corticotropin (adrenocorticotropic hormone, ACTH)
ACTH, Acthar, H.P. Acthar Gel

Available forms
Available by prescription only
Injection: 25 units/vial, 40 units/vial
Repository injection: 40 units/ml, 80 units/ml

Indications and dosages
 Diagnostic test of adrenocortical function. Adults: Up to 80 units I.M. or S.C. in divided doses; or a single dose of repository form; or 10 to 25 units (aqueous form) in 500 ml of D₅W I.V. over 8 hours, between blood samplings. Individual dosages vary with adrenal glands’ sensitivity to stimulation and with the specific disease. Infants and younger children require larger doses per kilogram than do older children and adults.
 Replacement hormone. Adults: 20 units S.C. or I.M. q.i.d.
 Exacerbations of multiple sclerosis. Adults: 80 to 120 units I.M. daily for 2 to 3 weeks.
 Severe allergic reactions, collagen disorders, dermatologic disorders, inflammation. Adults: 40 to 80 units I.M. or S.C. daily. Adjust dosage based on patient response.
 Infantile spasms. Infants: 20 to 40 units I.M. (of repository injection) daily or 80 units I.M. every other day for 3 months or 1 month after spasm ceases.

Pharmacodynamics
Diagnostic action: Corticotropin is used to test adrenocortical function. Corticotropin binds with a specific receptor in the adrenal cell plasma membrane, stimulating the synthesis of the entire spectrum of adrenal steroids, one of which is cortisol. The effect of corticotropin is measured by analyzing plasma cortisol before and after drug administration. In patients with primary adrenocortical insufficiency, corticotropin doesn’t increase plasma cortisol levels significantly.
Anti-inflammatory action: In nonsuppurative thyroiditis and acute exacerbations of multiple sclerosis, corticotropin stimulates release of adrenal cortex hormones, which combat tissue responses to inflammatory processes.

Pharmacokinetics
Absorption: Absorbed rapidly after I.M. administration.
Distribution: Exact distribution of corticotropin is unknown, but it’s removed rapidly from plasma by many tissues.
Metabolism: Unknown.
Excretion: Probably excreted by the kidneys. Half-life is about 15 minutes.

Contraindications and precautions
Contraindicated in patients with peptic ulcer, scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, peptic ulceration, heart failure, hypertension, sensitivity to pork and pork products, adrenocortical hyperfunction or primary insufficiency, or Cushing’s syndrome. Also contraindicated in those who have had recent surgery.
  Use cautiously in women who are pregnant or of childbearing age. Also use cautiously in patients being immunized and in those with latent tuberculosis, hypothyroidism, cirrhosis, acute gouty arthritis, psychotic tendencies, renal insufficiency, diverticulitis, ulcerative colitis, thromboembolic disorders, seizures, uncontrolled hypertension, or myasthenia gravis.
 Use cautiously if surgery or emergency treatment is required.

Interactions
Drug-drug. Amphotericin B, carbonic anhydrase inhibitors, diuretics: Increases electrolyte loss from diuretic therapy. Monitor serum blood levels, especially potassium.
Cardiac glycosides: May increase risk of arrhythmias or digitalis toxicity from hypokalemia. Monitor patient closely.
Cortisone, estrogens, hydrocortisone: May elevate plasma cortisol levels abnormally. Use cautiously.
Hepatic enzyme-inducing drugs: May increase corticotropin metabolism. Monitor patient closely.
Indomethacin, NSAIDs, salicylates: Increases risk of GI bleeding. Avoid use together.
Insulin, oral antidiabetics: Corticotropin may aggravate diabetes mellitus. Patient may need increased antidiabetic dosage. Monitor blood glucose levels closely.

Adverse reactions
CNS: seizures, dizziness, vertigo, increased intracranial pressure with papilledema, pseudotumor cerebri.
CV: hypertension, heart failure, necrotizing vasculitis, shock.
EENT: cataracts, glaucoma.
GI: peptic ulceration with perforation and hemorrhage, pancreatitis, abdominal distention, ulcerative esophagitis, nausea, vomiting, increased serum amylase level.
GU: menstrual irregularities.
Metabolic: activation of latent diabetes mellitus, sodium and fluid retention, calcium and potassium loss, hypokalemic alkalosis, negative nitrogen balance.
Musculoskeletal: muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, suppression of growth in children, vertebral compression fractures.
Respiratory: pneumonia.
Skin: ecchymoses, impaired wound healing; thin, fragile skin; petechiae; facial erythema; diaphoresis; acne; hyperpigmentation; allergic reactions; hirsutism.
Other: abscess and septic infection, cushingoid symptoms, progressive increase in antibodies, loss of corticotropin stimulatory effect, hypersensitivity reactions (rash, bronchospasm).

Effects on lab test results
• May increase blood glucose levels. May decrease potassium and calcium levels.

Overdose and treatment
No specific information available.
 Treatment is supportive, as appropriate.

Special considerations
• Cosyntropin is less antigenic and less likely to cause allergic reactions than corticotropin. However, allergic reactions occur rarely with corticotropin.
• In patient with suspected sensitivity to porcine proteins, perform skin testing. To decrease the risk of anaphylaxis in patient with limited adrenal reserves, 1 mg of dexamethasone may be given at midnight before the corticotropin test and 0.5 mg at start of test.
• Observe neonates of corticotropin-treated women for signs of hypoadrenalism.
• Counteract edema by low-sodium, high-potassium intake; nitrogen loss by high-protein diet; and psychotic symptoms by reducing corticotropin dosage or administering sedatives.
• Drug may mask signs of chronic disease and decrease host resistance and ability to localize infection.
• If administering gel, it must be warmed to room temperature, drawn into a large needle, and given slowly, deep I.M. with a 22G needle.
• Don’t discontinue drug abruptly, especially after prolonged therapy. An addisonian crisis may occur.
• Refrigerate reconstituted product and use within 24 hours.
• Corticotropin therapy alters protein-bound iodine levels; radioactive iodine (¹³¹I) uptake and T₃ uptake.
• Monitor weight, fluid exchange, and resting blood pressure levels until minimal effective dosage is achieved.
Breast-feeding patients
• Safety hasn’t been established. Because the potential for severe adverse reactions exists, benefits and risks must be weighed.
Pediatric patients
• Use with caution because prolonged use of drug inhibits skeletal growth. Intermittent administration is recommended.

Patient education
• Warn patient that injection is painful.
• Tell patient to report marked fluid retention, muscle weakness, abdominal pain, seizures, or headache.
• Instruct patient not to be vaccinated during corticotropin therapy.
• Teach patient how to monitor for edema, and tell him about the need for fluid and salt restriction as appropriate.
• Warn patient not to stop drug except as prescribed. Tell him that abrupt discontinuation may cause severe adverse reactions.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use