AndroGel 1 % (25MG / 2.5GM) Transdermal Gel

Details

Generic Name: TESTOSTERONE

Brand Name: Androgel

Substance Name(s):
TESTOSTERONE

DRUG INTERACTIONS

7 •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 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.

OVERDOSAGE

10 There is one report of acute overdosage with use of an approved injectable testosterone product: this subject had serum testosterone concentrations of up to 11,400 ng/dL with a cerebrovascular accident. Treatment of overdosage would consist of discontinuation of Testosterone Gel 1%, washing the application site with soap and water, and appropriate symptomatic and supportive care.

DESCRIPTION

11 Testosterone Gel 1% is a clear, colorless hydroalcoholic gel containing testosterone. The active pharmacologic ingredient in Testosterone Gel 1% is testosterone, an androgen. Testosterone USP is a white to practically white crystalline powder chemically described as 17-beta hydroxyandrost-4-en-3-one. The structural formula is: C 19H28O2 MW 288.42 Pharmacologically inactive ingredients in Testosterone Gel 1% are carbomer 940, ethanol 68.9%, isopropyl myristate, purified water and sodium hydroxide. These ingredients are not pharmacologically active. structure

CLINICAL STUDIES

14 14.1 Clinical Trials in Adult Hypogonadal Males Testosterone Gel 1% was evaluated in a multi-center, randomized, parallel-group, active-controlled, 180-day trial in 227 hypogonadal men. The study was conducted in 2 phases. During the Initial Treatment Period (Days 1-90), 73 patients were randomized to Testosterone Gel 1% 50 mg daily, 78 patients to Testosterone Gel 1% 100 mg daily, and 76 patients to a non-scrotal testosterone transdermal system. The study was double-blind for dose of Testosterone Gel 1% but open-label for active control. Patients who were originally randomized to Testosterone Gel 1% and who had single-sample serum testosterone concentrations above or below the normal range on Day 60 were titrated to 75 mg daily on Day 91. During the Extended Treatment Period (Days 91-180), 51 patients continued on Testosterone Gel 1% 50 mg daily, 52 patients continued on Testosterone Gel 1% 100 mg daily, 41 patients continued on a non-scrotal testosterone transdermal system (5 mg daily), and 40 patients received Testosterone Gel 1% 75 mg daily. Upon completion of the initial study, 163 enrolled and 162 patients received treatment in an open-label extension study of Testosterone Gel 1% for an additional period of up to 3 years. Mean peak, trough and average serum testosterone concentrations within the normal range (298‑1043 ng/dL) were achieved on the first day of treatment with doses of 50 mg and 100 mg of Testosterone Gel 1%. In patients continuing on Testosterone Gel 1% 50 mg and 100 mg, these mean testosterone concentrations were maintained within the normal range for the 180-day duration of the original study. Figure 2 summarizes the 24-hour pharmacokinetic profiles of testosterone administered as Testosterone Gel 1% for 30, 90 and 180 days. Testosterone concentrations were maintained as long as the patient continued to properly apply the prescribed Testosterone Gel 1% treatment. Figure2: MeanSteady-StateTestosteroneConcentrationsinPatientswithOnce-DailyTestosterone Gel1% Therapy Table 5 summarizes the mean testosterone concentrations on Treatment Day 180 for patients receiving 50 mg, 75 mg, or 100 mg of Testosterone Gel 1%. The 75 mg dose produced mean concentrations intermediate to those produced by 50 mg and 100 mg of Testosterone Gel 1%. Table 5: Mean (±SD) Steady-State Serum Testosterone Concentrations During Therapy (Day 180) 50 mg 75 mg 100 mg N= 44 N= 37 N= 48 Cavg 555 ± 225 601 ± 309 713 ± 209 Cmax 830 ± 347 901 ± 471 1083 ± 434 Cmin 371 ± 165 406 ± 220 485 ± 156 Of 129 hypogonadal men who were appropriately titrated with Testosterone Gel 1% and who had sufficient data for analysis, 87% achieved an average serum testosterone concentration within the normal range on Treatment Day 180. In patients treated with Testosterone Gel 1%, there were no observed differences in the average daily serum testosterone concentrations at steady state based on age, cause of hypogonadism, or body mass index. DHT concentrations increased in parallel with testosterone concentrations at Testosterone Gel 1% doses of 50 mg/day and100 mg/day, but the DHT/T ratio stayed within normal range, indicating enhanced availability of the major physiologically active androgen. Serum estradiol (E2) concentrations increased significantly within 30 days of starting treatment with Testosterone Gel 1% 50 or 100 mg/day and remained elevated throughout the treatment period but remained within the normal range for eugonadal men. Serum levels of SHBG decreased very slightly (1 to11%) during Testosterone Gel 1% treatment. In men with hypergonadotropic hypogonadism, serum levels of LH and FSH fell in a dose- and time-dependent manner during treatment with Testosterone Gel1% figure2 14.2 Phototoxicity in Humans The phototoxic potential of Testosterone Gel 1% was evaluated in a double-blind, single-dose study in 27 subjects with photosensitive skin types. The Minimal Erythema Dose (MED) of ultraviolet radiation was determined for each subject. A single 24 (+1) hour application of duplicate patches containing test articles (placebo gel, testosterone gel, or saline) was made to naive skin sites on Day 1. On Day 2, each subject received five exposure times of ultraviolet radiation, each exposure being 25% greater than the previous one. Skin evaluations were made on Days 2 to 5. Exposure of test and control article application sites to ultraviolet light did not produce increased inflammation relative to non-irradiated sites, indicating no phototoxic effect.

HOW SUPPLIED

16 Testosterone Gel 1% is supplied in unit-dose aluminum foil packets in cartons of 30. Each packet of 2.5 g or 5 g gel contains 25 mg or 50 mg testosterone, respectively. NDC Number Package Size 49884-418-72 30 packets(a unit dose packet containing 25 mg of testosterone provided in 2.5g of gel) 49884-510-72 30 packets(a unit dose packet containing 50 mg of testosterone provided in 5g of gel) Storage Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Disposal Used Testosterone Gel 1% pumps or used Testosterone Gel 1% packets should be discarded in household trash in a manner that prevents accidental application or ingestion by children or pets.

RECENT MAJOR CHANGES

Indications and Usage (1) 5/2015 Dosage and Administration (2) 5/2015 Dosage and Administration (2.2) 11/2014 Warnings and Precautions (5.4) 6/2014 Warnings and Precautions (5.5) 5/2015

GERIATRIC USE

8.5 Geriatric Use There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing Testosterone Gel 1% to determine whether efficacy in those over 65 years of age differs from younger subjects. Additionally, there is insufficient long-term safety data in geriatric patients to assess the potential 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.

DOSAGE FORMS AND STRENGTHS

3 Testosterone Gel 1% for topical use is available as follows: •A unit dose packet containing 25 mg of testosterone provided in 2.5 g of gel. •A unit dose packet containing 50 mg of testosterone provided in 5 g of gel. Testosterone Gel 1% for topical use is available as follows: •Packets containing 25 mg of testosterone. (3) •Packets containing 50 mg of testosterone. (3)

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 prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal chord thickening, 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 two main etiologies. Primary hypogonadism caused by defects of the gonads, such as Klinefelter’s Syndrome or Leydigcellaplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins(FSH, LH).

INDICATIONS AND USAGE

1 Testosterone Gel 1% 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% in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established. •Safety and efficacy of Testosterone Gel 1% 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 (1, 12.3). Testosterone Gel 1% 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% in men with “age-related hypogonadism” have not been established. (1) •Safety and efficacy of Testosterone Gel 1% 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)

PEDIATRIC USE

8.4 Pediatric Use The safety and efficacy of Testosterone Gel 1% 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.

PREGNANCY

8.1 Pregnancy Pregnancy Category X [see Contraindications (4)]: Testosterone Gel 1% is contraindicated during pregnancy or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a female fetus to androgens 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 apprised of the potential hazard to a fetus.

NUSRING MOTHERS

8.3 Nursing Mothers Although it is not known how much testosterone transfers into human milk, Testosterone Gel 1% is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants. Testosterone and other androgens may adversely affect lactation [see Contraindications (4)].

BOXED WARNING

WARNING: SECONDARY EXPOSURE TO TESTOSTERONE • Virilization has been reported in children who were secondarily exposed to testosterone gel [see Warnings and Precautions (5.2) and Adverse Reactions (6.2)]. • Children should avoid contact with unwashed or unclothed application sites in men using testosterone gel [see Dosage and Administration (2.2) and Warnings and Precautions (5.2)]. • Healthcare providers should advise patients to strictly adhere to recommended instructions for use [see Dosage and Administration (2.2), Warnings and Precautions (5.2) and Patient Counseling Information (17)]. WARNING: SECONDARY EXPOSURE TO TESTOSTERONE See full prescribing information for complete boxed warning •Virilization has been reported in children who were secondarily exposed to testosterone gel. (5.2, 6.2). •Children should avoid contact with unwashed or unclothed application sites in men using testosterone gel. (2.2, 5.2) •Healthcare providers should advise patients to strictly adhere to recommended instructions for use. (2.2, 5.2, 17).

WARNING AND CAUTIONS

5 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 1%. Secondary exposure to testosterone can produce signs of virilization. Testosterone Gel 1% 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. (5.7) •Edema, with or without congestive heart failure (CHF), may be a complication in patients with preexisting cardiac, renal, or hepatic disease. (5.9, 6.2) •Sleep apnea may occur in those with risk factors. (5.11) •Monitor serum testosterone, prostate specific antigen (PSA), hemoglobin, hematocrit, liver function tests, and lipid concentrations periodically. (5.1, 5.3, 5.8, 5.12) •Testosterone Gel 1% is flammable until dry. (5.15) 5.1 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 (4), Adverse Reactions (6.1) and Nonclinical Toxicology (13.1)]. 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 1% [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 1%. 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 Testosterone Gel 1% 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 been 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 1%. 5.6 Use in Women Due to lack of controlled evaluations in women and potential virilizing effects, Testosterone Gel 1% is not indicated for use in women [see Contraindications (4) and Use in Specific Populations (8.1, 8.3)]. 5.7 Potential for Adverse Effects on Spermatogenesis With large doses of exogenous androgens, including Testosterone Gel 1%, spermatogenesis maybe suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count. 5.8 Hepatic Adverse Effects Prolonged use of high doses of orally active17-alpha-alkylandrogens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosishepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosishepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. Testosterone Gel 1% is not known to cause these adverse effects. 5.9 Edema Androgens, including Testosterone Gel 1%, 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 [see Adverse Reactions (6.2)]. 5.10 Gynecomastia Gynecomastia may develop and persist in patients being treated with androgens, including Testosterone Gel 1%, for hypogonadism. 5.11 Sleep Apnea 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 [see Adverse Reactions (6.2)]. 5.12 Lipids Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy. 5.13 Hypercalcemia Androgens, including Testosterone Gel 1%, 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. 5.14 Decreased Thyroxine-binding Globulin Androgens, including Testosterone Gel 1%, may decrease concentrations of thyroxin-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. 5.15 Flammability Alcohol based products, including Testosterone Gel 1%, are flammable; therefore, patients should be advised to avoid fire, flame or smoking until the Testosterone Gel 1%has dried.

INFORMATION FOR PATIENTS

17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (Medication Guide) Patients should be informed of the following: 17.1 Use in Men with Known or Suspected Prostate or Breast Cancer Men with known or suspected prostate or breast cancer should not use Testosterone Gel 1% [see Contraindications (4) and Warnings and Precautions (5.1)]. 17.2 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 •Testosterone Gel 1% 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 1% should apply the product as directed and strictly adhere to the following: • Wash hands with soap and water 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 1% 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)]. 17.3 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 your urine stream, passing urine many times during the day, having an urge that you have to go to the bathroom right away, having a urine accident, being unable to pass urine and 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. 17.4 Patients Should Be Advised of the Following Instructions for Use: • Read the Medication Guide before starting Testosterone Gel 1% therapy and to reread it each time the prescription is renewed • Testosterone Gel 1% 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 1% out of the reach of children • Testosterone Gel 1% 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 1% is prescribed to meet the patient’s specific needs; therefore, the patient should never share Testosterone Gel 1% with anyone •Wait 5 hours before swimming or washing following application of Testosterone Gel 1%. This will ensure that the greatest amount of Testosterone Gel 1% is absorbed into their system Distributed by: Par Pharmaceutical Companies, Inc. Chestnut Ridge, NY 10977 Revised 05/2015

DOSAGE AND ADMINISTRATION

2 Dosage and Administration for Testosterone Gel 1% differs from Testosterone Gel 1.62 %. For dosage and administration of Testosterone Gel 1.62% refer to its full prescribing information. (2) Prior to initiating Testosterone Gel 1%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on a least two separate days and that these serum testosterone concentrations are below the normal range. • Dosage and Administration for Testosterone Gel 1% differs from Testosterone Gel 1.62 %. For dosage and administration of Testosterone Gel 1.62% refer to its full prescribing information. (2) •Prior to initiating Testosterone Gel 1%, 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% is 50 mg of testosterone (4 pump actuations, two 25 mg packets, or one 50 mg packet), applied once daily in the morning. (2.1) •Apply to clean, dry, intact skin of shoulders and upper arms and/or abdomen. Do NOT apply Testosterone Gel 1% to any other parts of the body including the genitals, chest, armpits (axillae), knees or back. (2.2) •Dose adjustment: Testosterone Gel 1% can be dose adjusted using 50 mg, 75 mg, or 100 mg of testosterone on the basis of total serum testosterone concentration. The dose should be titrated based on the serum testosterone concentration. Additionally, serum testosterone concentration should be assessed periodically. (2.1) •Patients should wash hands immediately with soap and water after applying Testosterone Gel 1% 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% is 50 mg of testosterone (two 25 mg packets, or one 50 mg packet), applied topically once daily in the morning to the shoulders and upper arms and/or abdomen area (preferably at the same time every day). Dose Adjustment To ensure proper dosing, serum testosterone concentrations should be measured at intervals. If the serum testosterone concentration is below the normal range, the daily Testosterone Gel 1% dose may be increased from 50 mg to 75 mg and from 75 mg to 100 mg for adult males as instructed by the physician. If the serum testosterone concentration exceeds the normal range, the daily Testosterone Gel 1% dose may be decreased. If the serum testosterone concentration consistently exceeds the normal range at a daily dose of 50 mg, Testosterone Gel 1% therapy should be discontinued. In addition, serum testosterone concentrations should be assessed periodically. The application site and dose of Testosterone Gel 1% are not interchangeable with other topical testosterone products. 2.2 Administration Instructions Testosterone Gel 1% should be applied to clean, dry, healthy, intact skin of the right and left upper arms/shoulders and/or right and left abdomen. Area of application should be limited to the area that will be covered by the patient’s short sleeve T-shirt. Do not apply Testosterone Gel 1% to any other part of the body including the genitals, chest, armpits (axillae), knees or back. Testosterone Gel 1% should be evenly distributed between the right and left upper arms/shoulders or both sides of the abdomen. The prescribed daily dose of Testosterone Gel 1% should be applied to the right and left upper arms/shoulders and/or right/left abdomen as shown in the shaded areas in the figure below. After applying the gel, the application site should be allowed to dry prior to dressing. Hands should be washed thoroughly with soap and water after application. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including Testosterone Gel 1%, are flammable. The patient should be advised to avoid swimming or showering for at least 5 hours after the application of Testosterone Gel 1%. Packets The entire contents should be squeezed into the palm of the hand and immediately applied to the application sites. Alternately, patients may squeeze a portion of the gel from the packet into the palm of the hand and apply to application sites. Repeat until entire contents have been applied. Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from Testosterone Gel 1%-treated skin: •Children and women should avoid contact with unwashed or unclothed application site(s) of men using Testosterone Gel 1%. •Patients should wash hands with soap and water immediately after application of Testosterone Gel 1%. •Patients should cover the application site(s) with clothing (e.g., a T-shirt) after the gel has dried. •Prior to situation in which direct skin-to-skin contact is anticipated, patients should wash the application site thoroughly with soap and water to remove any testosterone residue. •In the event that unwashed or unclothed skin to which Testosterone Gel 1% 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. New image