TESTIM® (testosterone gel) for topical use, CIII
TESTIM (testosterone gel) is a clear to translucent hydroalcoholic topical gel containing testosterone, an androgen. TESTIM provides continuous transdermal delivery of testosterone for 24 hours, following a single application to intact, clean, dry skin of the shoulders and/or upper arms.
One 5-g or two 5-g tubes of TESTIM contains 50 mg or 100 mg of testosterone, respectively, to be applied daily to the skin’s surface. Approximately 10% of the applied testosterone dose is absorbed across skin of average permeability during a 24-hour period.
The active pharmacological ingredient in TESTIM is testosterone. Testosterone USP is a white to practically white crystalline powder chemically described as 17-β hydroxyandrost-4-en-3-one.
Testim may have an alcoholic/musk odor. Inactive ingredients in TESTIM are purified water, pentadecalactone, carbopol, acrylates, propylene glycol, glycerin, polyethylene glycol, ethanol (74%), and tromethamine.
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 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. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range.
Limitations of use:
Safety and efficacy of TESTIM in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.
Safety and efficacy of TESTIM in males less than 18 years old have not been established.
Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure
Mechanism of Action
Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of 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; and alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics.
Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has 2 main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s syndrome or Leydig cell aplasia, while secondary hypogonadism (hypogonadotropic hypogonadism) is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).
Dosage and administration
Prior to initiating TESTIM, 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 testosterone concentrations are below the normal range.
The recommended starting dose of TESTIM is 50 mg of testosterone (one tube) applied once daily (preferably in the morning) to clean, dry intact skin of the shoulders and/or upper arms
To ensure proper dosing, serum testosterone concentrations should be measured. Morning, predose serum testosterone concentrations should be measured approximately 14 days after initiation of therapy to ensure proper serum testosterone concentrations are achieved. If the serum testosterone concentration is below the normal range (300 ng/dL to 1,000 ng/dL), the daily TESTIM dose may be increased from 50 mg testosterone (one tube) to 100 mg testosterone (two tubes) once daily.
The maximum recommended dose of TESTIM is 100 mg once daily.
The application site and dose of TESTIM are not interchangeable with other topical testosterone products.
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 (area of application should be limited to the area that will be covered by the patient’s short sleeve T-shirt. Do not apply TESTIM to the genitals or to the abdomen.
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. Avoid fire, flame or smoking during the application of TESTIM until the TESTIM has dried
In order to prevent transfer to another person, wear clothing 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
The patient should avoid swimming or showering or washing the administration site for a minimum of 2 hours after application
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 unwashed or unclothed application site(s) of men using TESTIM.
TESTIM should only be applied to the upper arms and shoulders. The area of application should be limited to the area that will be covered by a short sleeve T-shirt.
Patients should w ash their hands with soap and water immediately after applying TESTIM.
Patients should cover the application site(s) with clothing (e.g., a T-shirt) after the gel has dried.
Prior to situations in which direct 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.
TESTIM is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate.
TESTIM is contraindicated in women who are pregnant. Testosterone can cause virilization of the female fetus when administered to a pregnant woman
Warnings and precautions
- Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH.
- Avoid unintentional exposure of women or children to TESTIM. Secondary exposure to testosterone can produce signs of virilization. TESTIM should be discontinued until the cause of virilization is identified.
- Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), have been reported in patients using testosterone products. Evaluate patients with signs or symptoms consistent with DVT or PE.
- Some postmarketing studies have shown an increased risk of myocardial infarction and stroke associated with use of testosterone replacement therapy.
- Exogenous administration of androgens may lead to azoospermia.
- Edema, with or without congestive heart failure, may be a complication in patients with preexisting cardiac, renal, or hepatic disease.
- Sleep apnea may occur in those with risk factors.
- Monitor prostate specific antigen (PSA), hematocrit, and lipid concentrations periodically.
- TESTIM is flammable until dry.
Insulin: Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of anti-diabetic medication.
Oral Anticoagulants: Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking warfarin, especially at the initiation and termination of androgen therapy.
Corticosteroids: The concurrent use of testosterone with corticosteroids may result in increased fluid retention and requires careful monitoring particularly in patients with cardiac, renal or hepatic disease.
Use in specific populations
Pregnancy: TESTIM is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm based on data from animal studies and its mechanism of action
Lactation: TESTIM is not indicated for use in females.
Infertility: During treatment with large doses of exogenous androgens, including TESTIM, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis, possible leading to adverse effects on semen parameters including sperm count. Reduced fertility is observed in some men taking testosterone replacement therapy. Testicular atrophy, subfertility, and infertility have also been reported in men who abuse anabolic androgenic steroids. With either type of use, the impact on fertility may be irreversible.
Pediatric Use: The safety and effectiveness of TESTIM in pediatric patients less than 18 years old have not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.
Geriatric Use: There is insufficient long-term safety data in geriatric patients to assess the potentially increased risks of cardiovascular disease and prostate cancer
Drug abuse and dependence
Controlled Substance: TESTIM contains testosterone, a Schedule III controlled substance in the Controlled Substances Act.
Abuse: Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse of men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice.
Dependence: Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors:
Taking greater dosages than prescribed
Continued drug use despite medical and social problems due to drug use
Spending significant time to obtain the drug when supplies of the drug are interrupted
Giving a higher priority to drug use than other obligations
Having difficulty in discontinuing the drug despite desires and attempts to do so
Experiencing withdrawal symptoms upon abrupt discontinuation of use
There were no reports of overdose in the TESTIM clinical trials. There is a single report in the literature of acute overdosage after injection of testosterone enanthate. This subject had serum testosterone concentrations of up to 11,400 ng/dL, which were implicated in a cerebrovascular accident.
Treatment of overdosage would consist of discontinuation of TESTIM, washing the application site with soap and water, and appropriate symptomatic and supportive care.