ACTHAR GEL (AUTOINJECTOR)
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACTHAR GEL (AUTOINJECTOR) (ACTHAR GEL (AUTOINJECTOR)).
ACTHAR Gel (repository corticotropin injection) acts primarily by stimulating the adrenal cortex to secrete corticosteroids (cortisol, corticosterone, and aldosterone), which exert anti-inflammatory, immunosuppressive, and antiproliferative effects. The exact mechanism in specific indications (e.g., infantile spasms) is not fully understood but may involve modulation of the hypothalamic-pituitary-adrenal axis and direct effects on the central nervous system.
| Metabolism | Corticotropin (ACTH) is a polypeptide hormone; its metabolic pathway is primarily via proteolytic degradation in plasma and tissues by peptidases and endopeptidases. The half-life is approximately 15 minutes. The exogenous formulation (ACTHAR Gel) is designed for prolonged release, but the active component undergoes similar catabolism. |
| Excretion | ACTH (corticotropin) is metabolized by tissue peptidases; renal excretion accounts for <5% of unchanged drug. Biliary/fecal elimination is negligible. |
| Half-life | The terminal half-life of exogenously administered ACTH is approximately 15 minutes; however, the duration of adrenal cortisol stimulation persists for 6-12 hours after IM administration due to prolonged absorption from the gel formulation. |
| Protein binding | Approximately 15-25% bound to plasma proteins, primarily to alpha2-macroglobulin and albumin. Binding is low and not therapeutically significant. |
| Volume of Distribution | Approximately 0.2-0.4 L/kg, reflecting distribution primarily to extracellular fluid. The Vd is small, consistent with a peptide hormone that remains largely in the vascular space. |
| Bioavailability | IM: 100% (complete absorption from the gel formulation). Not administered IV due to formulation; absorption from subcutaneous injection is variable and not recommended. |
| Onset of Action | IM: Therapeutic effect (increased cortisol production) begins within 2-4 hours; maximal cortisol response is observed at 6-8 hours. |
| Duration of Action | IM: Adrenal suppression (or stimulated cortisol secretion) may last 6-12 hours after a single dose, but the gel formulation prolongs effects to approximately 24-48 hours in some clinical settings (e.g., infantile spasms). Repeated daily dosing leads to sustained adrenal stimulation. |
Initial: 40-80 units intramuscularly or subcutaneously every 24-48 hours; maintenance: 20-40 units intramuscularly or subcutaneously every 48 hours. Titrate based on response.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment due to risk of fluid retention and hypertension. |
| Liver impairment | No specific dose adjustment; use with caution in hepatic impairment due to potential for altered metabolism and adverse effects. |
| Pediatric use | Not established for ACTHAR GEL autoinjector; individualize based on weight and condition, typically starting at 0.5-1 unit/kg IM or SC every 24-48 hours. |
| Geriatric use | Initiate at lower end of dosing range; monitor for fluid retention, hypertension, and electrolyte imbalances due to increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACTHAR GEL (AUTOINJECTOR) (ACTHAR GEL (AUTOINJECTOR)).
| Breastfeeding | Corticosteroids pass into breast milk. ACTHAR GEL (corticotropin) has no specific M/P ratio data. At maternal doses up to 80 mg prednisone equivalent, amount in milk is low; however, monitor infant for adrenal suppression if mother on high doses. |
| Teratogenic Risk | First trimester: Corticosteroids are associated with a small increased risk of oral clefts. Second/third trimester: Chronic use may cause fetal adrenal suppression, intrauterine growth restriction, and premature rupture of membranes. Risk is dose-dependent. |
■ FDA Black Box Warning
ACTHAR Gel is not indicated for long-term use or for conditions other than those specified. Prolonged use may lead to adverse effects such as immunosuppression, hypothalamic-pituitary-adrenal axis suppression, and Cushing's syndrome. Live or live attenuated vaccines are contraindicated in patients receiving immunosuppressive doses of ACTHAR Gel. There is an increased risk of severe or fatal infections in immunocompromised patients. Because of the risk of serious adverse events, ACTHAR Gel should be reserved for patients who have not responded to or cannot tolerate other therapies for multiple sclerosis exacerbations.
| Serious Effects |
["Hypersensitivity to corticotropin or any component of the formulation (including porcine gelatin)","Administration of live or live attenuated vaccines in patients receiving immunosuppressive doses","Systemic fungal infections","Scleroderma and osteoporosis (relative contraindication due to risk of exacerbation)","Ocular herpes simplex (due to risk of corneal perforation)","Congestive heart failure and hypertension (relative contraindication due to mineralocorticoid effects)","Recent surgery or history of peptic ulcer disease (relative contraindication due to increased risk of GI perforation/bleeding)"]
| Precautions | ["Immunosuppression and increased risk of infections, including reactivation of latent infections (e.g., tuberculosis, hepatitis B, herpes simplex)","Hypothalamic-pituitary-adrenal axis suppression, potentially leading to adrenal insufficiency after withdrawal","Cushingoid symptoms with prolonged use (moon face, striae, weight gain, hypertension, osteoporosis)","Exacerbation of comorbid conditions such as diabetes mellitus, congestive heart failure, and hypertension due to mineralocorticoid effects","Gastrointestinal perforation or bleeding, especially in patients with peptic ulcer disease or inflammatory bowel disease","Psychiatric disturbances including euphoria, insomnia, mood swings, depression, and psychosis","Ocular effects including increased intraocular pressure, glaucoma, and cataracts","Growth suppression in pediatric patients with prolonged use","Rapid weight gain and fluid retention","Allergic reactions to porcine gelatin (the product is derived from porcine pituitary)","Use with caution in patients with recent myocardial infarction, renal insufficiency, hypothyroidism, cirrhosis, or thromboembolic disorders"] |
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| Fetal Monitoring |
| Monitor maternal blood pressure, blood glucose, weight gain, and signs of infection. Fetal monitoring for growth restriction via serial ultrasound. Assess fetal adrenal function if maternal therapy prolonged. |
| Fertility Effects | Corticosteroids may impair fertility by suppressing hypothalamic-pituitary-gonadal axis. Reversible upon dose reduction or discontinuation. |
| Food/Dietary | Grapefruit/grapefruit juice may increase ACTH levels; avoid concurrent use. High-sodium foods may exacerbate fluid retention and hypertension; patients should follow a low-sodium diet if advised. Alcohol may worsen gastrointestinal side effects (e.g., ulcer risk). |
| Clinical Pearls | ACTHAR Gel (repository corticotropin injection) is a purified preparation of adrenocorticotropic hormone (ACTH) used primarily for infantile spasms in infants under 2 years and for exacerbations of multiple sclerosis in adults. It must be administered intramuscularly or subcutaneously; the autoinjector is for subcutaneous use only. Monitor for adrenal suppression, hypertension, hyperglycemia, and increased susceptibility to infections. Do not withdraw therapy abruptly; taper dose to avoid acute adrenal insufficiency. Live vaccines are contraindicated during therapy. |
| Patient Advice | ACTHAR Gel is given as an injection under the skin (subcutaneously) using an autoinjector. Do not use if the gel appears cloudy or contains particles. · Store the autoinjector in the refrigerator (2-8°C/36-46°F) and protect from light. Do not freeze. · Report any signs of infection (fever, sore throat), mood changes, or swelling of the face/ankles immediately. · Do not receive live vaccines (e.g., MMR, varicella) during treatment. · Carry a medical alert card indicating you are on corticosteroid therapy. |