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Cosyntropin

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, Intravenous:

Generic: 0.25 mg/mL (1 mL [DSC])

Solution Reconstituted, Injection:

Cortrosyn: 0.25 mg (1 ea)

Generic: 0.25 mg (1 ea)

Solution Reconstituted, Injection [preservative free]:

Generic: 0.25 mg (1 ea)

Brand Names: U.S.

  • Cortrosyn

Pharmacologic Category

  • 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]: 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 test to differentiate primary adrenal from secondary (pituitary) 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.

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’s syndrome; treatment of primary adrenocortical insufficiency; adrenogenital syndrome

Dosing: Adult

Diagnostic use: Screening of adrenocortical insufficiency:

Cosyntropin powder for injection (IM, IV) or cosyntropin solution for injection (IV only [manufacturer labeling does not recommend IM administration of solution for injection]):

Conventional dose: 0.25 mg; Note: Doses in the range of 0.25-0.75 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).

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.

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: 0.5-1 mg every 2-3 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

Diagnostic use: Screening of adrenocortical insufficiency:

Cosyntropin powder for injection (IM, IV) or cosyntropin solution for injection (IV only [manufacturer labeling does not recommend IM administration of solution for injection]):

Children ≤2 years: 0.125 mg

Children >2 years: Refer to adult dosing.

Synacthen Depot [Canadian product]: IM: Children >3 years: Refer to adult dosing.

Therapeutic use: Synacthen Depot [Canadian product]: IM: Note: Titrate to lowest effective dose at the longest effective dosing interval.

Children 3-6 years: Initial: 0.25-0.5 mg daily; maintenance: 0.25-0.5 mg every 2-8 days

Children 7-15 years: Initial: 0.25-1 mg daily; maintenance: 0.25-1 mg every 2-8 days

Children ≥16 years: Refer to adult dosing.

Transferring from corticosteroids: Synacthen Depot [Canadian product]: IM: Children >3 years: Refer to adult dosing.

Transferring from animal-derived ACTH: Synacthen Depot [Canadian product]: IM: Children >3 years: Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling (has not been studied).

Reconstitution

Powder for injection:

IM: Reconstitute 0.25 mg with NS 1 mL.

IV push: Reconstitute 0.25 mg with NS 2-5 mL.

IV infusion: Mix in NS or D5W.

Solution for injection:

IV push: Reconstitute 0.25 mg with NS 2-5 mL.

IV infusion: Mix in NS or D5W.

Administration

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

IM: May administer IM (reconstituted powder for injection only); cosyntropin injection solution is not recommended for IM administration (manufacturer recommendation).

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

Storage

Powder for injection: Store at controlled room temperature of 15°C to 30°C (59°F to 86°F).

IV infusion: Stable for 12 hours at room temperature.

Solution for injection: Store refrigerated between 2°C to 8°C (36°F to 46°F). Protect from light and freezing.

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

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

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

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% (Limited to important or life-threatening): 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 4-6 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).

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?)

• Have patient report immediately to prescriber tachycardia, bradycardia, swelling of arms or legs, or severe headache (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.

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