Corticotropin

Pronunciation

(kor ti koe TROE pin)

Index Terms

• ACTH
• Acthar
• Adrenocorticotropic Hormone
• Corticotropin, Repository
• Repository Corticotropin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Gel, Injection:

Acthar HP: 80 units/mL (5 mL [DSC])

HP Acthar: 80 units/mL (5 mL) [contains phenol]

Brand Names: U.S.

• Acthar HP [DSC]
• HP Acthar

Pharmacologic Category

• Corticosteroid, Systemic

Pharmacology

Stimulates the adrenal cortex to secrete adrenal steroids (including cortisol), weakly androgenic substances, and aldosterone

Absorption

IM: Over 8-16 hours

Excretion

Urine

Onset of Action

Maximum effect: Cortisol serum concentration: IM, SubQ: 3-12 hours

Duration of Action

Repository: 10-25 hours, up to 3 days

Half-Life Elimination

ACTH: 15 minutes

Use: Labeled Indications

Collagen diseases: Treatment of exacerbations or as maintenance therapy of systemic lupus erythematosus, or systemic dermatomyositis (polymyositis).

Dermatologic diseases: Treatment of severe erythema multiforme or Stevens-Johnson syndrome.

Diuresis in nephrotic syndrome: To induce a diuresis or remission of proteinuria in patients with nephrotic syndrome without idiopathic uremia or due to lupus erythematosus.

Infantile spasms: Treatment of infantile spasms in infants and children younger than 2 years.

Multiple sclerosis: Treatment of acute exacerbations of multiple sclerosis in adults.

Ophthalmic diseases: Treatment of severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa (eg, keratitis, iritis, iridocyclitis, diffuse posterior uveitis, choroiditis, optic neuritis, chorioretinitis, anterior segment inflammation).

Rheumatic disorders: As adjunctive therapy for acute episodes/exacerbations of psoriatic arthritis, rheumatoid arthritis, including juvenile rheumatoid arthritis (select cases may require low-dose maintenance therapy) and/or ankylosing spondylitis.

Serum sickness: Treatment of serum sickness.

Symptomatic sarcoidosis: Treatment of symptomatic sarcoidosis.

Use: Unlabeled

Relief of the signs and symptoms of acute gout in patients unable to take oral medications

Contraindications

Hypersensitivity to proteins of porcine origin, scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, peptic ulcer, recent surgery, congestive heart failure (CHF), uncontrolled hypertension, primary adrenocortical insufficiency, adrenocortical hyperfunction, infants with suspected congenital infections, coadministration of live or live attenuated vaccines, IV administration

Dosing: Adult

Note: Sudden withdrawal may lead to adrenal insufficiency or recurrent symptoms; tapering the dose prior to discontinuation may be necessary following prolonged administration.

Acute exacerbation of multiple sclerosis: IM, SubQ: 80 to 120 units/day for 2 to 3 weeks

All other indications: IM, SubQ: 40 to 80 units every 24 to 72 hours

Acute gout (off-label use): SubQ: Initial: 25 to 40 units; may repeat as clinically indicated (ACR guidelines [Khanna, 2012])

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Sudden withdrawal may lead to adrenal insufficiency or recurrent symptoms; tapering the dose prior to discontinuation may be necessary following prolonged administration.

Infantile spasms: Infants and Children <2 years: IM: 75 units/m²/dose twice daily for 2 weeks; followed by a gradual taper over a 2-week period. One suggested taper: 30 units/m²/dose in the morning for 3 days, then 15 units/m²/dose in the morning for 3 days, then 10 units/m²/dose in the morning for 3 days, then 10 units/m²/dose every other morning for 6 days.

All other indications: Children >2 years and Adolescents: IM, SubQ: Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in manufacturer's labeling; use with caution.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer's labeling; use with caution in cirrhosis.

Administration

For IM or SubQ use; do not administer IV. Warm gel to room temperature before administration. Do not over-pressurize vial prior to withdrawing product.

Dietary Considerations

May require increased dietary or supplemental intake of potassium; may require decreased dietary intake of sodium.

Storage

Store in the refrigerator at 2°C to 8°C (36°F to 46°F).

Drug Interactions

Acetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Monitor therapy

Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid combination

Amphotericin B: Corticosteroids (Systemic) may enhance the hypokalemic effect of Amphotericin B. Monitor therapy

Androgens: Corticosteroids (Systemic) may enhance the fluid-retaining effect of Androgens. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Aprepitant: May increase the serum concentration of Corticosteroids (Systemic). Management: No dose adjustment is needed for single 40 mg aprepitant doses. For other regimens, reduce oral dexamethasone or methylprednisolone doses by 50%, and IV methylprednisolone doses by 25%. Antiemetic regimens containing dexamethasone reflect this adjustment. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Calcitriol (Systemic): Corticosteroids (Systemic) may diminish the therapeutic effect of Calcitriol (Systemic). Monitor therapy

Ceritinib: Corticosteroids may enhance the hyperglycemic effect of Ceritinib. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Corticosteroids (Systemic). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Corticosteroids (Systemic). Monitor therapy

Deferasirox: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Deferasirox: Corticosteroids may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Desirudin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Desirudin. More specifically, corticosteroids may increase hemorrhagic risk during desirudin treatment. Management: Discontinue treatment with systemic corticosteroids prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Consider therapy modification

DiltiaZEM: May increase the serum concentration of Corticosteroids (Systemic). Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Estrogen Derivatives: May increase the serum concentration of Corticosteroids (Systemic). Monitor therapy

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosaprepitant: May increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. Consider therapy modification

Hyaluronidase: Corticosteroids may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

Indacaterol: May enhance the hypokalemic effect of Corticosteroids (Systemic). Monitor therapy

Indium 111 Capromab Pendetide: Corticosteroids (Systemic) may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Avoid combination

Isoniazid: Corticosteroids (Systemic) may decrease the serum concentration of Isoniazid. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Loop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

MiFEPRIStone: May diminish the therapeutic effect of Corticosteroids (Systemic). MiFEPRIStone may increase the serum concentration of Corticosteroids (Systemic). Management: Avoid mifepristone in patients who require long-term corticosteroid treatment of serious illnesses or conditions (e.g., for immunosuppression following transplantation). Corticosteroid effects may be reduced by mifepristone treatment. Avoid combination

Mitotane: May decrease the serum concentration of Corticosteroids (Systemic). Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Neuromuscular-Blocking Agents (Nondepolarizing): May enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Consider therapy modification

Nicorandil: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nicorandil. Gastrointestinal perforation has been reported in association with this combination. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

NSAID (COX-2 Inhibitor): Corticosteroids (Systemic) may enhance the adverse/toxic effect of NSAID (COX-2 Inhibitor). Monitor therapy

NSAID (Nonselective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of NSAID (Nonselective). Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Quinolone Antibiotics: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Quinolone Antibiotics. Specifically, the risk of tendonitis and tendon rupture may be increased. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Salicylates: May enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Telaprevir: Corticosteroids (Systemic) may decrease the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Corticosteroids (Systemic). Management: Concurrent use of telaprevir and systemic corticosteroids is not recommended. When possible, consider alternatives. If used together, employ extra caution and monitor closely for excessive corticosteroid effects and diminished telaprevir effects. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Urea Cycle Disorder Agents: Corticosteroids (Systemic) may diminish the therapeutic effect of Urea Cycle Disorder Agents. More specifically, Corticosteroids (Systemic) may increase protein catabolism and plasma ammonia concentrations, thereby increasing the doses of Urea Cycle Disorder Agents needed to maintain these concentrations in the target range. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Consider therapy modification

Warfarin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Warfarin. Monitor therapy

Test Interactions

May suppress the wheal and flare reactions to skin test antigens

Adverse Reactions

Frequency not always defined. Adverse events associated with infantile spasm treatment unless otherwise indicated. Other adverse events associated with corticosteroids may also occur.

Cardiovascular: Hypertension (11%), cardiac hypertrophy (3%), increased blood pressure (associated with cortisol elevation)

Central nervous system: Seizure (12%), irritability (7%), behavioral changes (associated with cortisol elevation), mood changes (associated with cortisol elevation)

Endocrine & metabolic: Cushingoid state (3%), decreased glucose tolerance (associated with cortisol elevation), fluid retention (associated with cortisol elevation)

Gastrointestinal: Decreased appetite (3%), diarrhea (3%), vomiting (3%), weight gain (1%; associated with cortisol elevation), increased appetite (associated with cortisol elevation)

Infection: Infection (20%)

Respiratory: Nasal congestion (1%)

Miscellaneous: Fever (5%)

<1% (Limited to important or life-threatening): Abdominal distention, carbohydrate intolerance (infants), cardiac failure, diaphoresis (adults), epidermal thinning (adults), facial erythema, headache (adults), hirsutism, hypersensitivity reaction, hypokalemic alkalosis (infants), intracranial hemorrhage (adults), myasthenia, necrotizing angiitis (adults), pancreatitis (adults), reversible cerebral atrophy (infants; secondary to hypertension), subdural hematoma, ulcerative esophagitis, vertebral compression fracture (infants), vertigo (adults)

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal suppression: May cause hypercorticism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Symptoms of adrenal insufficiency may be difficult to detect in infants treated for infantile spasms.

• Electrolyte disturbances: May increase retention of sodium and wasting of calcium and potassium; sodium restriction and/or potassium supplementation may be required.

• Hypersensitivity reactions: Antibodies may develop following prolonged use and increase the risk of hypersensitivity reactions.

• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Close observation is required in patients with latent tuberculosis (TB) and/or TB reactivity; if therapy is prolonged, prophylaxis should be started.

• Psychiatric disturbances: Corticosteroids may cause psychiatric disturbances, including depression, euphoria, insomnia, irritability (especially in infants), mood swings, personality changes, and psychotic manifestations. Preexisting psychiatric conditions (eg, emotional instability, psychotic tendencies) may be exacerbated by corticosteroid use.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients hypertension; use has been associated with fluid retention and hypertension; use is contraindicated with uncontrolled hypertension or congestive heart failure (CHF).

• Diabetes: Use with caution in patients with diabetes mellitus; may alter glucose production/regulation leading to hyperglycemia.

• Gastrointestinal disease: Use with caution in patients with GI disease (diverticulitis, ulcerative colitis, risk of impending perforation, fresh intestinal anastomoses) or abscess/pyogenic infections due to risk of gastric ulcer, GI perforation, and GI bleeding; use is contraindicated with peptic ulcer disease.

• Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms has occurred, especially during initial treatment with corticosteroids.

• Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged corticosteroid use. Consider routine eye exams in chronic users. Contraindicated in patients with ocular herpes simplex.

• Osteoporosis: Use with caution in patients of any age at risk for osteoporosis; high doses and/or long-term use of corticosteroids have been associated with increased bone loss and osteoporotic fractures. Use is contraindicated in patients with osteoporosis.

• Renal impairment: Use with caution in patients with renal impairment; fluid retention may occur.

• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones.

Special populations:

• Pediatric: May affect growth velocity; growth should be routinely monitored in pediatric patients.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Vaccines: Concomitant use of live or live attenuated vaccines is contraindicated; use caution with inactivated vaccines (response may be variable).

Other warnings/precautions:

• Discontinuation of therapy: Withdraw therapy with gradual tapering of dose.

Monitoring Parameters

Blood pressure, cardiac function, weight; serum glucose, electrolytes; signs of adrenal insufficiency; signs of Cushing’s syndrome; secondary ocular infections

Following prolonged use: Bone mass density, growth in children, signs and symptoms of infection, cataract formation

Following discontinuation: Signs of infection, cardiac function, blood pressure, serum glucose, body weight, fecal blood

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Endogenous corticotropin concentrations are increased near delivery (Smith, 2007).

Some studies have shown an association between first trimester systemic corticosteroid use and oral clefts (Park-Wyllie, 2000; Pradat, 2003). Systemic corticosteroids may also influence fetal growth (decreased birth weight); however, information is conflicting (Lunghi, 2010). When systemic corticosteroids are needed in pregnancy, it is generally recommended to use the lowest effective dose for the shortest duration of time, avoiding high doses during the first trimester (Leachman, 2006; Lunghi, 2010; Makol, 2011; Østensen, 2009).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience signs of skin changes (acne, stretch marks, slow healing, or hair growth), diarrhea, or insomnia. Have patient report immediately to prescriber signs of infection; signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit); difficulty breathing; bruising; bleeding; abdominal pain; black, tarry, or bloody stools; vomiting blood; excessive weight gain or loss; vision changes; severe headache; severe dizziness; passing out; confusion; depression; mood changes; severe loss of strength and energy; injection site pain or irritation; seizures; muscle pain; muscle weakness; change in body fat; or weak bones (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.