testosterone 1 % (50 MG / 5 GM) Transdermal Gel
WARNINGS
Testim ® should not be applied to the 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 hepatitis, hepatic neoplasms, cholestatic hepatitis, and jaundice).
Peliosis hepatitis can be a life-threatening 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.
Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hyperplasia and prostatic carcinoma.
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 (see PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility and Laboratory Tests).
Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease.
In addition to discontinuation of the drug, diuretic therapy may be required.
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.
OVERDOSAGE
There were no reports of overdose in the Testim ® clinical trials.
There is one report of acute overdosage by injection of testosterone enanthate: testosterone levels of up to 11,400 ng/dL were implicated in a cerebrovascular accident.
DESCRIPTION
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CLINICAL STUDIES
Clinical Studies Testim ® was evaluated in a randomized multicenter, multi-dose, active and placebo controlled 90-day study in 406 adult males with morning testosterone levels ≤300 ng/dL.
The study was double-blind for the doses of Testim ® and placebo, but open label for the non-scrotal testosterone transdermal system.
During the first 60 days, patients were evenly randomized to Testim ® 50 mg, Testim ® 100 mg, placebo gel, or testosterone transdermal system.
At Day 60, patients receiving Testim ® were maintained at the same dose, or were titrated up or down within their treatment group, based on 24-hour averaged serum testosterone concentration levels obtained on Day 30.
Of 192 hypogonadal men who were appropriately titrated with Testim ® and who had sufficient data for analysis, 74% achieved an average serum testosterone level within the normal range on treatment Day 90.
Table 1 summarizes the mean testosterone concentrations on Day 30 for patients receiving Testim ® 50 mg or 100 mg.
Table 1: Mean (± SD) Steady-State Serum Testosterone Concentrations on Day 30 Testim® 50 mg n=94 Testim® 100 mg n=95 Placebo n=93 Cavg (ng/dL) 365 ± 187 612 ± 286 216 ± 79 Cmax (ng/dL) 538 ± 371 897 ± 565 271 ± 110 Cmin (ng/dL) 223 ± 126 394 ±189 164 ± 64 At Day 30, patients receiving Testim ® 100 mg daily showed significant improvement from baseline in multiple sexual function parameters as measured by patient questionnaires when compared to placebo.
These parameters included sexual motivation, sexual desire, sexual activity and spontaneous erections.
For Testim ® 100 mg, improvements in sexual motivation, spontaneous erections, and sexual desire were maintained through Day 90.
Sexual enjoyment and satisfaction with erection duration were improved compared to baseline but these improvements were not significant compared to the placebo group.
In Testim ® -treated patients, the number of days in which sexual activity was reported to occur increased by 123% from baseline at Day 30 and was still increased from baseline by 59% at Day 90.
The number of days with spontaneous erections increased by 137% at Day 30 and was maintained at 78% at Day 90 for Testim ®- treated patients compared to baseline.
Table 2 summarizes the changes in body composition at Day 90 for patients receiving Testim ® 50 mg or 100 mg as measured by standardized whole body DEXA (Dual Energy X-ray Absorptiometry) scanning.
Table 2: Effect of Testim® on Lean Body Mass, Total Fat Mass and % Body Fat Days of Treatment Lean Body Mass (Muscle) (kg) Total Fat Mass( kg) % Body Fat Baseline 61.6 29.4 30.9 Day 90 63.3 28.6 29.8 Change from Baseline ↑1.6 ↓0.8 ↓1.1 At Day 90, mean increases from baseline in lean body mass and mean decreases from baseline in total fat mass and percent body fat in Testim ® -treated patients were significant when compared to placebo-treated patients.
Potential for Testosterone Transfer The potential for dermal testosterone transfer following Testim ® use was evaluated in two clinical trials with males dosed with Testim ® and their untreated female partners.
In the first trial (AUX-TG-206), 30 couples were evenly randomized to five groups.
In the first four groups, 100 mg of Testim ® was applied to the male abdomen and the couples were then asked to rub abdomen-to-abdomen for 15 minutes at 1 hour, 4 hours, 8 hours or 12 hours after dose application, respectively.
In these couples, serum testosterone concentrations in female partners increased from baseline by at least 4 times and potential for transfer was seen at all timepoints.
When 6 males used a shirt to cover the abdomen at 15 minutes post-application and partners again rubbed abdomens for 15 minutes at the 1 hour timepoint, the potential for transfer was markedly reduced.
In the second trial (AUX-TG-209), 24 couples were evenly randomized to four groups.
Testim ® 100 mg was applied to the male arms and shoulders.
In one group, 15 minutes of direct skin-to-skin rubbing began at 4 hours after application.
In these six women, all of whom showered immediately after the rubbing activity, mean maximum serum testosterone concentrations increased from baseline by approximately 4 times.
When males wore a long-sleeved T-shirt and rubbing was started at 1 and at 4 hours after application, the transfer of testosterone from male to female partners was prevented.
HOW SUPPLIED
Testim ® contains testosterone, a Schedule III controlled substance as defined by the Anabolic Steroids Control Act.
Testim ® is supplied in unit-dose tubes in cartons of 30.
Each tube contains 50 mg testosterone in 5 g of gel, and is supplied as follows: NDC Number Strength Package Size 66887-001-05 1% (50 mg) 30 tubes: 5 g per tube Storage Store at room temperature 25°C (77°F); Excursions permitted to 15°-30°C (59°-86°F) [See USP Controlled Room Temperature].
Disposal Used Testim ® tubes should be discarded in household trash in a manner that prevents accidental application or ingestion by children or pets; contents flammable.
RX Only Manufactured for: Auxilium Pharmaceuticals, Inc.
Norristown, PA, 19401 USA By: Contract Pharmaceuticals Limited Mississauga, Ontario, Canada L5N 6L6 Labeling Code: AA2500.09 Issued: January 2005 0105-001.a 127997
INDICATIONS AND USAGE
Testim ® is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals.
These men usually have low serum testosterone levels and gonadotropins (FSH, LH) above the normal range.
Hypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation.
These men have low testosterone serum levels but have gonadotropins in the normal or low range.
Testim ® has not been clinically evaluated in males under 18 years of age.
INFORMATION FOR PATIENTS
Information for Patients Advise patients to carefully read the information brochure that accompanies each carton of 30 Testim ® single-use tubes.
Advise patients of the following : Testim ® should not be applied to the scrotum, penis, or abdomen.
Testim ® should be applied once daily at approximately the same time each day to clean dry skin of the shoulders and/or upper arms.
Washing or swimming may lessen testosterone levels; however, when washing occurs two or more hours post drug application, serum testosterone levels remain within the normal range.
Testim ® may be transferred to another person by vigorous contact with the application site.
Potential for transfer may be reduced by washing hands thoroughly after application, by wearing clothing to cover the sites, and by washing the application sites thoroughly with soap and water prior to any direct skin-to-skin contact.
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 (see DOSAGE AND ADMINISTRATION).
Drug Interactions Oxyphenbutazone: Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone.
Insulin: In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, insulin requirements.
Propranolol: 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 ® .
Corticosteroids: 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 Animal Data Testosterone has been tested by subcutaneous injection and implantation in mice and rats.
In mice, the implant induced cervical-uterine tumors, which metastasized in some cases.
There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma.
Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats.
Human Data 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.
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.
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 less than 18 years old has not been established.
DOSAGE AND ADMINISTRATION
The recommended starting dose of Testim ® is 5 g of gel (one tube) containing 50 mg of testosterone applied once daily (preferably in the morning) to clean, dry intact skin of the shoulders and/or upper arms.
Morning serum testosterone levels should then be measured approximately 14 days after initiation of therapy to ensure proper serum testosterone levels are achieved.
If the serum testosterone concentration is below the normal range, or if the desired clinical response is not achieved, the daily Testim ® dose may be increased from 5 g (one tube) to 10 g (two tubes) as instructed by the physician.
Upon opening the tube the entire contents should be squeezed into the palm of the hand and immediately applied to the shoulders and/or upper arms.
Application sites should be allowed to dry for a few minutes prior to dressing.
Hands should be washed thoroughly with soap and water after Testim ® has been applied.
In order to prevent transfer to another person, clothing should be worn to cover the application sites.
If direct skin-to-skin contact with another person is anticipated, the application sites must be washed thoroughly with soap and water.
In order to maintain serum testosterone levels in the normal range, the sites of application should not be washed for at least two hours after application of Testim ® .
Do not apply Testim ® to the genitals or to the abdomen.