Cosyntropin (Systemic)



INN:

Tetracosactide {02}

BAN:
Tetracosactrin {02}


JAN:
Tetracosactide acetate {02}

VA CLASSIFICATION
Primary: DX900
Secondary: HS701

Commonly used brand name(s): Cortrosyn.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Diagnostic aid (adrenal-pituitary function)—

Indications

Accepted

Adrenocortical insufficiency (diagnosis)—Cosyntropin is indicated as an aid for diagnosing adrenocortical insufficiency. {01} {04} {05}
—Cosyntropin is a synthetic subunit of corticotropin (adrenocorticotropic hormone; ACTH). {01} {04} Cosyntropin is preferable to ACTH for diagnosing primary adrenocortical insufficiency because it is less allergenic and may be tolerated by most patients who have had an allergic reaction to ACTH or those with a history of allergies. {01} {04}

Unaccepted
Cosyntropin is not indicated for the treatment of corticosteroid-responsive medical conditions.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Synthetic polypeptide identical to the first 24 of the 39 amino acids of corticotropin (ACTH). {01} {04}
Molecular weight—
    2933.5 {02}

Mechanism of action/Effect:

Cosyntropin combines with a specific receptor in the adrenal cell plasma membrane and, in patients with normal adrenocortical function, stimulates the initial reaction involved in the synthesis of adrenal steroids (including cortisol, cortisone, weak androgenic substances, and a limited quantity of aldosterone) from cholesterol by increasing the quantity of the substrate within the mitochondria. Cosyntropin does not significantly increase plasma cortisol concentration in patients with primary or secondary adrenocortical insufficiency. {04}

Cosyntropin has less immunogenic activity than ACTH because the amino acid sequence having most of the antigenic activity of ACTH, i.e., amino acids 25–39, is not present in cosyntropin. {01} {04} {05}

Time to peak effect:

The maximal increase in plasma cortisol concentration usually occurs approximately 45 to 60 minutes following intravenous or subcutaneous administration of cosyntropin. {01} {04} {05}


Precautions to Consider

Cross-sensitivity and/or related problems

Although most patients allergic to corticotropin (ACTH) do not exhibit an allergy to cosyntropin, some of these patients may be allergic to cosyntropin also. {01} {04}

Carcinogenicity/Mutagenicity

Long-term animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of cosyntropin. {01} {04}

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans. {01} {04}

Studies have not been done in animals. {01} {04}

FDA Pregnancy Category C. {01} {04}

Breast-feeding

It is not known whether cosyntropin is distributed into breast milk. {01} {04} However, problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of cosyntropin have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date.


Geriatrics


No information is available on the relationship of age to the effects of cosyntropin in geriatric patients.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Blood, whole{01}{05} or
Plasma{01}{05}    (cosyntropin may be inactivated by the enzymes present in blood and plasma {01} {04} {05} {06})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With results of this test

Due to other medications
Corticosteroids, glucocorticoid effects, especially cortisone or hydrocortisone{01}{04}{05}    (baseline plasma cortisol concentration may be elevated in patients receiving cortisone or hydrocortisone on the test day and may decrease during the test period; it is recommended that the pretest dose of cortisone or hydrocortisone be omitted on the test day {01} {05})

    (with the exception of dexamethasone, other glucocorticoids may interfere with plasma cortisol determinations if radioligand assay tests used are not specific for cortisol)


Estrogen{01}{05}    (baseline plasma cortisol concentration may be elevated in patients receiving estrogen on the test day {01} {05})


Spironolactone{01}{04}    (because spironolactone metabolites also fluoresce, plasma cortisol concentrations following cosyntropin administration may be falsely elevated in patients receiving spironolactone when the fluorometric procedure is used but not when radioimmunoassay [RIA] or competitive protein-binding methods are used; it is recommended that the pretest dose of spironolactone be omitted on the test day {01} {05})


Due to medical problems or conditions
Elevated plasma bilirubin concentrations{01}{04} or
Free hemoglobin in plasma, presence of{01}{04}    (falsely elevated plasma cortisol concentrations may occur when the fluorometric method is used)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Allergic disorders or history of{01}{04}{05}    (increased risk of allergic reactions)


Allergy to ACTH or cosyntropin{01}{04}{05}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

17-Hydroxycorticosteroids, urine{01}{03}{05}    (recommended before and after therapy to measure adrenal response {01} {05})


Cortisol, blood{01}{03}{05}    (recommended before and at the end of the cosyntropin injection to measure adrenal response; measurement of blood cortisol is preferred to measurement of urinary 17-hydroxycorticosteroids because the latter does not always accurately reflect adrenal response to ACTH {01} {05})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Anaphylaxis, generalized (dizziness; hives; irritability; itching of skin; lightheadedness; seizures; skin rash; slow heartbeat; trouble in breathing; wheezing)
{01}{04}{05}


Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare
    
Allergic reaction, mild (mild fever; nausea; vomiting){05}
    
redness or pain at injection site {05}





General Dosing Information
A dose of 250 mcg (0.25 mg) of cosyntropin is equivalent to 25 USP Units of corticotropin. {01} {04} {05}

When used as a diagnostic agent in the screening test for adrenocortical insufficiency, cosyntropin may be administered intramuscularly, {01} {04} {05} subcutaneously, {04} or by intravenous injection. {01} {04} {05} If greater stimulation of the adrenal gland is needed, cosyntropin may be administered as an intravenous infusion. {01} {04} {05}
The following criteria may be used as guidelines to determine if the patient has a normal response to cosyntropin. Some interlaboratory variation may occur.

   #149; Morning control plasma cortisol concentration exceeds 5 mcg (0.005 mg) per 100 mL. {01} {04} {05}
   #149; Thirty-minute cortisol concentration shows an increase of at least 7 mcg (0.007 mg) per 100 mL above the control level. {01} {04} {05}
   #149; Thirty-minute cortisol concentration exceeds l8 mcg (0.018 mg) per 100 mL. {01} {04} {05}
If a 60-minute test interval is used, a normal response to cosyntropin is shown by a plasma cortisol concentration that is approximately two times the baseline concentration. {01} {05}

Patients who fail to respond to a single-dose corticotropin stimulation test using a dose of 250 mcg (0.25 mg) of cosyntropin may be diagnosed as having primary or secondary adrenocortical insufficiency. {01} {04} {05} {07} Further studies with corticotropin are then indicated to determine which type of adrenocortical insufficiency exists. {01} {05}


Parenteral Dosage Forms

COSYNTROPIN FOR INJECTION

Usual adult and adolescent dose
Diagnostic aid
Intramuscular or subcutaneous, 250 mcg (0.25 mg). {01} {04} {05}

Intravenous, 250 mcg (0.25 mg), administered over a two-minute period. {01} {05} {06}

Intravenous infusion, 250 mcg (0.25 mg), administered at a rate of 40 mcg (0.04 mg) per hour over a six-hour period. {01} {04} {05} {06}


Usual pediatric dose
Diagnostic aid
Children up to 2 years of age: Intramuscular, 125 mcg (0.125 mg). {01} {04} {05}

Children 2 years of age and older: See Usual adult and adolescent dose .


Size(s) usually available:
U.S.—


250 mcg (0.25 mg) per vial (Rx) [Cortrosyn (mannitol 10 mg){01}{04}]

Canada—


250 mcg (0.25 mg) per vial (Rx) [Cortrosyn (glacial acetic acid) (mannitol) (sodium chloride){05}]

Packaging and storage:
Prior to reconstitution, store between 15 and 30 °C (59 and 86 °F), {04} unless otherwise specified by manufacturer.

Preparation of dosage form:
One mL of diluent provided (0.9% sodium chloride injection) should be added to the vial containing 250 mcg (0.25 mg) of cosyntropin. {01} {04} The resultant solution contains 250 mcg (0.25 mg) of cosyntropin per mL. {06}

For intravenous infusion, cosyntropin may be further diluted with 5% dextrose injection or 0.9% sodium chloride injection. {06}

Stability:
After reconstitution with 0.9% sodium chloride injection, 250 mcg (0.25 mg)-per-mL solutions are stable for 24 hours at room temperature or for 21 days when refrigerated at 2 to 8 °C (36 to 46 °F). {06} After further dilution, solutions are stable for 12 hours at room temperature. {06}





References
  1. Cortrosyn (Organon). In: PDR Physicians' desk reference. 53rd ed. 1999. Montvale, NJ: Medical Economics Company Inc; 1999. p. 2119-20.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 195.
  1. Jacobs DS, editor. Laboratory test handbook. 4th ed. Hudson, OH: Lexi-Comp Inc; 1994. p. 112-3, 147.
  1. The United States pharmacopeia. The national formulary. USP 21st revision (January 1, 1985). NF 16th ed. (January 1, 1985). Rockville, MD: The United States Pharmacopeial Convention Inc; 1984; and first through eighth supplements, 1988.
  1. Cortrosyn (Organon). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 385.
  1. Trissel LA. ASHP handbook on injectable drugs. 5th ed. Bethesda, MD: American Society of Hospital Pharmacists; 1988. p. 210.
  1. USP-DI Review 1986; 7(5): 1232. Reviewer comment, Rec 2/2/87.
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