VA Class:HS701
ATC Class:H01AA01
Corticotropin is a polypeptide, which is secreted by the basophilic cells of the anterior pituitary (adenohypophysis) that stimulates the adrenal cortex to secrete cortisol (hydrocortisone) and other hormones.
The principal indication for corticotropin is as an aid in the diagnosis of adrenocortical insufficiency. (See Cosyntropin 36:04.)
Corticotropin may be used in the palliative treatment of various nonendocrine disorders that are responsive to glucocorticoids. (See Corticosteroids General Statement 68:04.) Corticotropin also may be used in the symptomatic treatment of acute exacerbations of multiple sclerosis or other neuromuscular disorders such as dermatomyositis. Corticotropin therapy is not curative and is indicated only as supportive therapy to be used adjunctively with other indicated therapies. If prolonged therapy is required, continual attempts should be made to reduce the dosage or, preferably, to withdraw corticotropin therapy completely. (See Dosage and Administration: Dosage.)
In patients with normal adrenocortical function, corticotropin has been used for its anti-inflammatory and immunosuppressant properties and its effects on blood and lymphatic systems in the palliative treatment of various nonendocrine disorders that are responsive to glucocorticoids. (See Corticosteroids 68:04.) However, no studies have demonstrated that corticotropin is superior to glucocorticoids for the treatment of any disorder when comparable concentrations of cortisol or its derivatives are achieved. Glucocorticoids are preferred to corticotropin because their effectiveness does not depend on adrenocortical responsiveness and they produce a more predictable effect than does corticotropin; dosage of corticosteroids can be regulated more accurately and can be tapered more easily than corticotropin. Corticotropin also is less convenient to use because it must be given by injection while glucocorticoids can be administered orally in most conditions. If extremely large amounts of glucocorticoids are required, corticosteroids should be used rather than corticotropin, since the adrenal cortex secretes only 10-20 mg of cortisol per hour even with continuous maximal corticotropin stimulation. In immediately life-threatening situations, glucocorticoids are preferred since maximal blood concentrations are attained immediately after IV administration; in contrast, corticotropin increases plasma cortisol concentrations over a period of several hours, and maximal stimulation of the adrenal cortex may not be achieved until after a few days of therapy.
Because corticotropin stimulates the secretion of adrenal androgens which may minimize the myopathic effect of glucocorticoids, corticotropin has been used in the symptomatic treatment of acute exacerbations of multiple sclerosis or other neuromuscular disorders such as dermatomyositis. Corticotropin has been used effectively to increase muscle strength in patients with severe myasthenia gravis who were refractory to conventional therapy with anticholinesterase drugs. The patient must be treated in an intensive care unit (ICU) and receive respiratory support; muscle strength initially decreases markedly but subsequently is increased.
Corticotropin has been used effectively in patients with moderately to severly active and severe fulminant Crohn's disease†, including those with an abdominal mass, when a parenteral corticosteroid was indicated, usually in patients who have not responded to oral therapy.100, 101, 102 Individuals with an inflammatory abdominal mass should receive broad-spectrum anti-infective agents in conjunction with corticotropin.100, 102 Efficacy of IV corticotropin has been evaluated in a prospective, randomized, double-blind, comparative study in 88 hospitalized patients with moderately to severely active Crohn's disease.101 The major goals of therapy (clinical response) were elimination of primary bowel symptoms (e.g., abdominal pain, diarrhea, fever, malnutrition), reversal of small bowel obstruction, reduction of abdominal mass, healing of fistulizing or perirectal disease, and/or elimination of extraintestinal manifestations of the disease.101 Patients were randomized to receive IV infusion over 24 hours of corticotropin (initially 120 units daily then decreased to 80 units daily at day 3 or any day thereafter, if improvement was progressive) or hydrocortisone (initially 300 mg daily and decreased to 200 mg daily at day 3 or any day thereafter, if improvement was progressive).101 After 10 days of therapy, no statistically significant difference in clinical response was observed in patients receiving corticotropin compared with those receiving hydrocortisone (82% for corticotropin versus 93% for hydrocortisone); oral administration of corticosteroid therapy 30 days prior to hospitalization did not have a statistically significant effect on response rate with parenteral therapy.101 Long-term follow-up (1-3 years after the study) showed that 28% of patients required surgery, while 72% of patients continued to respond with maintenance therapy (e.g., amino derivatives of salicylic acid, mercaptopurine) for Crohn's disease; there was no substantial difference in the number of patients who had received corticotropin compared with those who had received hydrocortisone during the study.101
For further information on the management of Crohn's disease, see Uses: Crohn's Disease, in Mesalamine 56:36.
Primary Adrenocortical Insufficiency
Corticotropin is ineffective in the treatment of primary adrenocortical insufficiency and congenital adrenogenital syndrome. Although corticotropin has been given to restore adrenocortical responsiveness following HPA axis suppression, the drug is not indicated for this use because adrenocortical secretion of cortisol becomes inadequate again when corticotropin is stopped.
Reconstitution and Administration
For prolonged effects, repository corticotropin injection may be given IM or subcutaneously.
Patient responses are quite variable during therapeutic use of corticotropin since there are marked differences in the responsiveness of the adrenal gland to the drug. Since maximal corticotropin stimulation of the adrenal cortex may not occur during the first few days of therapy, the drug should not be used when an immediate therapeutic effect is required. If corticotropin is clearly necessary, the drug should be administered in the smallest dosage possible and should generally be used only as an adjunct to other treatments. For verification of adrenal responsiveness before treatment with corticotropin, up to 80 units may be given (by the route of administration proposed for treatment) as a single injection or a smaller dose may be given as 1 or more injections. Therapeutic dosage should be individualized according to the diagnosis, severity, prognosis, and probable duration of the disease; plasma and urine corticosteroid concentrations; and patient response and tolerance. Dosage should be adjusted gradually to the lowest level that maintains an adequate clinical response, and periodic attempts should be made to decrease dosage or, preferably, to withdraw the drug completely. Patients should be continually monitored for signs that indicate dosage adjustment is necessary, such as remissions or exacerbations of the disease. Supplemental doses of corticosteroids may be required during stress (surgery, infection, trauma). Following long-term therapy, corticotropin should be withdrawn gradually by reducing the dose and/or administering the drug at longer intervals.
Although corticotropin dosage may be reduced and discontinued quite rapidly after brief periods of therapy, withdrawal following long-term therapy should be very gradual until recovery of hypothalamic-pituitary function occurs. (See Cautions: Precautions and Contraindications.) If the disease flares up during withdrawal, dosage may need to be increased and followed by a more gradual withdrawal. In addition, supplemental doses of corticosteroids may be required during periods of stress. The time required for complete recovery of hypothalamic-pituitary function is variable.
For the treatment of acute exacerbations of multiple sclerosis, the usual adult dosage of repository corticotropin injection is 80-120 units IM daily in divided doses for 2-3 weeks. For anti-inflammatory and immunosuppressant effects, the usual adult IM or subcutaneous dosage of repository corticotropin injection is 40-80 units every 24-72 hours. Some clinicians have suggested an IM daily pediatric dosage of repository corticotropin of 0.8 units/kg or 25 units/m2 in 1-2 doses.
In patients with myasthenia gravis, 100 units of repository corticotropin injection has been given IM daily for 10 days; after 5-10 days, this dosage is repeated. Improvement may be maintained in some patients with IM administration of 100 units of the repository injection once weekly.
Except for hypersensitivity reactions (which are more frequent with corticotropin than with corticosteroids), short-term administration of corticotropin, even in massive doses, is unlikely to produce harmful effects. When the drug is used for longer than brief periods, however, it can produce a variety of devastating effects. When used therapeutically, corticotropin causes about the same adverse effects as do corticosteroids. Skin atrophy and thinning and easy bruising occur less frequently with corticotropin therapy than with glucocorticoids. Hyperpigmentation and adverse androgenic effects such as amenorrhea, acne, and hirsutism are more common with corticotropin than with glucocorticoids. Sodium and water retention occur more frequently with corticotropin than with synthetic glucocorticoids (except fludrocortisone) and about as often as with cortisone and hydrocortisone.
Hypothalamic-Pituitary Insufficiency
When given for prolonged periods, corticotropin may suppress pituitary release of corticotropin and cause hypothalamic-pituitary insufficiency (See Cautions: Precautions and Contraindications); unlike the corticosteroids, corticotropin causes adrenocortical hyperplasia rather than atrophy. The degree and duration of hypothalamic-pituitary insufficiency produced by corticotropin is highly variable among patients and depends on the dose, frequency and time of administration, and duration of therapy.
Muscle wasting, muscle pain or weakness, delayed wound healing, and atrophy of the protein matrix of the bone resulting in osteoporosis, vertebral compression fractures, aseptic necrosis of femoral or humeral heads, or pathologic fractures of long bones are manifestations of protein catabolism which may occur during prolonged corticotropin therapy and may be especially serious in geriatric or debilitated patients.
Hypersensitivity to corticotropin has occurred, even in patients who have not previously been treated with the drug, and may be manifested by skin reactions (urticaria, pruritus, scarlatiniform exanthema), dizziness, nausea, vomiting, and mild fever and, in some instances, anaphylactic shock, wheezing, circulatory failure, and death. Anaphylactic reactions should be treated immediately with IV epinephrine; less severe hypersensitivity reactions may be treated with IV or IM administration of a corticosteroid. Hypersensitivity may be caused by an impurity in the corticotropin preparation or the drug itself, and prolonged administration of corticotropin increases the risk of hypersensitivity reactions.
Endocrine and Metabolic Effects
When corticotropin is administered over a prolonged period, it may produce various endocrine disorders including hypercorticism (cushingoid state) and menstrual irregularities. Corticotropin may decrease glucose tolerance, produce hyperglycemia, and aggravate or precipitate diabetes mellitus especially in patients predisposed to diabetes mellitus. If corticotropin therapy is required in patients with diabetes mellitus, changes in insulin or oral hypoglycemic agent dosage or diet may be necessary. Corticotropin may cause hypotriglyceridemia.
Adverse GI effects of corticotropin include abdominal distension and ulcerative esophagitis. Acute, sometimes fatal, pancreatitis has been reported, especially with high doses or prolonged therapy. Increased serum amylase concentrations have occurred after short-term administration of corticotropin. Corticotropin has been implicated in the development, reactivation, perforation, hemorrhage, and delayed healing of peptic ulcers. Dyspepsia is less common with corticotropin than with corticosteroids.
Adverse neurologic effects of corticotropin have included headache, vertigo, EEG abnormalities, and seizures. Corticotropin may precipitate mental disturbances ranging from euphoria, mood swings, depression, insomnia, and personality changes to frank psychoses. Emotional instability or psychotic tendencies may be aggravated by the drug.
Dermatologic and Local Effects
Various adverse dermatologic effects are associated with corticotropin administration and include skin atrophy and thinning, acne, increased sweating, hirsutism, facial erythema, petechiae, ecchymoses, and easy bruising. Hyperpigmentation may occur during corticotropin therapy. Transient local induration, pain, and abscesses may occur at the IM or subcutaneous injection site.
Sodium retention with resultant edema, potassium loss, hypokalemic alkalosis, and hypertension may occur in patients receiving corticotropin. Congestive heart failure may occur in susceptible patients. Necrotizing angiitis has occurred during corticotropin therapy. Corticotropin increases calcium excretion and may cause hypocalcemia and hypophosphatemia. Anuria, renal cortical necrosis, and death have been reported in one patient.
Prolonged use of corticotropin may result in posterior subcapsular cataracts (particularly in children), exophthalmos, or increased intraocular pressure which may result in glaucoma or may occasionally damage the optic nerve.
Precautions and Contraindications
Before initiating therapy, adrenal responsiveness to corticotropin should be verified, and the drug should be given by the route of administration proposed for treatment. Prior to initiation of long-term corticotropin therapy, baseline electrocardiograms, blood pressures, chest and spinal radiographs, glucose tolerance tests, and evaluations of HPA axis function should be performed on all patients. Upper GI radiographs should be performed in patients predisposed to GI disorders. During long-term therapy, periodic height, weight, chest and spinal radiographs, hematopoietic, electrolyte, glucose tolerance, and ocular and blood pressure evaluations should be performed.
Patients who develop hypothalamic-pituitary insufficiency during corticotropin therapy require supplemental doses of corticosteroids when they are subjected to stress (e.g., illness, infection, surgery, trauma). In addition, relative adrenocortical insufficiency may occur if corticotropin is withdrawn abruptly. Therefore, the drug should be withdrawn very gradually following long-term therapy. (See Dosage and Administration: Dosage.) Hypothalamic-Pituitary insufficiency may persist for months in patients who receive the drug for prolonged periods. Until recovery occurs, patients may show signs and symptoms of adrenal insufficiency when they are subjected to stress and corticosteroid therapy may be required. Patients receiving corticotropin should be instructed to notify their physicians of any infections, signs of infections (e.g., fever, sore throat, pain during urination, muscle aches), or injuries that develop during therapy or within 12 months after therapy is discontinued, so that glucocorticoid therapy can be introduced if necessary. In addition, when surgery is required, patients should be advised to inform the attending physician, dentist, or anesthesiologist that they are receiving or have recently (within 12 months) received therapeutic doses of corticotropin. Patients should carry identification cards listing the diseases for which they are being treated, the drug they are receiving and its dosage, and the name and telephone number of their physicians.
Corticotropin may reduce resistance to and aid in the establishment of bacterial, viral, or fungal infections, including those of the eye, and mask the clinical signs of infection, preventing recognition of ineffectiveness of the antibiotic. Corticotropin should not be used, except in life-threatening situations, in patients with viral infections or bacterial infections not controlled by antibiotics. Although the manufacturers' literature states that corticotropin is contraindicated in patients with systemic fungal infections, most authorities believe that corticotropin therapy may be initiated in patients with known infections (including those from fungi but not in ocular fungal infection) if effective specific chemotherapy is administered concomitantly. Patients whose susceptibility to infection is high, such as those receiving corticotropin as immunosuppressive therapy, are especially likely to develop secondary infections. Vaccines and immunizations should not be administered to patients receiving corticotropin because neurologic reactions may be aggravated and because corticotropin inhibits antibody response. Patients with latent tuberculosis or a positive tuberculin skin test should be closely observed during corticotropin therapy. During prolonged corticotropin therapy, the manufacturers state that these patients should receive preventive therapy, but most clinicians believe that preventive therapy is not necessary.
Since corticotropin may cause sodium retention with resultant potassium loss, dietary salt restriction and potassium supplementation may be necessary in patients receiving the drug. Patients should be instructed to notify their physicians if edema develops.
Hypersensitivity skin testing should be performed before treatment of patients with suspected sensitivity to porcine proteins. During IV administration or immediately after IM or subcutaneous injection of corticotropin preparations, all patients should be carefully observed for hypersensitivity reactions. Prolonged treatment with corticotropin may cause formation of antibodies to the drug (usually to the 25-32 amino acid sequence) and theoretically result in loss of adrenal stimulation.
Corticotropin should be used with caution in patients with hypothyroidism or cirrhosis, because such patients often show exaggerated response to the drug. The drug should be used with caution in psychotic patients, in patients with diverticulitis or nonspecific ulcerative colitis (if there is a probability of impending perforation or recent intestinal anastomoses), and in patients with abscess or other pyogenic infections. The manufacturers say that corticotropin should not be used in patients with peptic ulcer or history of peptic ulcer. The drug should be used with extreme caution in patients with myasthenia gravis, since these patients always experience marked decrease in muscle strength initially and require respiratory support when they receive 100 units of the drug daily IM or IV (no longer commercially available in the US) for 10 days. Because corticotropin has been reported to increase blood coagulability and to precipitate intravascular thrombosis, thromboembolism, and thrombophlebitis rarely, the drug should be used with caution in patients with thromboembolic disorders. Corticotropin should be used with caution in patients with seizure disorders or renal insufficiency. The drug should be used with caution, if at all, in patients with osteoporosis, ocular herpes simplex infection, or uncontrolled hypertension. Before initiating corticotropin therapy in postmenopausal women, the fact that they are especially prone to osteoporosis should be considered.
Corticotropin is contraindicated in patients with scleroderma, recent surgery, congestive heart failure, sensitivity to porcine proteins, or previous hypersensitivity reaction to corticotropin. The drug is contraindicated in the treatment of primary adrenocortical insufficiency or adrenocortical hyperfunction and in any condition accompanying these adrenocortical disorders.
Long-term administration of corticotropin to children should be avoided if possible, since the drug may retard bone growth. Although results of some studies indicate that daily doses of corticotropin do not suppress linear growth, these studies have been questioned because of deficiencies in methodology. Most endocrinologists believe that long-term therapy with corticotropin will affect the rate of linear growth and the ultimate height of the child to the same extent as do daily pharmacologic doses of glucocorticoids. Alternate-day therapy with glucocorticoids minimizes growth suppression and should be used whenever possible in children who require systemic glucocorticoid therapy. If prolonged corticotropin therapy is necessary, the growth and development of infants and children should be closely monitored. Children receiving corticotropin have developed increases in intracranial pressure (pseudotumor cerebri) causing papilledema; oculomotor or abducens nerve paralysis, visual loss, and headache may also occur. Pseudotumor cerebri has occurred most frequently following reduction of dosage or immediately following discontinuance of the drug.
Safe use of corticotropin during pregnancy has not been established. In animals, corticotropin has resulted in fetal abnormalities. Fetal abnormalities (e.g., cleft palate) have been reported following administration of glucocorticoids to pregnant women, but these abnormalities could have resulted from the underlying disease as well as from the steroids. Women should be instructed to inform their physicians if they become or wish to become pregnant while receiving corticotropin. If corticotropin must be used during pregnancy or if the patient becomes pregnant while taking the drug, the potential risks should be carefully considered. Infants born to mothers who receive corticotropin during pregnancy should be carefully monitored for symptoms of adrenal insufficiency and appropriate therapy begun immediately if such symptoms appear.
Safe use of corticotropin during lactation has not been established.
Drugs such as barbiturates, phenytoin, and rifampin which induce hepatic enzymes may increase glucocorticoid metabolism, and patients stabilized on corticotropin therapy may experience a reduced corticosteroid effect if such drugs are added to or withdrawn from their drug regimen. Potentially, corticosteroids may inhibit hepatic enzymes that activate cyclophosphamide to its alkylating metabolites, and patients should be observed for a change in cyclophosphamide effects if corticotropin is given concomitantly.
Estrogens may potentiate effects of cortisol, possibly by increasing the concentration of transcortin and thus decreasing the amount of cortisol available to be metabolized. Adjustments of corticotropin dosage may be required if estrogens are added to or withdrawn from a stable dosage regimen.
Concomitant administration of ulcerogenic drugs such as salicylates or indomethacin and corticotropin may increase the risk of GI ulceration. In addition, aspirin should be used cautiously in conjunction with corticotropin in patients with hypoprothrombinemia. Glucocorticoids may also decrease blood concentrations of salicylates. If corticotropin therapy is withdrawn from a patient stabilized on both drugs, salicylism may occur.
Potassium-depleting diuretics (e.g., thiazides, furosemide, and ethacrynic acid) and other drugs which deplete potassium, such as amphotericin B, enhance the potassium-wasting effect of corticotropin. In addition, amphotericin B may decrease adrenocortical responsiveness to corticotropin. Serum potassium should be closely monitored in patients receiving corticotropin and potassium-depleting drugs.
Rarely, corticotropin has been reported to increase blood coagulability and to increase oral anticoagulant dosage requirements in some patients; in other patients receiving oral anticoagulants and corticotropin, hemorrhage has reportedly occurred. Since the clinical importance of these interactions has not been determined, corticotropin therapy should be started or discontinued with caution in patients stabilized on oral anticoagulants.
Corticotropin may decrease 131I uptake. The drug may suppress reactions to skin tests. Corticotropin reportedly may affect the method of Brown used for determination of urinary estradiol and estriol causing falsely decreased concentrations of these estrogens; the drug also may interfere with colorimetric/fluorometric procedures for determination of urinary estrogens causing a falsely decreased concentration of urinary estrogens.
Exogenous corticotropin elicits all the pharmacologic responses usually produced by endogenous corticotropin. In patients with normal adrenocortical function, corticotropin stimulates the adrenal cortex to secrete cortisol (hydrocortisone), corticosterone, several weakly androgenic substances, and to a very limited extent aldosterone. In healthy individuals, the rate of release of corticotropin from the anterior pituitary is determined by a balance of inhibitory effects of the secretions of the adrenal cortex on the pituitary (negative corticosteroid feedback mechanism) and the excitatory effects of the nervous system. In response to neurogenic stimuli, corticotropin-releasing factor (CRF) is released from neuronal endings in the median eminence of the hypothalamus and transported in the hypophyseal-portal vessels to the anterior pituitary, where corticotropin is released. Corticotropin, via cyclic 3',5'-adenosine monophosphate (cAMP), controls the initial rate-limiting step in steroidogenesis from cholesterol and leads to the synthesis of adrenocortical hormones. Corticotropin also stimulates growth of the adrenal cortex. In high concentrations, corticotropin may have extra-adrenal effects (i.e., melanocyte stimulation, activation of tissue lipase).
The primary physiologic and pharmacologic effects of corticotropin result from secretion of cortisol, a glucocorticoid which also has some mineralocorticoid activity. The mineralocorticoid effect of cortisol causes sodium retention with resultant edema and hypertension. In pharmacologic concentrations, cortisol decreases inflammation by preventing release of destructive acid hydrolases from leukocytes; inhibiting macrophage accumulation in inflamed areas; reducing leukocyte adhesion to capillary endothelium; reducing capillary wall permeability and edema formation; decreasing complement components; antagonizing histamine activity and release of kinin from substrates; reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation; and possibly by other mechanisms as yet unknown. Cortisol suppresses the immune response by reducing activity and volume of the lymphatic system, producing lymphocytopenia, decreasing complement concentrations, decreasing passage of immune complexes through basement membranes, and possibly by depressing reactivity of tissue to antigen-antibody interactions. Cortisol stimulates erythroid cells of bone marrow, prolongs survival time of erythrocytes and platelets, and produces neutrophilia and eosinopenia. Glucocorticoids promote protein catabolism, gluconeogenesis, and redistribution of fat from peripheral to central areas of the body. They reduce intestinal absorption and increase renal excretion of calcium.
Exogenous administration of corticotropin suppresses endogenous release of corticotropin from the pituitary. If the drug is administered for prolonged periods, the adrenal cortex hypertrophies and the adrenal gland maintains its activity; however, the ability of the hypothalamic-pituitary-adrenal (HPA) axis to respond to stress may be impaired because hypothalamic-pituitary activity may be suppressed. With prolonged therapy, corticotropin may cause HPA axis suppression similar to that produced by suppressive doses of glucocorticoids. Patients receiving prolonged corticotropin therapy may develop cushingoid (hypercorticism) features and respond to stress like patients with primary adrenocortical insufficiency (Addison's disease, hypocorticism). (See Cautions: Precautions and Contraindications.)
Following oral administration, corticotropin is inactivated by the proteolytic enzymes of the GI tract, and the drug is ineffective when applied topically to the skin or eye. Corticotropin injection is rapidly absorbed following IM injection. Following IM administration of repository corticotropin injection, the drug is absorbed over a period of about 8-16 hours. In most adults with normal adrenocortical function, maximal adrenal stimulation is attained after infusing 1-6 units of corticotropin injection IV (no longer commercially available in the US) over a period of 8 hours. With a fixed dose, corticotropin injection stimulates more cortisol secretion if the drug is given slowly IV rather than rapidly or if given IM as the repository injection rather than as corticotropin injection. Increasing the IM or IV dose increases the duration of action. Repeated doses of IV corticotropin injection over an 8-hour period on successive days increase the responsiveness of the adrenal cortex to further stimulation by the drug. Following IM administration of 100 units of corticotropin (as the repository injection) in patients with normal adrenocortical function, approximately 100 mg of cortisol is secreted in 16 hours. Following IM or rapid direct IV administration of 25 units of corticotropin injection in patients with normal adrenocortical function, peak plasma cortisol concentrations are achieved within 1 hour and begin to decrease after 2 hours. In one study in healthy individuals, subcutaneous administration of 80 units of repository corticotropin injection produced peak plasma 17-hydroxycorticosteroid (17-OHCS) concentrations in 3-12 hours and baseline concentrations were attained in 10-25 hours.
In healthy individuals who sleep at night, plasma concentrations of endogenous corticotropin undergo diurnal rhythm and are high in the morning and low in the evening. At rest, normal endogenous plasma concentrations of corticotropin in the morning are 5-95 pg/mL; with activity or stress in persons with normal HPA axis function, plasma concentrations may increase to 200-600 pg/mL.
In the circulation, corticotropin is transported with Cohn protein fractions II and III. The precise distribution and metabolic fate of corticotropin are not known, but the drug is rapidly removed from the plasma by many tissues. Corticotropin apparently does not cross the placenta. Circulating corticotropin may be enzymatically cleaved at the 16-17 lysine-arginine bond by the plasmin-plasminogen system.
Corticotropin is a polypeptide secreted by the basophilic cells of the anterior pituitary (adenohypophysis). The polypeptide, which contains 39 amino acids, has a molecular weight of about 4500. Only the first 24 amino acids (from the N -terminal end of the chain) are required for full biologic activity. The sequence of these 24 amino acids is the same in humans, cows, pigs, and sheep. For commercial use, corticotropin is extracted from the pituitaries of mammals (usually pigs) used for food by humans. The potency of corticotropin is standardized in hypophysectomized rats according to an assay in which depletion of adrenal ascorbic acid is measured; potency is expressed in USP Corticotropin Units. One USP Corticotropin Unit is equivalent to 1 mg of the international standard. For commercial use, corticotropin is available as corticotropin for injection and repository corticotropin injection.
Repository Corticotropin Injection
Repository corticotropin injection, which is corticotropin in a solution of partially hydrolyzed gelatin, occurs as a colorless or light straw-colored liquid, which may be quite viscid at room temperature. Repository corticotropin injection is adjusted to a pH of 3-7 with sodium hydroxide and/or acetic acid and may contain an antimicrobial agent.
Repository Corticotropin Injection
Repository corticotropin injection should be stored at 2-15°C.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IM or subcutaneous use | 80 units/mL | H.P. Acthar® Gel | Questcor |
Only references cited for selected revisions after 1984 are available electronically.
100. Hanauer SB, Sandborn W, and the Practice Parameters Committee of the American College of Gastroenterology. Management of Crohn's disease in adults: Practice Guidelines. Am J Gastroenterol . 2001; 96:635-43 [PubMed 11280528]
101. Chun A, Chadi RM, Korelitz BI et al. Intravenous corticotropin vs. hydrocortisone in the treatment of hospitalized patients with Crohn's disease: a randomized double-blind study and follow-up. Inflamm Bowel Dis . 1998; 4:177-81. [PubMed 9741018]
102. Felder JB, Adler DJ, Korelitz BI. The safety of corticosteroid therapy in Crohn's disease with an abdominal mass. Am J Gastroenterol . 1991; 86:1450-5. [PubMed 1656728]