Acthar

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

  Acthar Gel is indicated as monotherapy for the treatment of infantile spasms in infants and children under 2 years of age.
  )
• Acthar Gel is indicated for the treatment of exacerbations of multiple sclerosis in adults. (
  1.2 Multiple 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.
  )
• Acthar Gel may be used for the following disorders and diseases: rheumatic (
  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.
  ); collagen (
  1.4 Collagen Diseases

  During an exacerbation or as maintenance therapy in selected cases of: systemic lupus erythematosus, systemic dermatomyositis (polymyositis).
  ); dermatologic (
  1.5 Dermatologic Diseases

  Severe erythema multiforme, Stevens-Johnson syndrome.
  ); allergic states (
  1.6 Allergic States

  Serum sickness.
  ); ophthalmic (
  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.
  ); respiratory (
  1.8 Respiratory Diseases

  Symptomatic sarcoidosis.
  ); and edematous state. (
  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.
  )

• Acthar Gel vial is for either intramuscular or subcutaneous injection. (
  2.1 Important 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.
  )
• Acthar Gel single-dose pre-filled SelfJect injector:
  • is for subcutaneous administration by adults only. (
    2.1 Important 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.
    )
  • used to administer single doses of 40 units or 80 units only. (
    2.1 Important 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.
    )
• Infantile spasms: doses must be administered intramuscularly using the Acthar gel vial. The recommended dose is 150 U/m² divided into twice daily injections of 75 U/m². 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 Recommended 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/m²(divided into twice daily intramuscular (IM) injections of 75 U/m²) 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/m²in the morning for 3 days; 15 U/m²in the morning for 3 days; 10 U/m²in the morning for 3 days; and 10 U/m²every 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:

  

  

  )
• 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 Recommended 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.
  )
• 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 Recommended 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.
  )

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.

• Pediatric Use: Prolonged use of Acthar Gel in children may inhibit skeletal growth. If use is necessary, it should be given intermittently with careful observation. (
  5.12 Negative Effects on Growth and Physical Development

  Long-term use of Acthar Gel may have negative effects on growth and physical development in pediatric patients. Changes in appetite are seen with Acthar Gel therapy, with the effects becoming more frequent as the dose or treatment period increases. These effects are reversible once Acthar Gel therapy is stopped. Growth and physical development of pediatric patients on prolonged therapy should be carefully monitored.
  ,
  5.13 Decrease in Bone Density

  Decrease in bone formation and an increase in bone resorption both through an effect on calcium regulation (i.e., decreasing absorption and increasing excretion) and inhibition of osteoblast function may occur. These, together with a decrease in the protein matrix of the bone (secondary to an increase in protein catabolism) and reduced sex hormone production, may lead to inhibition of bone growth in children and adolescents and to the development of osteoporosis at any age. Special consideration should be given to patients at increased risk of osteoporosis (i.e., postmenopausal women) before initiating therapy, and bone density should be monitored in patients on long term therapy.
  , and
  8.4 Pediatric Use

  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 can occur in this population

  [see Warnings and Precautions (5)and Adverse Reactions (6.1)]

  .

  The efficacy of 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 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)]

  . 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)]

  .
  )
• Pregnancy: May cause fetal harm. (
  8.1 Pregnancy

  Risk Summary

  Based on Acthar Gel's pharmacological effect of stimulating an endogenous steroid response

  [see Clinical Pharmacology ( 12.1)]

  , Acthar Gel may cause fetal harm when administered to a pregnant woman. The published literature on systemic corticosteroid use during pregnancy, which may be relevant, suggests potential concerns. Intrauterine growth restriction, decreased birth weight, and preterm birth have been reported with maternal use of corticosteroids; however, the underlying maternal condition may also contribute to these risks. Hypoadrenalism has also been reported in infants after high-dose and/or long-term use of corticosteroids during pregnancy

  (see Clinical Considerations)

  . The potential adverse developmental effects of Acthar Gel have not been adequately assessed in animals.

  The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

  Clinical Considerations

  Fetal-Neonatal Adverse Reactions

  Hypoadrenalism has been reported in infants born to mothers treated with systemic corticosteroids during pregnancy. Infants born to mothers treated with Acthar Gel should be carefully observed for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting, and managed accordingly

  [see Warnings and Precautions (5.2)]

  .
  )