Video: Latest Treatment for Hep C.

Corticotropin (Systemic)


VA CLASSIFICATION
Corticotropin for Injection
Primary: DX900

Repository Corticotropin
Primary: CN400


Commonly used brand name(s): H.P. Acthar Gel.

Another commonly used name is
ACTH .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Diagnostic aid (adrenocortical function)—Corticotropin for Injection USP;

Anticonvulsant (specific in infantile myoclonic seizures)—Repository Corticotropin Injection USP;

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling. Additionally, because corticotropin for injection is not commercially available in the U.S. or Canada, the use of brackets and the superscript 1 in this monograph reflects the lack of labeled (approved) indications for this medication.

Accepted

[Adrenocortical insufficiency (diagnosis) 1]—Corticotropin for injection is indicated as an aid in diagnosing adrenocortical insufficiency {01} {03}; however, the synthetic fragment of corticotropin, cosyntropin, is the preferred diagnostic aid {05} because it is less antigenic {02}. Additionally, corticotropin is purified from animal pituitary glands and can contain significant amounts of vasopressin and other peptides, which are not found in cosyntropin {06}.

[Seizures, myoclonic, infantile (treatment) ]1 —Repository corticotropin is used in the treatment of infantile myoclonic seizures (infantile spasms), although there are only limited data suggesting that it has greater efficacy than do glucocorticoids {07} {10} {11} {12} {13}.

Unaccepted
Corticotropin is no longer recommended for its anti-inflammatory and immunosuppressant properties {03}. Although corticotropin is FDA-approved for the treatment of secondary adrenocortical insufficiency and many nonendocrine disorders that are responsive to glucocorticoid therapy {01}, treatment with a corticosteroid is preferred.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Hormone; obtained from porcine pituitary glands. {01} {03}

Mechanism of action/Effect:

Diagnostic aid (adrenocortical function)—Corticotropin combines with a specific receptor on the adrenal cell plasma membrane. In patients with normal adrenocortical function, it stimulates the initial reaction involved in the synthesis of adrenal steroids (including cortisol, cortisone, weak androgenic substances, and a limited quantity of aldosterone) from cholesterol by increasing the quantity of cholesterol within the mitochondria. Corticotropin does not significantly increase serum cortisol concentrations in patients with primary adrenocortical insufficiency (Addison's disease). {01} {02} {03}

Anticonvulsant (specific in infantile myoclonic seizures)—The mechanism of action of corticotropin in the treatment of infantile myoclonic seizures is unknown {07}.


Other actions/effects:

Corticotropin is not a corticosteroid. However, it shares many actions of the corticosteroids due to its ability to increase endogenous corticosteroid synthesis.

Absorption:

Corticotropin is rapidly absorbed following intramuscular administration; the repository dosage form is slowly absorbed over approximately 8 to 16 hours {02} {03}.

Half-life:

About 15 minutes following intravenous administration {02}.

Time to peak effect:

Peak plasma cortisol concentrations are usually achieved within 1 hour after intramuscular or rapid intravenous administration of corticotropin for injection {03}.

Duration of action:

Following intramuscular or rapid intravenous administration of corticotropin, peak plasma cortisol concentrations begin to decrease after 2 to 4 hours {03}.

The effects of repository corticotropin may last up to 3 days {01} {03}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients allergic to proteins of porcine origin {01} {03} or cosyntropin {03} may also be allergic to corticotropin.

Carcinogenicity

Adequate and well-controlled animal studies have not been done in animals; however, use in humans has not shown an increase in malignant disease {01}.

Pregnancy/Reproduction
Fertility—
Studies have not been done in humans or in animals.

Pregnancy—
Adequate and well-controlled studies have not been done in humans.

Studies in animals have shown that corticotropin is embryocidal {01} {03}.

FDA Pregnancy Category C.

Breast-feeding

It is not known whether corticotropin is distributed into breast milk. However, problems in humans have not been documented. {01}

Pediatrics

Appropriate studies performed to date using corticotropin have not demonstrated pediatrics-specific problems that would limit the usefulness of corticotropin in children. However, prolonged use of corticotropin in children will inhibit skeletal growth {01}; therefore, close monitoring is recommended.


Geriatrics


Appropriate studies performed to date using corticotropin have not demonstrated geriatrics-specific problems that would limit the usefulness of corticotropin in the elderly.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Estrogens    (estrogen may cause abnormally high plasma cortisol concentrations before and after corticotropin administration; however, a normal incremental response to corticotropin still occurs {03})


» Immunizations    (during chronic therapy, patients should not be vaccinated against smallpox; extreme caution is recommended if other immunizations are to be given, because of the risk of neurological complications and lack of antibody response {01})


Verapamil    (limited data show that chronic administration of oral verapamil may blunt the effect of corticotropin {08}, resulting in a false negative diagnostic test result)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):



With results of adrenocortical function testing

Due to other medications
» Corticosteroids, glucocorticoid    (if competitive protein binding assays or immunoassays showing cross-reactivity with prednisone or cortisone are used, a high baseline cortisol concentration with no response to corticotropin may be seen in patients taking these medications {04})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Infections, serious bacterial or viral, especially varicella    (possible immunosupression may lead to infectious complications with chronic use {07})


Risk-benefit should be considered when the following medical problems exist
» Allergy to corticotropin, cosyntropin, or porcine derivatives    (risk of allergic reaction)



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):


For treatment of infantile myoclonic seizures
» Blood pressure and
» Calcium, serum and
» Electroencephalogram, waking and sleeping and
» Electrolytes, serum and
» Glucose, urine and
» Phosphorus, serum and
» Urinalysis and
» Weight    (recommended at periodic intervals during therapy to assess therapeutic and/or adverse effects {07})


» Calcium, serum and
» Complete blood count and
» Electrolytes, serum and
» Endocrine profile and
» Glucose, serum, fasting and 2-hour postprandial and
» Phosphorus, serum, and
» Renal function tests and
» Urinalysis    (recommended prior to initiation of therapy; caution in using corticotropin is recommended if any of these tests are abnormal {07})




Side/Adverse Effects

Note: Except for rare allergic reactions, there are no side/adverse effects associated with the use of corticotropin as a diagnostic aid.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
—with chronic use only    
Cerebral ventriculomegaly {07}
    
congestive heart failure {01}
    
hyperglycemia {01}
    
hypertension {01}{07}
    
hypothalamic-pituitary suppression {01}{07}
    
metabolic abnormalities, such as {01}{07}
hypernatremia
hypokalemia
hypocalcemia
hypophosphatemia
    
sepsis {07}

Incidence rare
    
Allergic reaction {01}(dizziness; nausea and vomiting; shock; skin rash)
    
worsening of seizures —with chronic use only{07}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
—with chronic use only    
Irritability, extreme {07}



Those not indicating need for medical attention
Incidence more frequent
—with chronic use only    
Cushingoid facies {11}
    
cutaneous pigmentation {11}
    
hirsutism {11}
    
seborrheic dermatitis {11}





General Dosing Information
Following administration of corticotropin as a diagnostic agent, adrenal insufficiency can be confirmed when a plasma, serum, or urinary free cortisol concentration does not increase above a baseline concentration {02}.

During chronic therapy of infantile myoclonic seizures, patients should not be vaccinated against smallpox. Extreme caution is recommended if other immunizations are to be given, because of the risk of neurological complications and lack of antibody response. {01}

For treatment of adverse effects
Recommended treatment for hypertension that may develop during treatment of infantile spasms consists of sodium restriction and diuretic therapy rather than discontinuation of corticotropin {07}.


Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

CORTICOTROPIN FOR INJECTION USP

Note: Because corticotropin for injection is not commercially available in the U.S. or Canada, the bracketed uses and the use of the superscript 1 in this section reflect the lack of labeled (approved) indications for this medication in these countries.


Usual adult and adolescent dose
[Adrenocortical insufficiency (diagnosis)1]
Intravenous infusion, 10 to 25 Units in 500 mL of 5% dextrose in water, infused over an eight-hour period {01}.


Usual pediatric dose
[Adrenocortical insufficiency (diagnosis)1]
Use is not recommended. The synthetic fragment of corticotropin, cosyntropin, is the recommended diagnostic agent.

[Seizures, myoclonic, infantile (treatment)]1
Use is not recommended. Repository corticotropin injection USP is the preferred product. {07} {09}


Size(s) usually available:
U.S.—
Not commercially available.

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
Corticotropin for injection should be reconstituted with sterile water or sodium chloride for injection, so that the individual dose is contained in 1 to 2 mL of solution. {01}

Stability:
After reconstitution, solution should be used immediately {01}.


REPOSITORY CORTICOTROPIN INJECTION USP

Usual adult and adolescent dose
Use is not recommended.

Usual pediatric dose
[Seizures, myoclonic, infantile (treatment)]1
Intramuscular, 20 to 40 Units per day or 80 Units every other day {09}.

Note: The optimal dose of corticotropin for the treatment of infantile myoclonic seizures has not been established. Another recommended regimen for infantile myoclonic seizures is an initial dose of 150 Units per square meter of body surface area per day administered intramuscularly in two divided doses for one week, followed by 75 Units per square meter of body surface area per day for one week, then 75 Units per square meter of body surface area administered every other day for one week. Corticotropin dosage is then gradually tapered over the subsequent nine weeks. {07}
The optimal duration of therapy is not known {07}.
Dose should be tapered gradually when discontinuing corticotropin therapy {07} {09}.



Strength(s) usually available
U.S.—


80 USP Units per mL (Rx) [H.P. Acthar Gel]

Note: In the US, corticotropin gel is available through the National Organization of Rare Disorders, at 1–800–459–7599


Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F), unless otherwise specified by manufacturer {01}.



Revised: 12/30/1999



References
  1. Acthar product insert (Rhône-Poulenc Rorer—US), Rev 2/95.
  1. Gilman AG, Rall TW, Nies AS, Taylor P, editors. Goodman and Gilman"s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press, 1990: 1431-62.
  1. ACTH (Rhône-Poulenc Rorer). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 30th ed. Ontario: Canadian Pharmaceutical Association, 1995: 18-9.
  1. Becker KL, editor. Principles and practice of endocrinology and metabolism. Philadelphia: JB Lippincott Company, 1990: 1766-8.
  1. Miller WL, Tyrrell JB. The adrenal cortex. In: Felig P, Baxter JD, Frohman LA, editors. Endocrinology and metabolism. New York: McGraw-Hill, Inc., 1995: 652-4.
  1. Sheeler LR, Schumacher OP. Hyponatremia during ACTH infusions. Ann Intern Med 1979; 90: 798-9.
  1. Snead OC. Other antiepileptic drugs: adrenocorticotropic hormone (ACTH). In: Levy R, Mattson R, Meldrum B, editors. Antiepileptic drugs. New York: Raven Press, 1995: 941-8.
  1. Guthrie GP, McAllister RG, Kotchen TA. Effects of intravenous and oral verapamil upon pressor and adrenal steroidogenic responses in normal man. J Clin Endocrinol Metab 1983; 57: 339.
  1. Johnson KB, editor. The Harriet Lane handbook. A manual for pediatric house officers. 13th ed. St. Louis: Mosby, 1993: 378.
  1. Dreifuss F, Farwell J, Holmes G, et al. Infantile spasms: comparative trial of nitrazepam and corticotropin. Arch Neurol 1986; 43: 1107-10.
  1. Singer WD, Rabe EF, Haller JS. The effect of ACTH therapy on infantile spasms. J Pediatr 1980; 96: 485-9.
  1. Snead OC, Benton JW, Myers GJ. ACTH and prednisone in childhood seizure disorders. Neurology 1983; 33: 966-70.
  1. Snead OC, Benton JW, Hosey LC, et al. Treatment of infantile spasms with high dose ACTH: efficacy and plasma levels of ACTH and cortisol. Neurology 1989; 39: 1027-30.
  1. Product Information: H.P.Acthar Gel, corticotropin. Rhône–Poulenc Rorer, Collegeville, PA, USA, Rev. 04/1996
Hide
(web4)