Intervet

Description: Vetsulin™ (PORCINE INSULIN ZINC SUSPENSION)

CAUTION
Federal law restricts this drug to use by or on the order of a licensed veterinarian.

DESCRIPTION
Vetsulin™ is a sterile aqueous zinc suspension of purified porcine insulin.

Each mL contains:
purified porcine insulin 40 IU
(30% amorphous and 70% crystalline)
Zinc chloride 0.08 mg
Sodium acetate trihydrate 1.36 mg
Sodium chloride 7.0 mg
Methylparaben (preservative) 1.0 mg

pH is adjusted with hydrochloric acid and/or sodium hydroxide.

INDICATION
Vetsulin™ (porcine insulin zinc suspension) is indicated for the reduction of hyperglycemia and hyperglycemia-associated clinical signs in dogs with diabetes mellitus.

DOSAGE AND ADMINISTRATION
USE OF A SYRINGE OTHER THAN A U-40 SYRINGE WILL RESULT IN INCORRECT DOSING.
FOR SUBCUTANEOUS INJECTION IN DOGS ONLY

Vetsulin™ should be mixed by gentle rolling of the vial prior to withdrawing the dose from the vial. Using a U-40 insulin syringe, the injection should be administered subcutaneously, 2 to 5 cm (3/4 to 2 in) from the dorsal midline, varying from behind the scapulae to the mid-lumbar region and alternating sides.

The initial recommended Vetsulin™ dose is 1 IU insulin/kg body weight plus a body weight-dependent dose supplement as shown in the table below.

Initially, this dose should be given once daily concurrently with, or right after a meal. The veterinarian should re-evaluate the dog at appropriate intervals and adjust the dose based on clinical signs, urinalysis results, and glucose curve/spot check values until adequate glycemic control has been attained. In the US clinical study, glycemic control was considered adequate if an acceptable blood glucose curve was achieved (reduction in hyperglycemia and a nadir of 60 - 160 mg/dL), clinical signs of hyperglycemia (polyuria, polydipsia, and ketonuria) were improved, and hypoglycemia (blood glucose < 50 mg/dL) was avoided. Twice-daily therapy should be initiated if the duration of insulin action is determined to be inadequate. If twice-daily treatment is initiated, the two doses should be 25% less than the once daily dose required to attain an acceptable nadir.

Further adjustments in dosage may be necessary with changes in the dog’s diet, body weight, or concomitant medication, or if the dog develops concurrent infection, inflammation, neoplasia, or an additional endocrine or other medical disorder.

CONTRAINDICATIONS
Dogs known to have a systemic allergy to pork or pork products should not be treated with Vetsulin™. Vetsulin™ is contraindicated during periods of hypoglycemia.

WARNINGS
User Safety: For use in animals only. Keep out of the reach of children. Avoid contact with eyes. In case of contact, immediately flush eyes with copious amounts of water for 15 minutes. Accidental injection may cause clinical hypoglycemia. In case of accidental injection, seek medical attention immediately. Exposure to product may induce a local or systemic allergic reaction in sensitized individuals.

Animal Safety: Use of this product, even at established doses, has been associated with hypoglycemia. An animal with signs of hypoglycemia should be treated immediately. Glucose should be given orally or intravenously as dictated by clinical signs. Insulin should be temporarily withheld and, subsequently, the dosage should be adjusted, if indicated.

Any change in insulin should be made cautiously and only under a veterinarian’s supervision. Changes in insulin strength, manufacturer, type, species (animal, human) or method of manufacture (rDNA versus animal-source insulin) may result in the need for a change in dosage.

Appropriate diagnostic tests should be performed to rule out endocrinopathies, especially hyperadrenocorticism in diabetic dogs that are difficult to regulate.

PRECAUTIONS
Animals presenting with severe ketoacidosis, anorexia, lethargy, and/or vomiting should be stabilized with short-acting insulin and appropriate supportive therapy until their condition is stabilized. As with all insulin products, careful patient monitoring for hypoglycemia and hyperglycemia are essential to attain and maintain adequate glycemic control and associated complications. Overdosage can result in profound hypoglycemia and death. Progestogens, certain endocrinopathies and glucocorticoids can have an antagonistic effect on insulin activity. Intact bitches should be ovariohysterectomized. Progestogen and glucocorticoid use should be avoided.

Drug Interactions: In the US clinical effectiveness study, dogs received various medications while being treated with Vetsulin™ including antimicrobials, NSAIDs, thyroid hormone supplementation, internal and external parasiticides, anti-emetics, dermatological topical treatments and oral supplements, and ophthalmic preparations containing antimicrobials and antiinflammatories. No medication interactions were reported. This drug was not studied in dogs receiving steroids.

Reproductive Safety: The safety and effectiveness of Vetsulin™ in breeding, pregnant, and lactating dogs has not been evaluated.

Use in puppies: The safety and effectiveness of Vetsulin™ in puppies has not been evaluated.

Seven owners recorded the following observations about the injection site on the home monitoring forms: swollen, painful, sore, and a bleb under the skin.

During the 1995-2001 period, the following adverse reactions in 19 dogs treated with porcine insulin zinc suspension were reported to Intervet International: destabilization (defined as lack of adequate regulation), lack of expected efficacy, edema of the head and neck, development of a fibrous lump at the injection site, hypoglycemia and death following administration of typical doses (one death in two dogs) and overdosage (four deaths in four dogs).

To report adverse reactions, call 1-800-345-4735.

INFORMATION FOR DOG OWNERS
Please refer to the Client Information sheet for more information about Vetsulin™. Vetsulin™, like other drugs of this class, is not free from adverse reactions. Owners should be advised of the potential for adverse effects and be informed of the associated clinical signs. Potential adverse reactions include hypoglycemia, insulin antagonism/resistance, rapid insulin metabolism, insulin-induced hyperglycemia (“Somogyi Effect”), and local or systemic reactions. The primary adverse reaction observed is hypoglycemia. Signs may include weakness, depression, behavioral changes, muscle twitching, and anxiety. In cases of severe hypoglycemia seizures and coma can occur. Hypoglycemia can be fatal if an affected dog does not receive prompt treatment. Appropriate veterinary monitoring of blood glucose, adjustment of insulin dose and regimen as needed, and stabilization of diet and activity help minimize the risk of hypoglycemic episodes. The attending veterinarian should evaluate other adverse reactions on a case-by-case basis to determine if an adjustment in Vetsulin™ therapy is appropriate, or if alternative therapy should be considered.

GENERAL PHARMACOLOGY
Porcine insulin is similar in amino acid structure to canine insulin. Vetsulin™ is classified as an intermediate acting insulin. Vetsulin™ has two peaks of activity following subcutaneous administration (the first at around 4 hours and the second at around 11 hours) (1). The duration of activity varies between 14 and 24 hours (1). The peak(s), duration of activity and dose required to adequately control diabetic signs will vary between dogs.

EFFECTIVENESS
A total of 66 client-owned dogs were enrolled in and 53 completed the effectiveness and safety field study. The patients completing the study included 22 breeds of purebred and various mixed breed dogs ranging in age from 4.8 to 14 years, and ranging in weight from 4.2 to 51.3 kg. Of the dogs completing the study, 25 were spayed females and 28 were male (21 neutered and 7 intact).

Dogs were started on Vetsulin™ at a dose of 1IU/kg plus a body weight-dependent dose supplement once daily. The initial treatment time to reach acceptable glycemic control (Dose determination period) ranged from 5 to 151 days. Dogs were evaluated for treatment effectiveness three times at 30-day intervals (Study Period). The blood glucose curve means and mean nadirs were compared pre- and post-treatment to assess effectiveness. The blood glucose curve mean was reduced from 370 mg/dL pre-treatment to 151 mg/dL, 185 mg/dL, and 184 mg/dL at the three treatment period evaluations. The blood glucose mean nadir was reduced from 315 mg/dL pre-treatment to 93 mg/dL, 120 mg/dL, and 119 mg/dL at the three treatment period evaluations. Sixty days after an adequate Vetsulin™ dose was initially established, 94%, 96% and 83% of study dogs experienced a reduction in polyuria, polydipsia, and ketonuria, respectively. Investigators reported adequate glycemic control an average of 81% of the time during the Study Period.

The injection frequency and effective dose range for dogs varied substantially:

HOW SUPPLIED
Vetsulin™ is supplied as a sterile injectable suspension in multidose vials containing either 2.5 mL or 10 mL of 40 IU/mL porcine insulin zinc suspension. Vials are supplied in cartons of one, 10 mL vial and cartons of ten, 2.5 mL vials.

STORAGE CONDITIONS
Store in an upright position under refrigeration at 2° to 8° C (36° to 46° F). Do not freeze. Protect from light.