Testosterone
Gel · Topical, Transdermal, Oral
Uses
Testosterone gel is indicated for 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 (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 levels but have gonadotropins in the normal or low range. Limitations of Use: Safety and efficacy of testosterone gel in men with "age-related hypogonadism" (also referred to as "late-onset hypogonadism") have not been established. Safety and efficacy of testosterone gel in males less than 18 years old have not been established [see Use in Specific Populations (8.4) ] . Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure [see Dosage and Administration (2) and Clinical Pharmacology (12.3) ] . Testosterone gel is an androgen indicated for testosterone replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired). ( 1 ) Hypogonadotropic hypogonadism (congenital or acquired). ( 1 ) Limitations of Use: Safety and efficacy of testosterone gel in men with age-related hypogonadism have not been established ( 1 ) Safety and efficacy of testosterone gel in males less than 18 years old have not been established ( 8.4 ) Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure ( 1 , 12.3 )
Dosage and administration
Prior to initiating testosterone gel, 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. Prior to initiating testosterone gel, confirm the diagnosis of hypogonadism by ensuring that serum testosterone has been measured in the morning on at least two separate days and that these concentrations are below the normal range ( 2 ). Recommended starting dose for adult males: 50 mg of testosterone (one tube or one packet or 4 pump actuations) applied topically once daily at approximately the same time each day. ( 2.1 ) Apply to clean, dry, intact skin of the shoulders and/or upper arms. Do not apply testosterone gel to the genitals or abdomen. ( 2.1 , 2.2 ) If morning pre-dose serum testosterone concentration is below the normal range, increase dose to 100 mg. ( 2.1 ) Pre-dose serum testosterone concentration should be assessed periodically. ( 2.1 ) Patients should wash hands with soap and water immediately after applying testosterone gel and cover application site(s) with clothing after gel has dried. Wash the application sites thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated. ( 2.2 ) 2.1 Dosing and Dose Adjustment The recommended starting dose of testosterone gel is 50 mg of testosterone (one tube, one packet, or 4 pump actuations) applied topically once daily at approximately the same time each day to clean, dry intact skin of the shoulders and/or upper arms. Dose Adjustment 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 testosterone gel dose may be increased from 50 mg testosterone (one tube, one packet, or 4 pump actuations) to 100 mg of testosterone (two tubes, two packets, or 8 pump actuations) once daily. The maximum recommended dose of testosterone gel is 100 mg once daily. 2.2 Administration Instructions Unit-Dose Tube or Packet Upon opening the tube or packet 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 ]). Table 1 has specific dosing guidelines for when the unit-dose tubes or packets are used. Table 1: Specific Dosing Guideline for Using the Unit-Dose Tubes or Packets Prescribed Daily Dose Number of Unit-Dose Tubes or Packets Application Method 50 mg testosterone One unit-dose tube or packet (once daily) Apply one unit-dose tube or packet to one upper arm and shoulder. 100 mg testosterone Two unit-dose tubes or packets (once daily) Apply one unit-dose tube or packet to one upper arm and shoulder and then apply one unit-dose tube or packet to the opposite upper arm and shoulder. Multi-Dose Metered Pump Patients should be instructed to prime the pump before using it for the first time by fully depressing the pump mechanism (actuation) 3 times and discard this portion of the product to assure precise dose delivery. After the priming procedure, patients should completely depress the pump one time (actuation) for every 12.5 mg of testosterone required to achieve the daily prescribed dosage. Table 2 has specific dosing guidelines for when the metered pump is used. Table 2: Specific Dosing Guidelines for Using the Multi-Dose Pump Prescribed Daily Dose Number of Pump Actuations Application Method 50 mg testosterone 4 (once daily) Apply 4 pump actuations to one upper arm and shoulder 100 mg testosterone 8 (once daily) Apply 4 pump actuations to one upper arm and shoulder and then apply 4 pump actuations to the opposite upper arm and shoulder The prescribed amount of product should be delivered directly 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 testosterone gel to the genitals or to the abdomen. Application sites should be allowed to dry completely prior to dressing. Hands should be washed thoroughly with soap and water after testosterone gel has been applied. Avoid fire, flame or smoking during the application of testosterone gel until the gel has dried [see Warnings and Precautions (5.2 , 5.16) ] . In order to prevent transfer to another person, clothing should be worn to cover the application site(s). If direct skin-to-skin contact of the application site(s) with another person is anticipated, the application site(s) must be washed thoroughly with soap and water [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ] . The patient should avoid swimming or showering or washing the administration site for a minimum of 2 hours after application [see Clinical Pharmacology (12.3) ] . Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from testosterone gel treated skin: Children and women should avoid contact with unwashed or unclothed application site(s) of men using testosterone gel. Testosterone gel 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 testosterone gel. Patients should cover the application site(s) with clothing (e.g., a t-shirt) after the gel has dried.
Dosage forms and strengths
Testosterone gel is a clear to translucent hydroalcoholic topical gel for topical use available in unit-dose tubes, unit-dose packets, and multiple-dose metered pumps. Each tube or packet provides 50 mg testosterone in 5 g of gel. One pump actuation delivers 12.5 mg testosterone in 1.25 g of gel (4 actuations = 50 mg testosterone). Topical Gel available as: 50 mg of testosterone in a unit-dose tube. ( 3 ) 50 mg of testosterone in a unit-dose packet. ( 3 ) 12.5 mg of testosterone per one pump actuation in a metered-dose pump. ( 3 )
Contraindications
Testosterone gel is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions (5.1) ] . Testosterone gel is contraindicated in women who are pregnant. Testosterone gel can cause virilization of the female fetus when administered to a pregnant woman. Pregnant women need to be aware of the potential for skin transfer of testosterone from men treated with testosterone gel. If a pregnant woman is exposed to testosterone gel, she should be apprised of the potential hazard to the fetus [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1) ]. Men with known carcinoma of the breast or known or suspected carcinoma of the prostate. ( 4 , 5.1 ) Women who are pregnant. Testosterone may cause fetal harm. ( 4 , 8.1 )
Warnings and precautions
Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH. ( 5.1 ) Avoid unintentional exposure of women or children to testosterone gel. Secondary exposure to testosterone can produce signs of virilization. Testosterone gel should be discontinued until the cause of virilization is identified. ( 5.2 ) 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. ( 5.4 ) Some postmarketing studies have shown an increased risk of myocardial infarction and stroke associated with use of testosterone replacement therapy. ( 5.5 ) Exogenous administration of androgens may lead to azoospermia. ( 5.8 ) Edema, with or without congestive heart failure, may be a complication in patients with preexisting cardiac, renal, or hepatic disease. ( 5.10 ) Sleep apnea may occur in those with risk factors. ( 5.12 ) Monitor prostate specific antigen (PSA), hematocrit, and lipid concentrations periodically. ( 5.1 , 5.3 , 5.13 ) Testosterone gel is flammable until dry. ( 5.16 ) 5.1 Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer Men 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 (4) ]. 5.2 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 testosterone gel [see Dosage and Administration (2.2) , Use in Specific Populations (8.1) and Clinical Pharmacology (12.3) ] . 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. 5.3 Polycythemia 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. 5.4 Venous Thromboembolism 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 testosterone gel. Evaluate patients who report signs and 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 testosterone gel and initiate appropriate workup and management [see Adverse Reactions (6.2) ] . 5.5 Cardiovascular Risk 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 testosterone gel. 5.6 Abuse of Testosterone and Monitoring of Serum Testosterone Concentrations Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see Drug Abuse and Dependence (9) ] . If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.
Side effects
Most common adverse reactions (incidence ≥ 2% of the testosterone gel patients and greater than placebo) are application site reactions and increased hematocrit. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact UPSHER-SMITH LABORATORIES, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial 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 testosterone gel 50 mg or 100 mg or placebo gel for up to 90 days. Two hundred-five (205) patients received testosterone gel 50 mg or 100 mg daily and 99 patients received placebo. Subjects could be counted in both testosterone gel 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 ≥1% of the testosterone gel patients and greater than placebo are listed in Table 3. Table 3: Incidence of Adverse Reactions (Reported by ≥1% of the Testosterone Gel Patients and Greater than Placebo) in the Controlled Clinical Trial Through 90 Days Event Testosterone Gel 50 mg (n=103) Testosterone Gel 100 mg (n=149) Placebo (n=99) Application Site Reactions 2% 4% 3% Blood Pressure Increased 1% 1% 0% Gynecomastia 1% 0% 0% Headache 1% 1% 0% Hematocrit/Hemoglobin Increased 1% 2% 0% Hot Flushes 1% 0% 0% Insomnia 1% 0% 0% Mood Swings 1% 0% 0% Smell Disorder 1% 0% 0% Spontaneous Penile Erection 1% 0% 0% Taste Disorder 1% 1% 0% The following adverse reactions occurred in fewer than 1% of patients but were greater in testosterone gel 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 testosterone gel, six patients had adverse events that led to their discontinuation. These events included: depression with suicidal ideation, urinary tract infection, mood swings and hypertension. No testosterone gel patients discontinued due to skin reaction. In one foreign Phase 3 trial, one subject discontinued due to a skin-related adverse event. 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 (≥ 58%), respectively, compared to 1.0% and 1.5% of patients in the placebo group, respectively. In the combined U.S. and European open label extension studies, approximately 140 patients received testosterone gel for at least 6 months. The results from these studies are consistent with those reported for the U.S. controlled clinical trial. 6.2 Postmarketing Experience 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 fabrics, such as towels and sheets [see Warnings and Precautions (5.2) ] . Cardiovascular Disorders: Myocardial infarction, stroke [see Warnings and Precautions (5.5) ] Vascular Disorders: Venous thromboembolism [see Warnings and Precautions (5.4) ].
Drug interactions
Androgens may decrease blood glucose and therefore may decrease insulin requirements in diabetic patients. ( 7.1 ) Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of International Normalized Ratio (INR) and prothrombin time is recommended in patients taking warfarin. ( 7.2 ) Use of testosterone with corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal or hepatic disease. ( 7.3 ) 7.1 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. 7.2 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. 7.3 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
Geriatric Patients: There are insufficient long-term safety data to assess the potential risks of cardiovascular disease and prostate cancer. ( 8.5 ) 8.1 Pregnancy Risk Summary Testosterone gel is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action [see Contraindications (4) and Clinical Pharmacology (12.1) ] . Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies. Data Animal Data In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. Structural impairments observed in females included increased ano-genital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased or decreased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes. Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant female rats and their offspring exposed to doses approximately twice those used for testosterone replacement therapy. 8.2 Lactation Risk Summary Testosterone gel is not indicated for use in women. 8.3 Females and Males of Reproductive Potential Infertility During treatment with large doses of exogenous androgens, including testosterone gel, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis [see Warnings and Precautions (5.8) ] . 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 [see Drug Abuse and Dependence (9.2) ] . With either type of use, the impact on fertility may be irreversible. 8.4 Pediatric Use The safety and efficacy of testosterone gel 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. 8.5 Geriatric Use 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 (5.1) ] . 8.6 Renal Impairment No studies were conducted in patients with renal impairment. 8.7 Hepatic Impairment No studies were conducted in patients with hepatic impairment.
Pregnancy
8.1 Pregnancy Risk Summary Testosterone gel is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action [see Contraindications (4) and Clinical Pharmacology (12.1) ] . Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies. Data Animal Data In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. Structural impairments observed in females included increased ano-genital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased or decreased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes. Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant female rats and their offspring exposed to doses approximately twice those used for testosterone replacement therapy.
Pediatric use
8.4 Pediatric Use The safety and efficacy of testosterone gel 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
8.5 Geriatric Use 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 (5.1) ] .
Overdosage
There were no reports of overdose in the testosterone gel 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 testosterone gel, washing the application site with soap and water, and appropriate symptomatic and supportive care.
Description
Testosterone gel, for topical use is a clear to translucent hydroalcoholic topical gel containing testosterone, an androgen. Testosterone gel 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. Testosterone gel is available in unit-dose tubes, unit-dose packets, and a metered-dose pump. One 5-g or two 5-g tubes/packets of testosterone gel contains 50 mg or 100 mg of testosterone, respectively. One pump actuation dispenses 1.25 g of gel, which contains 12.5 mg of testosterone. Four pump actuations or eight pump actuations contain 50 mg or 100 mg of testosterone, respectively. Each metered-dose pump container is capable of dispensing 60 pump actuations. The active pharmacological ingredient in testosterone gel is testosterone. Testosterone USP is a white to practically white crystalline powder chemically described as 17-β hydroxyandrost-4-en-3-one. The structural formula is shown in the following figure: Inactive ingredients in testosterone gel are carbomer copolymer Type B, carbomer homopolymer Type C, diisopropyl adipate, ethyl alcohol, glycerin, methyl laurate, oleyl alcohol, polyethylene glycol, propylene glycol, purified water, and tromethamine. Chemical Structure
Mechanism of action
12.1 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 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, and 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).
How supplied
16.1 How Supplied Testosterone gel is supplied in unit-dose tubes in cartons of 30 and unit-dose packets in cartons of 30. Each tube or packet contains 50 mg testosterone in 5 g of gel. Testosterone gel is also supplied in a metered-dose pump that delivers 12.5 mg of testosterone per complete pump actuation. Each 88 g metered-dose pump is capable of dispensing 75 g of gel or 60-metered pump actuations. Each pump actuation delivers 1.25 g of gel. The metered-dose pump is supplied in cartons of 2. Testosterone gel is available as follows: NDC Number Strength Package Size 0832-1120-05 50 mg of testosterone 30 tubes (5 g of gel per tube) 0832-1120-65 50 mg of testosterone 1 tube (5 g of gel per tube) 0832-1120-35 50 mg of testosterone 30 packets (5 g of gel per packet) 0832-1120-89 50 mg of testosterone 1 packet (5 g of gel per packet) 0832-1121-42 12.5 mg of testosterone per pump actuation 2 × 75 g pumps (each pump dispenses 60 metered 1.25 g of gel) 16.2 Storage Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] 16.3 Handling and Disposal Used testosterone gel tubes, packets or pumps should be discarded in household trash in a manner that prevents accidental exposure of women, children, or pets [see Boxed Warning and Warnings and Precautions (5.2) ] . Contents are flammable [see Warnings and Precautions (5.16) ] .
Storage
16.2 Storage Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.]
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Men with Known or Suspected Carcinoma of the Breast or Prostate Men with known or suspected prostate or breast cancer should not use testosterone gel [see Contraindications (4) and Warnings and Precautions (5.1) ] . 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 products 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 Testosterone gel 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 [see Medication Guide ] Children and women should avoid contact with unwashed or unclothed application site(s) of men using testosterone gel Patients using testosterone gel 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 testosterone gel 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 (2.2) , Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ] . 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 testosterone gel therapy and reread it each time the prescription is renewed. Testosterone gel should be applied and used appropriately to maximize the benefits and to minimize the risk of secondary exposure in children and women. Keep testosterone gel out of the reach of children. The package is not child resistant. Testosterone gel 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. Testosterone gel is prescribed to meet the patient's specific needs; therefore, the patient should never share testosterone gel with anyone. Testosterone gel should be applied topically once daily at approximately the same time each day to clean dry skin of the shoulders and/or upper arms. Testosterone gel should not be applied to the scrotum, penis, or abdomen. Wait 2 hours before washing or swimming following application of testosterone gel. This will ensure that the greatest amount of testosterone gel is absorbed.
Label text from the FDA structured product label by Upsher-Smith Laboratories, LLC (revised Jul 9, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Testosterone in 43 products
Testosterone NDC products (43)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0591-2921 | Testosterone 10 mg/g Gel | Actavis Pharma, Inc. | ANDA · DEA CIII |
| 0591-2924 | Testosterone 16.2 mg/g Gel | Actavis Pharma, Inc. | ANDA · DEA CIII |
| 0591-2926 | Testosterone 16.2 mg/g Gel | Actavis Pharma, Inc. | ANDA · DEA CIII |
| 0591-3216 | Testosterone 10 mg/g Gel | Actavis Pharma, Inc. | ANDA · DEA CIII |
| 0591-3217 | Testosterone 10 mg/g Gel | Actavis Pharma, Inc. | ANDA · DEA CIII |
| 0591-3524 | Testosterone 50 mg/5g Gel | Actavis Pharma, Inc. | ANDA · DEA CIII |
| 0591-2114 | Testosterone 30 mg/1.5mL Solution | Actavis Pharma, Inc. | ANDA · DEA CIII |
| 62332-488 | Testosterone 30 mg/1.5mL Solution | Alembic Pharmaceuticals Inc. | ANDA · DEA CIII |
| 62332-552 | Testosterone 16.2 mg/g Gel | Alembic Pharmaceuticals Inc. | ANDA · DEA CIII |
| 69238-1013 | Testosterone 20.25 mg/1.25g Gel, Metered | Amneal Pharmaceuticals NY LLC | ANDA · DEA CIII |
| 72162-1962 | Testosterone 20.25 mg/1.25g Gel, Metered | Bryant Ranch Prepack | ANDA · DEA CIII |
| 72162-1426 | Testosterone 16.2 mg/g Gel | Bryant Ranch Prepack | ANDA · DEA CIII |
| 72162-1421 | Testosterone 30 mg/1.5mL Solution | Bryant Ranch Prepack | ANDA · DEA CIII |
| 71335-2742 | Testosterone 16.2 mg/g Gel | Bryant Ranch Prepack | ANDA · DEA CIII |
| 63629-9310 | Testosterone 30 mg/1.5mL Solution | Bryant Ranch Prepack | ANDA · DEA CIII |
| 63629-2352 | Testosterone 20.25 mg/1.25g Gel, Metered | Bryant Ranch Prepack | ANDA · DEA CIII |
| 63629-8455 | Testosterone 16.2 mg/g Gel | Bryant Ranch Prepack | ANDA · DEA CIII |
| 69097-363 | Testosterone 30 mg/1.5mL Solution | Cipla USA Inc. | ANDA · DEA CIII |
| 43598-304 | Testosterone 1.62 mg/g Gel, Metered | Dr. Reddy's Laboratories, Inc. | ANDA · DEA CIII |
| 21922-030 | Testosterone 16.2 mg/g Gel | Encube Ethicals, Inc. | ANDA · DEA CIII |
| 21922-109 | Testosterone 30 mg/1.5mL Solution | Encube Ethicals, Inc. | ANDA · DEA CIII |
| 68180-943 | Testosterone 30 mg/1.5mL Solution | Lupin Pharmaceuticals, Inc. | ANDA · DEA CIII |
| 68180-941 | Testosterone 16.2 mg/g Gel | Lupin Pharmaceuticals, Inc. | ANDA · DEA CIII |
| 16714-969 | Testosterone 40.5 mg/2.5g Gel | Northstar Rx LLC | ANDA · DEA CIII |
| 72603-265 | Testosterone 20.25 mg/1.25g Gel, Metered | Northstar Rx LLC | ANDA · DEA CIII |
| 16714-968 | Testosterone 20.25 mg/1.25g Gel | Northstar Rx LLC | ANDA · DEA CIII |
| 45802-754 | Testosterone 16.2 mg/g Gel | Padagis Israel Pharmaceuticals Ltd | ANDA · DEA CIII |
| 45802-281 | Testosterone 20.25 mg/1.25g Gel | Padagis Israel Pharmaceuticals Ltd | ANDA · DEA CIII |
| 45802-366 | Testosterone 40.5 mg/2.5g Gel | Padagis Israel Pharmaceuticals Ltd | ANDA · DEA CIII |
| 45802-610 | Testosterone 30 mg/1.5mL Solution | Padagis Israel Pharmaceuticals Ltd | ANDA · DEA CIII |
| 64380-152 | Testosterone 50 mg/5g Gel | Strides Pharma Science Limited | ANDA · DEA CIII |
| 64380-151 | Testosterone 25 mg/2.5g Gel | Strides Pharma Science Limited | ANDA · DEA CIII |
| 24979-078 | Testosterone 16.2 mg/g Gel | Upsher-Smith Laboratories, LLC | ANDA · DEA CIII |
| 70700-112 | Testosterone 20.25 mg/1.25g Gel, Metered | Xiromed, LLC | ANDA · DEA CIII |
| 66993-953 | Testosterone 12.5 mg/1.25g Gel | Prasco Laboratories | NDA AUTHORIZED GENERIC · DEA CIII |
| 66993-954 | Testosterone 25 mg/2.5g Gel | Prasco Laboratories | NDA AUTHORIZED GENERIC · DEA CIII |
| 66993-955 | Testosterone 50 mg/5g Gel | Prasco Laboratories | NDA AUTHORIZED GENERIC · DEA CIII |
| 66993-952 | Testosterone 16.2 mg/g Gel | Prasco Laboratories | NDA AUTHORIZED GENERIC · DEA CIII |
| 66993-951 | Testosterone 16.2 mg/g Gel | Prasco Laboratories | NDA AUTHORIZED GENERIC · DEA CIII |
| 0832-1121 | Testosterone 12.5 mg/1 Gel, Metered | Upsher-Smith Laboratories, LLC | NDA AUTHORIZED GENERIC · DEA CIII |
| 0832-1120 | Testosterone 50 mg/5g Gel | Upsher-Smith Laboratories, LLC | NDA AUTHORIZED GENERIC · DEA CIII |
| 43742-1242 | Testosterone 8 [hp_X]/mL Liquid | Deseret Biologicals, Inc. | UNAPPROVED HOMEOPATHIC · DEA CIII |
| 44117-0003 | Testosterone 30 [hp_X]/1 Tablet | Zoe Processing | UNAPPROVED HOMEOPATHIC · DEA CIII |
Testosterone recalls
- D-0198-2026 Dec 10, 2025 · Class III · Ongoing
Defective Container - A defect in the side-seal which allows leakage of product. - D-0293-2025 Apr 2, 2025 · Class II · Ongoing
Presence of foreign substance: Presence of Benzene. - D-0294-2025 Apr 2, 2025 · Class II · Ongoing
Presence of foreign substance: Presence of Benzene. - D-0637-2024 Aug 28, 2024 · Class II · Ongoing
Superpotent Drug - D-0127-2024 Dec 6, 2023 · Class III · Terminated
OOS for viscosity - D-1289-2022 Aug 3, 2022 · Class II · Terminated
Superpotent Drug: Out of specification assay result was obtained during stability testing. - D-0100-2021 Nov 25, 2020 · Class III · Terminated
Superpotent Drug: High out-of-specification assay results were obtained during stability testing. - D-1454-2019 Jul 10, 2019 · Class III · Terminated
Defective Container; actuator may improperly function and affect dose delivery. - D-1010-2019 Mar 27, 2019 · Class III · Terminated
Defective Container: Repetitive complaints received indicating pump not working. - D-0087-2019 Oct 31, 2018 · Class III · Terminated
Defective Container: Repetitive complaints received indicating pump not working.
Frequently asked questions
What is Testosterone used for?
Testosterone gel is indicated for 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…
What are the side effects of Testosterone?
Most common adverse reactions (incidence ≥ 2% of the testosterone gel patients and greater than placebo) are application site reactions and increased hematocrit. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact UPSHER-SMITH LABORATORIES, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely… See the full label for the complete list.
Who makes Testosterone?
Testosterone is listed by 16 labelers in the FDA NDC directory, including Actavis Pharma, Inc., Alembic Pharmaceuticals Inc., Amneal Pharmaceuticals NY LLC, Bryant Ranch Prepack.
Has Testosterone been recalled?
The FDA enforcement database lists 10 recalls for Testosterone, most recently D-0198-2026 (class iii): Defective Container - A defect in the side-seal which allows leakage of product.