Today's Veterinary Practice

MAY-JUN 2018

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Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Description: ProZinc® insulin is a sterile aqueous protamine zinc suspension of recombinant human insulin. Each mL con tains: recombinant human insulin 40 International Units (IU) protamine sulfate 0.466 mg zinc oxide 0.088 mg glycerin 16.00 mg dibasic sodium phosphate, heptahydrate 3.78 mg phenol (added as preservative) 2.50 mg hydrochloric acid 1.63 mg water for injection (maximum) 1005 mg pH is adjusted with hyd ro chlo ric acid and/o r sodium hyd roxide. Indication: ProZinc (protamine zinc recombinant human insulin) is indicated for the reduction of hyperglycemia and hyperglycemia-associated clinical signs in cats 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 C ATS ONLY. DO NOT SHAKE OR AGITATE THE VIAL. P roZinc insulin should be mi xed by gently rolling the vial p rior to withd ra wing ea ch dose from the vial. Once mixed, ProZinc suspension has a white, cloudy appearance. Clumps or visible white particles can form in insulin suspensions: do no t use the product if clumps or visible white particles persist after gently rolling the vial. Using a U-40 insulin syringe, the injection should be administered subcutaneously on the back of the neck or on the side of the cat. Always provide the Cat Owner Information Sheet with each prescription. The initial recommended ProZinc dose is 0.1 – 0.3 IU insulin/pound of body weight (0.2 – 0.7 IU/kg) every 12 hours. The dose should be given concurrently with or right after a meal. The veterinarian should re-evaluate the cat at appropriate intervals and adjust the dose based on both clinical signs and glucose nadirs until adequate glycemic control has been attained. In the effectiveness field study, glycemic co ntrol was considered adequate if the glucose nadir from a 9-hour blood glucose curve was between 80 and 150 mg/dL and clinical signs of hyperglycemia such as polyuria, polydipsia, and weight loss were improved. Fu rther adjustments in the do sage may be necessary with changes in the cat's diet, body weight, or concomitant medication, or if the cat develops concurrent infection, inflammation, neoplasia, or an additional endocrine or other medical disorder. Contraindi ca tions: P roZinc insulin is con trai ndi cated in cats sensitive to p ro tamine zinc recombinant human insulin or any other ingredients in the ProZinc product. ProZinc insulin is contraindicated during episodes of hypoglycemia. Warnings: User Safety: For use in cats only. Keep out of the reach of children. Avoid con tact with eyes. In case o f con tact, immediately flush eyes with runni ng water fo r at least 15 minutes. Accidental injection may cause hypoglycemia. In case o f acciden tal injection, seek medical attention immediately. Exposure to product may induce a local o r systemic allergic reaction in sensiti zed i ndi viduals. Animal Sa fety: Owners should be ad vised to observe fo r signs o f hypoglycemia (see Cat Owner Information Sheet). Use of this product, even at established doses, has been associated with hypoglycemia. An animal with signs o f hypoglycemia should be treated immediately. Glucose should be given orally or intravenously as dictated by clinical signs. Insulin should be temporarily withheld and, if indicated, the dosage adjusted. Any change in insulin should be made cautiously and only under a veterinarian's supervision. Changes in insulin strength, manu factu rer, typ e, speci es (human, animal) o r method of manufacture (rDNA versus animal-source insulin) may result in the need for a change in do sage. Appropriate diagnostic tests should be performed to rule out other endocrinopathies in diabetic cats that are difficult to regulate. P recau tions: Animals p resenti ng with severe ketoacidosis, ano rexia, lethargy, and/o r vomiting should be stabilized with short-acting insulin and appropriat e supportive therapy until their condition is stabilized. As with all insulin products, careful patient moni to ri ng fo r hypoglycemia and hyperglycemia is essential to attain and main tain adequate glycemic control and to prevent associated complications. Overdosage can result in p ro fou nd hypoglycemia and death. P rogestogens, certain endocrinopathi es and glucoco rticoids can have an an tagonistic effect on insulin acti vity. P rogestogen and glucoco rticoid use should be avoided. Rep roducti ve Sa fety: The safety and effectiven ess o f P roZinc insulin in b reedi ng, pregnant, and lactating cats has not been evaluated. Use in Kittens: The safety and effectiveness of ProZinc insulin in kittens has not been evaluated. Ad verse Reactions: Effectiven ess Field S tudy In a 45-d ay effectiven ess field stud y, 1 76 cats received P roZinc insulin. Hypoglycemia (defined as a blo od glucose value o f <50 mg/dL) occurred in 71 o f the cats at various times th roughou t the stud y. Clini cal signs o f hypoglycemia were generally mild in natu re (described as lethargic, slu ggish, weak, trembli ng, uncoo rdinated, gro ggy, glassy-eyed o r d azed). In 17 cases, the veterinarian p rovided o ral glucose supplemen tation o r fo od as treatmen t. Most cases were no t associated with clini cal signs and received no treatmen t. One cat had a serious hypoglycemic event associated with stupor, lateral recumbency, hypothermia and seizures. All cases of hypoglycemia resolved with appropriate therapy and, i f needed, a dose reduction. Three cats had injection site reactions, which were described as either small, punctate, red lesions; lesions on neck; or palpable subcutaneous thickening. All injection site reactions resolved without cessation of therapy. Four cats developed diabetic neuropathy during the study as evidenced by plantigrade stan ce. Th ree cats en tered the stud y with plantigrade stan ce, one o f whi ch resolved by Day 45. Four cats were diagnosed with diabetic ketoacidosis during the study. Two were euthanized due to poor response to treatment. Five other cats were euthanized during the study, one of which had hypoglycemia. Four cats had received ProZinc insulin for less than a week and were euthanized due to worsening concurrent medical conditions. The following additional clinical observations or diagnoses were reported in cats during the effectiveness field study: vomiting, lethargy, diarrhea, cystitis/hematuria, upper respiratory infection, dry coat, hair loss, ocular discharge, abnormal vocalization, black stool, and rapid b reathi ng. Extended Use Field St udy Cats that completed the effectiveness study were enrolled into an extended use field study. In this study, 145 cats received ProZinc insulin for up to an additional 136 days. Adverse reactions were similar to those reported during the 45-day effectiveness study and are listed in order of decreasing frequency: vomiting, hypoglycemia, anorexia/ poor appetite, diarrhea, lethargy, cystitis/hematuria, and weakness. Twenty cats had signs consisten t with hypoglycemia d escribed as: slu ggish, lethargic, unstead y, wobbly, seizures, trembling, or dazed. Most of these were treated by the owner or veterinarian with oral glucose supplementation or food; others received intravenous glucose. One cat had a serious hypoglycemic even t associated with seizu res and bli ndn ess. The cat fully recovered after supportive therapy and finished the study. All cases of hypoglycemia resolved with appropriate therapy and if needed, a dose reduction. Fourteen cats died or were euthanized during the extended use study. In two cases, continued use of insulin despite anorexia and signs of hypoglycemia contributed to the deaths. In one case, the owner decided not to continue therapy after a presumed episode of hypoglycemia. The rest were due to concurrent medical conditions or worsening of the diabetes mellitus. To repo rt suspected adverse reactions, o r to ob tain a co py o f the Material Safety Data Sheet (MSDS), call 1-866-638-2226. Information for Cat Owners: Please refer to the Cat Owner Information Sheet for more information about ProZinc insulin. ProZinc insulin, like other insulin products, is not free from adverse reactions. Owners should be ad vised o f the po tential fo r adverse reactions 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 sys temic reactions. The most common adverse reaction observed is hypoglycemia. Signs may include: weakness, depression, behavio ral changes, muscle twitchi ng, and anxiety. In severe cases o f hypoglycemia, seizures and coma can occur. Hypoglycemia can be fatal if an affected cat 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 b asis to determine i f an adjustmen t in therapy is appropriate, or if alternative therapy should be considered. Effectiveness: A total of 187 client-owned cats were enrolled in a 45-day field study, with 1 76 recei vi ng P roZinc insulin. One hu nd red and fifty-one cats were included in the effectiveness analysis. The patients included various purebred and mixed breed cats rangi ng in age from 3 to 19 years and in weigh t from 4.6 to 20.8 pou nds. Of the cats included in the effectiveness analysis, 101 were castrated males, 49 we re spayed females, and 1 was an in tact female. Cats were started on ProZinc insulin at a dose of 0.1-0.3 IU/lb (0.2-0.7 IU/kg) twice daily. Cats were evaluated at 7, 14, 30, and 45 days after initiation of therapy, and the dose was adjusted based on clinical signs and results of 9-hour blood glucose curves on Days 7, 14, and 30. Effectiveness was based on successful control of diabetes, which was defined as improvement in at least one blood glucose variable (glucose curve mean, nadir, or fructosamine) and at least one clinical sign (polyuria, polydipsia, or body weight). Based on this definition, 115 of 151 cases (7 6.2%) were considered successful. Blood glucose curve means decreased from 415.3 mg/dL on Day 0 to 203.2 mg/dL by Day 45, and the mean blood glucose nadir decreased from 407.9 mg/dL on Day 0 to 142.4 mg/dL on Day 45. Mean fructosamine values decreased from 505.9 µmol/L on Day 0 to 380.7 µmol/L on Day 45. Cats that completed the effectiveness study were enrolled in an extended use field study. The mean fructosamine value was 34 2.0 µmol/L after a total of 181 days of ProZinc therapy. How Supplied: P roZinc insulin is supplied as a sterile injectable suspension in 10-mL multidose vials. Each mL o f P roZinc p roduct con tains 40 IU recombinan t human insulin. S to rage Condi tions: S to re in an up righ t position u nder refrigeration at 36-46°F (2-8°C). Do no t freeze. P ro tect from ligh t. Manu factu red for: Boeh ri nger I ngelh eim Vetmedi ca, Inc. S t. Joseph, MO 64506 U. S.A. Manu factu red by: Alcami Carolinas Corporation, C harleston, SC 29405 ProZinc® is a registered trademark of Boehringer Ingelheim Vetmedica, Inc. © 2016 Boeh ri nger I ngelh eim Vetmedi ca, Inc. All Rights R eserved. 449901-02 Revised 06/2016 Code 449911 NADA 141-297, Approved by FDA ProZinc® (p ro tamine zinc recombinan t human insulin)

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