Cosyntropin

Medically reviewed by Drugs.com. Last updated on Feb 21, 2024.

Pronunciation

(koe sin TROE pin)

Index Terms

• Synacthen
• Tetracosactide
• Tetracosactrin

Dosage Forms

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

Solution Reconstituted, Injection:

Generic: 0.25 mg (1 ea [DSC])

Solution Reconstituted, Injection [preservative free]:

Cortrosyn: 0.25 mg (1 ea)

Generic: 0.25 mg (1 ea)

Brand Names: U.S.

• Cortrosyn

Pharmacologic Category

• Adrenocorticotropin Stimulating Hormone
• Corticosteroid, Systemic
• Diagnostic Agent

Pharmacology

Stimulates the adrenal cortex to secrete adrenal steroids (including hydrocortisone, cortisone), androgenic substances, and a small amount of aldosterone

Absorption

Synacthen Depot [Canadian product]: IM: Rapid

Distribution

Synacthen Depot [Canadian product]: V_d: ~43% of body weight

Excretion

Urine

Onset of Action

Onset of action: IM, IV: Within 5 minutes increases in plasma cortisol concentrations are observed in healthy individuals; Maximum effect: IM, IV: 45-60 minutes peak plasma cortisol concentration

Time to Peak

Serum: IM, IV push: ~1 hour; plasma cortisol levels rise in healthy individuals within 5 minutes

Duration of Action

Synacthen Depot [Canadian product]: IM: Plasma concentrations of 200-300 pg/mL maintained for 12 hours

Half-Life Elimination

Synacthen Depot [Canadian product]: 7 minutes

Use: Labeled Indications

Diagnostic use: Screening of adrenocortical insufficiency: Diagnostic agent used to screen patients presumed to have adrenocortical insufficiency

Synacthen Depot [Canadian product]: Additional indications: Treatment of various disease states (eg, collagen, dermatologic, endocrine, ocular, hemolytic). Consult manufacturer labeling for detailed list.

Off Label Uses

Diagnostic use: Adrenal vein sampling (AVS) in primary aldosteronism

Data from a clinical study in patients with primary aldosteronism support the use of continuous infusion cosyntropin with adrenal vein sampling to improve the success rate of differentiating unilateral versus bilateral aldosterone hypersecretion, compared to a CT scan ^{[Young 2004]}. Additionally, analysis of retrospective data from a cohort of the Japanese Primary Aldosteronism Study demonstrated that cosyntropin administration is effective at reducing apparent bilateral aldosterone suppression in patients with primary aldosteronism undergoing AVS ^{[Shibayama 2018]}.

Based on The Endocrine Society Guideline for the management of primary aldosteronism, use of a continuous cosyntropin infusion during AVS may be beneficial to minimize stress-induced fluctuations in aldosterone secretion during sequential AVS, confirm successful sampling of the adrenal vein, and maximize the secretion of aldosterone from an aldosterone producing adenoma ^{[Endocrine Society [Funder 2016]]}. Some centers may perform AVS without cosyntropin, or with a cosyntropin bolus regimen ^{[El Ghorayeb 2016]}, ^{[Endocrine Society [Funder 2016]]}, ^{[Rossi 2006]}, ^{[Rossi 2008]}.

Contraindications

Hypersensitivity to cosyntropin or any component of the formulation

Synacthen Depot [Canadian product]: Additional contraindications: Treatment of asthma or other allergic conditions (increased risk of anaphylactic reactions); use in premature babies and neonates <1 month; acute psychosis; untreated bacterial, fungal, and viral infections; active or latent peptic ulcer; refractory heart failure; Cushing syndrome; treatment of primary adrenocortical insufficiency; adrenogenital syndrome

Dosing: Adult

Diagnostic use: Screening of adrenocortical insufficiency: IM, IV:

Conventional dose: 0.25 mg; Note: Doses in the range of 0.25 to 0.75 mg have been used in clinical studies; however, maximal response is seen with 0.25 mg dose. When greater cortisol stimulation is needed, an IV infusion may be used: 0.25 mg administered at 0.04 mg/hour over 6 hours

Low-dose protocol (off-label dose): 1 mcg (Abdu 1999); Note: The use of the low-dose protocol has been advocated by some clinicians, particularly in mild or secondary adrenal insufficiency. The low-dose protocol is not recommended in critically ill patients (Marik 2008). The Endocrine Society practice guideline recommends the conventional dose (ie, 0.25 mg) for diagnosing primary adrenal insufficiency and suggests that the low-dose be used only when cosyntropin is in short supply (ES [Bornstein 2016]).

Synacthen Depot [Canadian product]: IM: 1 mg administered as a single dose or once daily for 3 or 4 days (depending on method of testing; refer to manufacturer labeling for detailed information). Note: For patients with severe adrenal insufficiency, some clinicians administer dexamethasone on days that Synacthen Depot is administered to provide steroid coverage.

Diagnostic use: Adrenal vein sampling (AVS) in primary aldosteronism (off-label use): IV: 50 mcg/hour continuous infusion started 30 minutes prior to adrenal vein catheterization and continued until procedure completion (Young 2004). Alternatively, may consider a 250 mcg bolus dose (with AVS performed prior to and after the bolus dose); however, some studies suggest that bolus administration followed by simultaneous AVS may fail to enhance the diagnostic accuracy of AVS (El Ghorayeb 2016; Endocrine Society [Funder 2016]; Rossi 2006; Rossi 2008).

Therapeutic use: Synacthen Depot [Canadian product]: IM (Note: Titrate to lowest effective dose at the longest effective dosing interval): Initial for acute treatment: 1 mg daily for 3 days; maintenance dose is individualized: 0.5 to 1 mg every 2 to 3 days or twice weekly or 2 mg once weekly or less frequently

Transferring from corticosteroids: Synacthen Depot [Canadian product]: IM: Initial: 1 mg daily; gradually reduce steroid by 25% of original dose on successive days. Upon withdrawal from steroid adjust Synacthen Depot dose as needed.

Transferring from animal-derived ACTH: Synacthen Depot [Canadian product]: IM: Conversion varies depending on product previously used. Manufacturer suggests that patients previously receiving ACTH gel 40 units daily should receive Synacthen Depot 0.5 mg every other day; adjust dose based on response, preferably by extending the dosing interval.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dosing units may vary (ie, mcg, mcg/kg, or mcg/m²); use extra precaution

Adrenocortical insufficiency, diagnostic test (ACTH stimulation test): Note: Both low-dose and standard-dose cosyntropin produce transient, supraphysiological plasma ACTH concentrations without significant adverse effects. Dosing should be determined by the clinician ordering and interpreting test results.

Low-dose ACTH stimulation test: Limited data available:

Infants and Children ≤2 years: IV: 1 mcg/m²/dose; maximum dose: 1 mcg/dose (Lomenick 2007; Rose 1999).

Children >2 years and Adolescents: IV: 1 mcg or 1 mcg/m²/dose; maximum dose: 1 mcg/dose (Borenstein 2016; Cemeroglu 2011; Kazlauskaite 2008; Kazlauskaite 2010; Rose 1999).

Standard-dose ACTH stimulation test:

Infants: IV: 15 mcg/kg; maximum dose: 125 mcg/dose (Borenstein 2016).

Children ≤2 years: IV: 125 mcg (Borenstein 2016).

Children >2 years and Adolescents: IM, IV: 250 mcg; doses in the range of 250 to 750 mcg have been used in clinical studies; however, maximal response is seen with 250 mcg dose. When greater cortisol stimulation is needed; an IV infusion may be used: 250 mcg administered over 6 hours (rate: 40 mcg/hour).

Congenital adrenal hyperplasia, evaluation: Limited data available: Infants and Children: IM, IV: 125 to 250 mcg (Speiser 2010).

Canadian labeling: Synacthen Depot [Canadian product]: Note: Canadian product is for IM administration and dosing is presented in mg; since product is a depot formulation, standard dose equivalencies are not accurate, dose must be individualized.

Adrenocortical insufficiency, diagnostic test (ACTH stimulation test): Synacthen Depot [Canadian product]: Children >3 years: IM: 1 mg/dose administered as a single dose or once daily for 3 or 4 days (depending on method of testing; refer to manufacturer's labeling for detailed information). Note: For patients with severe adrenal insufficiency, some clinicians administer dexamethasone on days that cosyntropin is administered to provide steroid coverage.

Anti-inflammatory or immunosuppressive: Note: Titrate to lowest effective dose at the longest effective dosing interval. Synacthen Depot [Canadian product]:

Children 3 to ≤6 years: IM: Initial: 0.25 to 0.5 mg daily for ~3 days; maintenance: 0.25 to 0.5 mg every 2 to 8 days.

Children ≥7 years and Adolescents ≤15 years: IM: Initial: 0.25 to 1 mg daily for ~3 days; maintenance: 0.25 to 1 mg every 2 to 8 days.

Adolescents ≥16 years: IM: Initial for acute treatment: 1 mg daily for 3 days; maintenance dose: 0.5 to 1 mg every 2 to 3 days or twice weekly or 2 mg once weekly or less frequently.

Transferring from corticosteroids: Synacthen Depot [Canadian product]: Children >3 years and Adolescents: IM: Initial: 1 mg daily; gradually reduce steroid by 25% of original dose on successive days. Upon withdrawal from steroid adjust cosyntropin depot dose as needed.

Transferring from animal-derived ACTH: Synacthen Depot [Canadian product]: Children >3 years and Adolescents: Conversion varies depending on product previously used. Manufacturer suggests that patients previously receiving ACTH gel 40 units daily should receive cosyntropin depot 0.5 mg every other day; adjust dose based on response, preferably by extending the dosing interval.

Reconstitution

Powder for injection:

IM: Reconstitute 0.25 mg with NS 1 mL.

IV push: Reconstitute 0.25 mg with NS 1 mL; further dilute in NS to a total volume of 2 to 5 mL.

IV infusion: Mix in NS or D5W.

Administration

IV: May administer by IV injection over 2 minutes or as an IV infusion over 4 to 8 hours. Synacthen Depot [Canadian product] should not be administered IV.

Adrenal vein sampling (off-label): Administer as continuous infusion beginning 30 minutes before adrenal vein catheterization and continue throughout the procedure (Endocrine Society [Funder 2016]; Young 2004). Alternatively, a bolus regimen has been studied that requires a baseline AVS followed by bolus cosyntropin followed by repeat AVS (El Ghorayeb 2016; Endocrine Society [Funder 2016]).

IM: May administer IM.

Synacthen Depot [Canadian product]: Shake ampule until uniform appearance; administer by IM injection in the buttocks. Self-administration by patient is not recommended.

Storage

Powder for injection: Store at 20°C to 25°C (68°F to 77°F). After dilution for IV infusion, stable for 12 hours at room temperature.

Suspension for injection: Synacthen Depot [Canadian product]: Store refrigerated between 2°C to 8°C (36°F to 46°F). Protect from light.

Drug Interactions

ClonazePAM: Cosyntropin may enhance the hepatotoxic effect of ClonazePAM. Monitor therapy

Corticosteroids (Orally Inhaled): May diminish the diagnostic effect of Cosyntropin. Monitor therapy

Corticosteroids (Systemic): May diminish the diagnostic effect of Cosyntropin. Monitor therapy

Cortisone: May diminish the diagnostic effect of Cosyntropin. Management: Patients receiving cortisone should omit their pre-test dose on the day selected for cosyntropin testing. Consider therapy modification

DiazePAM: Cosyntropin may enhance the hepatotoxic effect of DiazePAM. Monitor therapy

Estrogen Derivatives: May diminish the diagnostic effect of Cosyntropin. Management: Discontinue estrogen containing drugs 4 to 6 weeks prior to cosyntropin (ACTH) testing. Consider therapy modification

Hydrocortisone (Systemic): May diminish the diagnostic effect of Cosyntropin. Management: Patients receiving hydrocortisone should omit their pre-test dose on the day selected for cosyntropin testing. Consider therapy modification

Nitrazepam: Cosyntropin may enhance the hepatotoxic effect of Nitrazepam. Monitor therapy

PHENobarbital: Cosyntropin may enhance the hepatotoxic effect of PHENobarbital. Monitor therapy

Phenytoin: Cosyntropin may enhance the hepatotoxic effect of Phenytoin. Monitor therapy

Primidone: Cosyntropin may enhance the hepatotoxic effect of Primidone. Monitor therapy

Spironolactone: May diminish the diagnostic effect of Cosyntropin. Management: Patients receiving spironolactone should omit their pre-test dose on the day selected for cosyntropin testing. Consider therapy modification

Valproate Products: Cosyntropin may enhance the hepatotoxic effect of Valproate Products. Management: Avoid concomitant use of Synacthen Depot (dosage form available in Canada) with valproic acid. Avoid combination

Test Interactions

Concurrent or recent use of spironolactone, hydrocortisone, cortisone, etomidate, estrogens

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined. Adverse events associated with other corticosteroids may be observed when Synacthen Depot (Canadian product) is used for therapeutic purposes. Refer to corticosteroid monographs for comprehensive lists.

Cardiovascular: Bradycardia, hypertension, peripheral edema, tachycardia

Dermatologic: Skin rash, urticaria at injection site (with erythema)

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

<1%, postmarketing and/or case reports: Adrenal hemorrhage (Synacthen Depot)

Warnings/Precautions

Concerns related to adverse effects:

• Corticotropin allergy: Cortrosyn: Use with caution in patients with a history of allergic reactions to corticotropin or preexisting allergic disease. Synacthen Depot [Canadian product] is contraindicated in patients with allergic conditions.

• Hypersensitivity reactions: Synacthen Depot [Canadian product]: Hypersensitivity reactions (including severe reactions) may occur particularly in patients with asthma or other allergies and often within 30 minutes of administration; monitor for hypersensitivity for ~1 hour after administration. Prolonged use may increase the risk of allergic reactions.

Disease related concerns:

• Cardiovascular disease: Synacthen Depot [Canadian product]: Use caution in patients with hypertension or thromboembolic disease.

• Gastrointestinal disease: Synacthen Depot [Canadian product]: Use caution in patients with nonspecific ulcerative colitis, diverticulitis, or recent intestinal anastomosis.

• Hepatic disease: Synacthen Depot [Canadian product]: Enhanced effects may be observed in patients with cirrhosis of the liver.

• Infections: Synacthen Depot [Canadian product]: Use caution in patients with acute or chronic infections (especially varicella or vaccinia) or exanthematous and fungal diseases. Use with caution in patients with latent tuberculosis; treatment may reactivate latent tuberculosis. Rule out amebiasis prior to initiating therapy; may activate latent amebiasis.

• Myasthenia gravis: Synacthen Depot [Canadian product]: Use caution in patients with myasthenia gravis.

• Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use. Not recommended for the treatment of optic neuritis; may increase frequency of new episodes. Consider routine eye exams in chronic users.

• Osteoporosis: Synacthen Depot [Canadian product]: Use caution in patients with osteoporosis.

• Psychiatric disturbances: Corticosteroid use may cause psychiatric disturbances, including depression, euphoria, insomnia, mood swings, and personality changes. Preexisting psychiatric conditions may be exacerbated by corticosteroid use.

• Renal disease: Synacthen Depot [Canadian product]: Use caution in patients with renal insufficiency.

• Thyroid disease: Synacthen Depot [Canadian product]: Enhanced effects may be observed with hypothyroidism.

Dosage forms specific issues:

• Synacthen Depot [Canadian product]: Contains benzyl alcohol; avoid use in infants and children <3 years of age; contraindicated in neonates.

Other warnings/precautions:

• Immunizations: Synacthen Depot [Canadian product]: Live vaccines should not be given concurrently.

• Surgery/trauma: Synacthen Depot [Canadian product]: Augmentation or resumption of therapy may be necessary in patients undergoing surgery or subjected to trauma either during or within 1 year of therapy discontinuation; adjunctive rapid acting corticosteroids may be necessary during periods of stress.

Monitoring Parameters

Synacthen Depot [Canadian product]: Observe patient for ~1 hour after administration for signs/symptoms of hypersensitivity; for diagnosis of adrenocortical insufficiency measure plasma cortisol prior to and 4 to 6 hours after injection; with prolonged use monitor blood pressure, weight, urinalysis, glucose, electrolytes, signs and symptoms of infection, cataract formation, intraocular pressure, bone mass density and growth in children, ECG (in children)

Pregnancy Risk Factor C Pregnancy Considerations

Animal reproduction studies have not been conducted with cosyntropin; adverse events have been observed with corticosteroids in animal reproduction studies. 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). Cosyntropin is the recommended test to diagnose primary adrenal insufficiency during pregnancy. Pregnancy may alter cortisol levels, and higher concentrations are used to interpret the results based on trimester (Bornstein 2016).

Patient Education

What is this drug used for?

• It is used during a test to check adrenal function.

• It may be given to you for other reasons. Talk with the doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Fast heartbeat

• Slow heartbeat

• Swelling of arms or legs

• Passing out

• Severe dizziness

• Vision changes

• Severe headache

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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