Cosacthen (Canada)

Tetracosactide injection

Veterinary Use Only

For dogs

DIN 02498405

Description

Tetracosactide consists of the first 24 of the 39 amino acids in naturally occurring adrenocorticotropic hormone (ACTH). The sequence of amino acids in tetracosactide is as follows:

H - Ser - Tyr - Ser - Met - Glu - His - Phe - Arg - Trp - Gly - Lys - Pro - Val - Gly - Lys - Lys - Arg - Arg - Pro - Val - Lys - Val - Tyr - Pro - OH. The molecular formula is C₁₃₆H₂₁₀N₄₀O₃₁S.

Cosacthen is a clear, aqueous solution. Each milliliter contains 0.25 mg of tetracosactide. Inactive ingredients are 1 mg glacial acetic acid, 0.82 mg sodium acetate trihydrate, 8.1 mg sodium chloride and water for injection (to 100%).

Cosacthen is provided in a single use vial and does not contain a preservative.

Cosacthen Indications

To evaluate adrenal function as part of the diagnosis of adrenocortical insufficiency (Addison’s) or hyperadrenocorticism (Cushing’s) in dogs.

Cosacthen Dosage And Administration

The dose is 0.25 mg (1 mL) per dog weighing 4.5-50 kg, administered by intravenous or intramuscular injection, with the purpose of performing the ACTH stimulation test.

Collect the first blood sample for resting cortisol determination immediately prior to administering Cosacthen. Collect the second blood sample 1 hour after administration of Cosacthen to assess the dog’s cortisol response.

Contraindications

Do not use Cosacthen in dogs that have previously had a hypersensitivity reaction to tetracosactide.

Cosacthen Cautions

The safety of Cosacthen has not been established during pregnancy, lactation, or in breeding dogs.

Use only in dogs older than 5 months of age and weighing 4.5 kg or greater.

Warnings

Keep out of reach of children. Not for human use. Consult a physician in case of accidental human exposure.

Clinical Pharmacology

Tetracosactide, like ACTH, binds specific receptors in the plasma membrane of adrenal cortical cells in the zona fasciculata. The hormone-receptor complex activates adenylate cyclase, which stimulates the production of cyclic AMP. This leads to the conversion of cholesterol to pregnenolone, and thus to the production of various glucocorticoids via their respective synthetic pathways.

The cortisol response to tetracosactide injection was evaluated in a laboratory study in 32 healthy Beagle dogs. Tetracosactide was administered at the minimum dose exposure of 5 μg/kg of tetracosactide. Sixty minutes after intramuscular (IM) administration, the mean cortisol concentration was 347 nmol/L (12.6 μg/dL), range 303-430 nmol/L (11.0-15.6 μg/dL), and after intravenous (IV) administration was 334 nmol/L (12.1 μg/dL), range 265-391 nmol/L (9.6-14.2 μg/dL). In comparison, sixty minutes after IM saline administration, the mean cortisol concentration was 55 nmol/L (2.0 μg/dL), range 28-92 nmol/L (1.0-3.3 μg/dL), and after IV saline administration was mean 37 nmol/L (1.4 μg/dL), range 14-65 nmol/L (0.5-2.4 μg/dL). Route of administration did not influence the cortisol response to tetracosactide.

Animal Safety

In a placebo-controlled, masked laboratory safety study, tetracosactide was administered three times, one week apart, by IV or IM injection, to 32 Beagle dogs at multiples of 0, 1, 3, or 5 times the maximum possible dose exposure of 56 μg/kg (i.e. 250 μg per 4.5 kg dog) (IV-dosed dogs); or at multiples of 0, 1, and 2 times the maximum possible dose exposure of 56 μg/kg (i.e. 250 μg per 4.5 kg dog) (IM-dosed dogs). All dogs survived until scheduled necropsy. There were no effects of tetracosactide administration by IV or IM route on physical examinations; neurologic, ophthalmic, and electrocardiographic examinations; or clinical and anatomic pathology variables. Mild injection site abnormalities were observed after IV administration via butterfly catheter in one dog in the control group, one in the 1x group and 3 dogs each in the 3x and 5x dose groups. There were no abnormal injection site observations following IM administration. Clinical signs related to tetracosactide administration included transient salivation observed during and/or immediately after dosing in six of eight dogs in the 5X, IV-dosed group, during the third dose. Of these six dogs, one male and one female were also observed salivating during the second IV dose of tetracosactide. One of the 5X, IV-dosed dogs had an allergic-type reaction after the third injection. The reaction started within 3 minutes of dosing and included: transient salivation, injected mucous membranes, inguinal erythema, facial edema, and tachycardia. After an hour, the facial edema had improved; the other signs persisted for approximately 150 minutes. The dog recovered without medical intervention. One of four 1X, IV-dosed dogs and three of eight 5X, IV-dosed dogs vomited once within an hour of dosing.

Adverse Reactions

In the field study, which included 119 dogs with suspected hypoadrenocorticism (Addison’s) or hyperadrenocorticism (Cushing’s), two dogs vomited within 8 hours post-tetracosactide administration, and one dog developed a hematoma at the injection site after IV administration. Clinical pathology abnormalities were consistent with pre-existing hypoadrenocorticism and hyperadrenocorticism.

Efficacy

Tetracosactide was evaluated in a multi-site field study conducted in the USA involving client-owned dogs to demonstrate effectiveness (diagnostic performance) and safety. In this study, 119 dogs suspected of hypo- or hyperadrenocorticism (Addison’s or Cushing’s) were randomly administered tetracosactide by IV or IM injection. A blood sample was collected to assess baseline cortisol concentrations before injection of 0.25 mg of tetracosactide. Approximately 30-90 minutes after injection, a second blood sample was collected to measure cortisol concentration. A diagnosis of hypoadrenocorticism was made if the cortisol concentration after tetracosactide injection was less than 55 nmol/L (2 μg/dL). A diagnosis of hyperadrenocorticism was made if the cortisol concentration after tetracosactide injection was greater than 552 nmol/L (20 μg/dL).

Diagnostic performance was evaluated in 107 dogs and safety was evaluated in 119 dogs. All 20 dogs with suspected hypoadrenocorticism had either true positive or true negative results for both IM and IV administration routes. The accuracy of Cosacthen for the diagnosis of hypoadrenocorticism was assumed to be 100%, since no independent tests were available at the time of this study to confirm the diagnosis. Of the 87 dogs with suspected hyperadrenocorticism, in the IM group, 9% were classified as true negatives, 12% as false negatives, 60% as true positives, and 19% as false positives. In the IV group, 9% of dogs were classified as true negatives, 9% as false negatives, 61% as true positives, and 21% as false positives. For the diagnosis of hyperadrenocorticism, the accuracy for both IM and IV groups was 70%. For the IM administration route, positive predictive value was 76%, sensitivity was 84%, negative predictive value was 44% and specificity was 33%. For the IV administration route, positive predictive value was 75%, sensitivity was 87%, negative predictive value was 50% and specificity was 31%. In evaluating dogs with clinical signs consistent with suspected hyperadrenocorticism, a negative test result should be regarded with caution and confirmed with additional tests.

Storage

Store refrigerated between 2-8°C. Store in provided outer carton to protect from light. Single use vial; discard unused portion.

PRESENTATION

Cosacthen is supplied in a clear glass vial with 1 mL tetracosactide (0.25 mg/mL).

Dechra Ltd, Snaygill Industrial Estate, Keighley Rd, Skipton, North Yorkshire, UK

Distributed by:

Dechra Veterinary Products Inc., 1 Holiday Ave, East Tower, Suite 345, Pointe-Claire, Québec, H9R 5N3, Canada

F1833

CPN: 1786063.0