ANDROGEL- testosterone gel
For Healthcare Providers >

1. Abnormal Sexual Changes:
2. Behavior Problems:
3. Signs And Symptoms In Women When They Come In Direct Contact With Androgel 1% May Include:
4. Do Not Use Androgel 1% If You:
5. Before Using Androgel 1%, Tell Your Healthcare Provider About All Of Your Medical Conditions, Including If You:
6. Androgel 1% Can Cause Serious Side Effects Including:
7. The Most Common Side Effects Of Androgel 1% Include:
8. Active Ingredient:
9. Inactive Ingredients:
10. 2. How Should Androgel (pump Or Packet) Be Applied?
11. How To Use The Androgel Pump?
12. How To Use The Androgel Packets?
13. Before You Start Using Androgel, Tell Your Healthcare Professional If You :
14. Tell Your Healthcare Provider About All Of The Medicines You Take, Including Prescription And Non-prescription Medicines, Vitamins And Herbal Supplements. Androgel Can Affect How Your Body Handles Other Drugs. Changes In Your Dose Or Careful Monitoring May Be Needed If You Are Taking Any Of The Following Medications:
15. Most Common:
16. Contact Your Healthcare Professional If You Experience Any Of The Following Adverse Reactions:
17. Prostate Disorders:
18. Testosterone Transfer:
19. 6. How Should Androgel Be Stored?
20. Repackaged By:
21. Patient Information
22. What Is The Most Important Information I Should Know About Androgel?
23. Signs And Symptoms Of Early Puberty In A Child May Include:
24. Do Not Use Androgel If You:
25. Before You Use Androgel, Tell Your Healthcare Provider If You:
26. Especially, Tell Your Healthcare Provider If You Take:
27. How Should I Use Androgel?
28. Applying Androgel:
29. If You Are Using The Androgel Pump:
30. If You Are Using Androgel Packets:
31. Androgel Can Cause Serious Side Effects Including:
32. The Most Common Side Effects Of Androgel Include:
33. How Should I Store Androgel?
34. What Are The Ingredients In Androgel?active Ingredient:
35. Marketed By:
36. Revised: 12/2011document Id:

Abnormal Sexual Changes: ⮝

• enlarged penis or clitoris.
• early growth of hair near the vagina or around the penis (pubic hair).
• erections or acting out sexual urges (sex drive).

Behavior Problems: ⮝

• acting aggressively, behaving in an angry or violent way.

Women

Signs And Symptoms In Women When They Come In Direct Contact With Androgel 1% May Include: ⮝

• changes in body hair.
• an abnormal increase in pimples (acne).

Stop using ANDROGEL 1% and call your healthcare provider right away if you
ANDROGEL 1% is a prescription medicine that contains testosterone. ANDROGEL 1% is used to treat adult males who have low or no testosterone due to certain medical conditions.

• Your healthcare provider will test your blood before you start and while you are using ANDROGEL 1%.
• It is not known if ANDROGEL 1% is safe or effective to treat men who have low testosterone due to aging.
• It is not known if ANDROGEL 1% is safe or effective in children younger than 18 years old. Improper use of ANDROGEL 1% may affect bone growth in children.

ANDROGEL 1% is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your ANDROGEL 1% in a safe place to protect it. Never give your ANDROGEL 1% to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and is against the law.
ANDROGEL 1% is not meant for use in women.

Do Not Use Androgel 1% If You: ⮝

• have breast cancer.
• have or might have prostate cancer.
• are pregnant. ANDROGEL 1% may harm your unborn baby.
• Women who are pregnant should avoid contact with the area of skin where ANDROGEL 1% has been applied.

Before Using Androgel 1%, Tell Your Healthcare Provider About All Of Your Medical Conditions, Including If You: ⮝

• have breast cancer.
• have or might have prostate cancer.
• have urinary problems due to an enlarged prostate.
• have heart problems.
• have liver or kidney problems.
• have problems breathing while you sleep (sleep apnea).

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Using ANDROGEL 1% with certain other medicines can affect each other.
Especially, tell your healthcare provider if you take:

• insulin
• corticosteroids
• medicines that decrease blood clotting (blood thinners)

Androgel 1% Can Cause Serious Side Effects Including: ⮝

• If you already have an enlarged prostate, your symptoms can get worse while using ANDROGEL 1%.This can include:
  • increased urination at night.
  • trouble starting your urine stream.
  • having to pass 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 or weak urine flow.
• Possible increased risk of prostate cancer.Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use ANDROGEL 1%.
• Blood clots in the legs or lungs.Signs and symptoms of a blood clot in your leg can include leg pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain.
• Possible increased risk of heart attack or stroke.
• In large doses ANDROGEL 1% may lower your sperm count.
• Swelling of your ankles, feet, or body, with or without heart failure.
• Enlarged or painful breasts.
• Have problems breathing while you sleep (sleep apnea).

Call your healthcare provider right away if you have any of the serious side effects listed above.

The Most Common Side Effects Of Androgel 1% Include: ⮝

• acne
• skin irritation where ANDROGEL 1% is applied
• lab test changes
• increased prostate specific antigen (a test used to screen for prostate cancer).

Other side effects includemore erections than are normal for you or erections that last a long time.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of ANDROGEL 1%. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.General information about the safe and effective use of ANDROGEL 1%
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ANDROGEL 1% for a condition for which it was not prescribed. Do not give ANDROGEL 1% to other people, even if they have the same symptoms you have. It may harm them.
You can ask your pharmacist or healthcare provider for information about ANDROGEL 1% that is written for health professionals.

Active Ingredient: ⮝

testosterone

Inactive Ingredients: ⮝

carbomer 980, ethyl alcohol 67.0%, isopropyl myristate, purified water and sodium hydroxide.
Marketed by: AbbVie Inc., North Chicago, IL 60064, USA
2019 AbbVie Inc.
For more information, go to www.ANDROGEL.com or call 1-800-633-9110.

This Medication Guide has been approved by the U.S. Food and Drug Administration.
Revised: 05/2019

5044279

2. How Should Androgel (pump Or Packet) Be Applied? ⮝

It is important that you use AndroGel as prescribed by your healthcare professional. If you experience serious problems, contact your healthcare professional. Your healthcare professional will tell you how much AndroGel to use each day.

Figure3: Site(s) of Gel Application

• AndroGel should be applied once daily at the same time each day(preferably every morning) to clean, dry, healthy, intact skin of the shoulders, upper arms and/or abdomen. If you take a bath or shower in the morning, use AndroGelafteryour bath or shower.
• AndroGelshould notbe applied to thepenis or scrotum,or to skin with open sores, wounds or irritation.
• Wash your handswith soap and water immediatelyafter applicationto reduce the chance that the medication will spread from your hands to other people.
• Let AndroGel dry for a few minutes before you dress.
• AndroGel is flammable until dry; allow the gel to dry before smoking or going near an open flame.
• Wait 5 to 6 hoursbefore showering or swimming. This will ensure that the greatest amount of AndroGel is absorbed into your system.

How To Use The Androgel Pump? ⮝

It is important that you read and follow these directions on how to use the AndroGel Pump properly. Before using the pump for the first time, you must prime the AndroGel pump by fully depressing the pump three times and discarding the gel. The unused gel should be discarded in a manner to avoid accidental exposure or ingestion by household members or pets. Fully depress the pump the appropriate number of times to deliver the daily dose prescribed by your healthcare provider. The product may be delivered directly into the palm of your hand and then applied to the desired application sites, either one pump depression at a time or upon completion of all pump depressions required for the daily dose.

How To Use The Androgel Packets? ⮝

Open one AndroGel aluminum foil packet by folding the top edge at the perforation and tearing completely across the packet along the perforation. Squeeze the contents into the palm of your hand. Squeeze from the bottom of the packet toward the top. If you like, you may squeeze a portion of the gel from the packet into the palm of your hand and apply to application site(s). Repeat until the entire contents of the packet have been applied.

Before You Start Using Androgel, Tell Your Healthcare Professional If You : ⮝

• Have prostate cancer or breast cancer.
• Have a known hypersensitivity to any of AndroGel's components, including individuals who are hypersensitive to testosterone that is chemically synthesized from soy.

Tell Your Healthcare Provider About All Of The Medicines You Take, Including Prescription And Non-prescription Medicines, Vitamins And Herbal Supplements. Androgel Can Affect How Your Body Handles Other Drugs. Changes In Your Dose Or Careful Monitoring May Be Needed If You Are Taking Any Of The Following Medications: ⮝

• Insulin
• Corticosteroids
• Oral Anticoagulants

Most Common: ⮝

Skin irritation where gel is applied, breast development or tenderness, acne, prostate enlargement, changes in lab test results and changes in urinary habits.

Contact Your Healthcare Professional If You Experience Any Of The Following Adverse Reactions: ⮝

• Too frequent or persistent erections of the penis.
• Any nausea, vomiting, changes in skin color or ankle swelling.
• Breathing disturbances, including those associated with sleep, or excessive daytime sleepiness.
• Changes in urinary habits such as increased urination at night, trouble starting your urine stream, passing urine many times during the day, having an urge that you have to go to the bathroom right away, having a urine accident, being unable to pass urine and weak urine flow.

Prostate Disorders: ⮝

Patients treated with testosterone may be at an increased risk for prostate enlargement, and prostate cancer. Talk to your healthcare provider for more information on risk factors and ways to monitor for prostate disorders.

Testosterone Transfer: ⮝

Transfer of testosterone to others (including women and children) can occur when vigorous skin-to-skin contact is made with the application site. AndroGel must not be used by women, and exposure to the active ingredient testosterone in pregnancy can cause fetal harm. Notify your healthcare provider if your female partner develops changes in hair distribution, increases in acne or other signs of masculinity.

6. How Should Androgel Be Stored? ⮝

Store at 25 C (77 F); excursions permitted to 15 to 30 C (59 to 86 F) [

Your healthcare professional has prescribed AndroGel to meet your specific needs; never share your AndroGel with anyone. If you have any questions or concerns about your AndroGel treatment, ask your healthcare provider or pharmacist.

Manufactured By:
Laboratoires Besins International
Montrouge, France
For:
Unimed Pharmaceuticals, LLC
A Solvay Pharmaceuticals, Inc. Company
Marietta, GA 30062-2224

Repackaged By: ⮝

Rebel Distributors Corp.

Thousand Oaks, CA 91320

U.S. Patent No. 6,503, 894

2007 Solvay Pharmaceuticals, Inc.

Revised: December 2007

500122/500127 Rev Dec 2007(1)

Patient Information ⮝

Medication Guide

AndroGel(AN DROW JEL) CIII

(testosterone gel) 1%

Read the Medication Guide that comes with AndroGel before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What Is The Most Important Information I Should Know About Androgel? ⮝

1. Early signs and symptoms of puberty have happened in young children who were accidentally exposed to testosterone through contact with men using AndroGel.

Signs And Symptoms Of Early Puberty In A Child May Include: ⮝

• enlarged penis or clitoris
• early development of pubic hair
• increased erections or sex drive
• aggressive behavior

AndroGel can transfer from your body to others.

2. Women and children should avoid contact with the unwashed or unclothed area where AndroGel has been applied to your skin.

Stop using AndroGel and call your healthcare provider right away ifyou

AndroGel is a prescription medicine that contains testosterone. AndroGel is used to treat adult males who have low or no testosterone.

It is not known if AndroGel is safe or effective in children younger than 18 years old. Improper use of AndroGel may affect bone growth in children.

AndroGel is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your AndroGel in a safe place to protect it. Never give your AndroGel to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and is against the law.

AndroGel is not meant for use in women.

Do Not Use Androgel If You: ⮝

• have breast cancer
• have or might have prostate cancer
• are pregnant or may become pregnant or breast-feeding. AndroGel may harm your unborn or breast-feeding baby.

Women who are pregnant or who may become pregnant should avoid contact with the area of skin where AndroGel has been applied.

• are allergic to testosterone or any of the ingredients in AndroGel including soy.

Before You Use Androgel, Tell Your Healthcare Provider If You: ⮝

• have breast cancer or prostate cancer
• have urinary problems due to an enlarged prostate
• have heart problems
• have liver or kidney problems
• have problems breathing while you sleep (sleep apnea)
• have any other medical conditions

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Using AndroGel with certain other medicines can affect each other.

Especially, Tell Your Healthcare Provider If You Take: ⮝

• insulin
• corticosteroids
• medicines that decrease blood clotting

Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.

How Should I Use Androgel? ⮝

• It is important that you apply AndroGel exactly as prescribed by your healthcare provider. Your healthcare provider will tell you how much AndroGel to apply and when to apply it.
• Your healthcare provider may change your AndroGel dose. Do not change your AndroGel dose without talking to your healthcare provider.
• AndroGel is for skin use only.
• Do not allow others to apply AndroGel to your body.

Applying Androgel: ⮝

AndroGel comes in a pump or in packets.

If You Are Using The Androgel Pump: ⮝

• Before using the pump for the first time, you will need to prime the pump. To prime AndroGel, fully push down on the pump 3 times. Do not use any AndroGel that came out while priming. Wash it down the sink or throw it in the trash to avoid accidental exposure to others. Your AndroGel pump is ready to use now.
• Your healthcare provider will tell you the number of times to press the pump for each dose.

If You Are Using Androgel Packets: ⮝

• Tear open the packet completely at the dotted line.
• Squeeze all of the AndroGel out of the packet into the palm of your hand. Squeeze from the bottom of the packet to the top.
• Throw away the packet in the trash out of the reach of children to avoid accidental exposure.

• Squeeze the medicine into the palm of your hand and apply to clean dry, intact skin at the same time each day.
• You may also apply AndroGel from the pump or packet directly to your skin.
• Apply AndroGel only to areas that will be covered by a short sleeve t-shirt, as shown in the shaded areas in the figure below. These areas are your shoulders and upper arms, or stomach area, or shoulders, upper arm and stomach area.

  

• Do not apply AndroGel to your penis or scrotum.
• Wash your hands with soap and water right after you apply AndroGel.
• Let the application areas dry for a few minutes before putting on a shirt.
• To prevent transfer of AndroGel to others, clothes (such as a t-shirt) shouldalwaysbe worn to cover the AndroGel application areas until you have washed the application areas well with soap and water.

• Wait 5 hours before showering or swimming. This will ensure that the greatest amount of AndroGel is absorbed into your system.
• AndroGel is flammable until dry. Let the gel dry before smoking or going near an open flame.

Your healthcare provider will test your blood before you start and while you take AndroGel.

Androgel Can Cause Serious Side Effects Including: ⮝

• If you already have enlargement of your prostate gland your signs and symptoms can get worsewhile using AndroGel. This can include:

• increased urination at night
• trouble starting your urine stream
• having to pass urine many times during the day
• having an urge that you have to go to the bathroom right away
• having a urine accident
• being unable to pass urine or weak urine flow

• Possible increased risk of prostate cancer.Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use AndroGel.
• In large doses AndroGel may lower your sperm count.
• Swelling of your ankles, feet, or body, with or without heart failure.
• Enlarged or painful breasts.
• Have problems breathing while you sleep (sleep apnea).
• Blood clots in the legs.This can include pain, swelling or redness of your legs.

Call your healthcare provider right away if you have any of the serious side effects listed above.

The Most Common Side Effects Of Androgel Include: ⮝

• acne
• skin irritation where AndroGel is applied
• increased cholesterol levels
• increased prostate specific antigen (a test used to screen for prostate cancer)
• increased red blood cell count
• increased liver function tests

Other side effects includemore erections than are normal for you or erections that last a long time.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of AndroGel. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How Should I Store Androgel? ⮝

• Store AndroGel between 59 F to 86 F (15 C to 30 C).
• Safely throw away used AndroGel in household trash. Be careful to prevent accidental exposure of children or pets.
• Keep AndroGel away from fire.

Keep AndroGel and all medicines out of the reach of children.

General information about AndroGel

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use AndroGel for a condition for which it was not prescribed. Do not give AndroGel to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about AndroGel. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about AndroGel that is written for health professionals.

For more information, go to www.ANDROGEL.com or call 1-800-241-1643.

What Are The Ingredients In Androgel?active Ingredient: ⮝

testosterone

Marketed By: ⮝

Abbott Laboratories

North Chicago, IL 60064, U.S.A.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Issued Nov 2011

NDC 54868-4792-0

CIII

AndroGel(testosterone gel) 1%

30 Unit-dose Packets

Contains 2.5 grams per unit dose

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, upper arms, or abdomen.*

Rx Only

Dispense the enclosed Medication Guide to each patient.

*See accompanying package insert.

NDC 54868-4810-0

CIII

AndroGel(testosterone gel 1%)

30 Unit-dose Packets

Contains 5 grams per unit dose

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, upper arms, or abdomen.*

Dispense the enclosed Medication guide to each patient.

*See accompanying package insert.

Rx Only

NDC 54868-5814-0

CIII

AndroGel(testosterone 1% Pump

This package contains 2 multi-dose pumps. Each pump is capable of dispensing 75g doses each.

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, upper arms, or abdomen.*

Dispense the enclosed Medication Guide to each patient.

Rx Only

ANDROGEL testosterone gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-5814(NDC:0051-8488) Route of Administration TRANSDERMAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength testosterone(UNII: 3XMK78S47O) (testosterone - UNII:3XMK78S47O) testosterone 10 mg in 1 g

Inactive Ingredients Ingredient Name Strength carbomer homopolymer type C(UNII: 4Q93RCW27E) alcohol(UNII: 3K9958V90M) isopropyl myristate(UNII: 0RE8K4LNJS) water(UNII: 059QF0KO0R) sodium hydroxide(UNII: 55X04QC32I)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:54868-5814-0 2 in 1 CARTON 1 75 g in 1 BOTTLE, PUMP

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021015 08/29/2007

ANDROGEL testosterone gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-4792(NDC:0051-8425) Route of Administration TRANSDERMAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength testosterone(UNII: 3XMK78S47O) (testosterone - UNII:3XMK78S47O) testosterone 10 mg in 1 g

Inactive Ingredients Ingredient Name Strength carbomer homopolymer type C(UNII: 4Q93RCW27E) alcohol(UNII: 3K9958V90M) isopropyl myristate(UNII: 0RE8K4LNJS) water(UNII: 059QF0KO0R) sodium hydroxide(UNII: 55X04QC32I)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:54868-4792-0 30 in 1 CARTON 1 2.5 g in 1 PACKET

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021015 05/15/2003

ANDROGEL testosterone gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-4810(NDC:0051-8450) Route of Administration TRANSDERMAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength testosterone(UNII: 3XMK78S47O) (testosterone - UNII:3XMK78S47O) testosterone 10 mg in 1 g

Inactive Ingredients Ingredient Name Strength carbomer homopolymer type C(UNII: 4Q93RCW27E) alcohol(UNII: 3K9958V90M) isopropyl myristate(UNII: 0RE8K4LNJS) water(UNII: 059QF0KO0R) sodium hydroxide(UNII: 55X04QC32I)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:54868-4810-0 30 in 1 CARTON 1 5 g in 1 PACKET

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021015 06/05/2003

Labeler -Physicians Total Care, Inc. (194123980)

Establishment
Name	Address	ID/FEI	Business Operations
Physicians Total Care, Inc.		194123980	relabel

Revised: 12/2011document Id: ⮝

e1db502f-fa92-4a34-9c93-68bdfb38ba8534391-3Set id: d466910c-9a76-44e8-8759-4717ec2c591fVersion: 3Effective Time: 20111215Physicians Total Care, Inc.

1. No Title 1572547581
2. No Title 1572548471
3. Highlights Of Prescribing Information
4. Warning: Secondary Exposure To Testosterone
5. See Full Prescribing Information For Complete Boxed Warning.
6. Indications And Usage
7. Dosage And Administration
8. Dosage Forms And Strengths
9. Contraindications
10. Warnings And Precautions
11. Adverse Reactions
12. Drug Interactions
13. Use In Specific Populations
14. 1 Indications And Usage
15. 2 Dosage And Administration
16. 3 Dosage Forms And Strengths
17. 4 Contraindications
18. 5 Warnings And Precautions
19. 6 Adverse Reactions
20. 7 Drug Interactions
21. 8 Use In Specific Populations
22. 9 Drug Abuse And Dependence
23. 10 Overdosage
24. 11 Description
25. 12 Clinical Pharmacology
26. 13 Nonclinical Toxicology
27. 14 Clinical Studies
28. 16 How Supplied/storage And Handling
29. No Title 1572449648
30. Recent Major Changes
31. 2 Dosage And Administration
32. 12 Clinical Pharmacology
33. 14 Clinical Studies
34. 16 How Supplied/storage And Handling
35. See Full Prescribing Information For Complete Boxed Warning.
36. No Title 1572455108
37. 1 Indications And Usage
38. 3 Dosage Forms And Strengths
39. 4 Contraindications
40. 5 Warnings And Precautions
41. 6 Adverse Reactions
42. 7 Drug Interactions
43. 8 Use In Specific Populations
44. 9 Drug Abuse And Dependence
45. 10 Overdosage
46. 11 Description
47. 13 Noncllinical Toxicology
48. Principal Display Panel

No Title 1572547581 ⮝

INSTRUCTIONS FOR USE
ANDROGEL (AN DROW JEL) CIII
(testosterone gel) 1.62%
for topical use

Read this Instructions for Use for ANDROGEL1.62% before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment.

Applying ANDROGEL 1.62%:

• ANDROGEL 1.62% comes in a pump or in packets.
• Before applying ANDROGEL 1.62% make sure that your shoulders and upper arms are clean, dry, and that there is no broken skin.
• ANDROGEL 1.62% is to be applied to the area of your shoulders and upper arms that will be covered by a short sleeve t-shirt (See Figure A). Do not apply ANDROGEL 1.62% to any other parts of your body such as your stomach area (abdomen), penis, scrotum, chest, armpits (axillae), or knees.

(Figure A)

If you are using ANDROGEL 1.62% pump:

• Before using a new bottle of ANDROGEL 1.62 % for the first time, you will need to remove the cap and then prime the pump. To prime the ANDROGEL 1.62% pump, slowly push the pump all the way down 3 times, over the sink drain. Do not use any ANDROGEL 1.62% that came out while priming. Wash it down the sink to avoid accidental exposure to others. Your ANDROGEL 1.62% pump is now ready to use.
• Remove the cap from the pump. Then, put the spout opening at the top of the pump where the medicine comes out over the palm of your hand and slowly push the pump all the way down. Apply ANDROGEL 1.62% to the application site. You may also apply ANDROGEL 1.62% directly to the application site. Your healthcare provider will tell you the number of times to press the pump for each dose.
• Wash your hands with soap and water right away.

Find Your Dose as Prescribed by Your Healthcare Provider		Application Method
1 pump	20.25 mg	Apply 1 pump of ANDROGEL 1.62% to 1 upper arm and shoulder.
2 pumps	40.5 mg	Apply 1 pump of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply 1 pump of ANDROGEL 1.62% to the opposite upper arm and shoulder.
3 pumps	60.75 mg	Apply 2 pumps of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply 1 pump of ANDROGEL 1.62% to the opposite upper arm and shoulder.
4 pumps	81 mg	Apply 2 pumps of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply 2 pumps of ANDROGEL 1.62% to the opposite upper arm and shoulder.

If you are using ANDROGEL 1.62% packets:

• Tear open the packet completely at the dotted line. Squeeze from the bottom of the packet to the top.
• Squeeze all of the ANDROGEL 1.62% out of the packet into the palm of your hand.
• Apply ANDROGEL 1.62% to the application site. You may also apply ANDROGEL 1.62% directly to the application site.
• Let the application site dry completely before putting on a t-shirt.
• ANDROGEL 1.62% is flammable until dry. Let ANDROGEL 1.62% dry before smoking or going near an open flame.
• Avoid showering, swimming or bathing for at least 2 hours after you apply ANDROGEL 1.62%.
• Wash your hands right away with soap and water after applying ANDROGEL 1.62%.

Find Your Dose as Prescribed by Your Healthcare Provider		Application Method
One 20.25 mg packet	20.25 mg	Apply 1 packet of ANDROGEL 1.62% to 1 upper arm and shoulder.
One 40.5 mg packet	40.5 mg	Apply half of the 40.5 mg packet of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply the remaining packet contents to the opposite upper arm and shoulder.
One 40.5 mg packet and one 20.25 mg packet	60.75 mg	Apply one 40.5 mg packet of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply one 20.25 mg packet of ANDROGEL 1.62% to the opposite upper arm and shoulder.
Two 40.5 mg packets	81 mg	Apply one 40.5 mg packet of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply one 40.5 mg packet of ANDROGEL 1.62% to the opposite upper arm and shoulder.

How should I store ANDROGEL 1.62%?

• Store ANDROGEL 1.62% at room temperature between 68 F to 77 F (20 C to 25 C).
• When it is time to throw away the pump or packets, safely throw away used ANDROGEL 1.62% in the household trash. Be careful to prevent accidental exposure of children or pets.
• Keep ANDROGEL 1.62% away from fire.

Keep ANDROGEL 1.62% and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: 05/2019

5044281

NDC 0051 8462 31

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, and upper arms*

AndroGel (testosterone gel) 1.62% CIII

30 Unit-dose Packets

Contains 20.25 mg of testosterone in 1.25 Grams of gel per unit dose

Rx only

For Topical Use Only

Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure. Dispense the enclosed Medication Guide to each patient.

*See accompanying package insert.

abbvie

NDC 0051 8462 30

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, and upper arms*

AndroGel (testosterone gel) 1.62% CIII

30 Unit-dose Packets

Contains 40.5 mg of testosterone in 2.5 Grams of gel per unit dose

Rx Only

For Topical Use Only

Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure. Dispense the enclosed Medication Guide to each patient.

* See accompanying package insert.

abbvie

NDC 0051 8462 33

Dispense the accompanying Medication Guide to each patient.

AndroGel (testosterone gel) 1.62% CIII

20.25 mg of testosterone per pump actuation*

*Each actuation delivers 1.25 g of gel

For Topical Use Only

Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure.

Rx only

Multi-dose pump capable of dispensing 60 metered pump actuations.

abbvie

ANDROGEL testosterone gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0051-8462 Route of Administration TRANSDERMAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength testosterone (UNII: 3XMK78S47O) (testosterone - UNII:3XMK78S47O) testosterone 16.2 mg in 1 g

Inactive Ingredients Ingredient Name Strength alcohol (UNII: 3K9958V90M) isopropyl myristate (UNII: 0RE8K4LNJS) water (UNII: 059QF0KO0R) sodium hydroxide (UNII: 55X04QC32I) CARBOMER HOMOPOLYMER TYPE C (ALLYL PENTAERYTHRITOL CROSSLINKED) (UNII: 4Q93RCW27E)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0051-8462-33 1 in 1 CARTON 04/29/2011 1 88 g in 1 BOTTLE, PUMP; Type 0: Not a Combination Product 2 NDC:0051-8462-31 30 in 1 CARTON 04/29/2011 2 NDC:0051-8462-12 1.25 g in 1 PACKET; Type 0: Not a Combination Product 3 NDC:0051-8462-30 30 in 1 CARTON 04/29/2011 3 NDC:0051-8462-01 2.5 g in 1 PACKET; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022309 04/29/2011

Labeler - AbbVie Inc. (078458370)

Revised: 5/2019 Document Id: 1622cf7d-0e00-87a3-d58e-cd3f7730e76e 34391-3 Set id: 8677ba5b-8374-46cb-854c-403972e9ddf3 Version: 110 Effective Time: 20190522 AbbVie Inc.

No Title 1572548471 ⮝

INSTRUCTIONS FOR USE
ANDROGEL (AN DROW JEL) CIII
(testosterone gel) 1%
for topical use

Read this Instructions for Use for ANDROGEL 1% before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment.

Applying ANDROGEL 1%:

• Before applying ANDROGEL 1%, make sure that your shoulders, upper arms or stomach are clean, dry, and there is no broken skin.
• The application sites for ANDROGEL 1% are the shoulders, upper arms or stomach area (abdomen) that will be covered by a short sleeve t-shirt (see Figure A). Do not apply ANDROGEL 1% to any other parts of your body such as your penis, scrotum, chest, armpits (axillae), knees, or back.

(Figure A)

• Tear open the packet completely at the dotted line. Squeeze from the bottom of the packet to the top.
• Squeeze all of the ANDROGEL 1% out of the packet into the palm of your hand.
• Apply ANDROGEL 1% to the application site. You may also apply ANDROGEL 1% from the packet directly to the application site.
• Let the application areas dry completely before putting on a t-shirt.
• ANDROGEL 1% is flammable until dry. Let ANDROGEL 1% dry before smoking or going near an open flame.
• Wash your hands with soap and water right away after applying ANDROGEL 1%.
• Avoid showering, swimming, or bathing for at least 5 hours after you apply ANDROGEL 1%.

How should I store ANDROGEL 1%?

• Store ANDROGEL 1% at room temperature between 68 F to 77 F (20 C to 25 C).
• Safely throw away used ANDROGEL 1% in the household trash. Be careful to prevent accidental exposure of children or pets.
• Keep ANDROGEL 1% away from fire.

Keep ANDROGEL 1% and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: 05/2019

5044279

NDC 0051 8425 30

CIII

AndroGel (testosterone gel) 1%

30 Unit-dose Packets

Contains 25 mg of testosterone in 2.5 Grams of gel per unit dose

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, upper arms, or abdomen.*

Rx Only

For Topical Use Only

Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure.

Dispense the enclosed Medication Guide to each patient.

*See accompanying package insert.

abbvie

NDC 0051 8450 30

CIII

AndroGel (testosterone gel) 1%

30 Unit-dose Packets

Contains 50 mg of testosterone in 5 Grams of gel per unit dose

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, upper arms, or abdomen.*

Rx Only

For Topical Use Only

Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure.

Dispense the enclosed Medication Guide to each patient.

*See accompanying package insert.

abbvie

NDC 0051 8488 88

ANDROGEL testosterone gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0051-8488 Route of Administration TRANSDERMAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength testosterone (UNII: 3XMK78S47O) (testosterone - UNII:3XMK78S47O) testosterone 10 mg in 1 g

Inactive Ingredients Ingredient Name Strength isopropyl myristate (UNII: 0RE8K4LNJS) water (UNII: 059QF0KO0R) sodium hydroxide (UNII: 55X04QC32I) carbomer homopolymer type C (UNII: 4Q93RCW27E) alcohol (UNII: 3K9958V90M)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0051-8488-88 2 in 1 CARTON 03/14/2011 08/31/2015 1 NDC:0051-8488-33 75 g in 1 BOTTLE, PUMP; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021015 03/14/2011 08/31/2015

ANDROGEL testosterone gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0051-8425 Route of Administration TRANSDERMAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength testosterone (UNII: 3XMK78S47O) (testosterone - UNII:3XMK78S47O) testosterone 10 mg in 1 g

Inactive Ingredients Ingredient Name Strength alcohol (UNII: 3K9958V90M) isopropyl myristate (UNII: 0RE8K4LNJS) water (UNII: 059QF0KO0R) sodium hydroxide (UNII: 55X04QC32I) CARBOMER HOMOPOLYMER TYPE C (ALLYL PENTAERYTHRITOL CROSSLINKED) (UNII: 4Q93RCW27E)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0051-8425-30 30 in 1 CARTON 03/14/2011 1 NDC:0051-8425-01 2.5 g in 1 PACKET; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021015 03/14/2011

ANDROGEL testosterone gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0051-8450 Route of Administration TRANSDERMAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength testosterone (UNII: 3XMK78S47O) (testosterone - UNII:3XMK78S47O) testosterone 10 mg in 1 g

Inactive Ingredients Ingredient Name Strength alcohol (UNII: 3K9958V90M) isopropyl myristate (UNII: 0RE8K4LNJS) water (UNII: 059QF0KO0R) sodium hydroxide (UNII: 55X04QC32I) CARBOMER HOMOPOLYMER TYPE C (ALLYL PENTAERYTHRITOL CROSSLINKED) (UNII: 4Q93RCW27E)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0051-8450-30 30 in 1 CARTON 03/14/2011 1 NDC:0051-8450-01 5 g in 1 PACKET; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021015 03/14/2011

Labeler - AbbVie Inc. (078458370)

Revised: 5/2019 Document Id: 9869acf3-57ca-7943-a1c1-fd2a958bf275 34391-3 Set id: c506aaa3-04f8-4eb1-8dc4-e964cdd08e7f Version: 129 Effective Time: 20190522 AbbVie Inc.

Highlights Of Prescribing Information ⮝

These highlights do not include all the information needed to use AndroGel 1% safely and effectively. See full prescribing information for AndroGel 1%.

AndroGel (testosterone gel) 1% for topical use CIII
Initial U.S. Approval: 1953

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)].

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).

Indications And Usage ⮝

AndroGel 1% is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone:

• Primary hypogonadism (congenital or acquired). (1)
• Hypogonadotropic hypogonadism (congenital or acquired). (1)

Limitations of use:

• Safety and efficacy of AndroGel 1% in men with age-related hypogonadism have not been established. (1)
• Safety and efficacy of AndroGel 1% in males less than 18 years old have not been established. (8.4)
• Topical testosterone products may have different doses, strengths or application instructions that may result in different systemic exposure. (1, 12.3)

Dosage And Administration ⮝

2.1 General Dosing

The recommended starting dose of AndroGel is 5 g once daily (preferably in the morning) to clean, dry, intact skin of the shoulders and upper arms and/or abdomen. AndroGel must not be applied to the genitals. AndroGel is supplied as either a pump or in individual packets. After applying the gel, the application site should be allowed to dry for a few minutes prior to dressing. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including AndroGel, are flammable. Hands should be washed with soap and water after AndroGel has been applied. [see Warnings and Precautions (5.2, 5.10)].

2.2 Administration

Multi-Dose 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 1.25 g (AndroGel Pump) of product required to achieve the daily prescribed dosage. The product may be delivered directly into the palm of the hand and then applied to the desired application sites, either one pump actuation at a time or upon completion of all pump actuations required for the daily dose. Alternatively, the product can be applied directly to the application sites. Application directly to the sites may prevent loss of product that may occur during transfer from the palm of the hand onto the application sites. Table 1 has specific dosing guidelines for adult males when the 75 g AndroGel Pump is used.

Table 1: Specific Dosing Guidelines for Using the Adult Multi-Dose Pump

Prescribed Daily Dose	Number of Pump Actuations in 75 g Pump
5 g	4 (once daily)
7.5 g	6 (once daily)
10 g	8 (once daily)

Packets

The entire contents should be squeezed into the palm of the hand and immediately applied to the application sites. Alternately, patients may squeeze a portion of the gel from the packet into the palm of the hand and apply to application sites. Repeat until entire contents have been applied.

2.3 Dose Adjustment and Patient Assessments

• To ensure proper dosing, serum testosterone levels should be measured at intervals and replaced to serum testosterone levels in the normal range. If the serum testosterone concentration is below the normal range, the daily AndroGel dose may be increased from 5 g to 7.5 g and from 7.5 g to 10 g for adult males as instructed by the physician. If the serum testosterone concentration exceeds the normal range, the daily AndroGel dose may be decreased. If the serum testosterone concentration consistently exceeds the normal range at a daily dose of 5 g, AndroGel therapy should be discontinued.

The following is general advice for treating and monitoring adult patients on AndroGel. No specific recommendations can be made.

• Prescribers should be aware that testosterone is contraindicated in men with known or suspected prostate cancer. Therefore, evaluation for prostate cancer prior to initiation of AndroGel therapy is appropriate [see Contraindications (4)].
• Based on results from controlled studies, serum PSA may rise when taking AndroGel. Therefore, periodic assessment of serum PSA is recommended in patients taking AndroGel [see Adverse Reactions (6.1)].
• Based on results from controlled studies, worsening of BPH may occur in patients taking AndroGel [see Adverse Reactions (6.1)]. Therefore, periodic assessments for signs and symptoms of BPH are recommended in patients taking AndroGel.
• Hematocrit, serum lipid profile, and liver function test should be monitored in patients taking AndroGel [see Warnings and Precautions (5.9)].

Dosage Forms And Strengths ⮝

AndroGel (testosterone gel) 1% for topical use is available as follows:

• Packets containing 25 mg of testosterone. (3)
• Packets containing 50 mg of testosterone. (3)

Contraindications ⮝

• Men with carcinoma of the breast or known or suspected prostate cancer. (4, 5.1)
• Women who are pregnant. Testosterone may cause fetal harm. (4, 8.1)

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 AndroGel 1%. Secondary exposure to testosterone can produce signs of virilization. AndroGel 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)
• AndroGel 1% is flammable until dry. (5.16)

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 AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions ⮝

• Androgens may decrease blood glucose and therefore may decrease insulin requirements in diabetic patients. (7.1)
• Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of INR and prothrombin time is recommended. (7.2)
• Use of testosterone with adrenocorticotrophic hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease. (7.3)

Use In Specific Populations ⮝

There are insufficient long-term safety data in geriatric patients using AndroGel 1% to assess the potential risks of cardiovascular disease and prostate cancer. (8.5)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 5/2019

1 Indications And Usage  ⮝

AndroGel 1% is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

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

Limitations of use:

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

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. (2)

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.

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 interchangeable 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.

3 Dosage Forms And Strengths  ⮝

AndroGel (testosterone gel) 1% for topical use is available as follows:

• A unit dose packet containing 25 mg of testosterone provided in 2.5 g of gel.
• A unit dose packet containing 50 mg of testosterone provided in 5 g of gel.

4 Contraindications  ⮝

• AndroGel 1% is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions (5.1), Adverse Reactions (6.1), and Nonclinical Toxicology (13.1)].
• AndroGel 1% is contraindicated in women who are pregnant. AndroGel 1% can cause virilization of the female fetus when administered to a pregnant woman. Pregnant women need to be aware of the potential for transfer of testosterone from men treated with AndroGel 1%. If a pregnant woman is exposed to AndroGel 1%, she should be apprised of the potential hazard to the fetus [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1)].

5 Warnings And Precautions  ⮝

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 AndroGel 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 AndroGel 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 AndroGel 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 AndroGel 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, AndroGel 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 AndroGel 1%, 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 has produced multiple hepatic adenomas. AndroGel 1% is not known to cause these adverse effects.

5.10 Edema

Androgens, including AndroGel 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 AndroGel 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 AndroGel 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 AndroGel 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 AndroGel 1%, are flammable; therefore, patients should be advised to avoid fire, flame or smoking until the AndroGel 1% has dried.

6 Adverse Reactions  ⮝

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 AndroGel 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 AndroGel 1% in the 180-Day Controlled Clinical Trial

Adverse Event	Dose of AndroGel 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 AndroGel 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 AndroGel 1%. These events included: cerebral hemorrhage, convulsion (neither of which were considered related to AndroGel 1% administration), depression, sadness, memory loss, elevated prostate specific antigen, and hypertension. No AndroGel 1% patient discontinued due to skin reactions.

In a separate uncontrolled pharmacokinetic study of 10 patients, two had adverse events associated with AndroGel 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 AndroGel 1% and reported by > 1% of patients is shown in Table 2.

Table 2: Adverse Events Possibly, Probably or Definitely Related to Use of AndroGel 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 AndroGel 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 AndroGel 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 AndroGel 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)].

7 Drug Interactions  ⮝

7.1 Insulin

Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease insulin requirements.

7.2 Oral Anticoagulants

Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking anticoagulants, especially at the initiation and termination of androgen therapy.

7.3 Corticosteroids

The concurrent use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention and requires careful monitoring particularly in patients with cardiac, renal or hepatic disease.

8 Use In Specific Populations  ⮝

8.1 Pregnancy

Risk Summary

AndroGel 1% is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action [see Contraindications (4) and Clinical Pharmacology (12.1)]. Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies.

Data

Animal Data

In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. Structural impairments observed in females included increased ano-genital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes.

Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant female rats and their offspring exposed to doses approximately twice those used fortestosterone replacement therapy.

8.2 Lactation

Risk Summary

AndroGel 1% is not indicated for use in women.

8.3 Females and Males of Reproductive Potential

Infertility

Testis disorder, testicular atrophy, and oligospermia have been identified during use of AndroGel 1% [see Adverse Reactions (6.1, 6.2)].

During treatment with large doses of exogenous androgens, including AndroGel 1%, 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 AndroGel 1% in pediatric patients less than 18 years old has not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.

8.5 Geriatric Use

There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing AndroGel 1% to determine whether efficacy in those over 65 years of age differs from younger subjects. Additionally, there is insufficient long-term safety data in geriatric patients to assess the potential risks of cardiovascular disease and prostate cancer.

Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH.

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.

9 Drug Abuse And Dependence  ⮝

9.1 Controlled Substance

AndroGel 1% contains testosterone, a Schedule III controlled substance in the Controlled Substances Act.

9.2 Abuse

Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse by men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice.

Abuse-Related Adverse Reactions

Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression.

The following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility.

The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities.

The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty.

Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

9.3 Dependence

Behaviors Associated with Addiction

Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors:

• Taking greater dosages than prescribed
• Continued drug use despite medical and social problems due to drug use
• Spending significant time to obtain the drug when supplies of the drug are interrupted
• Giving a higher priority to drug use than other obligations
• Having difficulty in discontinuing the drug despite desires and attempts to do so
• Experiencing withdrawal symptoms upon abrupt discontinuation of use

Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism.

Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.

10 Overdosage  ⮝

There is one report of acute overdosage with use of an approved injectable testosterone product: this subject had serum testosterone concentrations of up to 11,400 ng/dL with a cerebrovascular accident.

Treatment of overdosage would consist of discontinuation of AndroGel 1%, washing the application site with soap and water, and appropriate symptomatic and supportive care.

11 Description  ⮝

AndroGel (testosterone gel) 1% is a clear, colorless hydroalcoholic gel containing testosterone.

The active pharmacologic ingredient in AndroGel 1% is testosterone, an androgen. Testosterone USP is a white to practically white crystalline powder chemically described as 17-beta hydroxyandrost-4-en-3-one. The structural formula is:

Pharmacologically inactive ingredients in AndroGel 1% are carbomer 980, ethanol 67.0%, isopropyl myristate, purified water, and sodium hydroxide. These ingredients are not pharmacologically active.

12 Clinical Pharmacology ⮝

12.1 Mechanism of Action

Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal chord thickening, alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism results from insufficient secretion of testosterone and is characterized by low serum testosterone concentrations. Signs/symptoms associated with male hypogonadism include erectile dysfunction and decreased sexual desire, fatigue and loss of energy, mood depression, regression of secondary sexual characteristics and osteoporosis.

Male hypogonadism has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter's Syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

12.3 Pharmacokinetics

Adult Males

Absorption

AndroGel delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal levels (298 1043 ng/dL) seen in healthy men. AndroGel provides continuous transdermal delivery of testosterone for 24 hours following a single application to intact, clean, dry skin of the shoulders, upper arms and/or abdomen.

AndroGel is a hydroalcoholic formulation that dries quickly when applied to the skin surface. The skin serves as a reservoir for the sustained release of testosterone into the systemic circulation. Approximately 10% of the testosterone dose applied on the skin surface from AndroGel is absorbed into systemic circulation. Therefore, 5 g and 10 g of AndroGel systemically deliver approximately 5 mg and 10 mg of testosterone, respectively. In a study with 10 g of AndroGel, all patients showed an increase in serum testosterone within 30 minutes, and eight of nine patients had a serum testosterone concentration within normal range by 4 hours after the initial application. Absorption of testosterone into the blood continues for the entire 24-hour dosing interval. Serum concentrations approximate the steady-state level by the end of the first 24 hours and are at steady state by the second or third day of dosing.

With single daily applications of AndroGel, follow-up measurements 30, 90 and 180 days after starting treatment have confirmed that serum testosterone concentrations are generally maintained within the eugonadal range. Figure 1 summarizes the 24-hour pharmacokinetic profiles of testosterone for hypogonadal men (less than 300 ng/dL) maintained on 5 g or 10 g of AndroGel for 30 days. The average ( SD) daily testosterone concentration produced by AndroGel 10 g on Day 30 was 792 ( 294) ng/dL and by AndroGel 5 g 566 ( 262) ng/dL.

Figure 1: Mean ( SD) Steady-State Serum Testosterone Concentrations on Day 30 in Patients Applying AndroGel Once Daily

When AndroGel treatment is discontinued after achieving steady state, serum testosterone levels remain in the normal range for 24 to 48 hours but return to their pretreatment levels by the fifth day after the last application.

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 bound to albumin and other proteins.

Metabolism

There is considerable variation in the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes. Testosterone is metabolized to various 17-keto steroids through two different pathways. The major active metabolites of testosterone are estradiol and DHT.

DHT concentrations increased in parallel with testosterone concentrations during AndroGel treatment. After 180 days of treatment in adult males, mean DHT concentrations were within the normal range with 5 g AndroGel and were about 7% above the normal range after a 10 g dose. The mean steady-state DHT/T ratio during 180 days of AndroGel treatment remained within normal limits and ranged from 0.23 to 0.29 (5 g/day) and from 0.27 to 0.33 (10 g/day).

Excretion

About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic 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.

13 Nonclinical Toxicology  ⮝

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats.

Mutagenesis

Testosterone was negative in the in vitro Ames and in the in vivo mouse micronucleus assays.

Impairment of Fertility

The administration of exogenous testosterone has been reported to suppress spermatogenesis in rats, dogs, and non-human primates, which was reversible on cessation of the treatment.

14 Clinical Studies ⮝

14.1 Clinical Trials in Adult Hypogonadal Males

AndroGel was evaluated in a multi-center, randomized, parallel-group, active-controlled, 180-day trial in 227 hypogonadal men. The study was conducted in 2 phases. During the Initial Treatment Period (Days 1-90), 73 patients were randomized to AndroGel 5 g daily, 78 patients to AndroGel 10 g daily, and 76 patients to a non-scrotal testosterone transdermal system. The study was double-blind for dose of AndroGel but open-label for active control. Patients who were originally randomized to AndroGel and who had single-sample serum testosterone levels above or below the normal range on Day 60 were titrated to 7.5 g daily on Day 91. During the Extended Treatment Period (Days 91-180), 51 patients continued on AndroGel 5 g daily, 52 patients continued on AndroGel 10 g daily, 41 patients continued on a non-scrotal testosterone transdermal system (5 mg daily), and 40 patients received AndroGel 7.5 g daily. Upon completion of the initial study, 163 enrolled and 162 patients received treatment in an open-label extension study of AndroGel for an additional period of up to 3 years.

Mean peak, trough and average serum testosterone concentrations within the normal range (298-1043 ng/dL) were achieved on the first day of treatment with doses of 5 g and 10 g. In patients continuing on AndroGel 5 g and 10 g, these mean testosterone levels were maintained within the normal range for the 180-day duration of the original study. Figure 2 summarizes the 24-hour pharmacokinetic profiles of testosterone administered as AndroGel for 30, 90 and 180 days. Testosterone concentrations were maintained as long as the patient continued to properly apply the prescribed AndroGel treatment.

Figure 2: Mean Steady-State Testosterone Concentrations in Patients with Once-Daily AndroGel Therapy

Table 5 summarizes the mean testosterone concentrations on Treatment Day 180 for patients receiving 5 g, 7.5 g, or 10 g of AndroGel. The 7.5 g dose produced mean concentrations intermediate to those produced by 5 g and 10 g of AndroGel.

Table 5: Mean ( SD) Steady-State Serum Testosterone Concentrations During Therapy (Day 180)

	5 g	7.5 g	10 g
	N = 44	N = 37	N = 48
Cavg	555 225	601 309	713 209
Cmax	830 347	901 471	1083 434
Cmin	371 165	406 220	485 156

Of 129 hypogonadal men who were appropriately titrated with AndroGel and who had sufficient data for analysis, 87% achieved an average serum testosterone level within the normal range on Treatment Day 180.

In patients treated with AndroGel, there were no observed differences in the average daily serum testosterone concentrations at steady-state based on age, cause of hypogonadism, or body mass index.

AndroGel 5 g/day and 10 g/day resulted in significant increases over time in total body mass and total body lean mass, while total body fat mass and the percent body fat decreased significantly. These changes were maintained for 180 days of treatment during the original study. Changes in the 7.5 g dose group were similar. Bone mineral density in both hip and spine increased significantly from Baseline to Day 180 with 10 g AndroGel.

AndroGel treatment at 5 g/day and 10 g/day for 90 days produced significant improvement in libido (measured by sexual motivation, sexual activity and enjoyment of sexual activity as assessed by patient responses to a questionnaire). The degree of penile erection as subjectively estimated by the patients, increased with AndroGel treatment, as did the subjective score for satisfactory duration of erection. AndroGel treatment at 5 g/day and 10 g/day produced positive effects on mood and fatigue. Similar changes were seen after 180 days of treatment and in the group treated with the 7.5 g dose. DHT concentrations increased in parallel with testosterone concentrations at AndroGel doses of 5 g/day and 10 g/day, but the DHT/T ratio stayed within the normal range, indicating enhanced availability of the major physiologically active androgen. Serum estradiol (E2) concentrations increased significantly within 30 days of starting treatment with AndroGel 5 or 10 g/day and remained elevated throughout the treatment period but remained within the normal range for eugonadal men. Serum levels of SHBG decreased very slightly (1 to 11%) during AndroGel treatment. In men with hypergonadotropic hypogonadism, serum levels of LH and FSH fell in a dose- and time-dependent manner during treatment with AndroGel.

14.2 Phototoxicity in Humans

The phototoxic potential of AndroGel was evaluated in a double-blind, single-dose study in 27 subjects with photosensitive skin types. The Minimal Erythema Dose (MED) of ultraviolet radiation was determined for each subject. A single 24 (+1) hour application of duplicate patches containing test articles (placebo gel, testosterone gel, or saline) was made to naive skin sites on Day 1. On Day 2, each subject received five exposure times of ultraviolet radiation, each exposure being 25% greater than the previous one. Skin evaluations were made on Days 2 to 5. Exposure of test and control article application sites to ultraviolet light did not produce increased inflammation relative to non-irradiated sites, indicating no phototoxic effect.

14.3 Testosterone Transfer from Male Patients to Female Partners

The potential for dermal testosterone transfer following AndroGel use was evaluated in a clinical study between males dosed with AndroGel and their untreated female partners. Two (2) to 12 hours after AndroGel (10 g) application by the male subjects, the couples (N = 38 couples) engaged in daily, 15-minute sessions of vigorous skin-to-skin contact so that the female partners gained maximum exposure to the AndroGel application sites. Under these study conditions, all unprotected female partners had a serum testosterone concentration greater than 2 times the baseline value at some time during the study. When a shirt covered the application site(s), the transfer of testosterone from the males to the female partners was completely prevented.

16 How Supplied/storage And Handling ⮝

AndroGel is supplied in non-aerosol, metered-dose pumps. The pump is composed of plastic and stainless steel and an LDPE/aluminum foil inner liner encased in rigid plastic with a polypropylene cap. Each 88 g AndroGel Pump in the twin package is capable of dispensing 75 g or 60 metered 1.25 g doses.

AndroGel is also supplied in unit-dose aluminum foil packets in cartons of 30. Each packet of 2.5 g or 5 g gel contains 25 mg or 50 mg testosterone, respectively.

NDC Number	Package Size
21695-112-30	30 packets (5 g per packet)

Keep AndroGel out of the reach of children.

Storage

Store at 25 C (77 F); excursions permitted to 15 to 30 C (59 to 86 F) [see USP Controlled Room Temperature].

Disposal

Used AndroGel pumps or used AndroGel packets should be discarded in household trash in a manner that prevents accidental application or ingestion by children or pets.

No Title 1572449648 ⮝

INSTRUCTIONS FOR USE
ANDROGEL (AN DROW JEL) CIII
(testosterone gel) 1.62%
for topical use

Read this Instructions for Use for ANDROGEL1.62% before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment.

Applying ANDROGEL 1.62%:

• ANDROGEL 1.62% comes in a pump or in packets.
• Before applying ANDROGEL 1.62% make sure that your shoulders and upper arms are clean, dry, and that there is no broken skin.
• ANDROGEL 1.62% is to be applied to the area of your shoulders and upper arms that will be covered by a short sleeve t-shirt (See Figure A). Do not apply ANDROGEL 1.62% to any other parts of your body such as your stomach area (abdomen), penis, scrotum, chest, armpits (axillae), or knees.

(Figure A)

If you are using ANDROGEL 1.62% pump:

• Before using a new bottle of ANDROGEL 1.62 % for the first time, you will need to remove the cap and then prime the pump. To prime the ANDROGEL 1.62% pump, slowly push the pump all the way down 3 times, over the sink drain. Do not use any ANDROGEL 1.62% that came out while priming. Wash it down the sink to avoid accidental exposure to others. Your ANDROGEL 1.62% pump is now ready to use.
• Remove the cap from the pump. Then, put the spout opening at the top of the pump where the medicine comes out over the palm of your hand and slowly push the pump all the way down. Apply ANDROGEL 1.62% to the application site. You may also apply ANDROGEL 1.62% directly to the application site. Your healthcare provider will tell you the number of times to press the pump for each dose.
• Wash your hands with soap and water right away.

Find Your Dose as Prescribed by Your Healthcare Provider		Application Method
1 pump	20.25 mg	Apply 1 pump of ANDROGEL 1.62% to 1 upper arm and shoulder.
2 pumps	40.5 mg	Apply 1 pump of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply 1 pump of ANDROGEL 1.62% to the opposite upper arm and shoulder.
3 pumps	60.75 mg	Apply 2 pumps of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply 1 pump of ANDROGEL 1.62% to the opposite upper arm and shoulder.
4 pumps	81 mg	Apply 2 pumps of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply 2 pumps of ANDROGEL 1.62% to the opposite upper arm and shoulder.

If you are using ANDROGEL 1.62% packets:

• Tear open the packet completely at the dotted line. Squeeze from the bottom of the packet to the top.
• Squeeze all of the ANDROGEL 1.62% out of the packet into the palm of your hand.
• Apply ANDROGEL 1.62% to the application site. You may also apply ANDROGEL 1.62% directly to the application site.
• Let the application site dry completely before putting on a t-shirt.
• ANDROGEL 1.62% is flammable until dry. Let ANDROGEL 1.62% dry before smoking or going near an open flame.
• Avoid showering, swimming or bathing for at least 2 hours after you apply ANDROGEL 1.62%.
• Wash your hands right away with soap and water after applying ANDROGEL 1.62%.

Find Your Dose as Prescribed by Your Healthcare Provider		Application Method
One 20.25 mg packet	20.25 mg	Apply 1 packet of ANDROGEL 1.62% to 1 upper arm and shoulder.
One 40.5 mg packet	40.5 mg	Apply half of the 40.5 mg packet of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply the remaining packet contents to the opposite upper arm and shoulder.
One 40.5 mg packet and one 20.25 mg packet	60.75 mg	Apply one 40.5 mg packet of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply one 20.25 mg packet of ANDROGEL 1.62% to the opposite upper arm and shoulder.
Two 40.5 mg packets	81 mg	Apply one 40.5 mg packet of ANDROGEL 1.62% to 1 upper arm and shoulder and then apply one 40.5 mg packet of ANDROGEL 1.62% to the opposite upper arm and shoulder.

How should I store ANDROGEL 1.62%?

• Store ANDROGEL 1.62% at room temperature between 68 F to 77 F (20 C to 25 C).
• When it is time to throw away the pump or packets, safely throw away used ANDROGEL 1.62% in the household trash. Be careful to prevent accidental exposure of children or pets.
• Keep ANDROGEL 1.62% away from fire.

Keep ANDROGEL 1.62% and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: 05/2019

5044281

NDC 0051 8462 31

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, and upper arms*

AndroGel (testosterone gel) 1.62% CIII

30 Unit-dose Packets

Contains 20.25 mg of testosterone in 1.25 Grams of gel per unit dose

Rx only

For Topical Use Only

Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure. Dispense the enclosed Medication Guide to each patient.

*See accompanying package insert.

abbvie

NDC 0051 8462 30

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, and upper arms*

AndroGel (testosterone gel) 1.62% CIII

30 Unit-dose Packets

Contains 40.5 mg of testosterone in 2.5 Grams of gel per unit dose

Rx Only

For Topical Use Only

Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure. Dispense the enclosed Medication Guide to each patient.

* See accompanying package insert.

abbvie

NDC 0051 8462 33

Dispense the accompanying Medication Guide to each patient.

AndroGel (testosterone gel) 1.62% CIII

20.25 mg of testosterone per pump actuation*

*Each actuation delivers 1.25 g of gel

For Topical Use Only

Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure.

Rx only

Multi-dose pump capable of dispensing 60 metered pump actuations.

abbvie

ANDROGEL testosterone gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0051-8462 Route of Administration TRANSDERMAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength testosterone (UNII: 3XMK78S47O) (testosterone - UNII:3XMK78S47O) testosterone 16.2 mg in 1 g

Inactive Ingredients Ingredient Name Strength alcohol (UNII: 3K9958V90M) isopropyl myristate (UNII: 0RE8K4LNJS) water (UNII: 059QF0KO0R) sodium hydroxide (UNII: 55X04QC32I) CARBOMER HOMOPOLYMER TYPE C (ALLYL PENTAERYTHRITOL CROSSLINKED) (UNII: 4Q93RCW27E)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0051-8462-33 1 in 1 CARTON 04/29/2011 1 88 g in 1 BOTTLE, PUMP; Type 0: Not a Combination Product 2 NDC:0051-8462-31 30 in 1 CARTON 04/29/2011 2 NDC:0051-8462-12 1.25 g in 1 PACKET; Type 0: Not a Combination Product 3 NDC:0051-8462-30 30 in 1 CARTON 04/29/2011 3 NDC:0051-8462-01 2.5 g in 1 PACKET; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022309 04/29/2011

Labeler - AbbVie Inc. (078458370)

Revised: 5/2019 Document Id: 1622cf7d-0e00-87a3-d58e-cd3f7730e76e 34391-3 Set id: 8677ba5b-8374-46cb-854c-403972e9ddf3 Version: 110 Effective Time: 20190522 AbbVie Inc.

Recent Major Changes ⮝

• Boxed Warning 9/2009
• WARNINGS AND PRECAUTIONS (5.2) 9/2009

2 Dosage And Administration  ⮝

Dosage and Administration for AndroGel 1% differs from AndroGel 1.62%. For dosage and administration of AndroGel 1.62% refer to its full prescribing information. (2)

Prior to initiating AndroGel 1%, 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.

2.1 Dosing and Dose Adjustment

The recommended starting dose of AndroGel 1% is 50 mg of testosterone (two 25 mg packets or one 50 mg packet), applied topically once daily in the morning to the shoulders and upper arms and/or abdomen area (preferably at the same time every day).

Dose Adjustment

To ensure proper dosing, serum testosterone concentrations should be measured at intervals. If the serum testosterone concentration is below the normal range, the daily AndroGel 1% dose may be increased from 50 mg to 75 mg and from 75 mg to 100 mg for adult males as instructed by the physician. If the serum testosterone concentration exceeds the normal range, the daily AndroGel 1% dose may be decreased. If the serum testosterone concentration consistently exceeds the normal range at a daily dose of 50 mg, AndroGel 1% therapy should be discontinued. In addition, serum testosterone concentrations should be assessed periodically.

The application site and dose of AndroGel 1% are not interchangeable with other topical testosterone products.

2.2 Administration Instructions

AndroGel 1% should be applied to clean, dry, healthy, intact skin of the right and left upper arms/shoulders and/or right and left abdomen. Area of application should be limited to the area that will be covered by the patient s short sleeve T-shirt. Do not apply AndroGel 1% to any other part of the body including the genitals, chest, armpits (axillae), knees, or back. AndroGel 1% should be evenly distributed between the right and left upper arms/shoulders or both sides of the abdomen.

The prescribed daily dose of AndroGel 1% should be applied to the right and left upper arms/shoulders and/or right/left abdomen as shown in the shaded areas in the figure below.

After applying the gel, the application site should be allowed to dry prior to dressing. Hands should be washed thoroughly with soap and water after application. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including AndroGel 1%, are flammable.

The patient should be advised to avoid swimming or showering for at least 5 hours after the application of AndroGel 1%.

Packets

The entire contents should be squeezed into the palm of the hand and immediately applied to the application sites. Alternately, patients may squeeze a portion of the gel from the packet into the palm of the hand and apply to application sites. Repeat until entire contents have been applied.

Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from AndroGel 1%-treated skin:

• Children and women should avoid contact with unwashed or unclothed application site(s) of men using AndroGel 1%.
• Patients should wash hands with soap and water immediately after application of AndroGel 1%.
• Patients should cover the application site(s) with clothing (e.g., a T-shirt) after the gel has dried.
• Prior to situation in which direct skin-to-skin contact is anticipated, patients should wash the application site thoroughly with soap and water to remove any testosterone residue.
• In the event that unwashed or unclothed skin to which AndroGel 1% has been applied comes in direct contact with the skin of another person, the general area of contact on the other person should be washed with soap and water as soon as possible.

12 Clinical Pharmacology  ⮝

12.1 Mechanism of Action

Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal chord thickening, alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics.

Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter s syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

12.2 Pharmacodynamics

No specific pharmacodynamic studies were conducted using AndroGel 1%.

12.3 Pharmacokinetics

Absorption

AndroGel 1% delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal concentrations (298 - 1043 ng/dL) seen in healthy men. AndroGel 1% provides continuous transdermal delivery of testosterone for 24 hours following a single application to intact, clean, dry skin of the shoulders, upper arms and/or abdomen.

AndroGel 1% is a hydroalcoholic formulation that dries quickly when applied to the skin surface. The skin serves as a reservoir for the sustained release of testosterone into the systemic circulation. Approximately 10% of the testosterone dose applied on the skin surface from AndroGel is absorbed into systemic circulation. In a study with AndroGel 1% 100 mg , all patients showed an increase in serum testosterone within 30 minutes, and eight of nine patients had a serum testosterone concentration within normal range by 4 hours after the initial application. Absorption of testosterone into the blood continues for the entire 24-hour dosing interval. Serum concentrations approximate the steady-state concentration by the end of the first 24 hours and are at steady state by the second or third day of dosing.

With single daily applications of AndroGel 1%, follow-up measurements 30, 90 and 180 days after starting treatment have confirmed that serum testosterone concentrations are generally maintained within the eugonadal range. Figure 1 summarizes the 24-hour pharmacokinetic profiles of testosterone for hypogonadal men (less than 300 ng/dL) maintained on AndroGel 1% 50 mg or 100 mg for 30 days. The average ( SD) daily testosterone concentration produced by AndroGel 1% 100 mg on Day 30 was 792 ( 294) ng/dL and by AndroGel 1% 50 mg 566 ( 262) ng/dL.

Figure 1: Mean ( SD) Steady-State Serum Testosterone Concentrations on Day 30 in Patients Applying AndroGel 1% Once Daily

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 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 dihydrotestosterone (DHT).

DHT concentrations increased in parallel with testosterone concentrations during AndroGel 1% treatment. The mean steady-state DHT/T ratio during 180 days of AndroGel treatment ranged from 0.23 to 0.29 (50 mg of AndroGel 1%/day) and from 0.27 to 0.33 (100 mg of AndroGel 1%/day).

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 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% treatment is discontinued after achieving steady state, serum testosterone concentrations remain in the normal range for 24 to 48 hours but return to their pretreatment concentrations by the fifth day after the last application.

Testosterone Transfer from Male Patients to Female Partners

The potential for dermal testosterone transfer following AndroGel 1% use was evaluated in a clinical study between males dosed with AndroGel 1% and their untreated female partners. Two (2) to 12 hours after application of 100 mg of testosterone administered as AndroGel 1% by the male subjects, the couples (N = 38 couples) engaged in daily, 15-minute sessions of vigorous skin-to-skin contact so that the female partners gained maximum exposure to the AndroGel 1% application sites. Under these study conditions, all unprotected female partners had a serum testosterone concentration >2 times the baseline value at some time during the study. When a shirt covered the application site(s), the transfer of testosterone from the males to the female partners was completely prevented.

14 Clinical Studies  ⮝

14.1 Clinical Trials in Adult Hypogonadal Males

AndroGel 1% was evaluated in a multi-center, randomized, parallel-group, active-controlled, 180-day trial in 227 hypogonadal men. The study was conducted in 2 phases. During the Initial Treatment Period (Days 1-90), 73 patients were randomized to AndroGel 1% 50 mg daily, 78 patients to AndroGel 1% 100 mg daily, and 76 patients to a non-scrotal testosterone transdermal system. The study was double-blind for dose of AndroGel 1% but open-label for active control. Patients who were originally randomized to AndroGel 1% and who had single-sample serum testosterone concentrations above or below the normal range on Day 60 were titrated to 75 mg daily on Day 91. During the Extended Treatment Period (Days 91-180), 51 patients continued on AndroGel 1% 50 mg daily, 52 patients continued on AndroGel 1% 100 mg daily, 41 patients continued on a non-scrotal testosterone transdermal system (5 mg daily), and 40 patients received AndroGel 1% 75 mg daily. Upon completion of the initial study, 163 enrolled and 162 patients received treatment in an open-label extension study of AndroGel 1% for an additional period of up to 3 years.

Mean peak, trough and average serum testosterone concentrations within the normal range (298-1043 ng/dL) were achieved on the first day of treatment with doses of 50 mg and 100 mg of AndroGel 1%. In patients continuing on AndroGel 1% 50 mg and 100 mg, these mean testosterone concentrations were maintained within the normal range for the 180-day duration of the original study. Figure 2 summarizes the 24-hour pharmacokinetic profiles of testosterone administered as AndroGel 1% for 30, 90 and 180 days. Testosterone concentrations were maintained as long as the patient continued to properly apply the prescribed AndroGel 1% treatment.

Figure 2: Mean Steady-State Testosterone Concentrations in Patients with Once-Daily AndroGel 1% Therapy

Table 4 summarizes the mean testosterone concentrations on Treatment Day 180 for patients receiving 50 mg, 75 mg, or 100 mg of AndroGel 1%. The 75 mg dose produced mean concentrations intermediate to those produced by 50 mg and 100 mg of AndroGel 1%.

Table 4: Mean ( SD) Steady-State Serum Testosterone Concentrations During Therapy (Day 180)

	50 mg	75 mg	100 mg
	N = 44	N = 37	N = 48
Cavg	555 225	601 309	713 209
Cmax	830 347	901 471	1083 434
Cmin	371 165	406 220	485 156

Of 129 hypogonadal men who were appropriately titrated with AndroGel 1% and who had sufficient data for analysis, 87% achieved an average serum testosterone concentration within the normal range on Treatment Day 180.

In patients treated with AndroGel 1%, there were no observed differences in the average daily serum testosterone concentrations at steady-state based on age, cause of hypogonadism, or body mass index.

DHT concentrations increased in parallel with testosterone concentrations at AndroGel 1% doses of 50 mg/day and 100 mg/day, but the DHT/T ratio stayed within the normal range, indicating enhanced availability of the major physiologically active androgen. Serum estradiol (E2) concentrations increased significantly within 30 days of starting treatment with AndroGel 1% 50 or 100 mg/day and remained elevated throughout the treatment period but remained within the normal range for eugonadal men. Serum levels of SHBG decreased very slightly (1 to 11%) during AndroGel 1% treatment. In men with hypergonadotropic hypogonadism, serum levels of LH and FSH fell in a dose- and time-dependent manner during treatment with AndroGel 1%.

14.2 Phototoxicity in Humans

The phototoxic potential of AndroGel 1% was evaluated in a double-blind, single-dose study in 27 subjects with photosensitive skin types. The Minimal Erythema Dose (MED) of ultraviolet radiation was determined for each subject. A single 24 (+1) hour application of duplicate patches containing test articles (placebo gel, testosterone gel, or saline) was made to naive skin sites on Day 1. On Day 2, each subject received five exposure times of ultraviolet radiation, each exposure being 25% greater than the previous one. Skin evaluations were made on Days 2 to 5. Exposure of test and control article application sites to ultraviolet light did not produce increased inflammation relative to non-irradiated sites, indicating no phototoxic effect.

16 How Supplied/storage And Handling  ⮝

AndroGel 1% is supplied in unit-dose aluminum foil packets in cartons of 30. Each packet of 2.5 g or 5 g gel contains 25 mg or 50 mg testosterone, respectively.

NDC Number	Package Size
0051-8425-30	30 packets (a unit dose packet containing 25 mg of testosterone provided in 2.5 g of gel)
0051-8450-30	30 packets (a unit dose packet containing 50 mg of testosterone provided in 5 g of gel)

Storage

Store at 25 C (77 F); excursions permitted to 15 to 30 C (59 to 86 F) [see USP Controlled Room Temperature].

Disposal

Used AndroGel 1% packets should be discarded in household trash in a manner that prevents accidental application or ingestion by children or pets.

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)

No Title 1572455108 ⮝

INSTRUCTIONS FOR USE
ANDROGEL (AN DROW JEL) CIII
(testosterone gel) 1%
for topical use

Read this Instructions for Use for ANDROGEL 1% before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment.

Applying ANDROGEL 1%:

• Before applying ANDROGEL 1%, make sure that your shoulders, upper arms or stomach are clean, dry, and there is no broken skin.
• The application sites for ANDROGEL 1% are the shoulders, upper arms or stomach area (abdomen) that will be covered by a short sleeve t-shirt (see Figure A). Do not apply ANDROGEL 1% to any other parts of your body such as your penis, scrotum, chest, armpits (axillae), knees, or back.

(Figure A)

• Tear open the packet completely at the dotted line. Squeeze from the bottom of the packet to the top.
• Squeeze all of the ANDROGEL 1% out of the packet into the palm of your hand.
• Apply ANDROGEL 1% to the application site. You may also apply ANDROGEL 1% from the packet directly to the application site.
• Let the application areas dry completely before putting on a t-shirt.
• ANDROGEL 1% is flammable until dry. Let ANDROGEL 1% dry before smoking or going near an open flame.
• Wash your hands with soap and water right away after applying ANDROGEL 1%.
• Avoid showering, swimming, or bathing for at least 5 hours after you apply ANDROGEL 1%.

How should I store ANDROGEL 1%?

• Store ANDROGEL 1% at room temperature between 68 F to 77 F (20 C to 25 C).
• Safely throw away used ANDROGEL 1% in the household trash. Be careful to prevent accidental exposure of children or pets.
• Keep ANDROGEL 1% away from fire.

Keep ANDROGEL 1% and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: 05/2019

5044279

NDC 0051 8425 30

CIII

AndroGel (testosterone gel) 1%

30 Unit-dose Packets

Contains 25 mg of testosterone in 2.5 Grams of gel per unit dose

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, upper arms, or abdomen.*

Rx Only

For Topical Use Only

Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure.

Dispense the enclosed Medication Guide to each patient.

*See accompanying package insert.

abbvie

NDC 0051 8450 30

CIII

AndroGel (testosterone gel) 1%

30 Unit-dose Packets

Contains 50 mg of testosterone in 5 Grams of gel per unit dose

Clear, colorless gel provides transdermal delivery of testosterone through the skin of the shoulders, upper arms, or abdomen.*

Rx Only

For Topical Use Only

Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure.

Dispense the enclosed Medication Guide to each patient.

*See accompanying package insert.

abbvie

NDC 0051 8488 88

ANDROGEL testosterone gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0051-8488 Route of Administration TRANSDERMAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength testosterone (UNII: 3XMK78S47O) (testosterone - UNII:3XMK78S47O) testosterone 10 mg in 1 g

Inactive Ingredients Ingredient Name Strength isopropyl myristate (UNII: 0RE8K4LNJS) water (UNII: 059QF0KO0R) sodium hydroxide (UNII: 55X04QC32I) carbomer homopolymer type C (UNII: 4Q93RCW27E) alcohol (UNII: 3K9958V90M)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0051-8488-88 2 in 1 CARTON 03/14/2011 08/31/2015 1 NDC:0051-8488-33 75 g in 1 BOTTLE, PUMP; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021015 03/14/2011 08/31/2015

ANDROGEL testosterone gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0051-8425 Route of Administration TRANSDERMAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength testosterone (UNII: 3XMK78S47O) (testosterone - UNII:3XMK78S47O) testosterone 10 mg in 1 g

Inactive Ingredients Ingredient Name Strength alcohol (UNII: 3K9958V90M) isopropyl myristate (UNII: 0RE8K4LNJS) water (UNII: 059QF0KO0R) sodium hydroxide (UNII: 55X04QC32I) CARBOMER HOMOPOLYMER TYPE C (ALLYL PENTAERYTHRITOL CROSSLINKED) (UNII: 4Q93RCW27E)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0051-8425-30 30 in 1 CARTON 03/14/2011 1 NDC:0051-8425-01 2.5 g in 1 PACKET; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021015 03/14/2011

ANDROGEL testosterone gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0051-8450 Route of Administration TRANSDERMAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength testosterone (UNII: 3XMK78S47O) (testosterone - UNII:3XMK78S47O) testosterone 10 mg in 1 g

Inactive Ingredients Ingredient Name Strength alcohol (UNII: 3K9958V90M) isopropyl myristate (UNII: 0RE8K4LNJS) water (UNII: 059QF0KO0R) sodium hydroxide (UNII: 55X04QC32I) CARBOMER HOMOPOLYMER TYPE C (ALLYL PENTAERYTHRITOL CROSSLINKED) (UNII: 4Q93RCW27E)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0051-8450-30 30 in 1 CARTON 03/14/2011 1 NDC:0051-8450-01 5 g in 1 PACKET; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021015 03/14/2011

Labeler - AbbVie Inc. (078458370)

Revised: 5/2019 Document Id: 9869acf3-57ca-7943-a1c1-fd2a958bf275 34391-3 Set id: c506aaa3-04f8-4eb1-8dc4-e964cdd08e7f Version: 129 Effective Time: 20190522 AbbVie Inc.

1 Indications And Usage ⮝

1.1 Testosterone Replacement Therapy

AndroGel, an androgen, 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 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 levels and gonadotropins (FSH, LH) above the normal range.
• Hypogonadotropic Hypogonadism (Congenital or Acquired) - idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum levels but have gonadotropins in the normal or low range.

3 Dosage Forms And Strengths ⮝

AndroGel (testosterone gel) 1% for topical use is available in either unit-dose packets or multiple-dose pumps. The 75 g (60 metered-dose) pump delivers 1.25 g of product when the pump mechanism is fully depressed once.

AndroGel is available in the following three package containers:

• 2 x 75 g pumps (each pump dispenses 60 metered 1.25 g doses)
• 2.5 g packet
• 5 g packet

4 Contraindications ⮝

AndroGel should not be used in any of the following patients:

• Men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions (5.1), Adverse Reactions (6.1), and Nonclinical Toxicology (13.1)].
• Women who are or may become pregnant, or who are breastfeeding. AndroGel can cause fetal harm when administered to a pregnant woman. AndroGel may cause serious adverse reactions in nursing infants. Exposure of a female fetus or nursing infant to androgens may result in varying degrees of virilization. Pregnant women or those who may become pregnant need to be aware of the potential for transfer of testosterone from men treated with AndroGel [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1, 8.3)].
• Men with known hypersensitivity to any of its ingredients, including alcohol and soy products.

5 Warnings And Precautions ⮝

5.1 Worsening of 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.
• Patients treated with androgens may be at increased risk for prostate cancer. Evaluation of the patient for prostate cancer prior to initiating and during treatment with androgens is appropriate [see Warnings and Precaution (5.9), Adverse Reactions (6.1), and Nonclinical Toxicology (13.1)].
• Increases in serum PSA from baseline values were seen in approximately 18% of individuals in an open label study of 162 hypogonadal men treated with AndroGel for up to 42 months. Most of these increases were seen within the first year of therapy [see Contraindications (4), Warnings and Precautions (5.9), Adverse Reactions (6), and Nonclinical Toxicology (13.1)].

5.2 Potential for Testosterone Transfer to Others

Transfer of testosterone to others (including women and children) can occur when vigorous skin-to-skin contact is made with the application site [see Clinical Studies (14.3)]. The following precautions are recommended to minimize potential transfer of testosterone from AndroGel-treated skin to another person:

• Patients should wash their hands immediately with soap and water after application of AndroGel.
• Patients should cover the application site(s) with clothing after the gel has dried (e.g., a shirt).
• In the event that unwashed or unclothed skin to which AndroGel has been applied does come 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. In vitro studies show that residual testosterone is removed from the skin surface by washing with soap and water.
• Women and children should avoid skin contact with AndroGel application sites in males. Changes in body hair distribution, significant increase in acne, or other signs of virilization should be brought to the attention of a physician. AndroGel may cause fetal harm in a pregnant woman due to virilization of a female fetus [see Use in Specific Populations (8.1)].

5.3 Use in Women

Due to lack of controlled evaluations in women and potential virilizing effects, AndroGel is not indicated for use in women [see Use in Specific Populations (8.1, 8.3)].

5.4 Potential for Adverse Effects on Spermatogenesis

At large doses of exogenous androgens, 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.

5.5 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 has produced multiple hepatic adenomas. AndroGel is not known to produce these adverse effects.

There are rare reports of hepatocellular carcinoma in patients receiving long-term oral therapy with androgens in high doses. Withdrawal of the drugs did not lead to regression of the tumors in all cases.

5.6 Edema

Drugs in the androgen class 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)].

5.7 Gynecomastia

Gynecomastia may develop and may persist in patients being treated with androgens, including AndroGel, for hypogonadism.

5.8 Sleep Apnea

The treatment of hypogonadal men with testosterone products may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases [see Adverse Reactions (6.2)].

5.9 Laboratory Tests

• Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Increase in red blood cell mass may increase the risk for a thromboembolic event.
• Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy.
• Androgens may decrease levels of thyroxin-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.
• Androgens 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.

5.10 Flammable until Dry

• Alcohol Based Products including AndroGel are flammable; therefore avoid fire, flame or smoking until the gel has dried.

6 Adverse Reactions ⮝

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 2 shows the incidence of all adverse events judged by the investigator to be at least possibly related to treatment with AndroGel and reported by >1% of patients in a 180 Day, Phase 3 study.

Table 2: Adverse Events Possibly, Probably or Definitely Related to Use of AndroGel in the 180-Day Controlled Clinical Trial

			___________ Dose of AndroGel ___
	Adverse Event
____________________	_ ___________	_________5 g________	_____ ______7.5 g________________	________ 10 g____________
		_______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 AndroGel, 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 AndroGel. These events included: cerebral hemorrhage, convulsion (neither of which were considered related to AndroGel administration), depression, sadness, memory loss, elevated prostate specific antigen, and hypertension No AndroGel patient discontinued due to skin reactions.

In a separate uncontrolled pharmacokinetic study of 10 patients, two had adverse events associated with AndroGel; 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 AndroGel and reported by greater than 1% of patients is shown in Table 3.

Table 3: Adverse Events Possibly, Probably or Definitely Related to Use of AndroGel 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 AndroGel 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 greater than 2X the baseline or any single serum PSA greater than 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 less than 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 greater than 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 AndroGel. 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.

Hypogonadal Men

Table 4 includes adverse reactions that have been identified postmarketing.

Table 4: Adverse Drug Reactions from Postmarketing Experience of AndroGel by MedDRA System Organ Class

Blood and the lymphatic system disorders:	Elevated Hgb, Hct (polycythemia)
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 GCTP, 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 levels, 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)

7 Drug Interactions ⮝

7.1 Insulin

Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, insulin requirements.

7.2 Corticosteroids

The concurrent use of testosterone with ACTH or corticosteroids may result in increased fluid retention and should be monitored cautiously, particularly in patients with cardiac, renal or hepatic disease.

7.3 Oral Anticoagulants

Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of INR and prothrombin time are recommended in patients taking anticoagulants, especially at the initiation and termination of androgen therapy.

8 Use In Specific Populations ⮝

8.1 Pregnancy

Pregnancy Category X: AndroGel is contraindicated during pregnancy or in women who may become pregnant. It is teratogenic and may cause fetal harm [see Contraindications (4)]. Exposure of a female fetus to androgens may result in varying degrees of virilization. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

8.3 Nursing Mothers

Although it is not known how much testosterone transfers into human milk, AndroGel is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants [see Contraindications (4)].

Testosterone and other androgens may adversely affect lactation.

8.4 Pediatric Use

Safety and efficacy of AndroGel in males less than 18 years old has not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.

8.5 Geriatric Use

There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing AndroGel to determine whether efficacy in those over 65 years of age differs from younger subjects. Additionally, there is insufficient long-term safety data in geriatric patients to assess the potential risks of cardiovascular disease and prostate cancer.

8.6 Renal or Hepatic Impairment

No formal studies were conducted involving patients with renal or hepatic insufficiencies.

9 Drug Abuse And Dependence ⮝

9.1 Controlled Substance

AndroGel contains testosterone, a Schedule III controlled substance as defined by the Anabolic Steroids Control Act.

Oral ingestion of AndroGel will not result in clinically significant serum testosterone concentrations due to extensive first-pass metabolism.

10 Overdosage ⮝

There is one report of acute overdosage with use of an approved injectable testosterone product: this subject had serum testosterone levels of up to 11,400 ng/dL with a cerebrovascular accident. Treatment of overdosage would consist of discontinuation of AndroGel together with appropriate symptomatic and supportive care.

11 Description ⮝

AndroGel (testosterone gel) 1% is a clear, colorless hydroalcoholic gel containing 1% testosterone. Topical administration of AndroGel 5 g, 7.5 g, or 10 g contains 50 mg, 75 mg, or 100 mg of testosterone, respectively, is to be applied daily to the skin's surface. Approximately 10% of the applied testosterone dose is absorbed across skin of average permeability during a 24-hour period.

The active pharmacologic ingredient in AndroGel is testosterone. Testosterone USP is a white to practically white crystalline powder chemically described as 17-beta hydroxyandrost-4-en-3-one. The structural formula is:

Inactive ingredients in AndroGel are carbomer 980, ethanol 67.0%, isopropyl myristate, purified water, and sodium hydroxide. These ingredients are not pharmacologically active.

13 Noncllinical Toxicology ⮝

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats.

Principal Display Panel ⮝

ANDROGEL testosterone gel

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:21695-112(NDC:0051-8450) Route of Administration TRANSDERMAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TESTOSTERONE (UNII: 3XMK78S47O) (TESTOSTERONE - UNII:3XMK78S47O) TESTOSTERONE 10 mg in 1 g

Inactive Ingredients Ingredient Name Strength CARBOMER HOMOPOLYMER TYPE C (UNII: 4Q93RCW27E) ISOPROPYL MYRISTATE (UNII: 0RE8K4LNJS) WATER (UNII: 059QF0KO0R) SODIUM HYDROXIDE (UNII: 55X04QC32I) ALCOHOL (UNII: 3K9958V90M)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:21695-112-30 30 in 1 CARTON 1 5 g in 1 PACKET

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021015 06/05/2003

Labeler - Rebel Distributors Corp. (118802834)

Establishment
Name	Address	ID/FEI	Business Operations
Rebel Distributors Corp.		118802834	RELABEL, REPACK

Revised: 9/2010 Document Id: 77215d87-ad22-4169-bd5f-a453f10b21ef 34391-3 Set id: 77215d87-ad22-4169-bd5f-a453f10b21ef Version: 1 Effective Time: 20100908 Rebel Distributors Corp.