ACTHAR GEL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACTHAR GEL (ACTHAR GEL).
Stimulates adrenal cortex to secrete cortisol, corticosterone, and aldosterone; also exerts extra-adrenal effects via melanocortin receptors.
| Metabolism | Endogenous corticosteroids are metabolized primarily in the liver via CYP3A4; ACTH itself is degraded by proteolysis. |
| Excretion | Renal metabolism and excretion (primarily as inactive metabolites); <5% unchanged in urine. Biliary/fecal excretion negligible. |
| Half-life | Terminal elimination half-life approximately 2–3 hours for corticotropin component; repository formulation (gel) extends to 15–20 hours due to slow absorption. |
| Protein binding | Corticotropin: low binding (~15–30%) to albumin and corticosteroid-binding globulin (CBG). |
| Volume of Distribution | Approximately 0.4 L/kg (restricted primarily to extracellular fluid); does not significantly penetrate erythrocytes. |
| Bioavailability | IM/SC: near 100% due to repository gel formulation designed for sustained release; oral: not applicable (degraded in GI tract). |
| Onset of Action | IM/SC: 2–6 hours for clinically detectable adrenal stimulation (cortisol rise); IV: rapid (minutes for ACTH effect, but gel not given IV). |
| Duration of Action | Single IM/SC dose: effect on cortisol secretion persists 12–24 hours; intended for daily or every-other-day dosing to mimic circadian rhythm. |
Initial: 40-80 Units intramuscularly or subcutaneously every 24-48 hours; maintenance: 40 Units intramuscularly or subcutaneously every 24-72 hours.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; monitor for fluid retention and hypertension. |
| Liver impairment | No specific adjustment, but caution in severe hepatic impairment due to risk of edema. |
| Pediatric use | Infants and children: 0.2-0.8 Units/kg intramuscularly or subcutaneously daily or divided every 12 hours; maximum 80 Units/day. |
| Geriatric use | Use lowest effective dose; monitor for fluid retention, hypertension, and electrolyte disturbances. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACTHAR GEL (ACTHAR GEL).
| Breastfeeding | ACTHAR GEL is not recommended during breastfeeding due to the potential for serious adverse reactions in the infant, including adrenal suppression. There is no data on the M/P ratio or excretion into human milk. |
| Teratogenic Risk | ACTHAR GEL (repository corticotropin injection) is a natural adrenocorticotropic hormone (ACTH) preparation. Chronic administration can cause maternal adrenal insufficiency. First trimester: Limited human data; animal studies show increased risk of cleft palate, placental insufficiency, and fetal growth restriction at high doses. Second and third trimesters: Prolonged use may lead to fetal adrenal suppression, low birth weight, and premature birth. Overall, the teratogenic risk is considered low with short-term use, but long-term exposure is associated with fetal harm. |
■ FDA Black Box Warning
ACTHAR gel is not recommended for use in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or active peptic ulcer, congestive heart failure, hypertension, or sensitivity to proteins of porcine origin.
| Serious Effects |
Hypersensitivity to ACTH or porcine proteins; scleroderma; osteoporosis; systemic fungal infections; ocular herpes simplex; recent surgery; history of or active peptic ulcer; congestive heart failure; hypertension; administration of live or live attenuated vaccines.
| Precautions | May cause immunosuppression and increase susceptibility to infections; may mask signs of infection. May cause suppression of hypothalamic-pituitary-adrenal (HPA) axis. May cause behavioral and mood disturbances. May cause osteoporosis, growth suppression in children, and Cushing's syndrome with prolonged use. Use caution in patients with diabetes mellitus, hypertension, renal insufficiency, or seizure disorders. |
| Food/Dietary | There are no specific food interactions with ACTHAR Gel. However, due to potential fluid retention and hypertension, patients are advised to follow a low-sodium diet. Grapefruit has no known interaction with ACTHAR Gel. Avoid excessive intake of potassium-rich foods if hypokalemia develops or while on concomitant potassium-depleting diuretics. |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood glucose, blood pressure, and electrolytes regularly. Evaluate for signs of infection, adrenal insufficiency, or Cushing's syndrome. For fetal monitoring, consider serial growth ultrasounds and non-stress tests if prolonged use occurs. Assess neonatal adrenal function if maternal treatment continues near term. |
| Fertility Effects | ACTHAR GEL may disrupt the hypothalamic-pituitary-adrenal (HPA) axis, potentially causing reversible menstrual irregularities or amenorrhea. Suppression of endogenous ACTH can impair ovulation. Fertility may return after discontinuation. |
| Clinical Pearls | ACTHAR Gel (repository corticotropin) is a purified adrenocorticotropic hormone (ACTH) analogue used primarily for infantile spasms and certain autoimmune/inflammatory conditions. It must be administered intramuscularly (IM) or subcutaneously (SQ); it is not for IV use. Monitor for hypersensitivity reactions, including anaphylaxis. Adrenal suppression is a risk; taper dosing gradually. Live vaccines are contraindicated during therapy. Efficacy in infantile spasms is typically assessed by cessation of spasms and EEG normalization within 2 weeks. For MS exacerbations, use short-term (1-3 weeks) with rapid taper. May cause electrolyte imbalances, hypertension, and hyperglycemia; monitor labs regularly. Avoid in patients with systemic fungal infections or recent vaccination. |
| Patient Advice | Shake the vial well before each dose; the gel should be uniform. · Inject exactly as prescribed, usually into a muscle (IM) or under the skin (SQ). · Do not stop suddenly; your doctor will need to taper the dose to avoid withdrawal symptoms such as fatigue, weakness, joint pain, or fever. · Report any signs of infection (fever, sore throat, cough) immediately as this medicine can lower your immune response. · Avoid live vaccines (e.g., MMR, varicella, nasal flu) while on ACTHAR Gel and for at least 1 month after stopping. · Common side effects include increased appetite, insomnia, mood swings, and fluid retention. Contact your doctor if you experience severe headache, vision changes, or swelling in your legs. · Limit salt and sodium intake to help reduce fluid retention. · If you have diabetes, monitor blood sugar levels closely as this medication can raise glucose. · Keep a list of all your medications and supplements, and show it to all healthcare providers. · Do not discontinue without medical advice even if you feel better. |