Triptorelin Pamoate for Injectable Suspension

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

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 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

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 two packaging configurations: (a) TRELSTAR vial alone or (b) TRELSTAR 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.

Dosage Forms And Strengths

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

Storage And Handling

TRELSTAR is supplied in a single dose vial with a Flip-Off seal containing sterile lyophilized triptorelin pamoate microgranules incorporated in a biodegradable copolymer of lactic and glycolic acids.

TRELSTAR is also 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 52544-153-02 (single dose vial) and NDC 52544-189-76 (TRELSTAR 3.75 mg with MIXJECT single-dose delivery system)

TRELSTAR 11.25 mg – NDC 52544-154-02 (single dose vial) and NDC 52544-188-76 (TRELSTAR 11.25 mg with MIXJECT single-dose delivery system)

TRELSTAR 22.5 mg – NDC 52544-156-02 (single dose vial) and NDC 52544-092-76 (TRELSTAR 22.5 mg with MIXJECT single-dose delivery system)

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

Address medical inquiries to: WATSON Medical Communications. P.O. Box 1953 Morristown, NJ 07962-1953 800-272-5525

Distributed By: Watson Pharma, Inc. Morristown, NJ 07962 USA. Manufactured By: Debio RP CH-1920 Martigny, Switzerland

Included as part of the PRECAUTIONS section.

Instruct patients that they will likely experience an increase in serum testosterone levels following their initial injection. This may cause a worsening of their symptoms of prostate cancer during the first weeks of treatment. These symptoms may include bone pain, spinal cord injury, hematuria, and urethral or bladder outlet obstruction. This increase in serum testosterone levels and associated symptoms should decline 3 to 4 weeks following their injection. Use of drugs appropriate for alleviating the risk associated with the increase should be discussed with patients prior to administration of the products. Patients should also be informed about the increased risk of developing diabetes, myocardial infarction, sudden cardiac death and stroke in men in association with use of GnRH agonists.

Advise patients that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment. Patients should report any previous hypersensitivity reactions to triptorelin, or other GnRH agonists, or GnRH.

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].

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

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

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

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.

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.

Read the entire FDA prescribing information for Trelstar (Triptorelin Pamoate for Injectable Suspension)

You should not use this medication if you are allergic to triptorelin or similar drugs such as leuprolide (Lupron, Viadur, Eligard) or goserelin (Zoladex).

Before using triptorelin, tell your doctor if you have any type of cancer that has spread to your spine, a bladder obstruction or problems with urination, diabetes, heart disease, high blood pressure, high cholesterol, a history of stroke or heart attack, or if you smoke.

After your injection, your prostate cancer symptoms may get worse for a short time because triptorelin raises your testosterone levels. These side effects should get better within 3 or 4 weeks. Call your doctor if your symptoms do not improve, or if they get worse while using triptorelin.

Some of the side effects of triptorelin are symptoms of prostate cancer that may occur because the medicine raises your testosterone levels. Call your doctor at once if you have pain or burning when you urinate, blood in your urine, bone pain, numbness, tingling, muscle weakness, or loss of movement in any part of your body.

Although triptorelin is not for use by women, this medication can cause birth defects and should not be used by a woman who is pregnant or who may become pregnant.

You should not use this medication if you are allergic to triptorelin or similar drugs such as leuprolide (Lupron, Viadur, Eligard) or goserelin (Zoladex).

If you have any of these other conditions, you may need a triptorelin dose adjustment or special tests:

• any type of cancer that has spread to your spine;
• a bladder obstruction or problems with urination;
• diabetes, heart disease, high blood pressure, recent weight gain, high cholesterol (especially in men);
• heart disease, high blood pressure, high cholesterol;
• a history of heart attack or stroke; or
• if you smoke.

FDA pregnancy category X. Although triptorelin is not for use by women, this medication can harm an unborn baby or cause birth defects. Triptorelin should not be used by a woman who is pregnant or who may become pregnant.

It is not known whether triptorelin passes into breast milk or if it could harm a nursing baby. Although triptorelin is not for use by women, this medication should not be used while breast-feeding a baby.