Usage
Tetracosactide is primarily used as a diagnostic agent to assess adrenocortical function, specifically in suspected cases of adrenocortical insufficiency (Addison’s disease). It can also be used, though less commonly, as a short-term alternative to corticosteroids in patients intolerant of oral glucocorticoids for conditions such as Crohn’s disease, rheumatoid arthritis, ulcerative colitis, acute exacerbations of multiple sclerosis, and certain types of seizures in children. It is classified as a pituitary hormone analogue or corticotropin analogue. Tetracosactide mimics the action of adrenocorticotropic hormone (ACTH), stimulating the adrenal cortex to produce and release corticosteroids (primarily cortisol) and, to a lesser extent, mineralocorticoids (like aldosterone) and androgens.
Alternate Names
Tetracosactide is also known as tetracosactrin or cosyntropin. Synacthen® is a commonly recognized brand name.
How It Works
Pharmacodynamics: Tetracosactide binds to melanocortin 2 receptors (MC2R) in the adrenal cortex. This binding activates intracellular signaling pathways (primarily cAMP), leading to increased production and release of corticosteroids (mainly cortisol), mineralocorticoids (aldosterone), and androgens.
Pharmacokinetics: Following intramuscular (IM) or intravenous (IV) administration, tetracosactide is rapidly absorbed. The duration of action varies depending on the formulation. Standard tetracosactide has a short duration of action (around 1 hour), whereas the depot formulation (tetracosactide zinc phosphate) has a prolonged effect (24-48 hours). Metabolism and elimination pathways are not fully elucidated, but a portion of the drug is thought to be metabolized by peptidases, and elimination is presumed to be renal.
Mode of Action: Tetracosactide, like ACTH, binds to the MC2R on adrenocortical cells. This triggers the activation of adenylate cyclase, leading to increased intracellular cAMP levels. Elevated cAMP activates protein kinase A, which then phosphorylates various downstream targets, ultimately promoting steroidogenesis and the release of cortisol, aldosterone, and adrenal androgens.
Dosage
Standard Dosage
Adults:
Diagnostic use (short Synacthen test): 0.25 mg IM or IV as a single dose. Plasma cortisol levels are measured before and 30 minutes after administration.
Children:
Diagnostic use (short Synacthen test): Maximum of 0.25 mg/1.73 m² IV as a single dose. Consult product-specific guidelines for precise pediatric dosages.
Special Cases:
- Elderly Patients: No specific dosage adjustments are typically required.
- Patients with Renal Impairment: No studies have been performed. Monitor carefully.
- Patients with Hepatic Dysfunction: No studies have been performed. Close monitoring is advised, as effects may be enhanced in cirrhosis.
- Patients with Comorbid Conditions: Monitor patients with diabetes or hypertension closely, as dose adjustments of existing medications may be necessary due to potential electrolyte imbalances.
Clinical Use Cases
Tetracosactide is not typically indicated for therapeutic use in these settings, except for short-term management as an alternative to corticosteroids when oral glucocorticoids are not tolerated.
Dosage Adjustments
Consider dosage reduction for therapeutic use in patients with hypothyroidism or cirrhosis, as the effects of tetracosactide may be enhanced.
Side Effects
Common Side Effects
Headache, increased appetite, stomach pain, increased sweating, facial flushing, injection site reactions.
Rare but Serious Side Effects
Hypersensitivity reactions (including anaphylaxis), psychological disturbances (euphoria, insomnia, mood swings, depression, psychosis), fluid retention, hypertension, hypokalemia.
Long-Term Effects
Prolonged use can lead to increased intraocular pressure, cataracts, glaucoma, and immunosuppression.
Adverse Drug Reactions (ADR)
Anaphylaxis, severe hypersensitivity reactions.
Contraindications
Hypersensitivity to tetracosactide or ACTH, asthma or other allergic conditions (due to increased risk of anaphylaxis), acute psychosis, infections (unless treated concurrently with antibiotics), peptic ulcer, refractory heart failure, Cushing’s syndrome, adrenogenital syndrome, primary adrenocortical insufficiency (for therapeutic use). Premature infants and neonates less than one month old due to benzyl alcohol content.
Drug Interactions
Valproate (severe jaundice reported in children), other anticonvulsants (increased risk of liver damage), synthetic estrogens (may interfere with diagnostic tests), diuretics (potentiate electrolyte loss). Live virus vaccines should not be administered during treatment. Interactions similar to corticosteroids may occur.
Pregnancy and Breastfeeding
Pregnancy Category D (Australia). Use only if the potential benefit outweighs the risk to the fetus. Some reports of miscarriage or fetal malformation. Not known if excreted in breast milk. Caution advised during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Stimulates adrenal cortex to produce corticosteroids, mineralocorticoids, and androgens via MC2R binding.
- Side Effects: Headache, sweating, flushing, gastrointestinal upset; rarely: hypersensitivity, psychological disturbances, fluid retention.
- Contraindications: Hypersensitivity, asthma, acute psychosis, infections, peptic ulcer, heart failure, Cushing’s syndrome.
- Drug Interactions: Anticonvulsants, valproate, estrogens.
- Pregnancy & Breastfeeding: Category D; use with caution.
- Dosage: Diagnostic: 0.25mg IM/IV; therapeutic doses vary.
- Monitoring Parameters: Blood pressure, electrolytes (potassium), cortisol levels, signs of hypersensitivity.
Popular Combinations
Not generally used in combination therapy except with concurrent antibiotics in patients with infections who require diagnostic testing with tetracosactide.
Precautions
Pre-existing allergies, cardiovascular disease, diabetes, hepatic/renal impairment, infections. Caution in pregnant/breastfeeding women, children. Avoid driving if dizziness or blurred vision occurs.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Tetracosactide for the short Synacthen test?
A: 0.25 mg IM or IV for adults. For children, the maximum dose is 0.25 mg/1.73 m² IV.
Q2: What is the primary use of Tetracosactide?
A: Diagnosis of adrenocortical insufficiency.
Q3: How does Tetracosactide work?
A: It mimics ACTH, stimulating the adrenal cortex to produce cortisol and other adrenal steroids.
Q4: What are the common side effects?
A: Headache, increased appetite, stomach pain, increased sweating, and facial flushing.
Q5: What are the serious side effects of Tetracosactide?
A: Hypersensitivity reactions (including anaphylaxis) and psychological disturbances.
Q6: Can Tetracosactide be used during pregnancy?
A: Only if the potential benefit outweighs the risk to the fetus. It’s a Pregnancy Category D drug.
Q7: What are the contraindications for Tetracosactide?
A: Hypersensitivity to tetracosactide or ACTH, asthma or other allergic conditions, acute psychosis, infections (unless on antibiotics), peptic ulcer, refractory heart failure, and Cushing’s syndrome.
Q8: Does Tetracosactide interact with other medications?
A: Yes, particularly with anticonvulsants (increased liver damage risk) and valproate. It may also interact with synthetic estrogens, potentially influencing diagnostic results, and diuretics, causing increased electrolyte loss.
Q9: What precautions should be taken with long-term Tetracosactide use?
A: Monitor for increased intraocular pressure, cataracts, and glaucoma. Be mindful of potential immunosuppression.
A: The standard formulation has a short duration of action (approximately 1 hour), while the depot formulation has a prolonged effect (24-48 hours).
