications should be instituted, and in extreme cases an immediate orchiectomy considered.

    Patients with metastatic vertebral lesions and/or with upper or lower urinary tract obstruction should be closely observed during the first few weeks of therapy.

    5.4       Effect on QT/QTc Interval

    Androgen deprivation therapy may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes. 

    5.5       Hyperglycemia and Diabetes

    Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia or diabetes.

    5.6       Cardiovascular Diseases

    Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice.

    5.7       Laboratory Tests

    Response to TRELSTAR should be monitored by measuring serum levels of testosterone periodically or as indicated. 

    5.8       Laboratory Test Interactions

    Chronic or continuous administration of triptorelin in therapeutic doses results in suppression of pituitary-gonadal axis.  Diagnostic tests of the pituitary-gonadal function conducted during treatment and after cessation of therapy may therefore be misleading.

    5.9       Embryo-Fetal Toxicity

    Based on findings from animal studies and mechanism of action, TRELSTAR can cause fetal harm when administered to a pregnant woman [Clinical Pharmacology (12.1)]. In animal developmental and reproductive toxicology studies, daily administration of triptorelin to pregnant rats during the period of organogenesis caused maternal toxicity and embryo-fetal toxicities, including loss of pregnancy, at doses as low as 0.2, 0.8, and 8 times the estimated human daily dose based on body surface area. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus [see Use in Specific Populations (8.1)].

  • 6       ADVERSE REACTIONS

    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, interstitial lung disease, 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.

  • 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.

  • 8       USE IN SPECIFIC POPULATIONS

    8.1       Pregnancy

    Risk Summary

    Based on findings in animal studies and mechanism of action, TRELSTAR can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. Expected hormonal changes that occur with TRELSTAR treatment increase the risk for pregnancy loss. In animal developmental and reproductive toxicology studies, daily administration of triptorelin to pregnant rats during the period of organogenesis caused maternal toxicity and embryo-fetal toxicities, including loss of pregnancy, at doses as low as 0.2, 0.8, and 8 times the estimated human daily dose based on body surface area. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus.

    Data

    Animal Data

    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).    

    8.2       Lactation

    The safety and efficacy of TRELSTAR have not been established in females.  There are no data on the presence of triptorelin in human milk, the effects of the drug on milk production, or the effects of the drug on the breastfed child.  Because of the potential for serious adverse reactions in a breastfed child from TRELSTAR, a decision should be made to either discontinue breastfeeding, or discontinue the drug taking into account the importance of the drug to the mother.

    8.3       Females and Males of Reproductive Potential

    Infertility

    Males

    Based on mechanism of action, TRELSTAR may impair fertility in males of reproductive potential [see Clinical Pharmacology (12.1)].

    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)].

  • 10       OVERDOSAGE

    There is no experience of overdosage in clinical trials.  In single dose toxicity studies in mice and rats, the subcutaneous LD50 of triptorelin was 400 mg/kg in mice and 250 mg/kg in rats, approximately 500 and 600 times, respectively, the estimated monthly human dose based on body surface area.  If overdosage occurs, therapy should be discontinued immediately and the appropriate supportive and symptomatic treatment administered.

  • 11       DESCRIPTION

    TRELSTAR is a white to slightly yellow lyophilized cake.  When reconstituted, TRELSTAR has a milky appearance.  It contains a pamoate salt of triptorelin, a synthetic decapeptide agonist analog of gonadotropin releasing hormone (GnRH). The chemical name of triptorelin pamoate is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-tryptophyl-L-leucyl-L-arginyl-L-prolylglycine amide (pamoate salt).  The empirical formula is C64H82N18O13 · C23H16O6 and the molecular weight is 1699.9. The structural formula is:

    The structural formula for TRELSTAR is a white to slightly yellow lyophilized cake.  When reconstituted, TRELSTAR has a milky appearance.  It contains a pamoate salt of triptorelin, a synthetic decapeptide agonist analog of gonadotropin releasing hormone (GnRH). The chemical name of triptorelin pamoate is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-tryptophyl-L-leucyl-L-arginyl-L-prolylglycine amide (pamoate salt).  The empirical formula is C64H82N18O13 • C23H16O6 and the molecular weight is 1699.9.

    Structural formula for TRELSTAR (triptorelin pamoate).

    The TRELSTAR products are sterile, lyophilized biodegradable microgranule formulations supplied as single dose vials.  Refer to Table 5 for the composition of each TRELSTAR product.

    Table 5. TRELSTAR Composition
     
    Ingredients
    TRELSTAR
    3.75 mg
    TRELSTAR
    11.25 mg
    TRELSTAR
    22.5 mg
     
    triptorelin pamoate
    (base units)
    3.75 mg11.25 mg22.5 mg
     
    poly-d,l-lactide-co-glycolide
    138 mg120 mg183 mg
     
    mannitol, USP
    71 mg74 mg74 mg
     
    carboxymethylcellulose sodium, USP
    25 mg26 mg26 mg
     
    polysorbate 80, NF
    1.7 mg1.7 mg1.7 mg

    When 2 mL sterile water is added to the vial containing TRELSTAR and mixed, a suspension is formed which is intended as an intramuscular injection.  TRELSTAR is available in a  vial plus a MIXJECT vial adapter, and a separate pre-filled syringe that contains sterile water for injection, USP, 2 mL, pH 6 to 8.5.

  • 12       CLINICAL PHARMACOLOGY

    12.1       Mechanism of Action

    Triptorelin is a synthetic decapeptide agonist analog of gonadotropin releasing hormone (GnRH).  Comparative in vitro studies showed that triptorelin was 100-fold more active than native GnRH in stimulating luteinizing hormone release from monolayers of dispersed rat pituitary cells in culture and 20-fold more active than native GnRH in displacing 125I-GnRH from pituitary receptor sites.  In animal studies, triptorelin pamoate was found to have 13‑fold higher luteinizing hormone-releasing activity and 21-fold higher follicle-stimulating hormone-releasing activity compared to the native GnRH.

    12.2       Pharmacodynamics

    Following the first administration, there is a transient surge in circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol [see Adverse Reactions (6)].  After chronic and continuous administration, usually 2 to 4 weeks after initiation of therapy, a sustained decrease in LH and FSH secretion and marked reduction of testicular steroidogenesis are observed.  A reduction of serum testosterone concentration to a level typically seen in surgically castrated men is obtained.  Consequently, the result is that tissues and functions that depend on these hormones for maintenance become quiescent.  These effects are usually reversible after cessation of therapy.

    Following a single intramuscular injection of TRELSTAR:

    TRELSTAR 3.75 mg: serum testosterone levels first increased, peaking on Day 4, and declined thereafter to low levels by Week 4 in healthy male volunteers.

    TRELSTAR 11.25 mg: serum testosterone levels first increased, peaking on Days 2 – 3, and declined thereafter to low levels by Weeks 3 – 4 in men with advanced prostate cancer.

    TRELSTAR 22.5 mg: serum testosterone levels first increased, peaking on Day 3, and declined thereafter to low levels by Weeks 3 – 4 in men with advanced prostate cancer.

    12.3       Pharmacokinetics

    Results of pharmacokinetic investigations conducted in healthy men indicate that after intravenous bolus administration, triptorelin is distributed and eliminated according to a 3-compartment model and corresponding half-lives are approximately 6 minutes, 45 minutes, and 3 hours. 

    Absorption

    Following a single intramuscular injection of TRELSTAR to patients with prostate cancer, mean peak serum concentrations of 28.4 ng/mL, 38.5 ng/mL, and 44.1 ng/mL occurred in 1 to 3 hours after the 3.75 mg, 11.25 mg, and 22.5 mg formulations, respectively. 

    Triptorelin did not accumulate over 9 months (3.75 mg and 11.25 mg) or 12 months (22.5 mg) of treatment.

    Distribution

    The volume of distribution following a single intravenous bolus dose of 0.5 mg of triptorelin peptide was 30 – 33 L in healthy male volunteers.  There is no evidence that triptorelin, at clinically relevant concentrations, binds to plasma proteins.

    Elimination

    Metabolism

    The metabolism of triptorelin in humans is unknown, but is unlikely to involve hepatic microsomal enzymes (cytochrome P-450). The effect of triptorelin on the activity of other drug metabolizing enzymes is also unknown.  Thus far, no metabolites of triptorelin have been identified.  Pharmacokinetic data suggest that C-terminal fragments produced by tissue degradation are either completely degraded in the tissues, or rapidly degraded in plasma, or cleared by the kidneys.

    Excretion

    Triptorelin is eliminated by both the liver and the kidneys.  Following intravenous administration of 0.5 mg triptorelin peptide to six healthy male volunteers with a creatinine clearance of 149.9 mL/min, 41.7% of the dose was excreted in urine as intact peptide with a total triptorelin clearance of 211.9 mL/min.  This percentage increased to 62.3% in patients with liver disease who have a lower creatinine clearance (89.9 mL/min).  It has also been observed that the nonrenal clearance of triptorelin (patient anuric, CIcreat = 0) was 76.2 mL/min, thus indicating that the nonrenal elimination of triptorelin is mainly dependent on the liver.

    Special Populations

    Age and Race

    The effects of age and race on triptorelin pharmacokinetics have not been systematically studied.  However, pharmacokinetic data obtained in young healthy male volunteers aged 20 to 22 years with an elevated creatinine clearance (approximately 150 mL/min) indicate that triptorelin was eliminated twice as fast in this young population as compared with patients with moderate renal insufficiency.  This is related to the fact that triptorelin clearance is partly correlated to total creatinine clearance, which is well known to decrease with age [see Use in Specific Populations (8.6) and (8.7)].

    Pediatric

    TRELSTAR has not been evaluated in patients less than 18 years of age [see Use in Specific Populations (8.4)].

    Hepatic and Renal Impairment

    After an intravenous bolus injection of 0.5 mg triptorelin, the two distribution half-lives were unaffected by renal and hepatic impairment.  However, renal insufficiency led to a decrease in total triptorelin clearance proportional to the decrease in creatinine clearance as well as increases in volume of distribution and consequently, an increase in elimination half-life (see Table 6).  In subjects with hepatic insufficiency, a decrease in triptorelin clearance was more pronounced than that observed with renal insufficiency.  Due to minimal increases in the volume of distribution, the elimination half-life in subjects with hepatic insufficiency was similar to subjects with renal insufficiency.  Subjects with renal or hepatic impairment had 2‑ to 4-fold higher exposure (AUC values) than young healthy males [see Use in Specific Populations (8.6) and (8.7)].

    Table 6.       Pharmacokinetic Parameters (Mean ± SD) in Healthy Volunteers and Special Populations Following an IV Bolus Injection of 0.5 mg Triptorelin
     
    Group
    Cmax
    (ng/mL)
    AUCinf
    (h·ng/mL)
    Clp
    (mL/min)
    Clrenal
    (mL/min)
    t1/2
    (h)
    Clcreat
    (mL/min)
     
    6 healthy male volunteers
    48.2
    ±11.8
    36.1
    ±5.8
    211.9
    ±31.6
    90.6
    ±35.3
    2.81
    ±1.21
    149.9
    ±7.3
     
    6 males with moderate renal impairment
    45.6
    ±20.5
    69.9
    ±24.6
    120.0
    ±45.0
    23.3
    ±17.6
    6.56
    ±1.25
    39.7
    ±22.5
     
    6 males with severe renal impairment
    46.5
    ±14.0
    88.0
    ±18.4
    88.6
    ±19.7
    4.3
    ±2.9
    7.65
    ±1.25
    8.9
    ±6.0
     
    6 males with liver disease
    54.1
    ±5.3
    131.9
    ±18.1
    57.8
    ±8.0
    35.9
    ±5.0
    7.58
    ±1.17
    89.9
    ±15.1
  • 13       NONCLINICAL TOXICOLOGY

    13.1       Carcinogenesis, Mutagenesis, Impairment of Fertility

    In rats, triptorelin doses of 120, 600, and 3000 mcg/kg given every 28 days (approximately 0.3, 2, and 8 times the human monthly dose based on body surface area) resulted in increased mortality with a drug treatment period of 13 – 19 months.  The incidences of benign and malignant pituitary tumors and histiosarcomas were increased in a dose-related manner.  No oncogenic effect was observed in mice administered triptorelin for 18 months at doses up to 6000 mcg/kg every 28 days (approximately 8 times the human monthly dose based on body surface area).

    Mutagenicity studies performed with triptorelin using bacterial and mammalian systems (in vitro Ames test and chromosomal aberration test in CHO cells and an in vivo mouse micronucleus test) provided no evidence of mutagenic potential.

    After 60 days of subcutaneous treatment followed by a minimum of four estrus cycles prior to mating, triptorelin, at doses of 2, 20, and 200 mcg/kg/day in saline (approximately 0.2, 2, and 16 times the estimated human daily dose based on body surface area) or 2 monthly injections as slow release microspheres (~20 mcg/kg/day), had no effect on the fertility or general reproductive function of female rats. 

    No studies were conducted to assess the effect of triptorelin on male fertility. 

  • 14       CLINICAL STUDIES

    TRELSTAR 3.75 mg

    TRELSTAR 3.75 mg was studied in a randomized, active control trial of 277 men with advanced prostate cancer.  The clinical trial population consisted of 59.9% Caucasian, 39.3% Black, and 0.8% Other.  There was no difference observed with triptorelin response between racial groups.  Men were between 47 and 89 years of age (mean = 71 years).  Patients received either TRELSTAR 3.75 mg (N = 140) or an approved GnRH agonist monthly for 9 months.  The primary efficacy endpoints were both achievement of castration by Day 29 and maintenance of castration from Day 57 through Day 253.

    Castration levels of serum testosterone (≤ 1.735 nmol/L; equivalent to 50 ng/dL) in patients treated with TRELSTAR 3.75 mg were achieved at Day 29 in 125 of 137 (91.2%) patients and at Day 57 in 97.7% of patients. Maintenance of castration levels of serum testosterone from Day 57 through Day 253 was found in 96.2% of patients treated with TRELSTAR 3.75 mg.

    The presence of an acute-on-chronic flare phenomenon was also studied as a secondary efficacy endpoint.  Serum LH levels were measured at 2 hours after repeat TRELSTAR 3.75 mg administration on Days 85 and 169.  One hundred twenty-four of the 126 evaluable patients (98.4%) on Day 85 had a serum LH level of ≤ 1.0 IU/L at 2 hours after dosing, indicating desensitization of the pituitary gonadotroph receptors.

    TRELSTAR 11.25 mg

    TRELSTAR 11.25 mg was studied in a randomized, active control trial of 346 men with advanced prostate cancer.  The clinical trial population consisted of 48% Caucasian, 38% Black, and 15% Other.  There was no difference observed with triptorelin response between racial groups.  Men were between 45 and 96 years of age (mean = 71 years).  Patients received either TRELSTAR 11.25 mg (N = 174) every 12 weeks for a total of up to 3 doses (maximum treatment period of 253 days) or TRELSTAR 3.75 mg (N = 172) every 28 days for a total of up to 9 doses.  The primary efficacy endpoints were both achievement of castration by Day 29 and maintenance of castration from Day 57 through Day 253.

    Castration levels of serum testosterone (≤ 1.735 nmol/L; equivalent to 50 ng/dL) were achieved at Day 29 in 167 of 171 (97.7%) patients treated with TRELSTAR 11.25 mg, and maintenance of castration levels of serum testosterone from Day 57 through Day 253 was found in 94.4% of patients treated with TRELSTAR 11.25 mg.

    TRELSTAR 22.5 mg

    TRELSTAR 22.5 mg was studied in a non-comparative trial of 120 men with advanced prostate cancer.  The clinical trial population consisted of 64% Caucasian, 23% Black, and 13% Other, with a mean age of 71.1 years (range 51-93).   Patients received TRELSTAR 22.5 mg (N = 120) every 24 weeks for a total of 2 doses (maximum treatment period of 337 days).  The primary efficacy endpoints included achievement of castration by Day 29 and maintenance of castration from Day 57 through Day 337.

    Castration levels of serum testosterone (≤ 1.735 nmol/L; equivalent to 50 ng/dL) were achieved at Day 29 in 97.5% (117 of 120) of patients treated with TRELSTAR 22.5 mg. Castration was maintained in 93.3% of patients in the period from Day 57 to Day 337.

    A summary of the clinical studies for TRELSTAR is provided in Table 7.

    Table 7.       Summary of TRELSTAR Clinical Studies
     
    Product
    Strength
    3.75 mg11.25 mg22.5 mg
     
    Number of
    Patients
    137171120
     
    Treatment
    Schedule
    every 4 weeksevery 12 weeksevery 24 weeks
     
    Duration of Study
    253 days253 days337 days
     
    Castration Rate*  
    on Day 29, %
    (n/N)
    91.2% (125/137)97.7% (167/171)97.5% (117/120)
     
    Rate of
    Castration
    Maintenance
    from Days 57 –
    253, %
    96.2%94.4%not applicable
     
    Rate of
    Castration
    Maintenance
    from Days 57 –
    337, % (n/N)
    not applicablenot applicable93.3% (112/120)

    *  Maintenance of castration was calculated using a frequency distribution.
     Cumulative maintenance of castration was calculated using a survival analysis (Kaplan-Meier) technique.
     Calculation includes 5 patients who discontinued the study but who had castrate levels of testosterone prior to discontinuation.

  • 16       HOW SUPPLIED/STORAGE AND HANDLING

    TRELSTAR is supplied in the TRELSTAR MIXJECT single-dose delivery system consisting of a vial with a Flip-Off seal containing sterile lyophilized triptorelin pamoate microgranules incorporated in a biodegradable copolymer of lactic and glycolic acids, a MIXJECT vial adapter, and a pre-filled syringe containing sterile water for injection, USP, 2 mL, pH 6 to 8.5.

    TRELSTAR 3.75 mg –NDC 0023-5902-04 (TRELSTAR 3.75 mg with MIXJECT single-dose delivery system)

    TRELSTAR 11.25 mg –NDC 0023-5904-12 (TRELSTAR 11.25 mg with MIXJECT single-dose delivery system)

    TRELSTAR 22.5 mg –NDC 0023-5906-23 (TRELSTAR 22.5 mg with MIXJECT single-dose delivery system)

    Storage
    Store at 20-25°C (68-77°F).  [See USP Controlled Room Temperature.]  Do not freeze TRELSTAR with MIXJECT.

  • 17       PATIENT COUNSELING INFORMATION

    Hypersensitivity

    • Inform patients that if they have experienced hypersensitivity with other GnRH agonist drugs like TRELSTAR, TRELSTAR is contraindicated [see Contraindications (4)].

    Tumor Flare

    • Inform patients that TRELSTAR can cause tumor flare during the first weeks of treatment. Inform patients that the increase in testosterone can cause an increase in urinary symptoms or pain. Advise patients to contact their healthcare provider if uretral obstruction, spinal cord compression, paralysis, or new or worsened symptoms occur after beginning TRELSTAR treatment [see Warnings and Precautions (5.2)].

    Hyperglycemia and Diabetes

    • Advise patients that there is an increased risk of hyperglycemia and diabetes with TRELSTAR therapy. Inform patients that periodic monitoring for hyperglycemia and diabetes is required when being treated with TRELSTAR [see Warnings and Precautions (5.5)].

    Cardiovascular Disease

    • Inform patients that there is an increased risk of myocardial infarction, sudden cardiac death, and stroke with TRELSTAR treatment. Advise patients to immediately report signs and symptoms associated with these events to their healthcare provider for evaluation [see Warnings and Precautions (5.6)].

    Urogenital Disorders

    • Advise patients that TRELSTAR may cause impotence.

    Infertility

    Continuation of TRELSTAR Treatment

    • Inform patients that TRELSTAR is usually continued, often with additional medication, after the development of metastatic castration-resistant prostate cancer [see Dosage and Administration (2.1)].

    For all medical inquiries contact:
    Allergan
    Medical Communications
    1-800-678-1605

    Distributed By:
    Allergan USA, Inc.
    Madison, NJ 07940

    Manufactured By:
    Debiopharm Research & Manufacturing SA
    CH-1920 Martigny, Switzerland

    MIXJECT is manufactured by:
    West Pharma. Services IL, Ltd.
    Ra'anana, Israel

    The pre-filled syringe containing sterile water for injection is manufactured by:
    Baxter Pharmaceutical Solutions, LLC
    927 South Curry Pike
    Bloomington, Indiana 47403

    TRELSTAR® and its design are registered trademarks of Allergan Sales, LLC

    MIXJECT® is a registered trademark of West Pharma. Services IL, Ltd.

    © 2018 Allergan. All rights reserved.

    v2.0USPI5902

  • PRINCIPAL DISPLAY PANEL

    PRINCIPAL DISPLAY PANEL
    NDC 0023-5902-04
    Trelstar 3.75 mg
    3.75 mg every 4 weeks
    Allergan

    NDC 0023-5902-04
Trelstar 3.75 mg
3.75 mg every 4 weeks
Allergan

  • PRINCIPAL DISPLAY PANEL

    PRINCIPAL DISPLAY PANEL
    NDC 0023-5904-12
    Trelstar 11.25 mg
    11.25 mg every 12 weeks
    Allergan

    NDC 0023-5904-12
Trelstar 11.25 mg
11.25 mg every 12 weeks
Allergan

  • PRINCIPAL DISPLAY PANEL

    PRINCIPAL DISPLAY PANEL
    NDC 0023-5906-23
    Trelstar 22.5 mg
    22.5 mg every 24 weeks
    Allergan

    NDC 0023-5906-23
Trelstar 22.5 mg
22.5 mg every 24 weeks
Allergan

  • INGREDIENTS AND APPEARANCE
    TRELSTAR 
    triptorelin pamoate kit
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0023-5902
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:0023-5902-041 in 1 CARTON; Type 0: Not a Combination Product06/15/2000
    Quantity of Parts
    Part #Package QuantityTotal Product Quantity
    Part 11 VIAL, SINGLE-DOSE 2 mL
    Part 21 SYRINGE 2 mL
    Part 1 of 2
    TRELSTAR 
    triptorelin pamoate injection, powder, lyophilized, for suspension
    Product Information
    Route of AdministrationINTRAMUSCULAR
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    TRIPTORELIN PAMOATE (UNII: 08AN7WA2G0) (TRIPTORELIN - UNII:9081Y98W2V) TRIPTORELIN3.75 mg  in 2 mL
    Inactive Ingredients
    Ingredient NameStrength
    MANNITOL (UNII: 3OWL53L36A)  
    CARBOXYMETHYLCELLULOSE SODIUM (UNII: K679OBS311)  
    POLYSORBATE 80 (UNII: 6OZP39ZG8H)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    12 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA02071506/15/2000
    Part 2 of 2
    DILUENT 
    diluent liquid
    Product Information
    Route of AdministrationINTRAMUSCULAR
    Inactive Ingredients
    Ingredient NameStrength
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    12 mL in 1 SYRINGE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA02071506/15/2000
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA02071506/15/2000
    TRELSTAR 
    triptorelin pamoate kit
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0023-5904
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:0023-5904-121 in 1 CARTON; Type 0: Not a Combination Product06/29/2001
    Quantity of Parts
    Part #Package QuantityTotal Product Quantity
    Part 11 VIAL, SINGLE-DOSE 2 mL
    Part 21 SYRINGE 2 mL
    Part 1 of 2
    TRELSTAR 
    triptorelin pamoate injection, powder, lyophilized, for suspension
    Product Information
    Route of AdministrationINTRAMUSCULAR
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    TRIPTORELIN PAMOATE (UNII: 08AN7WA2G0) (TRIPTORELIN - UNII:9081Y98W2V) TRIPTORELIN11.25 mg  in 2 mL
    Inactive Ingredients
    Ingredient NameStrength
    MANNITOL (UNII: 3OWL53L36A)  
    CARBOXYMETHYLCELLULOSE SODIUM (UNII: K679OBS311)  
    POLYSORBATE 80 (UNII: 6OZP39ZG8H)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    12 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA02128806/29/2001
    Part 2 of 2
    DILUENT 
    diluent liquid
    Product Information
    Route of AdministrationINTRAMUSCULAR
    Inactive Ingredients
    Ingredient NameStrength
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    12 mL in 1 SYRINGE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA02128806/29/2001
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA02128806/29/2001
    TRELSTAR 
    triptorelin pamoate kit
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0023-5906
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:0023-5906-231 in 1 CARTON; Type 0: Not a Combination Product03/11/2010
    Quantity of Parts
    Part #Package QuantityTotal Product Quantity
    Part 11 VIAL, SINGLE-DOSE 2 mL
    Part 21 SYRINGE 2 mL
    Part 1 of 2
    TRELSTAR 
    triptorelin pamoate injection, powder, lyophilized, for suspension
    Product Information
    Route of AdministrationINTRAMUSCULAR
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    TRIPTORELIN PAMOATE (UNII: 08AN7WA2G0) (TRIPTORELIN - UNII:9081Y98W2V) TRIPTORELIN22.5 mg  in 2 mL
    Inactive Ingredients
    Ingredient NameStrength
    MANNITOL (UNII: 3OWL53L36A)  
    CARBOXYMETHYLCELLULOSE SODIUM (UNII: K679OBS311)  
    POLYSORBATE 80 (UNII: 6OZP39ZG8H)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    12 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA02243703/11/2010
    Part 2 of 2
    DILUENT 
    diluent liquid
    Product Information
    Route of AdministrationINTRAMUSCULAR
    Inactive Ingredients
    Ingredient NameStrength
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    12 mL in 1 SYRINGE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA022437
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA02243703/11/2010
    Labeler - Allergan, Inc. (144796497)