indication

For use as a diagnostic agent in the screening of patients presumed to have adrenocortical insufficiency.

pharmacology

Corticotropin acts through the stimulation of cell surface ACTH receptors, which are primarily located on the adrenocortical cells. Corticotropin stimulates the cortex of the adrenal gland and boosts the synthesis of corticosteroids, mainly glucocorticoids but also sex steroids (androgens). Corticotropin is also related to the circadian rhythm in many organisms.

mechanism of action

As a 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). The mechanism of action of corticotropin in the treatment of infantile myoclonic seizures is unknown.

absorption

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

half life

About 15 minutes following intravenous administration.

drug interactions

Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid conccurent use of corticosteroids with aldesleukin.

Aprepitant: Aprepitant may increase the serum concentration of Corticosteroids (Systemic). Monitor for increased effects of systemic corticosteroids when coadmininistered with aprepitant; corticosteroid dose reduction may be necessary. The manufacturer of fosaprepitant (a prodrug of aprepitant) states that oral dexamethasone doses should be reduced by 50% when coadministered with a fosaprepitant/aprepitant regimen to achieve dexamethasone concentrations similar to those achieved with dexamethasone alone. Dexamethasone doses used in clinical chemotherapy nausea/vomiting studies with aprepitant reflect this 50% decrease. Similarly, it is recommended that in order to achieve concentrations similar to those achieved with methylprednisolone alone, the intravenous methylprednisolone dose should be reduced by 25% and the oral methylprednisolone dose should be reduced by 50% when given together with a fosaprepitant/aprepitant regimen.

Fosaprepitant: Fosaprepitant may increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. The manufacturer of fosaprepitant states that oral dexamethasone doses should be reduced by 50% when coadministered with a fosaprepitant/aprepitant regimen to achieve dexamethasone concentrations similar to those achieved with dexamethasone alone.1 Dexamethasone doses used in clinical chemotherapy nausea/vomiting studies with aprepitant reflect this 50% decrease. Similarly, it is recommended that in order to achieve concentrations similar to those achieved with methylprednisolone alone, the intravenous methylprednisolone dose should be reduced by 25% and the oral methylprednisolone dose should be reduced by 50% when given together with a fosaprepitant/aprepitant regimen. Monitor for increased effects of systemic corticosteroids when coadmininistered with fosaprepitant or aprepitant.

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Consider eliminating the use of a leflunomide loading dose in patients who are receiving other immunosuppressants in order to reduce the risk for serious adverse events such as hematologic toxicity. Also, patients receiving both leflunomide and another immunosuppressive medication should be monitored for bone marrow suppression at least monthly throughout the duration of concurrent therapy.

Pyridostigmine: The corticosteroid, corticotropin, may decrease the effect of the anticholinesterase, pyridostigmine.

Tacrine: Tacrine and Corticotropin may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.

Trastuzumab: Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

Vecuronium: Vecuronium may increase the adverse neuromuscular effects of systemic corticosteroids, such as Corticotropin. Monitor for increased muscle weakness and signs of polyneuropathies and myopathy.