Acthar Repository Corticotropin 80 [USP'U]/mL Injection — NDC 63004-8710-2 (Billing 63004-8710-02)

1 INDICATIONS AND USAGE Acthar Gel is indicated as monotherapy for the treatment of infantile spasms in infants and children under 2 years of age. ( 1.1 ) Acthar Gel is indicated for the treatment of exacerbations of multiple sclerosis in adults. ( 1.2 ) Acthar Gel may be used for the following disorders and diseases: rheumatic ( 1.3 ); collagen ( 1.4 ); dermatologic ( 1.5 ); allergic states ( 1.6 ); ophthalmic ( 1.7 ); respiratory ( 1.8 ); and edematous state.

( 1.9 )

1.1Infantile Spasms Acthar Gel is indicated as monotherapy for the treatment of infantile spasms in infants and children under 2 years of age.

1.2Multiple Sclerosis Acthar Gel is indicated for the treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown Acthar Gel to be effective in speeding the resolution of acute exacerbations of multiple sclerosis. However, there is no evidence that it affects the ultimate outcome or natural history of the disease.

1.3Rheumatic Disorders As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: Psoriatic arthritis; Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy); Ankylosing spondylitis.

1.4Collagen Diseases During an exacerbation or as maintenance therapy in selected cases of: systemic lupus erythematosus, systemic dermatomyositis (polymyositis).

1.5Dermatologic Diseases Severe erythema multiforme, Stevens-Johnson syndrome.

1.6Allergic States Serum sickness.

1.7Ophthalmic Diseases Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: keratitis; iritis, iridocyclitis, diffuse posterior uveitis and choroiditis, optic neuritis, chorioretinitis; anterior segment inflammation.

1.8Respiratory Diseases Symptomatic sarcoidosis.

1.9Edematous State To induce a diuresis or a remission of proteinuria in the nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus.

2 DOSAGE AND ADMINISTRATION Acthar Gel vial is for either intramuscular or subcutaneous injection. ( 2.1 ) Acthar Gel single-dose pre-filled SelfJect injector: is for subcutaneous administration by adults only. ( 2.1 ) used to administer single doses of 40 units or 80 units only.

( 2.1 ) Infantile spasms: doses must be administered intramuscularly using the Acthar gel vial. The recommended dose is 150 U/m 2 divided into twice daily injections of 75 U/m 2 . After 2 weeks of treatment dosing should be gradually tapered and discontinued over a 2-week period.

Acthar Gel single-dose pre-filled SelfJect injector is not to be used for the treatment of infantile spasms ( 2.2 ) Acute exacerbations of multiple sclerosis: daily intramuscular or subcutaneous doses of 80 to 120 units for 2-3 weeks may be administered. It may be necessary to taper the dose. ( 2.3 ) Other disorders and diseases: individualize dosing depending on the disease and patient.

The usual dose is 40 to 80 units given intramuscularly or subcutaneously every 24 to 72 hours. It may be necessary to taper the dose. ( 2.4 )

2.1Important Information Acthar Gel vial is intended for either intramuscular or subcutaneous injection. Acthar Gel single-dose pre-filled SelfJect injector is for subcutaneous administration by adults (18 years of age and older) only. The single-dose pre-filled SelfJect injector should only be used to administer single doses of either 40 units or 80 units. For administration of doses other than 40 units or 80 units, use the Acthar Gel multi-dose vial.

2.2Recommended Dosage for Infantile Spasms in Infants and Children Under 2 Years of Age In the treatment of infantile spasms, Acthar Gel must be administered intramuscularly using the Acthar gel vial. Do not use the Acthar Gel single-dose pre-filled SelfJect injector for the treatment of infantile spasms. The recommended regimen is a daily dose of 150 U/m 2 (divided into twice daily intramuscular (IM) injections of 75 U/m 2 ) administered over a 2-week period.

Dosing with Acthar Gel should then be gradually tapered over a 2-week period to avoid adrenal insufficiency. The following is one suggested tapering schedule: 30 U/m 2 in the morning for 3 days; 15 U/m 2 in the morning for 3 days; 10 U/m 2 in the morning for 3 days; and 10 U/m 2 every other morning for 6 days. Acthar Gel is typically dosed based on body surface area (BSA).

For calculation of body surface area, use the following formula: Equation Formula

2.3Recommended Dosage for the Treatment of Acute Exacerbations in Adults with Multiple Sclerosis The recommended dose is daily intramuscular or subcutaneous doses of 80 to 120 units for 2-3 weeks for acute exacerbations. Dosage should be individualized according to the medical condition of each patient. Frequency and dose of the drug should be determined by considering the severity of the disease and the initial response of the patient.

Although drug dependence does not occur, sudden withdrawal of Acthar Gel after prolonged use may lead to adrenal insufficiency or recurrent symptoms which make it difficult to stop the treatment. It may be necessary to taper the dose and increase the injection interval to gradually discontinue the medication.

2.4Recommended Dosage for Other Indications for Adults and Children Over 2 Years of Age Dosage should be individualized according to the disease under treatment and the general medical condition of each patient. Frequency and dose of the drug should be determined by considering severity of the disease and the initial response of the patient. The usual dose of Acthar Gel is 40 to 80 units given intramuscularly or subcutaneously every 24 to 72 hours.

Although drug dependence does not occur, sudden withdrawal of Acthar Gel after prolonged use may lead to adrenal insufficiency or recurrent symptoms which make it difficult to stop the treatment. It may be necessary to taper the dose and increase the injection interval to gradually discontinue the medication.

2.5P… [Excerpted — this section continues on DailyMed.]

3 DOSAGE FORMS AND STRENGTHS Injection available as: 400 USP Units/5 mL (80 USP Units/mL) in a multi-dose vial for subcutaneous or intramuscular injection. 40 USP Units/0.5 mL in a single-dose pre-filled SelfJect injector for subcutaneous injection. 80 USP Units/mL in a single-dose pre-filled SelfJect injector for subcutaneous injection.

Acthar Gel (repository corticotropin injection) is a clear light amber solution mobile at room temperature. Injection available as: 5 mL multi-dose vial containing 80 USP units/mL, for intramuscular or subcutaneous use. ( 3 ) 40 USP Units/0.5 mL Acthar Gel single-dose pre-filled SelfJect injector for subcutaneous injection.

( 3 ) 80 USP Units/mL Acthar Gel single-dose pre-filled SelfJect injector for subcutaneous injection. ( 3 )

17 PATIENT COUNSELING INFORMATION Advise caretakers of patients with infantile spasms to read the FDA-approved patient labeling (Medication Guide [for infantile spasms]). Advise caretakers or patients 18 years of age or older to read the FDA-approved Instructions for Use when administering Acthar Gel single-dose pre-filled SelfJect injector. Use and Monitoring Patients should be instructed to take Acthar Gel only as prescribed.

They should not stop treatment suddenly unless instructed by their healthcare provider to do so. Patients, their caregivers and families should be advised as to the importance of the need for careful monitoring while on and during titration from Acthar Gel treatment and the importance of not missing scheduled doctor's appointments. Infections Advise patients, their caregivers, and families to contact their healthcare provider if the patient develops an infection or fever.

Inform patients and caregivers that a fever may not necessarily be present during infection and to try to limit contact with other people with infections to minimize the risk of infection while taking Acthar Gel [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . Cushing's Syndrome and Adrenal Insufficiency Upon Withdrawal Advise patients to contact their healthcare provider if they develop signs or symptoms of Cushing's Syndrome, such as fat increases in the face (moon face) or trunk area, cutaneous striae, easy bruisability, weight gain, muscle weakness, hyperglycemia, and hypertension [see Warnings and Precautions (5.2) ] .

Inform patients that adrenal insufficiency can occur upon withdrawal of Acthar Gel. Advise patients to contact their healthcare provider if they develop weakness, hyperpigmentation, weight loss, hypotension, or abdominal pain. Advise caregivers of patients with infantile spasms that symptoms of adrenal insufficiency may be difficult to identify and that additional symptoms may include anorexia, fatigue, or lethargy [see Warnings and Precautions (5.2) ] .

Elevated Blood Pressure, Salt and Water Retention, and Hypokalemia Advise patients, their caregivers and families to contact their healthcare provider if the patient experiences an increase in blood pressure or water retention [see Warnings and Precautions (5.3) and Adverse Reactions (6.1) ] . Vaccinations Advise patients and caregivers of patients to not to be vaccinated with live or live attenuated vaccines during treatment with Acthar Gel. Additionally, other immunization procedures in patients or in family members who will be in contact with the patient should be undertaken with caution while the patient is taking Acthar Gel [see Warnings and Precautions (5.4) ] .

Masking Symptoms of Other Diseases Inform patients, their caregivers, and families that Acthar Gel may mask symptoms of other diseases/disorders without altering the course of the other disease/disorder. Monitor the patient carefully during and for a period following discontinuation of therapy and inform their healthcare provider if signs of infection, abnormal cardiac function, hypertension, hyperglycemia, change in body weight, or fecal blood loss occur [see Warnings and Precautions (5.5) ] . Gastrointestinal Perforation and Bleeding Advise patients, their caregivers and families to contact their healthcare provider if the patient or the caregiver notices blood or a change in color of the patient's stool [see Warnings and Precautions (5.6) ] .

Behavioral and Mood Disturbances Inform patients, their caregivers and families that signs of irritability, sleep disturbances, mood swings, personality changes, or severe depression may occur. These effects are reversible once Acthar Gel therapy is stopped [see Warnings and Precautions (5.7) and Adverse Reactions (6.1) ] . Negative Effects on Growth and Physical Development Advise patients, their caregivers and families that changes in appetite, most often leading to weight gain, are seen with Acthar Gel therapy, becoming more frequent as th… [Excerpted — this section continues on DailyMed.]

MEDICATION GUIDE Acthar® Gel (AK-thar jel) (repository corticotropin injection) This Medication Guide provides information only about the use of Acthar Gel for the treatment of Infantile Spasms. If your doctor prescribes Acthar Gel for you or your child for any other reason, talk to your doctor for information about how this medicine is used to treat your medical condition. Read this Medication Guide before your child receives Acthar Gel and each time you refill your child's prescription.

There may be new information. This Medication Guide does not take the place of talking with your doctor about your child's medical condition or treatment. What is the most important information I should know about Acthar Gel?

Acthar Gel can cause serious side effects including: 1. Increased risk of infections. Acthar Gel is a medicine that can affect your child's immune system.

When your child is taking Acthar Gel, it can lower the ability of your child's immune system to fight infections. Acthar Gel may: make your child more likely to get new infections worsen an infection that your child already has cause an inactive infection to become active, such as tuberculosis (TB) Before starting Acthar Gel, tell your doctor if your child has: an infection or signs of an infection, such as: fever cough vomiting diarrhea other signs of flu or illness a family member with an infection or signs of an infection While taking Acthar Gel, your child should: stay away from people who are sick or who have infections tell your doctor right away if your child has any sign of infection such as: fever (but your child may not have a fever with an infection) cough vomiting diarrhea or other signs of illness or flu and any open cuts or sores on his or her body 2.

Effects on the adrenal gland after stopping Acthar Gel. When your child stops taking Acthar Gel, his or her body may not produce enough of a hormone called cortisol on its own (adrenal insufficiency). Your child may need to take steroid medicine to protect the body until the adrenal gland recovers and is working well again, especially to protect the body if they have surgery or trauma.

Do not stop giving your child injections of Acthar Gel without talking to your doctor first. Your doctor will tell you when and how to slowly stop giving the injections to avoid serious side effects. While slowly stopping your child's injections of Acthar Gel or after you stop giving the injections, call your doctor right away if your child has any of the following: appears weak loses weight or has a decrease in appetite appears tired or lacking energy appears pale has stomach pain appears sick or is with a fever 3.

Effects on the adrenal gland while taking Acthar Gel. When your child is taking Acthar Gel, his or her adrenal gland may produce too much cortisol. This can cause symptoms of Cushing's syndrome.

Cushing's syndrome is more common in children who take Acthar Gel for a long time. Symptoms of Cushing's syndrome include: increased upper body fat around the neck, but not the arms and legs weight gain rounded or "moon" face thin skin, easy bruising, and stretch marks on thighs, belly and trunk slowed growth rates in children weak bones (osteoporosis) While receiving treatment with Acthar Gel other side effects can happen that are like side effects that happen due to treatment with steroid medicines. The risk of getting side effects may increase the longer your child is treated with Acthar Gel.

Side effects may include: increased blood pressure. Your doctor may check your child's blood pressure during treatment. If your child's blood pressure increases, your doctor may talk with you about possible treatment choices. too much water in the body (water retention), increased amount of body salts, and low potassium in the blood.

Acthar Gel may cause your child to have an increased amount of body salts and water that stays in the body, and may lower the amount of potassium in your child's blood. Follow your doctor's instructions… [Excerpted — this section continues on DailyMed.]

INSTRUCTIONS FOR USE ACTHAR ® GEL [AK-thar jel] (repository corticotropin injection) for subcutaneous use only Single-Dose Pre-filled SelfJect™ Injector Green Body Injector: 40 USP Units/0.5 mL of Acthar Gel Step 1: Read These Instructions Carefully read, understand, and follow this Instructions for Use before you use the Acthar Gel single-dose pre-filled SelfJect injector. Contact your healthcare provider if you are unsure of how to give the injection. Important Information The Acthar Gel single-dose pre-filled SelfJect injector is for under the skin (subcutaneous) injection only.

The Acthar Gel single-dose pre-filled SelfJect injector must only be given by adults 18 years of age and older. The Acthar Gel single-dose pre-filled SelfJect injector is a pre-filled injector for 1-time use only (single-dose). The Acthar Gel single-dose pre-filled SelfJect injector with the green body should only be used to give a single dose of 40 units.

Doses other than 40 units cannot be given with this Acthar Gel single-dose pre-filled SelfJect injector. This injector is not an auto-injector . The Handle must be pushed down by hand (see " The parts of the Acthar Gel single-dose pre-filled SelfJect injector " figure below).

The injector has a Needle Guard to protect you and others from injury after it has been used. The parts of the Acthar Gel single-dose pre-filled SelfJect injector are shown below: Before Use After the Injection is Complete Storing Your Injector Store the Acthar Gel single-dose pre-filled SelfJect injector in the refrigerator between 36°F and 46°F (2°C and 8°C). Store the Acthar Gel single-dose pre-filled SelfJect injector in the original plastic tray to protect the injector from light.

When it is time to use the Acthar Gel single-dose pre-filled SelfJect injector, take 1 injector from the refrigerator and return any unused injectors to the refrigerator. After removing the injector from the refrigerator, it can be stored at room temperature between 68°F and 77°F (20°C and 25°C) for up to 24 hours . If the Acthar Gel single-dose pre-filled SelfJect injector has been left at room temperature for more than 24 hours , contact Mallinckrodt: 1-800-844-2830.

Do not heat the Acthar Gel single-dose pre-filled SelfJect injector. Do not freeze the Acthar Gel single-dose pre-filled SelfJect injector. Do not put the Acthar Gel single-dose pre-filled SelfJect injector into direct sunlight.

Keep the Acthar Gel single-dose pre-filled SelfJect injector and all medicines out of the reach of children. Step 2: Prepare to Use the Acthar Gel single-dose pre-filled SelfJect injector Choose a clean, well-lit room to give the injection. Take the injector tray out of the refrigerator.

If the injector trays are in a multipack carton, take the injector tray out and return any unused injector trays to the refrigerator. Do not inject Acthar Gel right after removing it from the refrigerator. The injector does not work as well when cold.

Check that you have the correct medicine and dose. Check the expiration date (EXP) on the package. Do not use if the expiration date has passed.

Remove the injector from the injector tray and let it sit on a clean, dry, flat surface at room temperature to warm for a minimum of 45 minutes and no more than 24 hours before use. Do not heat the injector. Before use, the injector should look like this.

The Bottom Cap should remain on the injector until you give the injection. Do not use the injector if the Bottom Cap is missing or not securely attached. If dropped, inspect the injector.

Do not use if the injector is damaged or the Bottom Cap has come off. Gather an alcohol swab and sharps disposal container. You may also gather an adhesive bandage, gauze, or cotton ball to use after the injection to stop any bleeding.

Step 3: Choose and Clean the Injection Site The Acthar Gel single-dose pre-filled SelfJect injector is for under the skin (subcutaneous) injection only. Choose 1 of these sites for injection : Upper thigh Belly (abd… [Excerpted — this section continues on DailyMed.]