HYRIMOZ adalimumab-adaz 40 mg/.4mL Injection, Solution, 2 syringes — NDC 61314-473-20 (Billing 61314-0473-20)

1 INDICATIONS AND USAGE HYRIMOZ is a tumor necrosis factor (TNF)-blocker indicated for: • Reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. ( 1.1 ) • Reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. ( 1.2 ) • Reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis .

(1.3) • Reducing signs and symptoms in adult patients with active ankylosing spondylitis. (1.4) • Treatment of moderately to severely active Crohn’s disease in adults and pediatric patients 6 years of age and older. (1.5) • Treatment of moderately to severely active ulcerative colitis in adult patients.

( 1.6 ) Limitations of Use : Effectiveness has not been established in patients who have lost response to or were intolerant to TNF blockers. • Treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. ( 1.7 ) • Treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older. ( 1.8 ) • Treatment of non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older.

( 1.9 )

1.1Rheumatoid Arthritis HYRIMOZ is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. HYRIMOZ can be used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs).

1.2Juvenile Idiopathic Arthritis HYRIMOZ is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. HYRIMOZ can be used alone or in combination with methotrexate.

1.3Psoriatic Arthritis HYRIMOZ is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. HYRIMOZ can be used alone or in combination with non-biologic DMARDs.

1.4Ankylosing Spondylitis HYRIMOZ is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.

1.5Crohn’s Disease HYRIMOZ is indicated for the treatment of moderately to severely active Crohn’s disease in adults and pediatric patients 6 years of age and older.

1.6Ulcerative Colitis HYRIMOZ is indicated for the treatment of moderately to severely active ulcerative colitis in adult patients. Limitations of Use: The effectiveness of adalimumab products has not been established in patients who have lost response to or were intolerant to TNF-blockers [see Clinical Studies (14.7) ] .

1.7Plaque Psoriasis HYRIMOZ is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HYRIMOZ should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician [see Warnings and Precautions (5) ] .

1.8Hidradenitis Suppurativa HYRIMOZ is indicated for the treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older.

1.9Uveitis HYRIMOZ is indicated for the treatment of non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older.

1.6Ulcerative Colitis HYRIMOZ is indicated for the treatment of moderately to severely active ulcerative colitis in adult patients. Limitations of Use:… [Excerpted — this section continues on DailyMed.]

2 DOSAGE AND ADMINISTRATION • Administer by subcutaneous injection (2) Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis (2.2): • Adults: 40 mg every other week. Some patients with RA not receiving methotrexate may benefit from increasing the dosage to 40 mg every week or 80 mg every other week. Juvenile Idiopathic Arthritis or Pediatric Uveitis (2.3): Pediatric Weight 2 Years of Age and Older Recommended Dosage 10 kg (22 lbs) to less than 15 kg (33 lbs) 10 mg every other week 15 kg (33 lbs) to less than 30 kg (66 lbs) 20 mg every other week 30 kg (66 lbs) and greater 40 mg every other week Crohn's Disease (2.4): • Adults: 160 mg on Day 1 (given in one day or split over two consecutive days); 80 mg on Day 15; and 40 mg every other week starting on Day 29. • Pediatric Patients 6 Years of Age and Older: Pediatric Weight Recommended Dosage Days 1 and 15 Starting on Day 29 17 kg (37 lbs) to less than 40 kg (88 lbs) Day 1: 80 mg Day 15: 40 mg 20 mg every other week 40 kg (88 lbs) and greater Day 1: 160 mg (single dose or split over two consecutive days) Day 15: 80 mg 40 mg every other week Ulcerative Colitis (2.5): • Adults : 160 mg on Day 1 (given in one day or split over two consecutive days), 80 mg on Day 15 and 40 mg every other week starting on Day 29.

Discontinue in patients without evidence of clinical remission by eight weeks (Day 57). Plaque Psoriasis or Adult Uveitis (2.6): • Adults : 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose. Hidradenitis Suppurativa (2.7) : • Adults : o Day 1: 160 mg (given in one day or split over two consecutive days) o Day 15: 80 mg o Day 29 and subsequent doses: 40 mg every week or 80 mg every other week • Adolescents 12 years of age and older: Adolescent Weight Recommended Dosage 30 kg (66 lbs) to less than 60 kg (132 lbs) Day 1: 80 mg Day 8 and subsequent doses: 40 mg every other week 60 kg (132 lbs) and greater Day 1: 160 mg (given in one day or split over two consecutive days) Day 15: 80 mg Day 29 and subsequent doses: 40 mg every week or 80 mg every other week

2.1Recommended Tuberculosis Evaluation Prior to initiating HYRIMOZ and periodically during therapy, evaluate patients for active tuberculosis and test for latent infection [see Warnings and Precautions ( 5.1 )] .

2.2Recommended Dosage in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis The recommended subcutaneous dosage of HYRIMOZ for adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) [see Indication and Usage ( 1.1 , 1.3 , 1.4 )] is 40 mg administered every other week. Methotrexate (MTX), other non-biologic DMARDs, glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or analgesics may be continued during treatment with HYRIMOZ. In the treatment of RA, some patients not taking concomitant MTX may derive additional benefit from increasing the dosage of HYRIMOZ to 40 mg every week or 80 mg every other week.

2.3Recommended Dosage in Juvenile Idiopathic Arthritis or Pediatric Patients with Uveitis The recommended subcutaneous dosage of HYRIMOZ for pediatric patients 2 years of age and older with polyarticular juvenile idiopathic arthritis (JIA) or pediatric uveitis [see Indications and Usage ( 1.2 ), ( 1.9 )], based on weight, is shown below. MTX, glucocorticoids, NSAIDs, and/or analgesics may be continued during treatment with HYRIMOZ. Pediatric Weight (2 Years of Age and older) Recommended Dosage 10 kg (22 lbs) to less than 15 kg (33 lbs) 10 mg every other week 15 kg (33 lbs) to less than 30 kg (66 lbs) 20 mg every other week 30 kg (66 lbs) and greater 40 mg every other week Adalimumab products have not been studied in patients with polyarticular JIA or pediatric uveitis less than 2 years of age or in patients with a weight below 10 kg.

2.4Recommended Dosage in Crohn’s Disease Subcutaneous Adult Dosage Regimen The recommended subcutaneous dosage of HYRIMOZ for adult patients with mo… [Excerpted — this section continues on DailyMed.]

3 DOSAGE FORMS AND STRENGTHS HYRIMOZ is a clear, colorless or slightly yellowish solution available as: • Pen (Sensoready Pen) Injection: 40 mg/0.8 mL in a single-dose pen. Injection: 80 mg/0.8 mL in a single-dose pen. Injection: 40 mg/0.4 mL in a single-dose pen. • Prefilled Syringe with BD UltraSafe Passive™ Needle Guard Injection: 40 mg/0.8 mL in a single-dose prefilled glass syringe.

Injection: 20 mg/0.4 mL in a single-dose prefilled glass syringe. Injection: 80 mg/0.8 mL in a single-dose prefilled glass syringe. Injection: 40 mg/0.4 mL in a single-dose prefilled glass syringe. • Prefilled Syringe Injection: 20 mg/0.2 mL in a single-dose prefilled glass syringe.

Injection: 10 mg/0.1 mL in a single-dose prefilled glass syringe. Injection: • Single-dose prefilled pen (Sensoready Pen): 40 mg/0.8 mL, 40 mg/0.4 mL and 80 mg/0.8 mL (3) • Single-dose prefilled glass syringe (with BD UltraSafe Passive™ Needle Guard): 20 mg/0.4 mL, 40 mg/0.8 mL, 40 mg/0.4 mL and 80 mg/0.8 mL (3) • Single-dose prefilled glass syringe: 10 mg/0.1 mL and 20 mg/0.2 mL ( 3 )

17 PATIENT COUNSELING INFORMATION Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Infections Inform patients that HYRIMOZ may lower the ability of their immune system to fight infections. Instruct patients of the importance of contacting their doctor if they develop any symptoms of infection, including tuberculosis, invasive fungal infections, and reactivation of hepatitis B virus infections [see Warnings and Precautions ( 5.1 , 5.2 , 5.4 )] .

Malignancies Counsel patients about the risk of malignancies while receiving HYRIMOZ [see Warnings and Precautions ( 5.2 )] . Hypersensitivity Reactions Advise patients to seek immediate medical attention if they experience any symptoms of severe hypersensitivity reactions. Other Medical Conditions Advise patients to report any signs of new or worsening medical conditions such as congestive heart failure, neurological disease, autoimmune disorders, or cytopenias.

Advise patients to report any symptoms suggestive of a cytopenia such as bruising, bleeding, or persistent fever [see Warnings and Precautions ( 5.5 , 5.6 , 5.8 , 5.9 )] . Instructions on Injection Technique Inform patients that the first injection is to be performed under the supervision of a qualified health care professional. If a patient or caregiver is to administer HYRIMOZ, instruct them in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of HYRIMOZ [see Instructions for Use ].

For patients who will use the HYRIMOZ single-dose prefilled Sensoready Pen, tell them that they: • will hear 2 loud clicks . The 1 st click indicates that the injection has started . Several seconds later a 2 nd click will indicate that the injection is almost finished . • must keep holding the HYRIMOZ single-dose prefilled Sensoready Pen firmly against their skin until they see a green indicator fill the window and stop moving.

Instruct patients to dispose of their used syringes or used Sensoready Pens in an FDA-cleared sharps disposal container immediately after use. Instruct patients not to dispose of syringes or pens in their household trash. Instruct patients that if they do not have an FDA-cleared sharps disposal container, they may use a household container that is made of a heavy-duty plastic, can be closed with a tight-fitting and puncture-resistant lid without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container.

Instruct patients that when their sharps disposal container is almost full, they will need to follow their community guidelines for the correct way to dispose of their sharps disposal container. Instruct patients that there may be state or local laws regarding disposal of used needles and syringes. Refer patients to the FDA’s website at http://www.fda.gov/safesharpsdisposal for more information about safe sharps disposal, and for specific information about sharps disposal in the state that they live in.

Instruct patients not to dispose of their used sharps disposal container in their household trash unless their community guidelines permit this. Instruct patients not to recycle their used sharps disposal container. Manufactured by: Sandoz Inc.

Princeton, NJ 08540 US License No. 2003 All third party trademarks are the property of their respective owners.

MEDICATION GUIDE HYRIMOZ ® (hye-RI-moze) (adalimumab-adaz) injection, for subcutaneous use Read the Medication Guide that comes with HYRIMOZ 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 with your doctor about your medical condition or treatment.

What is the most important information I should know about HYRIMOZ? HYRIMOZ is a medicine that affects your immune system. HYRIMOZ can lower the ability of your immune system to fight infections.

Serious infections have happened in people taking adalimumab products. These serious infections include tuberculosis (TB) and infections caused by viruses, fungi or bacteria that have spread throughout the body. Some people have died from these infections. • Your doctor should test you for TB before starting HYRIMOZ. • Your doctor should check you closely for signs and symptoms of TB during treatment with HYRIMOZ.

You should not start taking HYRIMOZ if you have any kind of infection unless your doctor says it is okay. Before starting HYRIMOZ, tell your doctor if you: • think you have an infection or have symptoms of an infection such as: o fever, sweats or chills o warm, red, or painful skin or sores on your body o muscle aches o diarrhea or stomach pain o cough o burning when you urinate or urinate more often than normal o shortness of breath o feel very tired o blood in phlegm o weight loss • are being treated for an infection. • get a lot of infections or have infections that keep coming back. • have diabetes. • have TB, or have been in close contact with someone with TB. • were born in, lived in, or traveled to countries where there is more risk for getting TB.

Ask your doctor if you are not sure. • live or have lived in certain parts of the country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis). These infections may happen or become more severe if you use HYRIMOZ. Ask your doctor if you do not know if you have lived in an area where these infections are common. • have or have had hepatitis B. • use the medicine ORENCIA (abatacept), KINERET (anakinra), RITUXAN (rituximab), IMURAN (azathioprine), or PURINETHOL (6–mercaptopurine, 6-MP). • are scheduled to have major surgery.

After starting HYRIMOZ, call your doctor right away if you have an infection, or any sign of an infection. HYRIMOZ can make you more likely to get infections or make any infection that you may have worse. Cancer • For children and adults taking Tumor Necrosis Factor (TNF)-blockers, including HYRIMOZ, the chances of getting cancer may increase. • There have been cases of unusual cancers in children, teenagers, and young adults using TNF-blockers. • People with rheumatoid arthritis (RA), especially more serious RA, may have a higher chance for getting a kind of cancer called lymphoma. • If you use TNF-blockers including HYRIMOZ your chance of getting two types of skin cancer may increase (basal cell cancer and squamous cell cancer of the skin).

These types of cancer are generally not life-threatening if treated. Tell your doctor if you have a bump or open sore that does not heal. • Some people receiving TNF-blockers including HYRIMOZ developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death.

Most of these people were male teenagers or young men. Also, most people were being treated for Crohn’s disease or ulcerative colitis with another medicine called IMURAN (azathioprine) or PURINETHOL (6-mercaptopurine, 6–MP). What is HYRIMOZ?

HYRIMOZ is a medicine called a Tumor Necrosis Factor (TNF)-blocker. HYRIMOZ is used: • To reduce the signs and symptoms of: o moderate to severe rheumatoid arthritis (RA) in adults . HYRIMOZ can be used alone, with methotrexate, or with certain other medicines. o moderate to severe polyarticular juvenile idiopa… [Excerpted — this section continues on DailyMed.]

INSTRUCTIONS FOR USE HYRIMOZ ® (hye-RI-moze) (adalimumab-adaz) 40 mg/0.8 mL 20 mg/0.4 mL Single-dose prefilled Syringe with BD UltraSafe Passive™ Needle Guard and finger flange injection, for subcutaneous use To help avoid possible infections and to ensure that you use HYRIMOZ correctly, it is important that you follow these instructions. Be sure that you read, understand, and follow this Instructions for Use before injecting HYRIMOZ. Your doctor should show you how to prepare and inject HYRIMOZ properly using the HYRIMOZ single-dose prefilled syringe before you use it for the first time.

Talk to your doctor if you have any questions. Figure A : HYRIMOZ prefilled syringe with BD UltraSafe Passive™ Needle Guard and finger flange It is important that you: • do not use the prefilled syringe if the seals of the blister are broken, as it may not be safe for you to use. • do not open the outer box until you are ready to use the prefilled syringe. • never leave the prefilled syringe unattended where others might misuse it. • do not remove the needle cap until just before you give the injection. • be careful not to touch the needle guard wings before use.

Touching them may cause the needle guard to be activated too early. • do not remove the finger flange before the injection. • inject HYRIMOZ 15 to 30 minutes after taking it out of the refrigerator for a more comfortable injection. • throw away (dispose of) the used prefilled syringe right away after use. Do not re-use a prefilled syringe. See “4.

Disposing of used prefilled syringes” at the end of this Instructions for Use. Note: HYRIMOZ prefilled syringe and injection device are not made with natural rubber latex. How should you store HYRIMOZ single-dose prefilled syringe? • Store your outer carton of prefilled syringes in a refrigerator between 36°F to 46°F (2°C to 8°C). • If needed, for example if you are traveling, you may store the prefilled syringe at room temperature up to 77°F (25°C) for up to 21 days. • Throw away the prefilled syringe that has been stored at room temperature after 21 days. • Record the date you first remove HYRIMOZ from the refrigerator in the spaces provided on the carton. • Keep your prefilled syringes in the original carton until ready to use to protect from light. • Do not store your prefilled syringes in extreme heat or cold. • Do not freeze your prefilled syringes. • Do not drop or crush HYRIMOZ.

The prefilled syringe is glass. Keep HYRIMOZ and all medicines out of the reach of children. What do you need for your injection?

Included in your prefilled syringe carton are: • HYRIMOZ prefilled syringes (see Figure A ). Each prefilled syringe contains 40 mg/0.8 mL or 20 mg/0.4 mL of adalimumab-adaz. Not included in your HYRIMOZ prefilled syringe carton are: • Alcohol wipe • Cotton ball or gauze • Sharps disposal container.

See “4. Disposing of used prefilled syringes” at the end of this Instructions for Use. • Adhesive bandage Figure B : items not included in the carton Before your injection Figure C : needle guard is not activated – the single-dose prefilled syringe is ready for use Figure D : needle guard is activated – do not use • In Figure C the needle guard is not activated. • The prefilled syringe is ready for use (see Figure C ). • In Figure D the needle guard of your prefilled syringe is activated. • Do not use the prefilled syringe (see Figure D ).

Preparing the prefilled syringe • For a more comfortable injection, take the carton containing the prefilled syringe out of the refrigerator and leave it unopened on your work surface for about 15 to 30 minutes to allow it to reach room temperature. Do not try to warm the prefilled syringe by using a heat source such as hot water or a microwave. • Take the prefilled syringe out of the blister. The solution should be clear and colorless or slightly yellowish.

Do not use a prefilled syringe if the solution is cloudy, discolored, or has flakes or particles in it. If you are not sure what color the soluti… [Excerpted — this section continues on DailyMed.]