Repository Corticotropin Injection

H.P. Acthar Gel is a highly purified sterile preparation of the adrenocorticotropic hormone in 16% gelatin to provide a prolonged release after intramuscular or subcutaneous injection. Also contains 0.5% phenol, not more than 0.1% cysteine (added), sodium hydroxide and/or acetic acid to adjust pH and water for injection.

ACTH is a 39 amino acid peptide with the following chemical formula:

Mechanism Of Action

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

H.P. 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 H.P. 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.

H.P. Acthar Gel is also reported to bind to melanocortin receptors.

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

ACTH rapidly disappears from the circulation following its intravenous administration; in people, the plasma half-life is about 15 minutes. The pharmacokinetics of H.P. Acthar Gel have not been adequately characterized.

The maximal effects of a trophic hormone on a target organ are achieved when optimal amounts of hormone are acting continuously. Thus, a fixed dose of H.P. Acthar Gel will demonstrate a linear increase in adrenocortical secretion with increasing duration for the infusion.

Clinical Studies

The effectiveness of H.P. Acthar Gel as a treatment for infantile spasms was demonstrated in a single blinded (video EEG interpreter blinded) clinical trial in which patients were randomized to receive either a 2 week course of treatment with H.P. Acthar Gel (75 U/m2 intramuscular twice daily) or prednisone (1 mg/kg by mouth twice daily). The primary outcome was a comparison of the number of patients in each group who were treatment responders, defined as a patient having complete suppression of both clinical spasms and hypsarrhythmia on a full sleep cycle video EEG performed 2 weeks following treatment initiation, rated by an investigator blinded to treatment. Thirteen of 15 patients (86.7%) responded to H.P. Acthar Gel as compared to 4 of 14 patients (28.6%) given prednisone (p<0.002). The 2-week treatment was followed by a 2-week period of taper. Nonresponders to the prednisone treatment were eligible to receive H.P. Acthar Gel treatment. Seven of 8 patients (87.5%) responded to H.P. Acthar Gel after not responding to prednisone. Similarly, the 2 nonresponder patients from the H.P. Acthar Gel treatment were eligible to receive treatment with prednisone. One of the 2 patients (50%) responded to the prednisone treatment after not responding to H.P. Acthar Gel.

A supportive single-blind, randomized clinical trial comparing high-dose, long-duration treatment (150 U/m2 once daily for 3 weeks, n=30) of H.P. Acthar Gel with low-dose, short-duration treatment (20 U once daily for 2 weeks, n=29) for the treatment of infantile spasms was also evaluated in infants and children less than 2 years of age. Nonresponders (defined as in the previously described study) in the low-dose group received a dose escalation at 2 weeks to 30 U once daily. Nominal statistical superiority of the high dose treatment, as compared to the low dose treatment, was observed for cessation of spasms but not for the resolution of hypsarrhythmia.

You should not use this medication if you have:

• adrenal insufficiency (Addison's disease);
• scleroderma;
• a fungal infection anywhere in your body;
• herpes infection of the eyes;
• osteoporosis;
• past or present stomach ulcer;
• congestive heart failure;
• high blood pressure;
• if you have recently had surgery; or
• if you are allergic to pork proteins.

Corticotropin can worsen an infection you already have, or reactivate an infection you recently had. Before using this medication, tell your doctor about any illness or infection you have had within the past several weeks.

Other medical conditions you should tell your doctor about before using corticotropin include:

• liver disease (such as cirrhosis);
• kidney disease;
• a thyroid disorder;
• diabetes;
• a history of tuberculosis;
• a muscle disorder such as myasthenia gravis;
• glaucoma or cataracts;
• depression or mental illness; or
• a stomach or intestinal disorder.

If you have any of these conditions, you may need a dose adjustment or special tests to safely use corticotropin.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether corticotropin passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Steroids can affect growth in children. Talk with your doctor if you think your child is not growing at a normal rate while using this medication.

If you miss a dose or forget to use your medicine, contact your doctor or pharmacist for instructions.

Your pharmacist can provide more information about corticotropin.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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