Androgel

• Virilization has been reported in children who were secondarily exposed to testosterone gel
  [see Warnings and Precautions (
  5.1 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 AndroGel 1.62%

  [see Dosage and Administration , Use in Specific Populations

  and

  Clinical Pharmacology ].

  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.
  ) and Adverse Reactions (
  6.2 Postmarketing Experience

  The following adverse reactions have been identified during post approval use of AndroGel 1.62%. 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 5).

  Table 5: Adverse Reactions from Post Approval Experience of AndroGel 1.62% by System Organ Class

  System Organ Class	Adverse Reaction
  Blood and lymphatic system disorders:	Elevated hemoglobin or hematocrit, polycythemia, anemia
  Cardiovascular disorders:	Myocardial infarction, stroke
  Endocrine disorders:	Hirsutism
  Gastrointestinal disorders:	Nausea
  General disorders:	Asthenia, edema, malaise
  Genitourinary disorders:	Impaired urination*
  Hepatobiliary disorders:	Abnormal liver function tests
  Investigations:	Lab test abnormal**, elevated PSA, electrolyte changes (nitrogen, calcium, potassium [includes hypokalemia] , phosphorus, sodium), impaired glucose tolerance, hyperlipidemia, HDL, fluctuating testosterone levels, weight increase
  Neoplasms:	Prostate cancer
  Nervous system disorders:	Dizziness, headache, insomnia, sleep apnea
  Psychiatric disorders:	Amnesia, anxiety, depression, hostility, emotional lability, decreased libido, nervousness
  Reproductive system and breast disorders:	Gynecomastia, mastodynia, oligospermia, priapism (frequent or prolonged erections), prostate enlargement, BPH, testis disorder***
  Respiratory disorders:	Dyspnea
  Skin and subcutaneous tissue disorders:	Acne, alopecia, application site reaction (discolored hair, dry skin, erythema, paresthesia, pruritus, rash), skin dry, pruritus, sweating
  Vascular disorders:	Hypertension, vasodilation (hot flushes), venous thromboembolism
  * Impaired urination includes nocturia, urinary hesitancy, urinary incontinence, urinary retention, urinary urgency and weak urinary stream
  ** Lab test abnormal includes elevated AST, elevated ALT, elevated testosterone, elevated hemoglobin or hematocrit, elevated cholesterol, elevated cholesterol/LDL ratio, elevated triglycerides, or elevated serum creatinine
  *** Testis disorder includes atrophy or non-palpable testis, varicocele, testis sensitivity or tenderness

  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 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 (

  5.1

  )]

  .
  )].
  
  
  
• Children should avoid contact with unwashed or unclothed application sites in men using testosterone gel
  [see Dosage and Administration (
  2.2 Administration Instructions

  AndroGel 1.62% should be applied to clean, dry, intact skin of the upper arms and shoulders. Do not apply AndroGel 1.62% to any other parts of the body, including the abdomen, genitals, chest, armpits (axillae), or knees

  [see Clinical Pharmacology (

  12.3

  )]

  . Area of application should be limited to the area that will be covered by the patient's short sleeve t-shirt. Patients should be instructed to use the palm of the hand to apply AndroGel 1.62% and spread across the maximum surface area as directed in Table 2 (for pump) and Table 3 (for packets) and in Figure 1.

  Table 2: Application Sites for AndroGel 1.62%, Pump

  Total Dose of Testosterone	Total Pump Actuations	Pump Actuations Per Upper Arm and Shoulder
  		Upper Arm and Shoulder #1	Upper Arm and Shoulder #2
  20.25 mg	1	1	0
  40.5 mg	2	1	1
  60.75 mg	3	2	1
  81 mg	4	2	2

  Table 3: Application Sites for AndroGel 1.62%, Packets

  Total Dose of Testosterone	Total packets	Gel Applications Per Upper Arm and Shoulder
  		Upper Arm and Shoulder #1	Upper Arm and Shoulder #2
  20.25 mg	One 20.25 mg packet	One 20.25 mg packet	0
  40.5 mg	One 40.5 mg packet	Half of contents of One 40.5 mg packet	Half of contents of One 40.5 mg packet
  60.75 mg	One 20.25 mg packet AND One 40.5 mg packet	One 40.5 mg packet	One 20.25 mg packet
  81 mg	Two 40.5 mg packets	One 40.5 mg packet	One 40.5 mg packet

  The prescribed daily dose of AndroGel 1.62% should be applied to the right and left upper arms and shoulders as shown in the shaded areas in Figure 1.

  Figure 1. Application Sites for AndroGel 1.62%

  Once the application site is dry, the site should be covered with clothing

  [see Clinical Pharmacology (

  12.3

  )]

  . Wash hands thoroughly with soap and water. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including AndroGel 1.62%, are flammable.

  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

  )]

  .

  To obtain a full first dose, it is necessary to prime the canister pump. To do so, with the canister in the upright position, slowly and fully depress the actuator three times. Safely discard the gel from the first three actuations. It is only necessary to prime the pump before the first dose.

  After the priming procedure, fully depress the actuator once for every 20.25 mg of AndroGel 1.62%. AndroGel 1.62% should be delivered directly into the palm of the hand and then applied to the application sites.

  When using packets, the entire contents should be squeezed into the palm of the hand and immediately applied to the application sites. When 40.5 mg packets need to be split between the left and right shoulder, 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. Alternatively, AndroGel 1.62% can be applied directly to the application sites from the pump or packets.

  Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from AndroGel 1.62%-treated skin:

  • Children and women should avoid contact with unwashed or unclothed application site(s) of men using AndroGel 1.62%.
  • AndroGel 1.62% 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 AndroGel 1.62%.
  • Patients should cover the application site(s) with clothing (e.g., a t-shirt) after the gel has dried.
  • Prior to situations in which direct skin-to-skin contact 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 AndroGel 1.62% 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.

  

  

  ) and Warnings and Precautions (
  5.1 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 AndroGel 1.62%

  [see Dosage and Administration , Use in Specific Populations

  and

  Clinical Pharmacology ].

  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.
  )].
  
  
  
• Healthcare providers should advise patients to strictly adhere to recommended instructions for use
  [see Dosage and Administration (
  2.2 Administration Instructions

  AndroGel 1.62% should be applied to clean, dry, intact skin of the upper arms and shoulders. Do not apply AndroGel 1.62% to any other parts of the body, including the abdomen, genitals, chest, armpits (axillae), or knees

  [see Clinical Pharmacology (

  12.3

  )]

  . Area of application should be limited to the area that will be covered by the patient's short sleeve t-shirt. Patients should be instructed to use the palm of the hand to apply AndroGel 1.62% and spread across the maximum surface area as directed in Table 2 (for pump) and Table 3 (for packets) and in Figure 1.

  Table 2: Application Sites for AndroGel 1.62%, Pump

  Total Dose of Testosterone	Total Pump Actuations	Pump Actuations Per Upper Arm and Shoulder
  		Upper Arm and Shoulder #1	Upper Arm and Shoulder #2
  20.25 mg	1	1	0
  40.5 mg	2	1	1
  60.75 mg	3	2	1
  81 mg	4	2	2

  Table 3: Application Sites for AndroGel 1.62%, Packets

  Total Dose of Testosterone	Total packets	Gel Applications Per Upper Arm and Shoulder
  		Upper Arm and Shoulder #1	Upper Arm and Shoulder #2
  20.25 mg	One 20.25 mg packet	One 20.25 mg packet	0
  40.5 mg	One 40.5 mg packet	Half of contents of One 40.5 mg packet	Half of contents of One 40.5 mg packet
  60.75 mg	One 20.25 mg packet AND One 40.5 mg packet	One 40.5 mg packet	One 20.25 mg packet
  81 mg	Two 40.5 mg packets	One 40.5 mg packet	One 40.5 mg packet

  The prescribed daily dose of AndroGel 1.62% should be applied to the right and left upper arms and shoulders as shown in the shaded areas in Figure 1.

  Figure 1. Application Sites for AndroGel 1.62%

  Once the application site is dry, the site should be covered with clothing

  [see Clinical Pharmacology (

  12.3

  )]

  . Wash hands thoroughly with soap and water. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including AndroGel 1.62%, are flammable.

  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

  )]

  .

  To obtain a full first dose, it is necessary to prime the canister pump. To do so, with the canister in the upright position, slowly and fully depress the actuator three times. Safely discard the gel from the first three actuations. It is only necessary to prime the pump before the first dose.

  After the priming procedure, fully depress the actuator once for every 20.25 mg of AndroGel 1.62%. AndroGel 1.62% should be delivered directly into the palm of the hand and then applied to the application sites.

  When using packets, the entire contents should be squeezed into the palm of the hand and immediately applied to the application sites. When 40.5 mg packets need to be split between the left and right shoulder, 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. Alternatively, AndroGel 1.62% can be applied directly to the application sites from the pump or packets.

  Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from AndroGel 1.62%-treated skin:

  • Children and women should avoid contact with unwashed or unclothed application site(s) of men using AndroGel 1.62%.
  • AndroGel 1.62% 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 AndroGel 1.62%.
  • Patients should cover the application site(s) with clothing (e.g., a t-shirt) after the gel has dried.
  • Prior to situations in which direct skin-to-skin contact 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 AndroGel 1.62% 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.

  

  

  ), Warnings and Precautions (
  5.1 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 AndroGel 1.62%

  [see Dosage and Administration , Use in Specific Populations

  and

  Clinical Pharmacology ].

  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.
  ) and Patient Counseling Information (
  17 PATIENT COUNSELING INFORMATION

  Advise the patient to read the 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 AndroGel 1.62%

  [see Contraindications (

  4

  ) and Warnings and Precautions (

  5.4

  )]

  .

  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

  [see Warnings and Precautions (

  5.1

  )]

  . 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.
    
    
  • AndroGel 1.62% 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 AndroGel 1.62% in men

  [see

  Medication Guide

  ]

  :

  • Children and women should avoid contact with unwashed or unclothed application site(s)
    of men using AndroGel 1.62%.
  • Patients using AndroGel 1.62% 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 AndroGel 1.62% 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 (
    5.1
    ) and Clinical Pharmacology (
    12.3
    )]
    .

  17.3 Potential for Venous Thromboembolism

  Inform patients that AndroGel 1.62% can cause venous thromboembolism. Advise patients of the signs and symptoms of venous thromboembolism, which may include the following: lower limb pain, edema, or erythema; and dyspnea or chest pain. Advise patients to promptly report the signs and symptoms of venous thromboembolism, discontinue use of AndroGel 1.62%, and seek urgent medical care.

  17.4 Potential for Increase in Blood Pressure

  Inform patients that AndroGel 1.62% can increase BP which can increase cardiovascular risk over time. Instruct patients about the importance of monitoring BP periodically while on Androgel 1.62%. If BP increases while on AndroGel 1.62%, antihypertensive medications may need to be started, added, or adjusted to control BP, or AndroGel 1.62% may need to be discontinued.

  17.5 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 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.

  17.6 Patients Should Be Advised of the Following Instructions for Use

  • Read the Medication Guidebefore starting AndroGel 1.62% therapy and to reread it each time the prescription is renewed.
  • AndroGel 1.62% should be applied and used appropriately to maximize the benefits and to minimize the risk of secondary exposure in children and women.
  • Keep AndroGel 1.62% out of the reach of children.
  • AndroGel 1.62% 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.
  • AndroGel 1.62% is prescribed to meet the patient's specific needs; therefore, the patient should never share AndroGel 1.62% with anyone.
  • Wait 2 hours before swimming or washing following application of AndroGel 1.62%. This will ensure that the greatest amount of AndroGel 1.62% is absorbed into their system.

  Marketed by:

  ASCEND Therapeutics US, LLC
  
  Bridgewater, NJ 08807, USA 1-877-204-1013

  © 2025 ASCEND Therapeutics US, LLC 2025AG0003
  )].

AndroGel 1.62% is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

• Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range.
  
  
  
  
  
• Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations, but have gonadotropins in the normal or low range.

Limitations of use:

• Safety and efficacy of AndroGel 1.62% in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.
  
  
• Safety and efficacy of AndroGel 1.62% in males less than 18 years old have not been established
  
  
  
  [see Use in Specific Populations (
  8.4 Pediatric Use

  The safety and effectiveness of AndroGel 1.62% in pediatric patients less than 18 years old has not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.
  )]
  .
  
  
  
  
  
• Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure
  
  
  
  [see Indications and Usage (
  1 INDICATIONS AND USAGE

  AndroGel 1.62% is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

  • Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range.
    
    
  • Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations, but have gonadotropins in the normal or low range.

  Limitations of use:

  • Safety and efficacy of AndroGel 1.62% in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.
    
    
  • Safety and efficacy of AndroGel 1.62% in males less than 18 years old have not been established
    [see Use in Specific Populations (
    8.4
    )]
    .
    
    
  • Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure
    [see Indications and Usage (
    1
    ), and Clinical Pharmacology (
    12.3
    )]
    .

  AndroGel 1.62% is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone:

  • Primary hypogonadism (congenital or acquired)
  • Hypogonadotropic hypogonadism (congenital or acquired)

  Limitations of use:

  • Safety and efficacy of AndroGel 1.62% in men with “age-related hypogonadism” have not been established.
  • Safety and efficacy of AndroGel 1.62% in males less than 18 years old have not been established.
  • Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure.
  ), and Clinical Pharmacology (
  12.3 Pharmacokinetics

  Absorption

  AndroGel 1.62% delivers physiologic amounts of testosterone, producing circulating
  testosterone concentrations that approximate normal levels (300 – 1000 ng/dL) seen in healthy men. AndroGel 1.62% provides continuous topical delivery of testosterone for 24 hours
  following once daily application to clean, dry, intact skin of the shoulders and upper arms.
  Average serum testosterone concentrations over 24 hours (C_avg) observed when AndroGel 1.62% was applied to the upper arms/shoulders were comparable to average serum testosterone concentrations (C_avg) when AndroGel 1.62% was applied using a rotation method utilizing the abdomen and upper arms/shoulders. The rotation of abdomen and upper arms/shoulders was a method used in the pivotal clinical trial

  [see Clinical Studies ].

  

  Figure 2: Mean (±SD) Serum Total Testosterone Concentrations on Day 7 in Patients Following AndroGel 1.62% Once-Daily Application of 81 mg of Testosterone (N=33) for 7 Days

  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.

  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.

  When AndroGel 1.62% treatment is discontinued, serum testosterone concentrations return to approximately baseline concentrations within 48-72 hours after administration of the last dose.

  Potential for testosterone transfer

  The potential for testosterone transfer following administration of AndroGel 1.62% when it was applied only to upper arms/shoulders was evaluated in two clinical studies of males dosed with AndroGel 1.62% and their untreated female partners. In one study, 8 male subjects applied a single dose of AndroGel 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes. Serum concentrations of testosterone were monitored in female subjects for 24 hours after contact occurred. After direct skin-to-skin contact with the site of application, mean testosterone C_avgand C_maxin female subjects increased by 280% and 267%, respectively, compared to mean baseline testosterone concentrations. In a second study evaluating transfer of testosterone, 12 male subjects applied a single dose of AndroGel 1.62% 81 mg to their shoulders and upper arms. Two (2) hours after application, female subjects rubbed their hands, wrists, arms, and shoulders to the application site of the male subjects for 15 minutes while the site of application was covered by a t-shirt. When a t-shirt was used to cover the site of application, mean testosterone C_avgand C_maxin female subjects increased by 6% and 11%, respectively, compared to mean baseline testosterone concentrations.

  A separate study was conducted to evaluate the potential for testosterone transfer from 16 males dosed with AndroGel 1.62% 81 mg when it was applied to abdomen only for 7 days, a site of application not approved for AndroGel 1.62%. Two (2) hours after application to the males on each day, the female subjects rubbed their abdomens for 15 minutes to the abdomen of the males. The males had covered the application area with a T-shirt. The mean testosterone C_avgand C_maxin female subjects on day 1 increased by 43% and 47%, respectively, compared to mean baseline testosterone concentrations. The mean testosterone C_avgand C_maxin female subjects on day 7 increased by 60% and 58%, respectively, compared to mean baseline testosterone concentrations.

  Effect of showering

  In a randomized, 3-way (3 treatment periods without washout period) crossover study in 24 hypogonadal men, the effect of showering on testosterone exposure was assessed after once daily application of AndroGel 1.62% 81 mg to upper arms/shoulders for 7 days in each treatment period. On the 7th day of each treatment period, hypogonadal men took a shower with soap and water at either 2, 6, or 10 hours after drug application. The effect of showering at 2 or 6 hours post-dose on Day 7 resulted in 13% and 12% decreases in mean C_avg, respectively, compared to Day 6 when no shower was taken after drug application. Showering at 10 hours after drug application had no effect on bioavailability. The amount of testosterone remaining in the outer layers of the skin at the application site on the 7th day was assessed using a tape stripping procedure and was reduced by at least 80% after showering 2-10 hours post-dose compared to on the 6th day when no shower was taken after drug application.

  Effect of hand washing

  In a randomized, open-label, single-dose, 2-way crossover study in 16 healthy male subjects, the effect of hand washing on the amount of residual testosterone on the hands was evaluated. Subjects used their hands to apply the maximum dose (81 mg testosterone) of AndroGel 1.62% to their upper arms and shoulders. Within 1 minute of applying the gel, subjects either washed or did not wash their hands prior to study personnel wiping the subjects’ hands with ethanol dampened gauze pads. The gauze pads were then analyzed for residual testosterone content. A mean (SD) of 0.1 (0.04) mg of residual testosterone (0.12% of the actual applied dose of testosterone, and a 96% reduction compared to when hands were not washed) was recovered after washing hands with water and soap.

  Effect of sunscreen or moisturizing lotion on absorption of testosterone

  In a randomized, 3-way (3 treatment periods without washout period) crossover study in 18 hypogonadal males, the effect of applying a moisturizing lotion or a sunscreen on the absorption of testosterone was evaluated with the upper arms/shoulders as application sites. For 7 days, moisturizing lotion or sunscreen (SPF 50) was applied daily to the AndroGel 1.62% application site 1 hour after the application of AndroGel 1.62% 40.5 mg. Application of moisturizing lotion increased mean testosterone C_avgand C_maxby 14% and 17%, respectively, compared to AndroGel 1.62% administered alone. Application of sunscreen increased mean testosterone C_avgand C_maxby 8% and 13%, respectively, compared to AndroGel 1.62% applied alone.

  

  )]
  .
  
  

Dosage and Administration for AndroGel 1.62% differs from AndroGel 1%. For dosage and administration of AndroGel 1% refer to its full prescribing information. (

2 DOSAGE AND ADMINISTRATION

Dosage and Administration for AndroGel 1.62% differs from AndroGel 1%. For dosage and administration of AndroGel 1% refer to its full prescribing information.

Prior to initiating AndroGel 1.62%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range.

• Dosage and Administration for AndroGel 1.62% differs from AndroGel 1%. For dosage and administration of AndroGel 1% refer to its full prescribing information. (
  2
  )
  
  
  
• Prior to initiating AndroGel 1.62%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone has been measured in the morning on at least two separate days and that these concentrations are below the normal range .
  
  
• Starting dose of AndroGel 1.62% is 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet), applied topically once daily in the morning.
  
  
• Apply to clean, dry, intact skin of the shoulders and upper arms. Do not apply AndroGel 1.62% to any other parts of the body including the abdomen, genitals, chest, armpits (axillae), or knees.
  
  Dose adjustment: AndroGel 1.62% can be dose adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation or a single 20.25 mg packet) and a maximum of 81 mg of testosterone (4 pump actuations or two 40.5 mg packets). The dose should be titrated based on the pre-dose morning serum testosterone concentration at approximately 14 days and 28 days after starting treatment or following dose adjustment. Additionally, serum testosterone concentration should be assessed periodically thereafter.
  
  
• Patients should wash hands immediately with soap and water after applying AndroGel 1.62% and cover the application site(s) with clothing after the gel has dried. Wash the application site thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated.

2.1 Dosing and Dose Adjustment

The recommended starting dose of AndroGel 1.62% is 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet) applied topically once daily in the morning to the shoulders and upper arms.

The dose can be adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation or a single 20.25 mg packet) and a maximum of 81 mg of testosterone (4 pump actuations or two 40.5 mg packets). To ensure proper dosing, the dose should be titrated based on the pre-dose morning serum testosterone concentration from a single blood draw at approximately 14 days and 28 days after starting treatment or following dose adjustment. In addition, serum testosterone concentration should be assessed periodically thereafter. Table 1 describes the dose adjustments required at each titration step.

Table 1: Dose Adjustment Criteria

Pre-Dose Morning Total Serum Testosterone Concentration	Dose Titration
Greater than 750 ng/dL	Decrease daily dose by 20.25 mg (1 pump actuation or the equivalent of one 20.25 mg packet)
Equal to or greater than 350 and equal to or less than 750 ng/dL	No change: continue on current dose
Less than 350 ng/dL	Increase daily dose by 20.25 mg (1 pump actuation or the equivalent of one 20.25 mg packet)

The application site and dose of AndroGel 1.62% are not substitutable with other topical testosterone products.

2.2 Administration Instructions

AndroGel 1.62% should be applied to clean, dry, intact skin of the upper arms and shoulders. Do not apply AndroGel 1.62% to any other parts of the body, including the abdomen, genitals, chest, armpits (axillae), or knees

[see Clinical Pharmacology (

12.3

)]

. Area of application should be limited to the area that will be covered by the patient's short sleeve t-shirt. Patients should be instructed to use the palm of the hand to apply AndroGel 1.62% and spread across the maximum surface area as directed in Table 2 (for pump) and Table 3 (for packets) and in Figure 1.

Table 2: Application Sites for AndroGel 1.62%, Pump

Total Dose of Testosterone	Total Pump Actuations	Pump Actuations Per Upper Arm and Shoulder
		Upper Arm and Shoulder #1	Upper Arm and Shoulder #2
20.25 mg	1	1	0
40.5 mg	2	1	1
60.75 mg	3	2	1
81 mg	4	2	2

Table 3: Application Sites for AndroGel 1.62%, Packets

Total Dose of Testosterone	Total packets	Gel Applications Per Upper Arm and Shoulder
		Upper Arm and Shoulder #1	Upper Arm and Shoulder #2
20.25 mg	One 20.25 mg packet	One 20.25 mg packet	0
40.5 mg	One 40.5 mg packet	Half of contents of One 40.5 mg packet	Half of contents of One 40.5 mg packet
60.75 mg	One 20.25 mg packet AND One 40.5 mg packet	One 40.5 mg packet	One 20.25 mg packet
81 mg	Two 40.5 mg packets	One 40.5 mg packet	One 40.5 mg packet

The prescribed daily dose of AndroGel 1.62% should be applied to the right and left upper arms and shoulders as shown in the shaded areas in Figure 1.

Figure 1. Application Sites for AndroGel 1.62%

Once the application site is dry, the site should be covered with clothing

[see Clinical Pharmacology (

12.3

)]

. Wash hands thoroughly with soap and water. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including AndroGel 1.62%, are flammable.

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

)]

.

To obtain a full first dose, it is necessary to prime the canister pump. To do so, with the canister in the upright position, slowly and fully depress the actuator three times. Safely discard the gel from the first three actuations. It is only necessary to prime the pump before the first dose.

After the priming procedure, fully depress the actuator once for every 20.25 mg of AndroGel 1.62%. AndroGel 1.62% should be delivered directly into the palm of the hand and then applied to the application sites.

When using packets, the entire contents should be squeezed into the palm of the hand and immediately applied to the application sites. When 40.5 mg packets need to be split between the left and right shoulder, 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. Alternatively, AndroGel 1.62% can be applied directly to the application sites from the pump or packets.

Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from AndroGel 1.62%-treated skin:

• Children and women should avoid contact with unwashed or unclothed application site(s) of men using AndroGel 1.62%.
• AndroGel 1.62% 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 AndroGel 1.62%.
• Patients should cover the application site(s) with clothing (e.g., a t-shirt) after the gel has dried.
• Prior to situations in which direct skin-to-skin contact 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 AndroGel 1.62% 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.

)

Prior to initiating AndroGel 1.62%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range.

AndroGel (testosterone gel) 1.62% for topical use only, is available as follows:

• A metered-dose pump. Each pump actuation delivers 20.25 mg of testosterone in 1.25 g of gel.
  
  
  
  
  
• A unit dose packet containing 20.25 mg of testosterone in 1.25 g of gel.
  
  
  
  
  
• A unit dose packet containing 40.5 mg of testosterone in 2.5 g of gel.

There are insufficient long-term safety data in geriatric patients using AndroGel 1.62% to assess the potential risks of cardiovascular disease and prostate cancer. (