g 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.

genous testosterone: primary hypogonadism (congenital or acquired). ( 1 ) hypogonadotropic hypogonadism (congenital or acquired). ( 1 ) limitations of use: safety and efficacy of vogelxo in men with age-related hypogonadism have not been established ( 1 ) safety and efficacy of vogelxo 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 ) limitations of use: safety and efficacy of vogelxo in men with "age-related hypogonadism" (also referred to as "late-onset hypogonadism") have not been established. safety and efficacy of vogelxo 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) ] .

factors. ( 5.12 ) monitor prostate specific antigen (psa), hematocrit, and lipid concentrations periodically. ( 5.1 , 5.3 , 5.13 ) vogelxo 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 vogelxo [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 vogelxo. 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 vogelxo 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 vogelxo. 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, vogelxo 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 vogelxo, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (fsh) which could possibly lead to adverse effects on semen parameters including sperm count. 5.9 hepatic adverse effects prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). peliosis hepatis can be a life-threatening or fatal complication. long-term therapy with intramuscular testosterone enanthate, which elevate blood levels for prolonged periods, has produced multiple hepatic adenomas. vogelxo is not known to produce these adverse effects. nonetheless, patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g., jaundice). if these occur, promptly discontinue vogelxo while the cause is evaluated. 5.10 edema androgens, including vogelxo, may promote retention of sodium and water. edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. in addition to discontinuation of the drug, diuretic therapy may be required. 5.11 gynecomastia gynecomastia occasionally develops and occasionally persists in patients being treated for hypogonadism [see adverse reactions (6.1) ] . 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. 5.13 lipids changes in the serum lipid profile may occur. monitor the lipid profile periodically, particularly after starting testosterone therapy and after any dose increases. 5.14 hypercalcemia androgens, including vogelxo, 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 vogelxo, may decrease concentrations of thyroxine-binding globulins, resulting in decreased total t4 serum concentrations and increased resin uptake of t3 and t4. free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction. 5.16 flammability alcohol-based products, including vogelxo, are flammable; therefore, patients should be advised to avoid fire, flame or smoking until the vogelxo has dried.

be assessed periodically. ( 2.1 ) patients should wash hands with soap and water immediately after applying vogelxo 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 vogelxo 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 vogelxo 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 vogelxo 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 vogelxo 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 vogelxo has been applied. avoid fire, flame or smoking during the application of vogelxo until the vogelxo 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 vogelxo treated skin: children and women should avoid contact with unwashed or unclothed application site(s) of men using vogelxo. vogelxo 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 vogelxo. patients should cover the application site(s) with clothing (e.g., a t-shirt) after the gel has dried. prior to any situation in which direct skin-to-skin contact of the application site(s) with another person is anticipated, patients should wash the application site(s) thoroughly with soap and water to remove any testosterone residue. in the event that unwashed or unclothed skin to which vogelxo 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. figure

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 testosterone gel 50 mg testosterone gel 100 mg placebo event (n=103) (n=149) (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) ].

g 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.

tion 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 vogelxo 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 vogelxo, 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 vogelxo 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.

ral 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.

. 12.3 pharmacokinetics in a single-dose, replicate crossover clinical study evaluating 58 hypogonadal males, the serum testosterone exposures (auc 0-24 and auc 0-t ) and maximum testosterone concentration (c max ) following a topical administration of 100 mg testosterone administration as a 2 × 5 g vogelxo tubes (applied to the shoulders/upper arms) were bioequivalent to those following a topical administration of an approved testosterone gel product. absorption testosterone gel delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal levels (e.g., 300 – 1000 ng/dl) seen in healthy men. the skin serves as a reservoir for the sustained release of testosterone into the systemic circulation. approximately 10% of the testosterone applied on the skin surface is absorbed into the systemic circulation during a 24-hour period. single dose in a single dose, replicate crossover study, when vogelxo 100 mg was applied, absorption of testosterone into the blood continued for the entire 24 hour dosing period. the average (± sd) auc 0-24 and auc 0-t and c max were 6625 (±3671) ng∙hr/dl, 10425 (±5521) ng∙hr/dl, and 573 (±284) ng/dl, respectively. multiple dose with single daily applications of testosterone gel 50 mg and 100 mg, follow-up measurements at 30 and 90 days after starting treatment have confirmed that serum testosterone and dht concentrations are generally maintained within the normal range. figure 1 summarizes the 24-hour pharmacokinetic profile of testosterone for patients maintained on testosterone gel 50 mg or testosterone gel 100 mg for 30 days. figure 1 mean steady-state serum testosterone (±sd) (ng/dl) concentrations on day 30 in patients applying testosterone once daily the average daily testosterone concentration produced by testosterone gel 100 mg at day 30 was 612 (± 286) ng/dl and by testosterone gel 50 mg at day 30 was 365 (± 187) ng/dl. figure 1 distribution circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (shbg) and albumin. approximately 40% of testosterone in plasma is bound to shbg, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins. metabolism testosterone is metabolized to various 17-keto steroids through two different pathways. the major active metabolites of testosterone are estradiol and dht. the average daily dht concentration produced by testosterone gel 100 mg at day 30 was 555 (± 293) pg/ml and by testosterone gel 50 mg at day 30 was 346 (± 212) pg/ml. figure 2 summarizes the 24-hour pharmacokinetic profile of dht for patients maintained on testosterone gel 50 mg or testosterone gel 100 mg for 30 days. figure 2 mean steady-state serum dihydrotestosterone (±sd) (pg/ml) concentrations on day 30 in patients applying testosterone once daily figure 2 excretion there is considerable variation in the half-life of testosterone concentration as reported in the literature, ranging from 10 to 100 minutes. about 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic acid and sulfuric acid conjugates of testosterone and its metabolites. about 6% of a dose is excreted in the feces, mostly in the unconjugated form. inactivation of testosterone occurs primarily in the liver. potential for transfer from male patients to female partners the potential for dermal testosterone transfer following vogelxo use was evaluated in a clinical study between males dosed with vogelxo and their untreated female partners. two (2) hours after application of 50 mg of testosterone from 5 g of vogelxo to upper arm and shoulder of one side by the male subjects, the couples (n = 48 couples) engaged in a 15 minute session of skin-to-skin contact. serum concentrations of testosterone were monitored in the female subjects for 24 hours after the transfer procedure. under these study conditions, unprotected female partners had a mean testosterone auc 0-24 and c max that were 2.8 and 4 times greater than their mean baseline values, respectively. when a shirt covered the application site or the application site was washed, study results showed less than 10% increase in testosterone auc 0-24 and c max , compared to baseline in these females. effect of hand washing in a clinical study conducted to evaluate the effect of hand washing on the residual amount of testosterone, 36 healthy male subjects received 50 mg of testosterone from 5 g of vogelxo on a hand and applied testosterone gel to the upper arm and shoulder of one side. subjects washed their hands with liquid soap and warm water immediately after drug application. then the hand was allowed to air dry or patted dry with a cloth towel. a skin swab sample was collected and analyzed for testosterone content. a mean (sd) of 0.16 (0.46) to 0.65(1.03) µg of residual testosterone (i.e., 99% reduction compared to when hands were not washed) was recovered after washing hands with liquid soap and warm water. effect of showering the effect of showering (with mild soap) at 1, 2 and 6 hours post application of testosterone gel 100 mg was evaluated in a clinical trial in 12 men. the study demonstrated that the overall effect of washing was to decrease testosterone concentrations; however, when washing occurred two or more hours post drug application, serum testosterone concentrations remained within the normal range.

n of testosterone into the blood continued for the entire 24 hour dosing period. the average (± sd) auc 0-24 and auc 0-t and c max were 6625 (±3671) ng∙hr/dl, 10425 (±5521) ng∙hr/dl, and 573 (±284) ng/dl, respectively. multiple dose with single daily applications of testosterone gel 50 mg and 100 mg, follow-up measurements at 30 and 90 days after starting treatment have confirmed that serum testosterone and dht concentrations are generally maintained within the normal range. figure 1 summarizes the 24-hour pharmacokinetic profile of testosterone for patients maintained on testosterone gel 50 mg or testosterone gel 100 mg for 30 days. figure 1 mean steady-state serum testosterone (±sd) (ng/dl) concentrations on day 30 in patients applying testosterone once daily the average daily testosterone concentration produced by testosterone gel 100 mg at day 30 was 612 (± 286) ng/dl and by testosterone gel 50 mg at day 30 was 365 (± 187) ng/dl. figure 1 distribution circulating testosterone is primarily bound in the serum to sex hormone-binding globulin (shbg) and albumin. approximately 40% of testosterone in plasma is bound to shbg, 2% remains unbound (free) and the rest is loosely bound to albumin and other proteins. metabolism testosterone is metabolized to various 17-keto steroids through two different pathways. the major active metabolites of testosterone are estradiol and dht. the average daily dht concentration produced by testosterone gel 100 mg at day 30 was 555 (± 293) pg/ml and by testosterone gel 50 mg at day 30 was 346 (± 212) pg/ml. figure 2 summarizes the 24-hour pharmacokinetic profile of dht for patients maintained on testosterone gel 50 mg or testosterone gel 100 mg for 30 days. figure 2 mean steady-state serum dihydrotestosterone (±sd) (pg/ml) concentrations on day 30 in patients applying testosterone once daily figure 2 excretion there is considerable variation in the half-life of testosterone concentration as reported in the literature, ranging from 10 to 100 minutes. about 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic acid and sulfuric acid conjugates of testosterone and its metabolites. about 6% of a dose is excreted in the feces, mostly in the unconjugated form. inactivation of testosterone occurs primarily in the liver. potential for transfer from male patients to female partners the potential for dermal testosterone transfer following vogelxo use was evaluated in a clinical study between males dosed with vogelxo and their untreated female partners. two (2) hours after application of 50 mg of testosterone from 5 g of vogelxo to upper arm and shoulder of one side by the male subjects, the couples (n = 48 couples) engaged in a 15 minute session of skin-to-skin contact. serum concentrations of testosterone were monitored in the female subjects for 24 hours after the transfer procedure. under these study conditions, unprotected female partners had a mean testosterone auc 0-24 and c max that were 2.8 and 4 times greater than their mean baseline values, respectively. when a shirt covered the application site or the application site was washed, study results showed less than 10% increase in testosterone auc 0-24 and c max , compared to baseline in these females. effect of hand washing in a clinical study conducted to evaluate the effect of hand washing on the residual amount of testosterone, 36 healthy male subjects received 50 mg of testosterone from 5 g of vogelxo on a hand and applied testosterone gel to the upper arm and shoulder of one side. subjects washed their hands with liquid soap and warm water immediately after drug application. then the hand was allowed to air dry or patted dry with a cloth towel. a skin swab sample was collected and analyzed for testosterone content. a mean (sd) of 0.16 (0.46) to 0.65(1.03) µg of residual testosterone (i.e., 99% reduction compared to when hands were not washed) was recovered after washing hands with liquid soap and warm water. effect of showering the effect of showering (with mild soap) at 1, 2 and 6 hours post application of testosterone gel 100 mg was evaluated in a clinical trial in 12 men. the study demonstrated that the overall effect of washing was to decrease testosterone concentrations; however, when washing occurred two or more hours post drug application, serum testosterone concentrations remained within the normal range.

90. table 4 summarizes the mean testosterone concentrations on day 30 for patients receiving testosterone gel 50 mg or 100 mg. table 4: mean (± sd) steady-state serum testosterone concentrations on day 30 testosterone gel 50 mg testosterone gel 100 mg placebo gel n=94 n=95 n=93 c avg (ng/dl) 365 ± 187 612 ± 286 216 ± 79 c max (ng/dl) 538 ± 371 897 ± 565 271 ± 110 c min (ng/dl) 223 ± 126 394 ±189 164 ± 64

�° 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 vogelxo 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) ] .

one effects the possibility of secondary exposure to vogelxo should be brought to the attention of a healthcare provider vogelxo 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 vogelxo in men [see medication guide ] children and women should avoid contact with unwashed or unclothed application site(s) of men using vogelxo patients using vogelxo 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 vogelxo 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 vogelxo therapy and reread it each time the prescription is renewed. vogelxo should be applied and used appropriately to maximize the benefits and to minimize the risk of secondary exposure in children and women. keep vogelxo out of the reach of children. the package is not child resistant. vogelxo 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. vogelxo is prescribed to meet the patient's specific needs; therefore, the patient should never share vogelxo with anyone. vogelxo should be applied topically once daily at approximately the same time each day to clean dry skin of the shoulders and/or upper arms. vogelxo should not be applied to the scrotum, penis, or abdomen. wait 2 hours before washing or swimming following application of vogelxo. this will ensure that the greatest amount of vogelxo is absorbed.