H.P. ACTHAR GEL

1.1 Infantile spasms: H.P. Acthar Gel (repository corticotropin injection) is indicated as monotherapy for the treatment of infantile spasms in infants and children under 2 years of age. 1.2 Multiple Sclerosis: H.P. Acthar Gel (repository corticotropin injection) is indicated for the treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown H.P. 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. 1.3 Rheumatic 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. 1.4 Collagen Diseases: During an exacerbation or as maintenance therapy in selected cases of: systemic lupus erythematosus, systemic dermatomyositis (polymyositis). 1.5 Dermatologic Diseases: Severe erythema multiforme, Stevens-Johnson syndrome. Page 2 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda H.P. Acthar Gel is typically dosed based on body surface area (BSA). For calculation of body surface area, use the following formula 1.6 Allergic St ates: Serum sickness. 1.7 Ophthalmic 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. 1.8 Respiratory Diseases: Symptomatic sarcoidosis 1.9 Edematous 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.

H.P. Acthar Gel (repository corticotropin injection) is supplied as 5 mL multi-dose vial (63004 7731-1) containing 80 USP Units per mL. H.P. Acthar Gel (repository corticotropin injection) should be warmed to room temperature before using. Do not over pressurize the vial prior to withdrawing the product. Store H.P. Acthar Gel (repository corticotropin injection) under refrigeration between 2°-8°C (36°-46°F). Product is stable for the period indicated on the label when stored under the conditions described.

2.1 Specific Recommended Dosage Regimen for Infantile Spasms in Infants and Children Under 2 Years of Age In the treatment of infantile spasms, H.P. Acthar Gel must be administered intramuscularly. The recommended regimen is a daily dose of 150 U/m2 (divided into twice daily intramuscular injections of 75 U/m2) administered over a 2-week period. Dosing with H.P. 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/m2 in the morning for 3 days; 15 U/m2 in the morning for 3 days; 10 U/m2 in the morning for 3 days; and 10 U/m2 every other morning for 6-days. 2.2 Recommended Dosage Regimen fo r the Treatment of Acute Exacerbations in Adults with Multiple Sclerosis. The recommended dose is daily intramuscular or subcutaneous doses of 80-120 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. Page 3 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda Although drug dependence does not occur, sudden withdrawal of H.P. 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. 2.3 Recommended Dosage Regimen 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 H.P. Acthar Gel is 40-80 units given intramuscularly or subcutaneously every 24-72 hours. Although drug dependence does not occur, sudden withdrawal of H.P. 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. 2.4 Preparation H.P. Acthar Gel should be warmed to room temperature before using. Caution should be taken not to over-pressurize the vial prior to withdrawing the product.

H.P. Acthar Gel is contraindicated for intravenous administration. H.P. Acthar Gel is contraindicated where congenital infections are suspected in infants. Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of H.P Acthar Gel. H.P. Acthar Gel is contraindicated in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, adrenocortical hyperfunction or sensitivity to proteins of porcine origin. Page 4 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda

Caretakers of patients with infantile spasms should be informed of the availability of a Medication Guide, and they should be instructed to read the Medication Guide prior to administering H.P Acthar Gel. Patients should be instructed to take H.P. Acthar Gel only as prescribed. They should not stop treatment suddenly unless instructed by their physician 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 H.P. Acthar Gel treatment and the importance of not missing and scheduled doctor’s appointments. Patients, their caregivers and families should be advised that if the patient develops an infection or fever they should contact their physician. They should be educated that a fever may not necessarily be present during infection. The pati ent should also try to limit contact with other people with infections to minimize the risk of infection while taking H.P. Acthar Gel. [see Warnings and Precautions (5.1) and Adverse Reactions (6.1.1)] Patients, their caregivers and families should be advised that if the patient experiences an increase in blood pressure they should contact their physician. [see Warnings and Precautions (5.3) and Adverse Reactions (6.1.1)] Page 14 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda Patients, their caregivers and families should be advised that if the patient or the caregiver notices blood or a change in color of the patient’s stool they should contact their physician. [see Warnings and Precautions (5.6)]. Caregivers and families of infants and children treated with H.P. Acthar Gel should be informed that the patient may show signs of irritability and sleep disturbances. These effects are reversible once H.P. Acthar Gel therapy is stopped. [see Warnings and Precautions (5.7) and Adverse Reactions (6.1.1)]. Patients, their caregivers and families should be advised that changes in appetite, most often leading to weight gain, are seen with H.P. Acthar Gel therapy, becoming more frequent as the dose or treatment period increases. These effects are reversible once H.P. Acthar Gel therapy is stopped. [see Warnings and Precautions (5.12) and Adverse Reactions (6.1.1]. Patients, their caregivers and families should be advised that the patient may be monitored for signs of adrenal insufficiency such as weakness, fatigue, lethargy, anorexia, weight loss, hypotension, abdominal pain or hyperpigmentation (adults only) after treatment has stopped. Since the recovery of the adrenal gland varies from days to months, patients may need to be protected from the stress of trauma or surgery by the use of corticosteroids during the period of stress. [ see Warnings and Precautions (5.2)]. Patients should be advised not to be vaccinated with live or live attenuated vaccines during treatment with H.P. 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 H.P. Acthar Gel. [see Warnings and Precautions (5.4)]. Patients, their caregivers and families should be advised that prolonged use of H.P. Acthar Gel in children may result in Cushing’s syndrome and associated adverse reactions, may inhibit skeletal growth, and may cause osteoporosis and decreased bone density. If prolonged use is necessary, H.P. Acthar Gel should be given intermittently along with careful observation. [see Warnings and Precautions (5.2), (5.12), and (5.13) and Adverse Reactions (6.1.1)]. Patients, their caregivers and families should be informed that H.P. Acthar may mask symptoms of other diseases/disorders without altering the course of the other disease/disorder. The patient will need to be monitored carefully during and for a period following discontinuation of therapy for signs of infection, abnormal cardiac function, hypertension, hyperglycemia, change in body weight, and fecal blood loss. [see Warnings and Precautions (5.5)]. In the treatment of Infantile Spasms, other types of seizures may occur because some patients with infantile spasms progress to other forms of seizures (for example, Lennox-Gastaut Syndrome). Additionally the spasms sometimes mask other seizures and once the spasms resolve after treatment with H.P. Acthar gel, the other seizures may become visible. Parents and caregivers should inform their physician of any new onset of seizures so that appropriate management can then be instituted. [see Adverse Reactions (6.1.1)]. Page 15 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda H.P. Acthar® Gel (repository corticotropin injection) Manufactured for Questcor Pharmaceuticals, Inc. Questcor Pharmaceuticals, Inc. 3260 Whipple Road Union City, CA 94587 USA phone (800) 411-3065 (510) 400-0700 fax (510) 400-0799 PL065/Rev. 02 No. 1350 Issued: 10/2010 Page 16 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda MEDICATION GUIDE H.P. Acthar® Gel (H P AK-thar jel) (repository corticotropin) Injection This Medication Guide provides information only about the use of H.P. Acthar Gel for the treatment of Infantile Spasms. If your doctor prescribes H.P. 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 H.P 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 H.P. ACTHAR GEL? H.P. Acthar Gel can cause serious side effects including: 1. Increased risk of infections. H.P Acthar Gel is a medicine that can affect your child’s immune system. When your child is taking H.P. Acthar Gel, it can lower the ability of your child’s immune system to fight infections. H.P. 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 H.P. Acthar Gel, tell your doctor if your child has: o an infection or signs of an infection, such as: ƒ fever ƒ cough ƒ vomiting ƒ diarrhea ƒ other signs of illness or flu o a family member with an infection or signs of an infection While taking H.P. Acthar Gel, your child should: o stay away from people who are sick or who have infections o tell your doctor right away if your child has any sign of infection such as: ƒ fever (but your child may not have a fever with an infection) ƒ cough ƒ vomiting ƒ diarrhea or This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda ƒ other signs of illness or flu and ƒ any open cuts or sores on his or her body 2. Effects on the adrenal gland after stopping H.P. Acthar Gel. When your child stops taking H.P. 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 H.P. 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 H.P. 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 H.P. Acthar Gel When your child is taking H.P. 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 H.P. 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 H.P. 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 H.P. Acthar Gel. Side effects may include: This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda • 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. H.P. 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 about if you need to decrease your child’s salt intake or if you need to feed your child foods high in potassium. 4. Your child should not receive certain vaccines during treatment with H.P. Acthar Gel. Your child may receive killed or inactivated vaccines while receiving Acthar Gel. Before your child receives any vaccines, talk to your doctor about which vaccines are safe for your child. Certain vaccines could cause your child to have serious side effects, or the vaccine may not be effective. 5. Hiding (masking) symptoms of other conditions or diseases. It may be more difficult for your doctor to diagnose other conditions or diseases in your child during treatment with H.P. Acthar Gel. During treatment and after treatment ends, tell your doctor if your child has: • any signs or symptoms of infection. See number 1 of this section in the Medication Guide. • changes in body weight • bloody or black tarry stool • vomiting • stomach pain • excessive tiredness • increased thirst • fast heart rate • difficulty breathing 6. Stomach and intestinal problems. H.P. Acthar Gel may cause bleeding of the stomach or intestine. Your child has an increased risk for bleeding from the stomach or having a stomach ulcer. . Tell your doctor if your child has any pain in the stomach area (abdominal pain), vomits blood, or has bloody or black stools. 7. Changes in mood and behavior. During treatment with H.P. Acthar Gel your child may be irritable, have rapid changes in his or her mood, be depressed, have other changes in his or her behavior, or have trouble sleeping. This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda Tell your doctor if your child has any of the side effects or symptoms listed above. What is H.P. ACTHAR GEL? H.P. Acthar Gel is a prescription medicine that is used to treat infantile spasms in infants and children under 2 years of age. What should I tell my doctor before my child takes H.P. ACTHAR GEL? Before your child takes H.P. Acthar Gel, read the section above “What is the most important information I should know about H.P. Acthar Gel?” and tell your doctor if your child has: • an infection • Diabetes • heart problems • kidney problems • stomach or intestinal problems • thyroid problems • liver problems • neuromuscular problems • convulsions or seizures • had exposure to someone with Tuberculosis (TB) • a previous allergic reaction such as hives, itching or trouble breathing, to H.P. Acthar Gel or pork products • had recent surgery • had a recent vaccination or is scheduled to receive a vaccination • a family member who is receiving vaccinations Tell your doctor about all the medicines your child takes, including prescription and non-prescription medicines, vitamins and herbal supplements. Do not start giving a new medicine to your child without first speaking to your doctor. How should I give H.P. Acthar Gel to my child? H.P. Acthar Gel is given as an injection into the muscle. Do not inject it under the skin, into a vein, or give it to your child by mouth. • Inject H.P. Acthar Gel exactly as your doctor tells you. Your doctor will tell you where to give the injection, how much to give, how often and when to give it to your child. • Do not use H.P. Acthar Gel until your doctor has taught you how to give the injection to your child. • To give H.P. Acthar Gel: o Take the bottle from the refrigerator. Do not open the bottle or pry the cap (rubber stopper) off. o Warm the contents by rolling the bottle between your hands for a few minutes. o Wash your hands. This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda o Prepare the skin where you are going to give the injection by wiping it with a new sterile alcohol wipe. Before giving the injection, look at the site prepared for the injection and make sure that it no longer looks wet. A wet site can cause burning. o Wipe the top of the vial rubber stopper with a new sterile alcohol wipe. o Use a new sterile needle and syringe to draw up the amount of H.P. Acthar Gel the doctor has told you to use. o Give the injection the way the doctor has instructed you. o Return the bottle to the refrigerator as soon as possible. • Keep all of your child’s follow-up appointments with your doctor • It is important for you to tell your doctor if your child’s spasms continue or change in any way during treatment or after treatment has stopped so that they can monitor your child’s progress. Infantile Spasms sometimes hides (masks) other seizures your child or infant may have. Once treated with H.P. Acthar Gel, the Infantile Spasms symptoms may disappear. This may allow the other seizures to become visible for the first time. Tell your child’s doctor right away if you see a change in your child’s seizures/spasms. What are the possible side effects of H.P. Acthar Gel? H.P Acthar Gel can cause serious side effects. • See “What is the most important information I should know about Acthar Gel.” • H.P. Acthar Gel may make certain other medical conditions worse, such as diabetes (may increase blood sugar). • Eye problems. Your child can get cataracts, increased pressure in the eye (glaucoma), and possible damage to the optic nerve if treated with H.P. Acthar Gel for a long time. • Allergic reactions to H.P. Acthar Gel. Your child may have an allergic reaction to H.P. Acthar Gel. Allergic reactions may not happen until your child has received several injections of H.P. Acthar Gel. Tell your doctor right away if your child has any of the following signs of an allergic reaction: • skin rash • swelling of the face, tongue, lips, or throat • trouble breathing This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda • Changes in growth and physical development. H.P. Acthar Gel may affect your child’s growth and physical development and may weaken his or her bones. This is more likely to happen with long term use of Acthar Gel. • Enlarged heart. H.P. Acthar Gel may cause an increase in the size of your child’s heart. This is more likely to happen with long term use of Acthar Gel but usually goes away after H.P. Acthar Gel is stopped. Common side effects of Acthar Gel may include: • infections • increased blood pressure • irritability and changes in behavior • changes in appetite and weight • diarrhea • vomiting These are not all the possible side effects of H.P. Acthar Gel. Tell your doctor if your child has any side effect that bothers them or does not go away. For more information ask your child’s doctor 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 H.P. ACTHAR GEL? • Store vials of H.P. Acthar Gel in the refrigerator between 360F to 460F (20C to 80C). • Throw away any vials after the expiration date printed on the label. Keep H.P. Acthar Gel and all other medicines out of the reach of children General information About H.P. Acthar Gel Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use H.P. Acthar Gel for a condition for which it has not been prescribed. Do not give H.P. Acthar Gel to other people, even if they have the same symptoms. It may harm them. This Medication Guide summarizes the most important information about H.P. Acthar Gel. If you would like more information, talk with your child’s doctor. You can ask your child’s doctor or pharmacist for information about H.P. Acthar Gel that is written for healthcare professionals. For more information, go to www.acthar.com or call 1-800-465-9217. What are the ingredients in H.P. Acthar Gel? Active ingredient: Corticotropin This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda Inactive ingredients: gelatin, phenol, cysteine, sodium hydroxide and/or acetic acid to adjust pH, and water for injection Manufactured for: Questcor Pharmaceuticals, Inc. 3260 Whipple Road Union City, CA 94587 USA PL122/ Rev. 00 Issued: 10/2010 This Medication Guide has been approved by the U.S. Food and Drug Administration. H.P. Acthar® Gel is a registered trademark of Questcor Pharmaceuticals, Inc. This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda

Formal drug-drug interaction studies have not been performed. H.P. Acthar Gel may accentuate the electrolyte loss associated with diuretic therapy.

Adequate and well-controlled studies have not been done in animals. Human use has not been associated with an increase in malignant disease. [see Warnings and Precautions (5.14) and Use in Specific Populations (8.1)].

Pregnancy Class C: H.P. Acthar Gel has been shown to have an embryocidal effect. There are no adequate and well-controlled studies in pregnant women. H.P. Acthar Gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

H.P. Acthar Gel is indicated as monotherapy for the treatment of infantile spasms in infants and children less than 2 years of age. Both serious and other adverse reactions in this population are discussed in Warnings and Adverse Reactions in Infants and Children Under 2 Years of Age [see Sections 5 and 6.1.1]. The efficacy of H.P. Acthar Gel for the treatment of infantile spasms in infants and children less than 2 years of age was evaluated in a randomized, single blinded (video EEG interpreter Page 11 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda blinded) clinical trial and an additional active control supportive trial [see Clinical Studies (14)]. A responding patient was defined as having both complete cessation of spasms and elimination of hypsarrhythmia. Safety in the pediatric population for infantile spasms was evaluated by retrospective chart reviews and data from non-sponsor conducted clinical trials [see Adverse Reactions (6.1.1)]. While the types of adverse reactions seen in infants and children under 2 years of age treated for infantile spasms are similar to those seen in older patients, their frequency and severity may be different due to the very young age of the infant, the underlying disorder, the duration of therapy and the dosage regimen. Effects on growth are of particular concern [see Warnings and Precautions (5.12)]. Serious adverse reactions observed in adults may also occur in children [see Warnings and Precautions (5)].

While chronic exposure to H.P. Acthar Gel at high doses can be associated with a variety of potential serious adverse effects, it is not expected that a single high dose, or even several large doses, has the potential for serious adverse effects compared to a standard dose. There have been no reports of death or acute overdose symptoms from H.P. Acthar Gel in clinical studies or in the published literature. The intramuscular route of administration makes it unlikely that an inadvertent acute overdose will occur. The typical daily dose of H.P. Acthar Gel to treat an infant that has a BSA of 0.4 m2 would be 60 U/day. Using the 1-cc syringe supplied with H.P. Acthar Gel, the maximum amount that can be injected is 80 U/injection, which is a well-tolerated single dose.