Trelstar Side Effects, and Drug Interactions - Triptorelin pamoate

Trelstar Side Effects, and Drug Interactions - Triptorelin pamoate

SIDE EFFECTS

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.

*Expected pharmacologic consequences of testosterone suppression.

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

DRUG INTERACTIONS

No drug-drug interaction studies involving triptorelin have been conducted. In the absence of relevant data and as a precaution, hyperprolactinemic drugs should not be prescribed concomitantly with TRELSTAR^TM 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 the pituitary-gonadal 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^TM 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 ter-atogenic 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.

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^TM DEPOT have been conducted primarily in patients ³65 years.

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

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