The mechanism of action of Acthar Gel in the treatment of infantile spasms is unknown.

Acthar Gel and endogenous ACTH stimulate the adrenal cortex to secrete cortisol, corticosterone, aldosterone, and a number of weakly androgenic substances. Prolonged administration of large doses of Acthar Gel induces hyperplasia and hypertrophy of the adrenal cortex and continuous high output of cortisol, corticosterone and weak androgens. The release of endogenous ACTH is under the influence of the nervous system via the regulatory hormone released from the hypothalamus and by a negative corticosteroid feedback mechanism.

Elevated plasma cortisol suppresses ACTH release.

Acthar Gel is also reported to bind to melanocortin receptors.

The trophic effects of endogenous ACTH and Acthar Gel on the adrenal cortex are not well understood beyond the fact that they appear to be mediated by cyclic AMP.

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. 

Acthar Gel may be used for the following disorders and diseases: rheumatic; collagen; dermatologic ; allergic states; ophthalmic ; respiratory; and edematous state. 

• Acthar Gel vial is for either intramuscular or subcutaneous injection.
• Acthar Gel single-dose pre-filled SelfJect injector:
  • is for subcutaneous administration by adults only. 
  • used to administer single doses of 40 units or 80 units only. 
• Infantile spasms: doses must be administered intramuscularly using the Acthar gel vial. The recommended dose is 150 U/m divided into twice daily injections of 75 U/m . 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.
• 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.
• 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.

Commonly reported postmarketing adverse reactions for Acthar Gel include injection site reaction, asthenic conditions (including fatigue, malaise, asthenia and lethargy), fluid retention (including peripheral swelling), insomnia, headache, and blood glucose increased.

The most common adverse reactions (5% or greater in the recommended twice daily dosing group) for the treatment of infantile spasms are increased risk of infections, convulsions, hypertension, irritability, and pyrexia. 

Acthar Gel is contraindicated:

• for intravenous administration
• in infants under 2 years of age who have suspected congenital infections
• with concomitant administration of live or live attenuated vaccines in patients receiving
• immunosuppressive doses of Acthar Gel
• 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

Infections: Increased susceptibility to new infection and increased risk of exacerbation, dissemination or reactivation of latent infections. Signs and symptoms of infection may be masked. 

Adrenal Insufficiency after Prolonged Therapy: Monitor for effects of hypothalamic-pituitary-adrenal axis suppression after stopping treatment. 

Cushing's Syndrome: May occur after prolonged therapy. Monitor for signs and symptoms. 

Elevated Blood Pressure, Salt and Water Retention, and Hypokalemia: Monitor blood pressure and sodium and potassium levels. 

Masking of Symptoms of Other Underlying Disease/Disorders: Monitor patients for signs of other underlying disease/disorders that may be masked. 

Gastrointestinal Perforation and Bleeding: There is a risk for gastric ulcers and bleeding. There is an increased risk of perforation in patients with certain GI disorders. Signs and symptoms may be masked. Monitor for signs of perforation and bleeding. 

Behavioral and Mood Disturbances: May include euphoria, insomnia, mood swings, personality changes, severe depression and psychosis. Existing conditions may be aggravated. 

Comorbid Diseases: Symptoms of diabetes and myasthenia gravis may be worsened with treatment.

Ophthalmic Effects: Monitor for cataracts, infections and glaucoma. 

Immunogenicity Potential: Neutralizing antibodies with chronic administration may lead to a loss of endogenous ACTH activity. 

Use in Patients with Hypothyroidism or Liver Cirrhosis: May result in an enhanced effect. 

Negative Effects on Growth and Physical Development: Monitor pediatric patients on long term therapy.

Decrease in Bone Density: Monitor for osteoporosis in patients on long term therapy.