Testosterone cypionate

AZMIRO is indicated for testosterone replacement therapy in males in conditions associated with a deficiency or absence of endogenous testosterone: • Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchiectomy, Klinefelter’s syndrome, or toxic damage from alcohol or heavy metals, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle stimulating hormone (FSH), luteinizing hormone (LH)) above the normal range. • Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.

Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include growth and maturation of the prostate, seminal vesicles, penis, and scrotum, the development of male hair distribution, such as facial, pubic, chest, and axillary hair, laryngeal enlargement, vocal cord thickening, alterations in body musculature and fat distribution. Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's Syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

• Injectable testosterone products may have different doses, strengths, or administration instructions and they are not substitutable on a milligram-per-milligram basis. Administer AZMIRO by deep gluteal intramuscular injection only. • Prior to initiating AZMIRO, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum concentrations are below the normal range. • Recommended dosage is 50 mg to 400 mg administered every two to four weeks as a deep intramuscular injection in the gluteal muscle. Individualize the dose and schedule based on the patient’s age, diagnosis, response to treatment, and the appearance of adverse reactions. • The prefilled syringe should be administered as an intramuscular injection by a healthcare professional only.

AZMIRO is contraindicated in: • Known hypersensitivity to AZMIRO or to any of its components. Hypersensitivity, including skin manifestations and anaphylactoid reactions have been reported. • Men with carcinoma of the breast or known or suspected carcinoma of the prostate gland. • Women who are pregnant. Testosterone can cause virilization of the female fetus when administered to a pregnant woman. • Known hypersensitivity to AZMIRO or any of its components, skin manifestations and anaphylactoid reactions have been reported. • Men with carcinoma of the breast or known or suspected carcinoma of the prostate. • Women who are pregnant. Testosterone may cause fetal harm.

• Polycythemia: Monitor hematocrit periodically during treatment. Discontinue AZMIRO, if necessary. • Venous thromboembolism (VTE): VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients using testosterone products. Discontinue AZMIRO if VTE is suspected and initiate appropriate workup and management. • Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer: Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH. Evaluate patients for prostate cancer, including monitoring prostate specific antigen (PSA) prior to initiating and during treatment with androgens. • Blood Pressure Increases: Testosterone can increase blood pressure, which can increase cardiovascular risk over time. Measure blood pressure periodically.

The following clinically significant adverse reactions are discussed elsewhere in the labeling: • Polycythemia • Venous Thromboembolism • Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer • Blood Pressure Increases • Hepatic Adverse Effects • Edema • Sleep Apnea • Gynecomastia • Lipid Changes • Hypercalcemia • Decreased Thyroxine-binding Globulin • Increases in Prolactin • Adverse Effects on Bone Maturation Common adverse reactions (incidence ≥4%) are injection site erythema and injection site reaction. Other adverse reactions include: polycythemia, gynecomastia, headache, and depression.

• Insulin: In patients with diabetes, concomitant use with AZMIRO may decrease blood glucose and insulin requirements. • Oral Anticoagulants: Concomitant use with AZMIRO may cause changes in anticoagulant activity. Monitor International Normalized Ratio and prothrombin time frequently. • Corticosteroids: Concomitant use with AZMIRO may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease.

Store at 15°C to 25°C (59°F to 77°F), excursions permitted to 2°C to 30°C (36°F to 86°F). Store product in carton to protect contents from light.