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)
Pharmacology
Mechanism of Action
Stimulates the adrenal cortex to secrete adrenal steroids (including hydrocortisone, cortisone), androgenic substances, and a small amount of aldosterone
Pharmacokinetics/Pharmacodynamics
Absorption
Synacthen Depot [Canadian product]: IM: Rapid
Distribution
Synacthen Depot [Canadian product]: Vd: ~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.
Use: Off Label
Diagnostic use: Adrenal vein sampling (AVS) in primary aldosteronismcyes
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
Dosage and Administration
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. Cosyntropin solution for injection formulation is not recommended for IM administration; use powder for injection formulation.
Low-dose ACTH stimulation test: Limited data available:
Infants and Children ≤2 years: IV (solution or powder for injection): 1 mcg/m2/dose; maximum dose: 1 mcg/dose (Lomenick 2007; Rose 1999)
Children >2 years and Adolescents: IV (solution or powder for injection): 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 (solution or powder for injection): 15 mcg/kg; maximum dose: 125 mcg/dose (Borenstein 2016)
Children ≤2 years: IV (solution or powder for injection): 125 mcg (Borenstein 2016)
Children >2 years and Adolescents: IM (powder for injection), IV (solution or powder for injection): 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 (powder for injection), IV (solution or powder for injection): 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 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
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
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.
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Fast heartbeat
- Slow heartbeat
- Swelling of arms or legs
- Passing out
- Severe dizziness
- Vision changes
- Severe headache
- Signs of a significant reaction like 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. 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
