Testim - Product Information
|Manufacture:||Endo Pharmaceuticals Inc.|
|Condition:||Breast Cancer, Palliative, Delayed Puberty, Male, Hypogonadism, Male, Postpartum Breast Pain|
|Class:||Androgens and anabolic steroids|
|Form:||Cream, gel, liniment or balm, lotion, ointment, etc|
|Ingredients:||Testosterone, purified water, pentadecalactone, carbopol, acrylates, propylene glycol, glycerin, polyethylene glycol, ethanol (74%), 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 [see Use in Specific Populations].
- Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure [see Dosage and Administration].
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.
Dosing and Dose Adjustment
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, pre-dose 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 (see figure below). 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 [see Warnings and Precautions].
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 [see Warnings and Precautions].
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 wash 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.
Dosage Forms and Strengths
Testim (testosterone gel) for topical use is available in a unit-dose tube. Each tube contains 50 mg testosterone in 5 g of gel.
- Testim is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions].
- Testim is contraindicated in women who are or may become pregnant, or who are breastfeeding. Testim may cause fetal harm when administered to a pregnant woman. Testim may cause serious adverse reactions in nursing infants. Exposure of a fetus or nursing infant to androgens may result in varying degrees of virilization. Pregnant women or those who may become pregnant need to be aware of the potential for transfer of testosterone from men treated with Testim. If a pregnant woman is exposed to Testim, she should be apprised of the potential hazard to the fetus [see Warnings and Precautions and Use in Specific Populations].
Warnings and Precautions
Warning: Secondary Exposure to Testosterone
- Virilization has been reported in children who were secondarily exposed to testosterone gel [see Warnings and Precautions and Adverse Reactions].
- Children should avoid contact with unwashed or unclothed application sites in men using testosterone gel [see Dosage and Administration and Warnings and Precautions]
- Healthcare providers should advise patients to strictly adhere to recommended instructions for use [see Dosage and Administration, Warnings and Precautions].
Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer
- Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms.
- Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens [see Contraindications].
Potential for Secondary Exposure to Testosterone
Cases of secondary exposure resulting in virilization of children have been reported in postmarketing surveillance. 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 gel. 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 topical testosterone product. Children and women should avoid contact with unwashed or unclothed application sites in men using Testim [see Dosage and Administration), Use in Specific Populations].
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.
Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events.
There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as Testim. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with Testim and initiate appropriate workup and management [see Adverse Reactions].
Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use Testim.
Use in Women
Due to lack of controlled evaluations in women and potential virilizing effects, Testim is not indicated for use in women [see Contraindications and Use in Specific Populations].
Potential for Adverse Effects on Spermatogenesis
With large doses of exogenous androgens, including Testim, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count.
Hepatic Adverse Effects
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 life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate, which elevates blood levels for prolonged periods, has produced multiple hepatic adenomas. Testim is not known to cause these adverse effects. Nonetheless, patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue Testim while the cause is evaluated.
Androgens, including Testim, may promote retention of sodium and water. 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 [see Adverse Reactions].
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.
Changes in the serum lipid profile may occur. Monitor the lipid profile periodically, particularly after starting testosterone therapy and after dose increases.
Androgens, including Testim, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients.
Decreased Thyroxine-binding Globulin
Androgens, including Testim, may decrease concentrations of thyroxine-binding globulins, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4.
Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.
Alcohol-based products, including Testim, are flammable; therefore, patients should be advised to avoid fire, flame or smoking until the Testim has dried.
Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In a controlled clinical study, 304 patients were treated with Testim 50 mg or 100 mg or placebo gel for up to 90 days. Two hundred-five (205) patients received Testim 50 mg or 100 mg daily and 99 patients received placebo. Subjects could be counted in both Testim treatment groups if they received both 50 mg and 100 mg at different points in the study and experienced an adverse reaction at both dose levels. Adverse reactions reported by ³1% of the Testim patients and greater than placebo are listed in Table 1.
|Application Site Reactions||2%||4%||3%|
|Blood Pressure Increased||1%||1%||0%|
|Spontaneous Penile Erection||1%||0%||0%|
The following adverse reactions occurred in fewer than 1% of patients but were greater in Testim groups compared to the placebo group: activated partial thromboplastin time prolonged, blood creatinine increased, prothrombin time prolonged, appetite increased, sensitive nipples, and acne.
In this clinical trial of Testim, six patients had adverse reactions that led to their discontinuation. These events included: depression with suicidal ideation, urinary tract infection, mood swings and hypertension. No Testim patients discontinued due to skin reaction. In one foreign Phase 3 trial, one subject discontinued due to a skin-related adverse reaction.
In the pivotal U.S. and European Phase 3 trials combined, at the 50 mg dosage strength, the percentage of subjects reporting clinically notable increases in hematocrit or hemoglobin were similar to placebo. However, in the 100 mg dose group, 2.3% and 2.8% of patients had a clinically notable increase in hemoglobin (≥ 19 g/dL) or hematocrit (³ 58%), respectively, compared to 1.0% and 1.5% of patients in the placebo group, respectively.
In the combined US and European open label extension studies, approximately 140 patients received Testim for at least 6 months. The results from these studies are consistent with those reported for the US controlled clinical trial.
The following adverse reactions have been identified during post-approval use of testosterone gel products. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Secondary Exposure to Testosterone in Children
Cases of secondary exposure to testosterone resulting in virilization of children have been reported in postmarketing surveillance of testosterone gel products. Signs and symptoms of these reported cases have included enlargement of the clitoris (with surgical intervention) or of the penis, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases with a reported outcome, these signs and symptoms were reported to have regressed with removal of the testosterone gel exposure. 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. In some of the cases, direct contact with the sites of application on the skin of men using testosterone gel was reported. In at least one reported case, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user’s shirts and/or other fabric, such as towels and sheets [see Warnings and Precautions].
Venous thromboembolism [see Warnings and Precautions]
Myocardial infarction, stroke [see Warnings and Precautions]
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.
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.
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 Category X [see Contraindications]: Testim is contraindicated in pregnant women or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a fetus to androgens, such as testosterone, may result in varying degrees of virilization. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be made aware of the potential hazard to the fetus.
Although it is not known how much testosterone transfers into human milk, Testim is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants [see Contraindications].
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.
There is insufficient long-term safety data in geriatric patients to assess the potentially increased risks of cardiovascular disease and prostate cancer [see Warnings and Precautions].
No studies were conducted in patients with renal impairment.
No studies were conducted in patients with hepatic impairment.
Drug Abuse and Dependence
Testim contains testosterone, a Schedule III controlled substance in the Controlled Substances Act.
Anabolic steroids, such as testosterone, are abused. Abuse is often associated with adverse physical and psychological effects.
Although drug dependence is not documented in individuals using therapeutic doses of anabolic steroids for approved indications, dependence is observed in some individuals abusing high doses of anabolic steroids. In general, anabolic steroid dependence is characterized by any three of the following:
- Taking more drug than intended
- Continued drug use despite medical and social problems
- Significant time spent in obtaining adequate amounts of drug
- Desire for anabolic steroids when supplies of the drugs are interrupted
- Difficulty in discontinuing use of the drug despite desires and attempts to do so
- Experience of a withdrawal syndrome upon discontinuation of anabolic steroid 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.
How Supplied/Storage and Handling
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||Package Size|
|66887-001-05||30 tubes: 50 mg testosterone in 5 g of gel per tube|
Store at 20 to 25°C (68°F to 77°F). Excursions permitted to 15°-30°C (59°-86°F) [See USP Controlled Room Temperature].
Discard used Testim tubes in household trash in a manner that prevents accidental exposure of women, children, or pets [see Warnings and Precautions]. Contents are flammable [see Warnings and Precautions].
Patient Counseling Information
See FDA-approved patient labeling (Medication Guide).
Advise patients of the following:
Men with Known or Suspected Carcinoma of the Breast or Prostate
Men with known or suspected prostate or breast cancer should not use Testim[see Contraindications and Warnings and Precautions].
Potential for Secondary Exposure to Testosterone and Steps to Prevent Secondary Exposure
Secondary exposure to testosterone in children and women can occur with the use of testosterone gel in men. Cases of secondary exposure to testosterone have been reported in children.
Physicians should advise patients of the reported signs and symptoms of secondary exposure which may include the following:
- In children; unexpected sexual development including inappropriate enlargement of the penis or clitoris, premature development of pubic hair, increased erections, and aggressive behavior
- In women; changes in hair distribution, increase in acne, or other signs of testosterone effects
- The possibility of secondary exposure to testosterone gel should be brought to the attention of a healthcare provider
- Testim should be promptly discontinued until the cause of virilization is identified.
Strict adherence to the following precautions is advised to minimize the potential for secondary exposure to testosterone from testosterone gel in men:
- Children and women should avoid contact with unwashed or unclothed application site(s) of men using testosterone gel
- Patients using Testim should apply the product as directed and strictly adhere to the following:
- Wash hands with soap and water immediately after application
- Cover the application site(s) with clothing after the gel has dried
- Wash the application site(s) thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated
- In the event that unwashed or unclothed skin to which Testim has been applied comes in 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 [see Dosage and Administration, Warnings and Precautions].
Potential Adverse Reactions with Androgens
Patients should be informed that treatment with androgens may lead to adverse reactions which include:
- Changes in urinary habits, such as increased urination at night, trouble starting the urine stream, passing urine many times during the day, having an urge to go the bathroom right away, having a urine accident, or being unable to pass urine or weak urine flow
- Breathing disturbances, including those associated with sleep or excessive daytime sleepiness.
- Too frequent or persistent erections of the penis
- Nausea, vomiting, changes in skin color, or ankle swelling
Patients Should Be Advised of the Following Instructions for Use
- Read the Medication Guide before starting Testim therapy and reread it each time the prescription is renewed.
- Testim should be applied and used appropriately to maximize the benefits and to minimize the risk of secondary exposure in children and women
- Keep Testim out of the reach of children. The package is not child resistant.
- Testim is an alcohol-based product and is flammable; therefore avoid fire, flame or smoking until the gel has dried
- It is important to adhere to all recommended monitoring
- Report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and mood
- Testim is prescribed to meet the patient’s specific needs; therefore, the patient should never share Testim with anyone.
- Testim should be applied once daily at approximately the same time each day to clean dry skin of the shoulders and/or upper arms.
- Testim should not be applied to the scrotum, penis, or abdomen.
- Wait 2 hours before swimming or washing following application of Testim. This will ensure that the greatest amount of Testim is absorbed into their system.
Auxilium Pharmaceuticals, Inc.
Malvern, PA 19355 USA
DPT Laboratories, Ltd.
San Antonio, TX 78215