CORTROPHIN-ZINC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CORTROPHIN-ZINC (CORTROPHIN-ZINC).
Corticotropin (ACTH) stimulates the adrenal cortex to release glucocorticoids, mineralocorticoids, and androgens. In gel formulation, zinc complex prolongs absorption, providing sustained adrenocortical stimulation.
| Metabolism | Corticotropin is a peptide hormone degraded by proteolysis in plasma and tissues. The zinc complex does not alter metabolic pathways; enzymes involved include various peptidases and proteases. |
| Excretion | Renal: ~90% as metabolites; biliary/fecal: ~10% |
| Half-life | Terminal half-life: 16-24 hours; clinical context: prolonged due to zinc complex, allows once-daily dosing |
| Protein binding | ~30% bound to alpha-globulins and albumin |
| Volume of Distribution | 0.4 L/kg; clinical meaning: limited distribution primarily to extracellular fluid |
| Bioavailability | IM/SC: ~100% (complete absorption); no oral bioavailability |
| Onset of Action | IM/SC: 4-6 hours; intravenous not recommended |
| Duration of Action | 24-48 hours; clinical note: duration longer than immediate-release corticotropin due to slow absorption from injection site |
40-80 units subcutaneously or intramuscularly every 24-72 hours, titrated to individual patient response.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment guidelines for renal impairment; use with caution in severe renal disease due to potential fluid retention. |
| Liver impairment | No specific dose adjustment guidelines for hepatic impairment; use with caution in severe hepatic disease as metabolism may be altered. |
| Pediatric use | 0.25-0.5 units/kg subcutaneously or intramuscularly every 24-72 hours, not to exceed adult dose. |
| Geriatric use | Use lower initial doses (e.g., 20-40 units) due to increased sensitivity and risk of adverse effects such as hyperglycemia and immunosuppression. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CORTROPHIN-ZINC (CORTROPHIN-ZINC).
| Breastfeeding | Corticotropin is not expected to be excreted in breast milk in significant amounts; its large molecular weight (~4.5 kDa) and short half-life limit transfer. However, corticosteroids (which ACTH stimulates) are excreted in breast milk. Prednisolone M/P ratio is ~0.1-0.2. Exogenous ACTH administration may lead to elevated endogenous cortisol and potential infant effects. Manufacturer recommends caution or avoid due to lack of data. Use only if clearly needed. |
| Teratogenic Risk | Corticotropin (ACTH) is classified as FDA Pregnancy Category C. In animal studies, corticosteroids (which ACTH stimulates) have been shown to be teratogenic (cleft palate, placental insufficiency) at high doses. Human data are limited; however, systemic corticosteroid use in the first trimester is associated with a small increased risk of oral clefts (absolute risk increase ~0.1-0.2%). Chronic use later in pregnancy may increase risk of intrauterine growth restriction, adrenal suppression in the newborn, and premature rupture of membranes. The risk is dose- and duration-dependent. |
■ FDA Black Box Warning
Corticotropin (ACTH) can suppress the hypothalamic-pituitary-adrenal (HPA) axis, leading to secondary adrenal insufficiency. Prolonged use may cause irreversible adrenal atrophy. Gradual withdrawal is essential. Do not abruptly discontinue.
| Serious Effects |
Hypersensitivity to corticotropin or zinc, adrenocortical insufficiency, active fungal infections, recent vaccination with live vaccines, congestive heart failure, peptic ulcer disease, severe hypertension, herpes simplex keratitis, and primary adreocortical insufficiency (Addison's disease).
| Precautions | May cause HPA axis suppression, Cushing's syndrome, increased susceptibility to infections, masking of signs of infection, exacerbation of psychiatric disorders, hypertension, electrolyte disturbances, osteoporosis, impaired growth in children, and myopathy. |
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| Fetal Monitoring | Monitor maternal blood pressure, blood glucose, serum electrolytes, and signs of infection. Fetal monitoring includes serial growth ultrasound to detect intrauterine growth restriction. Newborn should be monitored for adrenal insufficiency (hypoglycemia, hypotension, jaundice) if mother received prolonged therapy. |
| Fertility Effects | Corticotropin may alter gonadotropin secretion via ACTH-mediated cortisol elevation, potentially suppressing GnRH and leading to menstrual irregularities, anovulation, and impaired fertility. Reversible upon discontinuation. No known irreversible effects on fertility. |