H.P. ACTHAR(repository corticotropin)injection(九)
d 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 eva luated 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 eva luated 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)].
10 OVERDOSAGE
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.
11 DESCRIPTION
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:
H- Ser- Tyr- Ser- Met- Glu- His- Phe- Arg- Trp- Gly-
1 2 3 4 5 6 7 8 9 10
Lys- Pro- Val- Gly- Lys- Lys- Arg- Arg- Pro- Val-
11 12 13 14 15 16 17 18 19 20
Lys- Val- Try- Pro- Asp- Gly- Ala- Glu- Asp- Gln-
21 22 23 24 25 26 27 28 29 30
Leu- Ala- Glu- Ala- Phe- Pro- Leu- Glu- Phe- OH
31 32 33 34 35 36 37 38 39
12 CLINICAL PHARMACOLOGY
12.1 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 corti |
