testosterone

Warnings and Precautions, Venous Thromboembolism ( 5.3 ) Revised: 07/2025 Warnings and Precautions, Blood Pressure Increases ( 5.5 ) Revised: 07/2025 Warnings and Precautions, Cardiovascular Risk ( 5.5 ) Removed Revised: 07/2025

1 INDICATIONS AND USAGE Testosterone Gel, 1.62% 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 conditions such as 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 Testosterone Gel, 1.62% in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established. • Safety and efficacy of Testosterone Gel, 1.62% 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 Indications and Usage (1) , and Clinical Pharmacology (12.3) ] . Testosterone Gel, 1.62% is indicated for 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, 1.62% in men with “age-related hypogonadism” have not been established. ( 1 ) • Safety and efficacy of Testosterone Gel, 1.62% in males less than 18 years old have not been established. ( 1 , 8.4 ) • Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure. ( 1 , 12.3 )

2 DOSAGE AND ADMINISTRATION Dosage and Administration for testosterone gel 1.62% differs from testosterone gel 1%. For dosage and administration of testosterone gel 1% refer to its full prescribing information. ( 2 ) Prior to initiating testosterone gel 1.62%, 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. Dosage and Administration for testosterone gel 1.62% differs from testosterone gel 1%. For dosage and administration of testosterone gel 1% refer to its full prescribing information. ( 2 ) Prior to initiating testosterone gel 1.62%, 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 ). Starting dose of testosterone gel 1.62% is 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet), applied topically once daily in the morning. ( 2.1 ) Apply to clean, dry, intact skin of the shoulders and upper arms. Do not apply testosterone gel 1.62% to any other parts of the body including the abdomen, genitals, chest, armpits (axillae), or knees. ( 2.2 , 12.3 ) Dose adjustment: Testosterone gel 1.62% can be dose adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation) and a maximum of 81 mg of testosterone (4 pump actuations). The dose should be titrated based on the pre-dose morning serum testosterone concentration at approximately 14 days and 28 days after starting treatment or following dose adjustment. Additionally, serum testosterone concentration should be assessed periodically thereafter. ( 2.1 ) Patients should wash hands immediately with soap and water after applying testosterone gel 1.62% and cover the application site(s) with clothing after the gel has dried. Wash the application site 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 1.62% is 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet) applied topically once daily in the morning to the shoulders and upper arms. The dose can be adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation) and a maximum of 81 mg of testosterone (4 pump actuations). To ensure proper dosing, the dose should be titrated based on the pre-dose morning serum testosterone concentration from a single blood draw at approximately 14 days and 28 days after starting treatment or following dose adjustment. In addition, serum testosterone concentration should be assessed periodically thereafter. Table 1 describes the dose adjustments required at each titration step. Table 1: Dose Adjustment Criteria Pre-Dose Morning Total Serum Testosterone Concentration Dose Titration Greater than 750 ng/dL Decrease daily dose by 20.25 mg (1 pump actuation Equal to or greater than 350 and equal to or less than 750 ng/dL No change: continue on current dose Less than 350 ng/dL Increase daily dose by 20.25 mg (1 pump actuation The application site and dose of testosterone gel 1.62% are not interchangeable with other topical testosterone products. 2.2 Administration Instructions Testostrone gel 1.62% should be applied to clean, dry, intact skin of the upper arms and shoulders. Do not apply testostrone gel 1.62% to any other parts of the body, including the abdomen, genitals, chest, armpits (axillae), or knees [see Clinical Pharmacology ( 12.3 )] . Area of application should be limited to the area that will be covered by the patient's short sleeve t-shirt. Patients should be instructed to use the palm of the hand to apply testostrone gel 1.62% and spread across the maximum surface area as directed in Table 2 and in Figure 1 . Table 2: Application Sites for Tes …

3 DOSAGE FORMS AND STRENGTHS Testosterone Gel, 1.62% for topical use only, is available as follows: • A metered-dose pump. Each pump actuation delivers 20.25 mg of testosterone in 1.25 g of gel. • A unit dose packet containing 20.25 mg of testosterone in 1.25 g of gel. • A unit dose packet containing 40.5 mg of testosterone in 2.5 g of gel. Testosterone Gel, 1.62% for topical use is available as follows: • a metered-dose pump that delivers 20.25 mg testosterone per actuation. ( 3 ) • packets containing 20.25 mg testosterone. ( 3 ) • packets containing 40.5 mg testosterone. ( 3 )

4 CONTRAINDICATIONS Testosterone gel 1% is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6.1 ), and Nonclinical Toxicology ( 13.1 )] . Testosterone gel 1% is contraindicated in women who are pregnant. Testosterone gel 1% can cause virilization of the female fetus when administered to a pregnant woman. Pregnant women need to be aware of the potential for transfer of testosterone from men treated with testosterone gel 1%. If a pregnant woman is exposed to testosterone gel 1%, 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 carcinoma of the breast or known or suspected prostate cancer. ( 4 , 5.1 ) Women who are pregnant. Testosterone may cause fetal harm. ( 4 , 8.1 )

6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥ 5%) are acne, application site reaction, abnormal lab tests, and prostatic disorders. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Strides Pharma Inc. at 1-877-244-9825 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. Clinical Trials in Hypogonadal Men Table 1 shows the incidence of all adverse events judged by the investigator to be at least possibly related to treatment with Testosterone Gel 1% and reported by >1% of patients in a 180 Day, Phase 3 study. Table 1: Adverse Events Possibly, Probably or Definitely Related to Use of Testosterone Gel 1% in the 180-Day Controlled Clinical Trial Adverse Event Dose of Testosterone Gel 1% 50 mg 75 mg 100 mg N = 77 N = 40 N = 78 Acne 1% 3% 8% Alopecia 1% 0% 1% Application Site Reaction 5% 3% 4% Asthenia 0% 3% 1% Depression 1% 0% 1% Emotional Lability 0% 3% 3% Gynecomastia 1% 0% 3% Headache 4% 3% 0% Hypertension 3% 0% 3% Lab Test Abnormal* 6% 5% 3% Libido Decreased 0% 3% 1% Nervousness 0% 3% 1% Pain Breast 1% 3% 1% Prostate Disorder** 3% 3% 5% Testis Disorder*** 3% 0% 0% * Lab test abnormal occurred in nine patients with one or more of the following events reported: elevated hemoglobin or hematocrit, hyperlipidemia, elevated triglycerides, hypokalemia, decreased HDL, elevated glucose, elevated creatinine, elevated total bilirubin. ** Prostate disorders included five patients with enlarged prostate, one with BPH, and one with elevated PSA results. *** Testis disorders were reported in two patients: one with left varicocele and one with slight sensitivity of left testis. Other less common adverse reactions, reported in fewer than 1% of patients included: amnesia, anxiety, discolored hair, dizziness, dry skin, hirsutism, hostility, impaired urination, paresthesia, penis disorder, peripheral edema, sweating, and vasodilation. In this 180 day clinical trial, skin reactions at the site of application were reported with Testosterone Gel 1%, but none was severe enough to require treatment or discontinuation of drug. Six patients (4%) in this trial had adverse events that led to discontinuation of Testosterone Gel 1%. These events included: cerebral hemorrhage, convulsion (neither of which were considered related to Testosterone Gel 1% administration), depression, sadness, memory loss, elevated prostate specific antigen, and hypertension. No Testosterone Gel 1% patient discontinued due to skin reactions. In a separate uncontrolled pharmacokinetic study of 10 patients, two had adverse events associated with Testosterone Gel 1%; these were asthenia and depression in one patient and increased libido and hyperkinesia in the other. In a 3 year, flexible dose, extension study, the incidence of all adverse events judged by the investigator to be at least possibly related to treatment with Testosterone Gel 1% and reported by > 1% of patients is shown in Table 2. Table 2: Adverse Events Possibly, Probably or Definitely Related to Use of Testosterone Gel 1% in the 3 Year, Flexible Dose, Extension Study Adverse Event Percent of Subjects (N = 162) Lab Test Abnormal+ 9.3 Skin dry 1.9 Application Site Reaction 5.6 Acne 3.1 Pruritus 1.9 Enlarged Prostate 11.7 Carcinoma of Prostate 1.2 Urinary Symptoms* 3.7 Testis Disorder** 1.9 Gynecomastia 2.5 Anemia 2.5 + Lab test abnormal occurred in 15 patients with one or more of the following events reported: elevated AST, elevated ALT, elevated testosterone, elevated hemoglobin or hematocrit, elevated cholesterol, elevated cholesterol/LDL ratio, elevated triglycerides, elevated HDL, elevated serum creatinine. * Urinary symptoms included nocturia, urinary hesitancy, urinary incontinence, urinary retention, urin …

7 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 ( 7.2 ) • Use of testosterone with adrenocorticotrophic hormone (ACTH) or 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 decrease insulin requirements. 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 anticoagulants, especially at the initiation and termination of androgen therapy. 7.3 Corticosteroids The concurrent use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention and requires careful monitoring particularly in patients with cardiac, renal or hepatic disease.

8 USE IN SPECIFIC POPULATIONS There are insufficient long-term safety data in geriatric patients using testosterone gel, 1.62% to assess the potential risks of cardiovascular disease and prostate cancer. ( 8.5 ) 8.1 Pregnancy Risk Summary Testosterone gel, 1.62% 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 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, 1.62% is not indicated for use in women. 8.3 Females and Males of Reproductive Potential Infertility Testis disorder, testicular atrophy, and oligospermia have been identified during use of testosterone gel, 1.62% [ see Adverse Reactions ( 6.1 , 6.2 )]. During treatment with large doses of exogenous androgens, including testosterone gel, 1.62%, 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 effectiveness of testosterone gel, 1.62% in pediatric patients less than 18 years old has not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses. 8.5 Geriatric Use There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing testosterone gel, 1.62% to determine whether efficacy in those over 65 years of age differs from younger subjects. Of the 234 patients enrolled in the clinical trial utilizing testosterone gel, 1.62%, 21 were over 65 years of age. Additionally, there is insufficient long-term safety data in geriatric patients to assess the potentially increased risks of cardiovascular disease and prostate cancer. Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH. 8.6 Renal Impairment No studies were conducted involving patients with renal impairment. 8.7 Hepatic Impairment No studies were conducted in patients with hepatic impairment.

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 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).

11 DESCRIPTION Testosterone gel 1% is a clear to translucent hydroalcoholic topical gel containing testosterone USP, an androgen. Testosterone gel 1% 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 tube of Testosterone gel 1% contains 50 mg of testosterone, USP 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 testosterone gel 1% is testosterone, USP. 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: Testosterone gel 1% may have an alcoholic/musk odor. Inactive ingredients in testosterone gel 1% are carbomer copolymer type B, carbopol 980, dehydrated alcohol (85% v/v), glycerin, pentadecalactone, polyethylene glycol 1000, propylene glycol, purified water, and tromethamine. 1

10 OVERDOSAGE There is a single report of acute overdosage after parenteral administration of an approved testosterone product in the literature. This subject had serum testosterone concentrations of up to 11,400 ng/dL, which were implicated in a cerebrovascular accident. There were no reports of overdosage in the testosterone gel, 1.62% clinical trial. Treatment of overdosage would consist of discontinuation of testosterone gel, 1.62%, washing the application site with soap and water, and appropriate symptomatic and supportive care.

16 HOW SUPPLIED/STORAGE AND HANDLING Testosterone Gel, 1.62% is supplied in non-aerosol, metered-dose pumps that deliver 20.25 mg of testosterone per complete pump actuation. The pumps are composed of plastic and stainless steel and an LDPE/aluminum foil inner liner encased in rigid plastic with a polypropylene cap. Each 88 g metered-dose pump is capable of dispensing 75 g of gel or 60-metered pump actuations; each pump actuation dispenses 1.25 g of gel. Testosterone Gel, 1.62% is also supplied in unit-dose aluminum foil packets in cartons of 30. Each packet of 1.25 g or 2.5 g gel contains 20.25 mg or 40.5 mg testosterone, respectively. NDC Number Package Size 16714- 967 -01 88 g pump (each pump dispenses 60 metered pump actuations with each pump actuation containing 20.25 mg of testosterone in 1.25 g of gel) 16714- 968 -01 Each unit dose packet contains 20.25 mg of testosterone provided in 1.25 g of gel 16714- 968 -02 30 packets (each unit dose packet contains 20.25 mg of testosterone provided in 1.25 g of gel) 16714- 969 -01 Each unit dose packet contains 40.5 mg of testosterone provided in 2.5 g of gel 16714- 969 -02 30 packets (each unit dose packet contains 40.5 mg of testosterone provided in 2.5 g of gel) Store at controlled room temperature 20°C to 25°C (68°-77°F); excursions permitted to 15°C to 30°C (59°- 86°F) [see USP Controlled Room Temperature]. Used Testosterone Gel, 1.62% pumps or used Testosterone Gel, 1.62% packets should be discarded in household trash in a manner that prevents accidental application or ingestion by children or pets.