CLINICAL PHARMACOLOGY
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.
NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
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)].
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