Corticotropin

Usage

Corticotropin, also known as adrenocorticotropic hormone (ACTH), is prescribed for various medical conditions, including:

• Infantile spasms (West syndrome): This is the primary FDA-approved indication for corticotropin.
• Multiple sclerosis (MS) exacerbations: Corticotropin can help manage acute flare-ups in adults.
• Diagnosis of adrenal insufficiency: It is used to assess adrenal gland function.
• Other conditions: Though not always FDA-approved, corticotropin is sometimes used for nephrotic syndrome, rheumatic disorders, collagen diseases, dermatological conditions, allergic states, ophthalmic diseases, respiratory illnesses, and edematous states.

Pharmacological classification: Corticotropin is classified as a corticotropin-releasing factor agonist, meaning it mimics the action of the naturally occurring hormone corticotropin-releasing hormone (CRH). It’s also categorized as an endocrine drug, a hormone, and more specifically, a pituitary hormone.

Mechanism of action: Corticotropin stimulates the adrenal cortex to produce and release corticosteroids, primarily cortisol (a glucocorticoid), aldosterone (a mineralocorticoid), and androgens.

Alternate Names

• Corticotrophin
• ACTH
• Adrenocorticotropic hormone

Brand names:

• H.P. Acthar® Gel
• Purified Cortrophin® Gel

How It Works

Pharmacodynamics: Corticotropin exerts its effects by binding to melanocortin 2 receptors (MC2R) in the adrenal cortex, initiating a cascade of intracellular events leading to steroidogenesis. Cortisol has widespread effects, including regulation of metabolism, immune responses, and stress responses. Aldosterone regulates sodium and potassium balance, affecting blood pressure. Androgens have various roles in development and sexual function.

Pharmacokinetics:

• Absorption: Corticotropin is administered intramuscularly (IM) or subcutaneously (SC). The repository gel formulation provides sustained release.
• Metabolism: Primarily occurs in the liver and kidneys. The natural hormone has a short half-life (around 15 minutes).
• Elimination: Metabolites are excreted mainly in the urine.

Mode of Action (Cellular/Molecular): Corticotropin binds to MC2R, activating adenylate cyclase, which increases intracellular cyclic adenosine monophosphate (cAMP). cAMP activates protein kinase A, leading to phosphorylation of various proteins involved in cholesterol transport and steroid hormone synthesis.

Receptor Binding: MC2R in the adrenal cortex.

Elimination Pathways: Primarily renal excretion of metabolites.

Dosage

Standard Dosage

Adults:

• Verification of adrenal function: 40–80 units IM/SC every 24–72 hours.
• MS exacerbations: 80–120 units IM/SC daily for 2–3 weeks. Tapering may be necessary.
• Other conditions: 40–80 units IM/SC every 24–72 hours. Dosage is individualized based on the specific condition and patient response. Tapering is often required.

Children:

• Infantile spasms: 150 units/m² per day divided into two equal IM doses for 2 weeks. A tapering schedule is essential after the initial 2 weeks. Pediatric use should be determined by a specialist, and safety needs close monitoring.

Special Cases:

• Elderly patients: Careful monitoring for adverse effects. Dosage adjustments might be needed.
• Patients with renal impairment: No specific guidelines but dose adjustments may be considered based on clinical assessment.
• Patients with hepatic dysfunction: No specific guidelines but dose adjustments may be considered based on clinical assessment.
• Patients with comorbid conditions: Careful assessment and monitoring are crucial. Adjust dosages accordingly.

Clinical Use Cases

Dosing is highly individualized based on the specific clinical context and patient response.

• Intubation: Not typically used.
• Surgical procedures: Not typically used.
• Mechanical ventilation: Not typically used.
• ICU use: Not typically used, unless specifically indicated for an underlying condition.
• Emergency situations: Not typically used.

Dosage Adjustments

Individualize and adjust the dosage based on patient-specific factors such as age, disease severity, response to therapy, and the presence of comorbidities. Monitor renal and hepatic function and adjust accordingly. Metabolic disorders and genetic polymorphisms affecting drug metabolism should be considered when determining the appropriate dose.

Side Effects

Common Side Effects

• Injection site reactions (pain, swelling, bruising)
• Fluid retention
• Changes in mood or behavior (irritability, depression)
• Insomnia
• Acne
• Hirsutism
• Increased appetite
• Weight gain

Rare but Serious Side Effects

• Infections
• Peptic ulcers
• Hypertension
• Hyperglycemia
• Osteoporosis
• Adrenal suppression
• Cushing’s syndrome
• Psychiatric disturbances
• Vision problems
• Seizures
• Pancreatitis
• Hypokalemia

Long-Term Effects

• Growth retardation in children
• Cataracts
• Glaucoma
• Osteoporosis
• Immunosuppression
• Adrenal insufficiency

Adverse Drug Reactions (ADR)

• Anaphylaxis
• Severe hypertension
• Cardiac arrhythmias
• Severe psychiatric reactions

Contraindications

• Hypersensitivity to corticotropin or porcine proteins
• Systemic fungal infections
• Ocular herpes simplex
• Scleroderma
• Osteoporosis
• Active peptic ulcer
• Uncontrolled hypertension
• Congestive heart failure
• Recent surgery
• Infants under 2 years with suspected congenital infections
• Concomitant live or live-attenuated vaccines with immunosuppressive doses

Drug Interactions

Corticotropin interacts with many medications. Consult a comprehensive drug interaction database for a complete list. Some clinically relevant interactions include:

• Immunosuppressants: Increased risk of infection.
• Live vaccines: Reduced vaccine efficacy and increased risk of infection.
• Diuretics: Increased risk of hypokalemia.
• Antidiabetic agents: Hyperglycemia.
• Anticoagulants: Altered anticoagulant effect.

Pregnancy and Breastfeeding

• Pregnancy: Pregnancy Category C. There is evidence of teratogenic effects in animal studies. Use only if the potential benefit justifies the potential risk to the fetus.
• Breastfeeding: Unknown if excreted in human milk. Decision to discontinue breastfeeding or the drug should be made considering the risks and benefits.

Drug Profile Summary

• Mechanism of Action: Stimulates adrenal cortex to release corticosteroids.
• Side Effects: Fluid retention, mood changes, insomnia, infections, peptic ulcers, hypertension, osteoporosis.
• Contraindications: Hypersensitivity, systemic fungal infections, ocular herpes, active peptic ulcer, uncontrolled hypertension, heart failure.
• Drug Interactions: Immunosuppressants, live vaccines, diuretics.
• Pregnancy & Breastfeeding: Use with caution. Weigh risks and benefits.
• Dosage: Individualized based on indication and patient factors.
• Monitoring Parameters: Blood pressure, electrolytes, blood glucose, cortisol levels, signs of infection, growth in children (if applicable), ophthalmic exams for long-term use.

Popular Combinations

Not typically used in combination therapies for long-term management. Short-term co-administration with other medications is determined based on the specific indication and patient’s comorbidities.

Precautions

• Pre-screening for allergies, metabolic disorders, infections, and relevant organ dysfunction is essential.
• Careful monitoring of patients with hypertension, diabetes, gastrointestinal disorders, psychiatric conditions, osteoporosis risk factors, and thyroid disease is necessary.
• Pregnant women: Use only if potential benefit justifies potential risk to the fetus.
• Breastfeeding mothers: Consider risks and benefits to both mother and infant.
• Children and elderly: Monitor for growth retardation (children) and adverse effects. Adjust dosage accordingly.
• Lifestyle considerations: Limit alcohol intake. Monitor dietary intake and weight.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Corticotropin?

A: Dosage is individualized based on the indication and patient factors. Standard adult doses range from 40–120 units IM/SC, while pediatric dosing for infantile spasms is 150 units/m² per day, divided into two doses.

Q2: What are the common side effects?

A: Common side effects include fluid retention, mood swings, insomnia, increased appetite, weight gain, and injection site reactions.

Q3: What are the serious side effects?

A: Serious side effects include infections, peptic ulcers, hypertension, hyperglycemia, adrenal suppression, osteoporosis, Cushing’s syndrome, psychiatric disturbances, vision problems, and seizures.

Q4: What are the contraindications for Corticotropin?

A: Contraindications include hypersensitivity to the drug or porcine proteins, systemic fungal infections, ocular herpes simplex, recent surgery, uncontrolled hypertension, active peptic ulcer, and congestive heart failure.

Q5: How should Corticotropin be administered?

A: Corticotropin repository gel is administered via IM or SC injection. The solution formulation can be administered IM, IV, or SC. The intravenous route is primarily used for diagnostic testing.

Q6: What are the key monitoring parameters during Corticotropin therapy?

A: Monitor blood pressure, electrolytes, blood glucose, cortisol levels, and signs of infection. Long-term therapy necessitates regular ophthalmologic examinations. For pediatric patients, growth parameters require careful observation.

Q7: Is Corticotropin safe during pregnancy and breastfeeding?

A: Corticotropin is a Pregnancy Category C drug, indicating potential fetal risk. It should be used during pregnancy only if the potential benefit justifies the risk. Its safety during breastfeeding is unknown, and the decision to continue or discontinue breastfeeding or the drug should be carefully considered.

Q8: What are the potential long-term consequences of Corticotropin use?

A: Long-term use can lead to iatrogenic Cushing’s syndrome, adrenal suppression, osteoporosis, cataracts, glaucoma, immunosuppression, and growth retardation in children.

Q9: What is the role of Corticotropin in diagnosing adrenal insufficiency?

A: Corticotropin stimulation testing evaluates the adrenal glands’ ability to produce cortisol in response to ACTH stimulation. Subnormal cortisol responses suggest adrenal insufficiency.

Q10: How should Corticotropin therapy be discontinued?

A: To mitigate the risk of adrenal insufficiency, corticotropin therapy should be tapered gradually, especially after prolonged use. The tapering schedule varies depending on the patient’s condition and the duration of treatment.