TRELSTAR DEPOT contains a pamoate salt of triptorelin, and triptorelin is a synthetic decapeptide agonist analog of luteinizing hormone releasing hormone (LHRH or GnRH) with greater potency than the naturally occurring LHRH. 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 shown below.

TRELSTAR DEPOT is a sterile, lyophilized biodegradable microgranule formulation supplied as a single-dose vial containing triptorelin pamoate (3.75 mg as the peptide base), 170 mg poly-d,l-lactide-co-glycolide, 85 mg mannitol, USP, 30 mg carboxymethylcellulose sodium, USP, 2 mg polysorbate 80, NF. When 2 mL sterile water for injection is added to the vial containing TRELSTAR DEPOT and mixed, a suspension is formed which is intended as a monthly intramuscular injection. TRELSTAR DEPOT is available in 2 packaging configurations: (a) TRELSTAR DEPOT vial alone or (b) TRELSTAR DEPOT vial plus a separate pre-filled syringe that contains sterile water for injection, USP, 2 mL, pH 6 to 8.5 (Clip'n'Ject®).

Last updated on RxList: 5/19/2008

TRELSTAR DEPOT is indicated in the palliative treatment of advanced prostate cancer. It offers an alternative treatment for prostate cancer when orchiectomy or estrogen administration are either not indicated or unacceptable to the patient.

TRELSTAR DEPOT Must Be Administered Under the Supervision of a Physician.

The recommended dose of TRELSTAR DEPOT is 3.75 mg incorporated in a depot formulation and is administered monthly as a single intramuscular injection. The lyophilized microgranules are to be reconstituted in sterile water. No other diluent should be used.

Reconstitute in accord with the following: For TRELSTAR DEPOT:

1. Using a syringe fitted with a sterile 20-gauge needle, withdraw 2 mL sterile water for injection, USP, and after removing the flip-off seal from the vial, inject into the vial.
2. Shake well to thoroughly disperse particles to obtain a uniform suspension. The suspension will appear milky.
3. Withdraw the entire content of the reconstituted suspension into the syringe and inject it immediately.

For the TRELSTAR DEPOT Clip'n'Ject® single-dose delivery system, see adjacent INSTRUCTIONS FOR CLIP'N'JECT® USE section. The suspension should be discarded if not used immediately after reconstitution. As with other drugs administered by intramuscular injection, the injection site should be altered periodically.

Dosage Adjustments: Patients with renal or hepatic impairment showed 2- to 4-fold higher exposure than young healthy males. The clinical consequences of this increase, as well as the potential need for dose adjustment, is unknown.

TRELSTAR DEPOT (NDC 52544-153-02) is supplied in a single-dose vial with a flip-off seal containing sterile lyophilized triptorelin pamoate microgranules equivalent to 3.75 mg triptorelin peptide base, incorporated in a biodegradable copolymer of lactic and glycolic acids. A single dose vial of TRELSTAR DEPOT contains triptorelin pamoate (3.75 mg as peptide base units), poly-d,l-lactide-co-glycolide (170 mg), mannitol, USP (85 mg), carboxymethylcellulose sodium, USP (30 mg), and polysorbate 80, NF (2 mg).

TRELSTAR DEPOT (NDC 52544-153-76) is also supplied in the TRELSTAR DEPOT Clip'n'Ject® single- dose delivery system consisting of a vial with a flip-off seal containing sterile lyophilized triptorelin pamoate microgranules equivalent to 3.75 mg of triptorelin peptide base, incorporated in a biodegradable copolymer of lactic and glycolic acids, and a pre-filled syringe containing sterile water for injection, USP, 2 mL, pH 6 to 8.5. When mixed with sterile water for injection, TRELSTAR DEPOT is administered every 28 days as a single intramuscular injection. Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

Revised: August 2006. Clip'n'Ject and Flip-Off button are manufactured by and are registered trademarks of West Pharmaceutical Services, Inc. Lionville, PA 19341, USA. Tyvek® is a registered trademark of E.I. du Pont de Nemours and Company. Manufactured for: Watson Pharma, Inc. A subsidiary of Watson Pharmaceuticals Inc. Corona, CA 92880, USA. by: Debio RP CH-1920 Martigny, Switzerland. FDA Rev date: 4/14/2008

Last updated on RxList: 5/19/2008

In the majority of patients, 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, hematuria, and bladder outlet obstruction. Isolated cases of spinal cord compression with weakness or paralysis of the lower extremities have occurred (see WARNINGS).

In a controlled, comparative clinical trial, the following adverse reactions were reported to have a possible or probable relationship to therapy as ascribed by the treating physician in 1% or more of the patients receiving triptorelin (Table 3). Often, causality is difficult to assess in patients with metastatic prostate cancer. Reactions considered not drug-related are excluded.

Changes in Laboratory Values During Treatment: There were no clinically meaningful changes in laboratory values during or following therapy with TRELSTAR DEPOT.

Pituitary apoplexy: During post-marketing 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.

No drug-drug interaction studies involving triptorelin have been conducted. In the absence of relevant data as a precaution, hyperprolactinemic drugs should not be prescribed concomitantly with TRELSTAR DEPOT since hyperprolactinemia reduces the number of pituitary GnRH receptors.

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

Pregnancy, Teratogenic Effects: Pregnancy Category X (see CONTRAINDICATIONS). TRELSTAR DEPOT is contraindicated in women who are or may become pregnant while receiving the drug. Studies in pregnant rats administered triptorelin at doses of 2, 10, and 100 µg/kg/day (approximately equivalent to 0.2, 0.8, and 8 times the recommended human therapeutic dose based on body surface area) during the period of organogenesis displayed maternal toxicity and embryotoxicity, but no fetotoxicity or teratogenicity. Similarly, no teratogenic effects were observed when mice were administered doses of 2, 20, and 200 µg/kg/day (approximately equivalent to 0.1, 0.7, and 7 times the recommended human therapeutic dose based on body surface area). If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus.

Last updated on RxList: 5/19/2008

Initially, triptorelin, like other LHRH 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 LHRH agonists. Patients may experience worsening of symptoms or onset of new symptoms, including bone pain, neuropathy, hematuria, or urethral or bladder outlet obstruction. Cases of spinal cord compression, which may contribute to paralysis with or without fatal complications, have been reported with LHRH 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. TRELSTAR DEPOT should not be administered to individuals who are hypersensitive to triptorelin, other LHRH agonists, or LHRH. In the event of a hypersensitivity reaction, therapy with TRELSTAR DEPOT should be discontinued immediately and the appropriate supportive and symptomatic care should be administered.

General: 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 (see WARNINGS). Hypersensitivity and anaphylactic reactions have been reported with triptorelin with other LHRH agonists (see CONTRAINDICATIONS and WARNINGS).

Laboratory Tests: Response to TRELSTAR DEPOT should be monitored by measuring serum levels of testosterone and prostate-specific antigen.

Carcinogenesis, Mutagenesis, Impairment of Fertility: In rats, doses of 120, 600, and 3000 µg/kg given every 28 days (approximately 0.3, 2.0, and 8 times the recommended human therapeutic dose based on body surface area) resulted in increased mortality with a drug treatment period of 13-19 months. The incidence 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 µg/kg every 28 days (approximately 8 times the human therapeutic 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 treatment followed by a minimum of four estrus cycles prior to mating, triptorelin, at doses of 2, 20, and 200 µg/kg/day in saline (approximately 0.2, 2.0, and 16 times the recommended human therapeutic dose based on body surface area) or 20 µg/kg/day in slow release microspheres, had no effect on the fertility or general reproductive performance of female rats. Treatment did not elicit embryotoxicity, teratogenicity, or any effects on the development of the offspring (F1 generation) or their reproductive performance.

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

Geriatric Use: Prostate cancer occurs primarily in an older patient population. Clinical studies with TRELSTAR DEPOT have been conducted primarily in patients > 65 years.

Nursing Mothers: It is not known whether TRELSTAR DEPOT is excreted in human milk. Because many drugs are excreted in human milk, and because the effects of TRELSTAR DEPOT on lactation and/or the breastfed child have not been determined, TRELSTAR DEPOT should not be used by nursing mothers.

Pediatric Use: TRELSTAR DEPOT has not been studied in pediatric patients.

Last updated on RxList: 5/19/2008

The pharmacological properties of triptorelin and its mode of administration make accidental or intentional overdosage unlikely. There were no reported overdoses 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 7000 and 4000 times, respectively, the usual human dose. If overdosage occurs however, therapy should be discontinued immediately and the appropriate supportive and symptomatic treatment administered.

TABLE 3. RELATED ADVERSE EVENTS REPORTED BY 1% OR MORE OF PATIENTS DURING TREATMENT WITH TRELSTAR DEPOT

Adverse Event	TRELSTAR DEPOT N=140
	N	%
Application Site Disorders
Injection site pain	5	3.6
Body As A Whole
Hot Flushes*	82	58.6
Pain	3	2.1
Leg Pain	3	2.1
Fatigue	3	2.1
Cardiovascular
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
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
Urinary retention	2	1.4
Urinary tract infection	2	1.4
* Expected pharmacologic consequences of testosterone suppression.

TRELSTAR DEPOT is contraindicated in individuals with a known hypersensitivity to triptorelin or any other component of the product, other LHRH agonists or LHRH. Three postmarketing reports of anaphylactic shock and seven postmarketing reports of angioedema related to triptorelin administration have been reported since 1986 (see WARNINGS).

TRELSTAR DEPOT may cause fetal harm when administered to a pregnant woman.

Last updated on RxList: 5/19/2008

Mechanism of Action

Triptorelin is a potent inhibitor of gonadotropin secretion when given continuously and in therapeutic doses. 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). 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 and ovarian steroidogenesis is observed. In men, 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 (IM) injection of TRELSTAR DEPOT to healthy male volunteers, serum testosterone levels first increased, peaking on day 4, and declined thereafter to low levels by week 4. Similar testosterone profiles were observed in patients with advanced prostate cancer, when injected with TRELSTAR DEPOT. In healthy volunteers, testosterone serum levels returned to near baseline by week 8.

Pharmacokinetics

Results of pharmacokinetic investigations conducted in healthy men indicate that after intravenous (IV) 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: Triptorelin pamoate is not active when given orally. Intramuscular injection of the depot formulation provides plasma concentrations of triptorelin over a period of 1 month. The pharmacokinetic parameters following a single IM injection of 3.75 mg of TRELSTAR DEPOT to 20 healthy male volunteers are listed in Table 1. The plasma concentrations declined to 0.084 ng/mL at 4 weeks.

TABLE 1. PHARMACOKINETIC PARAMETERS FOLLOWING INTRAMUSCULAR ADMINISTRATION OF TRELSTAR DEPOT TO HEALTHY MALE VOLUNTEERS

Dose (No. of subjects)	C max (ng/mL)	T max (h)	AUC0-28d (h·ng/mL)	F (%)3 (No. of days)
3.75 mg (n=20)	28.43 ± 7.311	1.0 (1.0 - 3.0)2	223.15 ± 46.961	83 (28 d)
1 Mean ± SD 2 Median (range) 3 Computed as the mean AUC of the study divided by the mean AUC of healthy volunteers corrected for dose where AUC=36.1 h•ng/mL and 500 µg IV bolus doseof triptorelin was administered.

Distribution: The volume of distribution following an IV 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.

Metabolism: The metabolism of triptorelin in humans is unknown, but is unlikely to involve hepatic microsomal enzymes (cytochrome P-450). However, the effect of triptorelin on the activity of other drug metabolizing enzymes is 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 IV administration of 0.5 mg triptorelin peptide to 6 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 non-renal clearance of triptorelin (patient anuric, Clcreat=0) was 76.2 mL/min, thus indicating that the nonrenal elimination of triptorelin is mainly dependent on the liver (see Special Populations).

Special Populations

Renal and Hepatic Impairment: After an IV injection of 0.5 mg triptorelin peptide, the two distribution half-lives were unaffected by renal and hepatic impairment, but renal insufficiency led to a decrease in total triptorelin clearance proportional to the decrease in creatinine clearance as well as an increase in volume of distribution and consequently an increase in elimination half-life (Table 2). The decrease in triptorelin clearance was more pronounced in subjects with liver insufficiency, but the half-life was prolonged similarly in subjects with renal insufficiency, since the volume of distribution was only minimally increased.

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) indicates that triptorelin was eliminated twice as fast in this young population (see Special Populations, Renal and Hepatic Impairment) as compared to 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.

TABLE 2. PHARMACOKINETIC PARAMETERS (MEAN ±SD) IN HEALTHY VOLUNTEERS AND SPECIAL POPULATIONS

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

Pharmacokinetic Drug-Drug Interactions: No pharmacokinetic drug-drug interaction studies have been conducted with triptorelin (see PRECAUTIONS: DRUG INTERACTIONS).

Clinical Trials

TRELSTAR DEPOT 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 (71 mean). Patients received either TRELSTAR DEPOT 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) were achieved in 91.2% of TRELSTAR DEPOT patients at Day 29 and in 97.7% of patients at Day 57.

Maintenance of castration levels of serum testosterone from Day 57 through Day 253 was found in 96.4% of TRELSTAR DEPOT patients.

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 DEPOT administration on Days 85 and 169. One hundred twenty-four of 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.

Last updated on RxList: 5/19/2008

Please read complete instructions before you begin.

Clip'n'Ject® Preparation

Wash your hands with soap and hot water and put on gloves immediately prior to preparing the injection. Place the package containing the Clip'n'Ject system and the Trelstar® vial on a clean, flat surface that is covered with a sterile pad or cloth. Peel the Tyvek® cover away from the blister package, and place the vial, connector, alcohol swab, and plunger rod on the prepared surface. Be sure to begin by removing the Flip- Off® button from the top of the vial, revealing the rubber stopper. Disinfect the rubber portion of the vial cap with the alcohol swab. Discard the alcohol swab and let the alcohol dry. Proceed to Clip'n'Ject Activation.

Clip'n'Ject® Activation

Holding the vial upright and flat on the table surface with one hand, place the plastic connector directly over the top of the Trelstar® vial with the other hand. Press the connector down firmly on the vial top. This will ensure proper positioning of the vial.

Still holding the vial with one hand, press the syringe barrel downward as far as it will go in the connector. This results in insertion of the needle into the rubber stopper in the vial top to the predetermined depth.

Check to make sure that the needle is inserted into the vial. Now, screw the plunger rod into the end of the plastic grip on the syringe barrel.

1. With the vial still on the flat surface, place your thumb on the plunger rod and depress the plunger rod to inject the sterile water diluent into the vial.
2. With your thumb on the plunger rod, place two fingers under the plastic tab on the connector to keep the assembly together. Gently rotate the system so that the diluent rinses the vial sides to ensure complete mixing of Trelstar® and the sterile water diluent. The solution will now have a milky appearance. In order to avoid separation of the solution, proceed to the next steps without delay.

Hold the Clip'n'Ject system in a vertical position with the connector at 12 o'clock and the syringe plunger rod at 6 o'clock.

Double check to make sure that the syringe is still as far forward as possible in the connector with the needle situated in the vial.

Grasp the Clip'n'Ject system firmly by the syringe barrel and pull back the plunger rod to draw the reconstituted Trelstar® into the syringe.

Immediately before injecting Trelstar®, remove the filled syringe from the connector by holding the syringe by the barrel and pressing your thumbs against the plastic tabs of the connector and pulling the syringe section from the connector. Trelstar is now ready for administration. The suspension should be discarded if not used immediately after reconstitution.

Clip'n'Ject® Disposal

After administering Trelstar®, dispose of the Clip'n'Ject system as follows:

1. Place Clip'n'Ject with attached vial in standing upright position on a flat surface.
2. Using one hand, replace the syringe into the Clip'n'Ject connector.
3. Dispose of syringe and attached Clip'n'Ject connector with vial into a suitable sharps container.

Last updated on RxList: 5/19/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

TRIPTORELIN DEPOT SUSPENSION - INJECTION

(trip-toe-REL-in)

COMMON BRAND NAME(S): Trelstar Depot

USES: Triptorelin is used to treat advanced prostate cancer in men. It is not a cure. Most types of prostate cancer need the male hormone testosterone to grow and spread. Triptorelin is similar to a natural hormone made by the body (luteinizing hormone releasing hormone-LHRH). It works by reducing the amount of testosterone that the body makes. This effect helps slow or stop the growth of cancer cells and helps relieve symptoms such as painful/difficult urination.

HOW TO USE: This medication is given by injection into a muscle by a health care professional. Learn all preparation and usage instructions in the product package. If any of the information is unclear, consult your doctor or pharmacist.

This medication is usually injected every 4 weeks or as directed by your doctor. Follow the dosing schedule carefully to get the most benefit from the drug. To help you remember, mark your calendar to keep track of when to receive the next dose. Do not stop this medication without your doctor's approval.

This medication should be mixed only with sterile water for injection. Shake the vial well after mixing.

The medication should appear milky after mixing. Before using, check this product visually for unusual particles or discoloration. If either is present, do not use the liquid.

After mixing, use the medication right away. Do not save for later use.

Before injecting each dose, clean the injection site with rubbing alcohol. It is important to change the location of the injection site with each dose to avoid problem areas in the muscle.

During the first few weeks of treatment, your hormone levels will actually increase before they decrease. This is a normal response by your body to this drug. This effect may result in new symptoms or worsening of symptoms (e.g., bone pain, tumor size) for the first few weeks.

Tell your doctor if your condition persists or worsens after the first month.

SIDE EFFECTS: Hot flashes (flushing), pain at injection site, dizziness, headache, bone pain, decreased sexual interest/ability, or trouble sleeping may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: unusual tiredness, fast/pounding heartbeat.

Rarely, a very serious problem with your pituitary gland (pituitary apoplexy) may occur, usually in the first hour to 2 weeks after your first dose of this medication. Seek immediate medical attention if any of these very serious side effects occur: sudden severe headache, mental/mood changes (e.g., confusion), vision changes, vomiting, fainting.

A rare but very serious urinary blockage problem or spinal cord problem (compression) can occur, especially during the first month of treatment. Tell your doctor immediately if you experience any of the following serious side effects: severe back pain, numbness/tingling/weakness of the arms/legs, inability to move, painful/difficult urination, blood in the urine.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using triptorelin, tell your doctor or pharmacist if you are allergic to it; or to LHRH or other LHRH-like hormones (e.g., goserelin); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, urinary blockage problem, spinal cord problem.

This drug is only recommended for use in men. If used in women, it must not be used during pregnancy. If you become pregnant or think you may be pregnant, tell your doctor immediately.

This drug is only recommended for use in men. It is not known whether this drug passes into breast milk. If this medication is used in women, breast-feeding is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: drugs that increase prolactin levels (e.g., metoclopramide, methyldopa, phenothiazines such as prochlorperazine, antipsychotic medications such as haloperidol/olanzapine).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., testosterone/PSA levels) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss an appointment to receive your next dose, reschedule the appointment as soon as you remember.

STORAGE: Store the unmixed vials at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Once mixed, the medication should be used right away. Do not freeze. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.