FDA label 60ea4698-32ec-4159-800f-12c19d5f13a3

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 ).

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. ( 5.8 ) Edema, with or without congestive heart failure (CHF), may be a complication in patients with preexisting cardiac, renal, or hepatic disease. ( 5.10 , 6.2 ) Sleep apnea may occur in those with risk factors. ( 5.12 ) Monitor serum testosterone, prostate specific antigen (PSA), hemoglobin, hematocrit, liver function tests, and lipid concentrations periodically. ( 5.1 , 5.3 , 5.9 , 5.13 ) Testosterone Gel 1% is flammable until dry. ( 5.16 ) 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 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 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. 5.7 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 , 8.2 )]. 5.8 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. 5.9 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. 5.10 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 )]. 5.11 Gynecomastia Gynecomastia may develop and persist in patients being treated with androgens, including Testosterone Gel 1%, for hypogonadism. 5.12 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 )] . 5.13 Lipids Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy. 5.14 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. 5.15 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. 5.16 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.

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 Par Pharmaceutical at 1-800-828-9393 or www.parpharm.com 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, urinary urgency and weak urinary stream. ** Testis disorders included three patients. There were two with a non-palpable testis and one with slight right testicular tenderness. Two patients reported serious adverse events considered possibly related to treatment: deep vein thrombosis (DVT) and prostate disorder requiring a transurethral resection of the prostate (TURP). Discontinuation for adverse events in this study included: two patients with application site reactions, one with kidney failure, and five with prostate disorders (including increase in serum PSA in 4 patients, and increase in PSA with prostate enlargement in a fifth patient). Increases in Serum PSA Observed in Clinical Trials of Hypogonadal Men During the initial 6-month study, the mean change in PSA values had a statistically significant increase of 0.26 ng/mL. Serum PSA was measured every 6 months thereafter in the 162 hypogonadal men on Testosterone Gel 1% in the 3-year extension study. There was no additional statistically significant increase observed in mean PSA from 6 months through 36 months. However, there were increases in serum PSA observed in approximately 18% of individual patients. The overall mean change from baseline in serum PSA values for the entire group from month 6 to 36 was 0.11 ng/mL. Twenty-nine patients (18%) met the per-protocol criterion for increase in serum PSA, defined as >2X the baseline or any single serum PSA >6 ng/mL. Most of these (25/29) met this criterion by at least doubling of their PSA from baseline. In most cases where PSA at least doubled (22/25), the maximum serum PSA value was still <2 ng/mL. The first occurrence of a pre-specified, post- baseline increase in serum PSA was seen at or prior to Month 12 in most of the patients who met this criterion (23 of 29; 79%). Four patients met this criterion by having a serum PSA >6 ng/mL and in these, maximum serum PSA values were 6.2 ng/mL, 6.6 ng/mL, 6.7 ng/mL, and 10.7 ng/mL. In two of these patients, prostate cancer was detected on biopsy. The first patient's PSA levels were 4.7 ng/mL and 6.2 ng/mL at baseline and at Month 6/Final, respectively. The second patient's PSA levels were 4.2 ng/mL, 5.2 ng/mL, 5.8 ng/mL, and 6.6 ng/mL at baseline, Month 6, Month 12, and Final, respectively. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of Testosterone Gel 1%. 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 (Table 3) . Table 3: Adverse Drug Reactions from Postmarketing Experience of Testosterone Gel 1% by MedDRA System Organ Class Blood and the lymphatic system disorders: Elevated Hgb, Hct (polycythemia) Cardiovascular disorders: Myocardial infarction, stroke Endocrine disorders: Hirsutism Gastrointestinal disorders: Nausea General disorders and administration site reactions: Asthenia, edema, malaise Genitourinary disorders: Impaired urination Hepatobiliary disorders: Abnormal liver function tests (e.g. transaminases, elevated GGTP, bilirubin) Investigations: Elevated PSA, electrolyte changes (nitrogen, calcium, potassium, phosphorus, sodium), changes in serum lipids (hyperlipidemia, elevated triglycerides, decreased HDL), impaired glucose tolerance, fluctuating testosterone concentrations, weight increase Neoplasms benign, malignant and unspecified (cysts and polyps): Prostate cancer Nervous system: Headache, dizziness, sleep apnea, insomnia Psychiatric disorders: Depression, emotional lability, decreased libido, nervousness, hostility, amnesia, anxiety Reproductive system and breast disorders: Gynecomastia, mastodynia, prostatic enlargement, testicular atrophy, oligospermia, priapism(frequent or prolonged erections) Respiratory disorders: Dyspnea Skin and subcutaneous tissue disorders: Acne, alopecia, application site reaction(pruritus, dry skin, erythema, rash, discolored hair , paresthesia), sweating Vascular disorders: Hypertension, vasodilation (hot flushes), venous thromboembolism Secondary Exposure to Testosterone in Children Cases of secondary exposure to testosterone resulting in virilization of children have been reported in postmarket surveillance. Signs and symptoms of these reported cases have included enlargement of the clitoris (with surgical intervention) or the penis, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases with a reported outcome, these signs and symptoms were reported to have regressed with removal of the testosterone gel exposure. In a few cases, however, enlarged genitalia did not fully return to age appropriate normal size, and bone age remained modestly greater than chronological age. In some of the cases, direct contact with the sites of application on the skin of men using testosterone gel was reported. In at least one reported case, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user's shirts and/or other fabric, such as towels and sheets [see Warnings and Precautions ( 5.2 )].

<table><col width="1px"/><col width="1px"/><col width="1px"/><col width="1px"/><tbody><tr><td align="center" valign="top" rowspan="3" styleCode=" Botrule Toprule Lrule Rrule "><paragraph>Adverse Event </paragraph></td><td align="center" valign="top" colspan="3" styleCode=" Botrule Toprule Lrule Rrule "><paragraph>Dose of Testosterone Gel 1%</paragraph></td></tr><tr><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>50 mg</paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>75 mg</paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>100 mg</paragraph></td></tr><tr><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>N = 77</paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>N = 40</paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>N = 78</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Acne </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3%</paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>8%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Alopecia </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>0% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Application Site Reaction </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>5% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>4%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Asthenia </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>0% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Depression </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>0% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Emotional Lability </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>0% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Gynecomastia </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>0% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Headache </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>4% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>0%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Hypertension </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>0% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Lab Test Abnormal* </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>6% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>5% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Libido Decreased </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>0% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Nervousness </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>0% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Pain Breast </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Prostate Disorder** </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>5%</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Testis Disorder*** </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>0% </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>0%</paragraph></td></tr></tbody></table>

<table><caption>Table 2: Adverse Events Possibly, Probably or Definitely Related to Use of Testosterone Gel 1% in the 3 Year, Flexible Dose, Extension Study</caption><col width="50%"/><col width="1px"/><tbody><tr><td align="center" valign="top" rowspan="2" styleCode=" Botrule Toprule Lrule Rrule "><paragraph>Adverse Event </paragraph></td><td align="center" valign="top" styleCode=" Botrule Toprule Rrule "><paragraph>Percent of Subjects</paragraph></td></tr><tr><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>(N = 162)</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Lab Test Abnormal+ </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>9.3</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Skin dry </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1.9</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Application Site Reaction </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>5.6</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Acne </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3.1</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Pruritus </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1.9</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Enlarged Prostate </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>11.7</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Carcinoma of Prostate </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1.2</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Urinary Symptoms* </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>3.7</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Testis Disorder** </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>1.9</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Gynecomastia </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>2.5</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Anemia </paragraph></td><td align="center" valign="top" styleCode=" Botrule Rrule "><paragraph>2.5</paragraph></td></tr></tbody></table>

<table><col width="33%"/><col width="67%"/><tbody><tr><td valign="top" styleCode=" Botrule Toprule Lrule Rrule "><paragraph>Blood and the lymphatic system disorders:</paragraph></td><td valign="top" styleCode=" Botrule Toprule Lrule Rrule "><paragraph>Elevated Hgb, Hct (polycythemia)</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Cardiovascular disorders:</paragraph></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Myocardial infarction, stroke</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Endocrine disorders:</paragraph></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Hirsutism</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Gastrointestinal disorders:</paragraph></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Nausea</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><list listType="unordered" styleCode="Disk"><item> General disorders and administration site reactions:</item></list></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Asthenia, edema, malaise</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><list listType="unordered" styleCode="Disk"><item> Genitourinary disorders:</item></list></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Impaired urination</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><list listType="unordered" styleCode="Disk"><item> Hepatobiliary disorders:</item></list></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Abnormal liver function tests (e.g. transaminases, elevated GGTP, bilirubin)</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><list listType="unordered" styleCode="Disk"><item> Investigations:</item></list></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Elevated PSA, electrolyte changes (nitrogen, calcium, potassium, phosphorus, sodium), changes in serum lipids (hyperlipidemia, elevated triglycerides, decreased HDL), impaired glucose tolerance, fluctuating testosterone concentrations, weight increase</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><list listType="unordered" styleCode="Disk"><item> Neoplasms benign, malignant and unspecified (cysts and polyps):</item></list></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Prostate cancer</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><list listType="unordered" styleCode="Disk"><item> Nervous system:</item></list></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Headache, dizziness, sleep apnea, insomnia</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><list listType="unordered" styleCode="Disk"><item> Psychiatric disorders:</item></list></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Depression, emotional lability, decreased libido, nervousness, hostility, amnesia, anxiety</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><list listType="unordered" styleCode="Disk"><item> Reproductive system and breast disorders:</item></list></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Gynecomastia, mastodynia, prostatic enlargement, testicular atrophy, oligospermia, priapism(frequent or prolonged erections)</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><list listType="unordered" styleCode="Disk"><item> Respiratory disorders:</item></list></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Dyspnea</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><list listType="unordered" styleCode="Disk"><item> Skin and subcutaneous tissue disorders:</item></list></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Acne, alopecia, application site reaction(pruritus, dry skin, erythema, rash, discolored hair , paresthesia), sweating</paragraph></td></tr><tr><td valign="top" styleCode=" Botrule Lrule Rrule "><list listType="unordered" styleCode="Disk"><item> Vascular disorders:</item></list></td><td valign="top" styleCode=" Botrule Lrule Rrule "><paragraph>Hypertension, vasodilation (hot flushes), venous thromboembolism</paragraph></td></tr></tbody></table>