Corticotropin Disease Interactions

In patients with latent tuberculosis or tuberculin reactivity, the use of pharmacologic dosages of adrenocorticotropic agents may cause a reactivation of the disease. Close monitoring for signs and symptoms of tuberculosis is recommended if adrenocorticotropic therapy is administered to these patients. During prolonged use, tuberculosis chemoprophylaxis may be considered.

The use of adrenocorticotropic agents is contraindicated in patients with primary adrenocortical insufficiency because of the lack of adrenal responsiveness.

Adrenocorticotropic agents may cause hypernatremia, hypokalemia, hypocalcemia, and fluid retention. Therapy with these agents, particularly if intended for longer than brief periods, should be administered cautiously in patients with preexisting electrolyte disturbances. Caution is also advised when treating patients with seizure disorders, since electrolyte disturbances may trigger seizure activity.

Adrenocorticotropic agents may cause hypernatremia, hypokalemia, fluid retention, and elevation in blood pressure. Therapy with these agents, particularly if intended for longer than brief periods, should be administered cautiously in patients with preexisting fluid retention or conditions that may be aggravated by these effects. Dietary sodium restriction and potassium supplementation may be advisable. The manufacturers consider the use of adrenocorticotropic agents to be contraindicated in patients with congestive heart failure or uncontrolled hypertension.

Adrenocorticotropic agents may cause gastrointestinal perforation and hemorrhage, usually when given in high dosages or for prolonged periods. They may also mask symptoms of complications such as peritonitis or intraabdominal sepsis. Therapy with adrenocorticotropic agents should be administered cautiously in patients with diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), or recent intestinal anastomoses.

The use of adrenocorticotropic agents is contraindicated in patients with adrenocortical hyperfunction. These agents stimulate the release of cortisol and aldosterone and may aggravate symptoms of hyperadrenocorticism.

The immunosuppressant and anti-inflammatory effects of adrenocorticotropic agents, particularly in higher dosages, may decrease host resistance to infectious agents, decrease the ability to localize infections, and mask the symptoms of infection. Secondary infections may be more likely to develop. In general, adrenocorticotropic agents should not be used in patients with active infections, especially systemic fungal infections, unless they are medically necessary and effective antimicrobial therapy or other appropriate treatment has been instituted. For patients who have received prolonged adrenocorticotropic therapy who develop a severe or life-threatening infection, supplemental doses of rapid-acting corticosteroids may be required, since these patients may have hypothalamic-pituitary insufficiency.

Adrenocorticotropic agents should be used cautiously, if at all, in patients with ocular herpes simplex because of the risk of corneal perforation. The manufacturers consider their use to be contraindicated in such setting.

Adrenocorticotropic agents inhibit the absorption of intestinal calcium and increase urinary excretion of calcium, which can result in bone resorption and bone loss during prolonged therapy. In addition, bone matrix may be affected by the protein-catabolic effects of these agents, especially when given in high dosages or for prolonged periods, leading to aseptic necrosis and fractures. Long-term or high-dose adrenocorticotropic therapy should be administered cautiously and only if necessary in patients with or at risk for osteoporosis. The manufacturers consider the use of adrenocorticotropic agents to be contraindicated in such setting.

Adrenocorticotropic agents may cause peptic ulcer disease and gastrointestinal (GI) hemorrhage, usually when given in high dosages or for prolonged periods. Delayed healing of peptic ulcers has also been reported. Therapy with adrenocorticotropic agents, if necessary, should be administered cautiously in patients with active or latent peptic ulcers or other risk factors for GI bleeding. The manufacturers consider their use to be contraindicated in such setting.

The use of adrenocorticotropic agents is contraindicated in patients with scleroderma. Adrenocorticotropic agents may precipitate renal crisis with malignant hypertension in these patients, possibly via steroid-induced increases in renin substrate and angiotensin II levels and decreases in vasodilator prostaglandin production. Renal failure may ensue. If treatment is required for inflammatory myositis or pericarditis, glucocorticoids are preferable because of their more predictable pharmacologic effect. However, glucocorticoids should also be avoided in the long-term treatment of patients with scleroderma for similar reasons.

The administration of live or live, attenuated vaccines is contraindicated in patients receiving large or immunosuppressive doses of adrenocorticotropic agents. Inactivated viral or bacterial vaccines should be used with caution, since their administration may pose a risk of neurological complications in these patients. Additionally, a diminished or inadequate serum antibody response may be anticipated.

Adrenocorticotropic agents may have enhanced effects in patients with cirrhosis. Dosage adjustments may be necessary in these patients.

Adrenocorticotropic agents may aggravate the symptoms of psychosis and emotional instability. Patients with these conditions should be monitored for increased or worsened symptoms during adrenocorticotropic therapy.

Adrenocorticotropic agents may impair glucose tolerance and cause hyperglycemia. Therapy with these agents should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during adrenocorticotropic therapy, and their antidiabetic regimen adjusted accordingly.

Prolonged use of adrenocorticotropic agents may cause elevated intraocular pressure and glaucoma with possible damage to the optic nerves. Long-term therapy with these agents should be administered cautiously in patients with preexisting glaucoma (particularly open-angle glaucoma) or increased intraocular pressure.

Adrenocorticotropic agents may have enhanced effects in patients with hypothyroidism. Dosage adjustments may be necessary in these patients.

While corticotropin has been used effectively in severe, refractory myasthenia gravis to increase muscle strength, it should nevertheless be administered with extreme caution in such setting. Patients must be treated in an intensive care unit and receive respiratory support, since muscle strength will markedly decrease initially. Improvement usually occurs several days after the first or second course of treatment. Similar responses might be expected of other adrenocorticotropic agents, although their use in myasthenia gravis has not been studied extensively.

Toxic myopathy may occur with the prolonged use of adrenocorticotropic agents, often in patients with disorders of neuromuscular transmission such as myasthenia gravis or in patients receiving neuromuscular blocking agents. Steroid myopathy is generalized and sometimes accompanied by respiratory weakness and dyspnea. In some cases, it has resulted in quadraparesis. Elevations of creatine kinase may also occur, albeit infrequently. After withdrawal of ACTH therapy, recovery may be slow and incomplete. Therapy with adrenocorticotropic agents should be administered cautiously in patients with preexisting myopathy or myoneural disorders, since these conditions may confound the diagnosis of steroid-induced myopathy. The presence of a normal serum CK level, minimal or no changes of myopathy on EMG, and type 2 muscle fiber atrophy on biopsy are helpful in suggesting steroid-induced weakness. If steroid myopathy is suspected, a dosage reduction or discontinuation of adrenocorticotropic therapy should be considered.

Adrenocorticotropic agents may increase blood coagulability and have rarely been associated with the development of intravascular thrombosis, thromboembolism, and thrombophlebitis. These agents should be used cautiously in patients with thrombotic or thromboembolic disorders.