Contraindications

Androgens are contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate. Testim® 1% (testosterone gel) is not indicated for use in women, has not been evaluated for use in women, and must not be used in women.

Pregnant and nursing women should avoid skin contact with Testim application sites on men. Testosterone may cause fetal harm. Testosterone exposure during pregnancy has been reported to be associated with fetal abnormalities. In the event that unwashed or unclothed skin to which Testim has been applied comes in direct contact with the skin of a pregnant or nursing woman, the general area of contact on the woman should be immediately washed with soap and water.

Testim should not be used in patients with known hypersensitivity to any of its ingredients, including testosterone USP that is chemically synthesized from soy.

Warnings

Men with benign prostatic hyperplasia (BPH) are at an increased risk for worsening of BPH. In addition, men treated with androgens may be at an increased risk for prostate cancer. Geriatric patients and other patients with clinical or demographic characteristics that are recognized to be associated with an increased risk of prostate cancer should be evaluated for the presence of prostate cancer prior to initiation of testosterone replacement therapy. In men receiving testosterone replacement therapy, surveillance for prostate cancer should be consistent with current practices for eugonadal men.

Potential for Secondary Exposure to Testosterone

• – Secondary exposure to testosterone in children and women can occur with testosterone gel use in men. Cases of secondary exposure resulting in virilization of children have been reported in postmarketing surveillance of testosterone-containing gel products. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with removal of the exposure to testosterone. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of the testosterone gel product.
• – Inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician, and the possibility of secondary exposure to testosterone gel should also be brought to the attention of a physician. Testosterone gel should be promptly discontinued until the cause of virilization has been identified.

Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from Testim-treated skin:

• – Children and women should avoid contact with Testim application sites on the skin of men using Testim.
• – Testim should only be applied to the shoulders or upper arms (area of application should be limited to the area that will be covered by the patient’s short sleeve t-shirt).
• – Patients should wash their hands thoroughly and immediately with soap and water after application of Testim.
• – Patients should cover the application site(s) with clothing (e.g., a shirt) after the gel has dried.
• – Prior to any situation in which skin-to-skin contact is anticipated, patients should wash the application site(s) thoroughly with soap and water to remove any testosterone residue.
• – In the event that unwashed or unclothed skin to which Testim has been applied comes in direct contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible. Studies show that residual testosterone is removed from the skin surface by washing with soap and water.

Testim should not be applied to the scrotum, penis or abdomen.

Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a lifethreatening or fatal complication. Long-term therapy with testosterone enanthate, which elevates blood levels for prolonged periods has produced multiple hepatic adenomas. Transdermal testosterone is not known to produce these adverse effects.

Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease.

Gynecomastia occasionally develops and occasionally persists in patients being treated for hypogonadism.

The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases.

General Precautions

The physician should instruct patients to report any of the following: too frequent or persistent erections of the penis; any changes in skin color, ankle swelling or unexplained nausea and vomiting; breathing disturbances, including those associated with sleep.

Testim® 1% (testosterone gel) should be applied once daily at approximately the same time each day to clean dry skin of the shoulders and/or upper arms. Please also see Precautions, Information for Patients in the Prescribing Information for Testim.

Laboratory tests

Hemoglobin and hematocrit levels should be checked periodically (to detect polycythemia) in patients on long-term androgen therapy.

Liver function, prostate specific antigen (PSA), cholesterol, and high-density lipoprotein (HDL) should be checked periodically.

To ensure proper dosing, serum testosterone concentrations should be measured.

Drug Interactions

Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone.

In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, insulin requirements.

In a published pharmacokinetic study of an injectable testosterone product, administration of testosterone cypionate led to an increased clearance of propranolol in the majority of men tested. It is unknown if this would apply to Testim.

The concurrent administration of testosterone with ACTH or corticosteroids may enhance edema formation; thus these drugs should be administered cautiously, particularly in patients with cardiac or hepatic disease.

Drug/Laboratory Test Interactions

Androgens may decrease levels of thyroxin-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.

Carcinogenesis, Mutagenesis, Impairment of Fertility

There are rare reports of hepatocellular carcinoma in patients receiving long-term oral therapy with androgens in high doses. Withdrawal of the drugs did not lead to regression of the tumors in all cases. Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hyperplasia and prostatic carcinoma.

Pregnancy Category X (see Contraindications) – Teratogenic Effects

Testim is not indicated for women and must not be used in women. Testosterone may cause fetal harm.

Nursing Mothers

Testim is not indicated for women and must not be used in nursing mothers.

Pediatric Use

Safety and efficacy of Testim in patients <18 years old has not been established

Adverse Reactions

Patients with adverse events that were judged possibly, probably or definitely related to study drug and reported by greater than or equal to 1% of the Testim patients and greater than placebo include application site reactions (2%, 4%, 3%) [Testim 50 mg, Testim 100 mg, placebo respectively]; benign prostatic hyperplasia (0%, 1%, 1%); decreased diastolic blood pressure (1%, 0%, 0%); increased blood pressure (1%, 1%, 0%); gynecomastia (1%, 0%, 0%); headache (1%, 1%, 0%); increased hematocrit/hemoglobin (1%, 2%, 0%); hot flushes (1%, 0%, 0%); insomnia (1%, 0%, 0%); increased lacrimation (1%, 0%, 0%); mood swings (1%, 0%, 0%); smell disorder (1%, 0%, 0%); spontaneous penile erection (1%, 0%, 0%); taste disorder (1%, 1%, 0%).