Vetsulin IS WITH YOU AND YOUR DOG FOR LIFE

Reduced or loss of appetiteWeakness, seizures, or severe mental depressionBehavioral change, muscle twitching, or anxietyConstipation, vomiting, or diarrheaSigns of a bladder infection (small, frequent urinations, straining, blood in the urine)Swelling of the head or neckWhat else can I do to keep my pet’s blood sugar stable? Your pet’s diet should be consistent and appropriate. A nutritionally complete pet foodshould be fed in consistent amounts at the same times each day or, at the discretion ofyour veterinarian, be available continuously. “Treats” and changes in diet should generally be avoided unless recommended by yourveterinarian. Your veterinarian will advise you on how much and when to feed your pet based on theresponse to vetsulin . Your pet’s exercise should remain consistent. Consult with your veterinarian if you expecta major change in activity. Develop a schedule with your veterinarian for regular evaluations of your pet’s diabetes.Can vetsulin be used with other medications?Progestogen (such as megestrol) and glucocorticoids (such as cortisone, prednisone,dexamethasone, triamcinolone) should be avoided during vetsulin therapy. Progestogen,glucocorticoids, and certain endocrine diseases may counter the effect of insulin. Othermedications may also interfere with your pet’s response to insulin. Tell your veterinarianabout all the medicines you have given your pet in the past, and any medicines that you areplanning to give with vetsulin . This should include other medicines that you can get withouta prescription. Your veterinarian may want to check that all of your pet’s medications can begiven together.What do I do in case my pet receives more than the prescribedamount of vetsulin ?If your pet is given too much vetsulin , severe (life-threatening) hypoglycemia (low bloodsugar) can result. Contact your veterinarian immediately. If your veterinarian is not available,seek other veterinary advice at once. Your pet may need to be hospitalized for observation ortreatment.What do I do if my pet receives less than the prescribed dose, or Imiss an injection? A missed or inadequate dose may cause temporary recurrence of signs (such as excessthirst and urination) but is not life threatening. Contact your veterinarian as soon as possible for advice on your pet’s next dose. If you cannot reach your veterinarian and your pet is eating and acting normal, give yourpet the usual dose at the next regularly scheduled injection time.How to give vetsulin to your petDoses of insulin are measured in units. U-40 insulin contains 40 units/mL (1 mL 1 cc).vetsulin is available in vials for use with U-40 syringes or in cartridges for use with theVetPen injection device. If you are using vials, refer to the section below. If you are usingcartridges, refer to the VetPen instructions for use provided with the VetPen .Use vetsulin with U-40 syringes only. Use of a syringe other than a U-40 syringe willresult in incorrect dosing. A licensed veterinarian must prescribe vetsulin for your pet, and itshould be administered according to your veterinarian’s instructions.Your veterinarian will determine the amount of insulin needed (based on the weight of yourpet, clinical signs such as water consumption, and laboratory results), instruct you on properstorage and handling, show you how to draw the insulin from the bottle, and instruct you on

how to administer the injection. Once you can do this correctly, your veterinarian will provideyou with everything you need to care for your pet at home. vetsulin should be administeredwith a U-40 insulin syringe according to the following instructions:Preparing the Dose: Wash your hands Remove the vetsulin bottle from the refrigerator and shake the vial thoroughly untila homogeneous, uniformly milky suspension is obtained. Foam on the surface of thesuspension formed during shaking should be allowed to disperse before the product isused and, if required, the product should be gently mixed to maintain a homogeneous,uniformly milky suspension before use. If you see large particles floating in the suspensionafter thoroughly shaking, do not use the product and contact your veterinarian. Carefully remove the cap from the needle. Using a U-40 insulin syringe, pull the plunger back to draw air into the syringe to equal thevetsulin dose. Insert the syringe needle into the bottle and inject the air into the bottle. Turn the bottle and syringe upside down. Making sure the tip of the needle is in thevetsulin , withdraw the correct dose into the syringe. Before removing the needle from the bottle, check the syringe for any air bubbles. Ifbubbles are present, hold the syringe straight up and tap its side until the bubbles float tothe top. Push them out with the plunger and withdraw the correct dose. Remove the needle from the bottle, being careful not to inject yourself.Giving the injection: Injections should be given just under the skin (subcutaneously) 2-5cm (3/4-2 inches) fromthe midline of the back (middle of your pet’s back running from tail to head), varying fromjust behind the shoulder blade to slightly in front of the hipbone. The injection site should be alternated between your pet’s left and right side. Using your free hand, pinch up a fold of skin, insert the needle into the center of the foldas instructed by your veterinarian, and push the plunger in as far as it will go. Pull the needle out being careful not to inject yourself. Dispose of the syringe in an appropriate manner (sharps/biohazard disposal).How do I store vetsulin ?vetsulin should be stored in an upright position under refrigeration (2-8 Degrees Celsius /36-46 Degrees Fahrenheit).Do not freeze. Protect from light. Use contents within 42 days of first vial puncture.What else should I know about vetsulin ?This sheet provides a summary of information about vetsulin . If you have any questions orconcerns about vetsulin or DM, talk to your veterinarian.As with all prescribed medicines, vetsulin should only be given to the pet for which it wasprescribed and for the condition for which it was prescribed.It is important that your veterinaran periodically evaluate your pet’s response to vetsulin atregular checkups that include blood glucose monitoring. Your veterinarian will best determineif your pet is responding as expected.Additional information about vetsulin and DM can be found at www.vetsulin.comDistributed by: Intervet Inc (d/b/a Merck Animal Health) Madison, NJ 07940 Made inGermany2 Giralda Farms, Madison, NJ 07940 Customer Service: 1-800-521-5767Copyright 2014 Intervet Inc., a subsidiary of Merck & Co., Inc. All rights reserved.04/18 MAH-VET-04

vetsulin (porcine insulin zinc suspension)Approved by FDA under NADA # 141-236CAUTIONFederal law restricts this drug to use by or on the order of a licensed veterinarian.DESCRIPTIONvetsulin is a sterile aqueous zinc suspension of purified porcine insulin.Each mL contains: purified porcine insulin (35% amorphous and 65% crystalline)40 IUZinc (as chloride)0.08 mgSodium acetate trihydrate1.36 mgSodium chloride7.0 mgMethylparaben (preservative)1.0 mgpH is adjusted with hydrochloric acid and/or sodium hydroxide.INDICATIONvetsulin (porcine insulin zinc suspension) is indicated for the reduction of hyperglycemia and hyperglycemiaassociated clinical signs in dogs and cats with diabetes mellitus. DOSAGE AND ADMINISTRATIONFOR SUBCUTANEOUS INJECTION IN DOGS AND CATS ONLYVials: USE OF A SYRINGE OTHER THAN A U-40 SYRINGE WILL RESULT IN INCORRECT DOSING.Shake the vial thoroughly until a homogeneous, uniformly milky suspension is obtained. Foam on thesurface of the suspension formed during shaking should be allowed to disperse before the product is usedand, if required, the product should be gently mixed to maintain a homogeneous, uniformly milky suspensionbefore use. Clumps or white particles can form in insulin suspensions: do not use the product if visibleclumps or white particles persist after shaking thoroughly.Cartridges: VETSULIN CARTRIDGES SHOULD BE USED EXCLUSIVELY WITH VETPEN AND 29G/12MM PEN NEEDLES. Prior to loading vetsulin cartridges, shake the cartridge until a homogeneous, uniformlymilky suspension is obtained. Clumps or white particles can form in insulin suspensions: do not use theproduct if visible clumps or white particles persist after shaking. The detailed instructions for use provided with VetPen should be strictly followed.The injection should be administered subcutaneously, 2 to 5 cm (3/4 to 2 in) from the dorsal midline, varyingfrom behind the scapulae to the mid-lumbar region and alternating sides.Always provide the Owner Information Sheet with each prescription.DogsThe initial recommended vetsulin dose is 0.5 IU insulin/kg body weight. Initially, this dose should be givenonce daily concurrently with, or right after a meal. 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 each be 25% less than the once daily doserequired to attain an acceptable nadir. For example, if a dog receiving 20 units of vetsulin once daily hasan acceptable nadir but inadequate duration of activity, the vetsulin dose should be changed to 15 unitstwice daily. The veterinarian should re-evaluate the dog at appropriate intervals and adjust the dose based onclinical signs, urinalysis results, and glucose curve values until adequate glycemic control has beenattained. 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 anadditional endocrine or other medical disorder.CatsThe initial recommended dose in cats is 1 to 2 IU per injection. The injections should be given twice daily atapproximately 12 hour intervals. For cats fed twice daily, the injections should be given concurrently with, orright after each meal. For cats fed ad libitum, no change in feeding schedule is needed.The veterinarian should re-evaluate the cat at appropriate intervals and adjust the dose based onclinical signs, urinalysis results, and glucose curve values until adequate glycemic control has beenattained. Further adjustments in dosage 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 anadditional endocrine or other medical disorder.

CONTRAINDICATIONSDogs and cats known to have a systemic allergy to pork or pork products should not be treated withvetsulin . vetsulin is contraindicated during periods of hypoglycemia. WARNINGSUser Safety: For use in animals only. Keep out of the reach of children. Avoid contact with eyes. In caseof contact, immediately flush eyes with copious amounts of water for 15 minutes. Accidental injection maycause clinical hypoglycemia. In case of accidental injection, seek medical attention immediately. Exposureto product may induce a local or systemic allergic reaction in sensitized individuals.Animal Safety: Owners should be advised to observe for signs of hypoglycemia (see Owner InformationSheet). Use of this product, even at established doses, has been associated with hypoglycemia. An animalwith signs of hypoglycemia should be treated immediately. Glucose should be given orally or intravenouslyas dictated by clinical signs. Insulin should be temporarily withheld and, subsequently, the dosage shouldbe adjusted, if indicated. Any change in insulin should be made cautiously and only under a veterinarian’ssupervision. Changes in insulin strength, manufacturer, type, species (animal, human) or method ofmanufacture (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 in pets that are difficult toregulate (e.g., hyperadrenocorticism in dogs and hyperthyroidism in cats).PRECAUTIONSAnimals presenting with severe ketoacidosis, anorexia, lethargy, and/or vomiting should be stabilizedwith short-acting insulin and appropriate supportive therapy until their condition is stabilized. As with allinsulin products, careful patient monitoring for hypoglycemia and hyperglycemia are essential to attainand maintain adequate glycemic control and prevent associated complications. Overdosage can result inprofound hypoglycemia and death. Progestogens, certain endocrinopathies, and glucocorticoids can havean antagonistic effect on insulin activity. Intact bitches should be ovariohysterectomized.Progestogen and glucocorticoid use should be avoided.Drug Interactions:In the US clinical effectiveness studies, dogs and cats received various medications while being treatedwith vetsulin including antimicrobials, antivirals, antifungals, antihistamines, analgesics, anesthetics/tranquilizers, diuretics, bronchodilators, corticosteroids (cats), NSAIDs, thyroid hormone supplementation,hyperthyroid medication (methimazole), internal and external parasiticides, anti-emetics, dermatologicaltopical treatments and oral supplements, ophthalmic preparations containing antimicrobials andantiinflammatories, and various vaccines. No medication interactions were reported. This drug was notstudied in dogs receiving corticosteroids. Reproductive Safety: The safety and effectiveness of vetsulin in breeding, pregnant, and lactating dogsand cats has not been evaluated. Use in puppies and kittens: The safety and effectiveness of vetsulin in puppies and kittens has not beenevaluated. ADVERSE REACTIONSDogsIn the field effectiveness and safety study, 66 dogs were treated with vetsulin . Sixty-two dogs wereincluded in the assessment of safety. Hypoglycemia (defined as blood glucose 50 mg/dL) with or withoutassociated clinical signs occurred in 35.5% (22/62) of the dogs at various times during the study. Clinicalsigns of hypoglycemia were generally mild in nature (described as weakness, lethargy, stumbling, fallingdown, and/or depression). Disorientation and collapse were reported less frequently and occurred in 16.1%(10/62) of the dogs. Two dogs had a seizure and one dog died during the seizure. Although never confirmed,the presumptive diagnosis was hypoglycemia-induced seizures. In the rest of the dogs, hypoglycemiaresolved with appropriate therapy and adjustments in insulin dosage. Seven owners recorded the followingobservations about the injection site on the home monitoring forms: swollen, painful, sore, and a bleb underthe skin. The following clinical observations occurred in the field study following treatment with vetsulin and may bedirectly attributed to the drug or may be secondary to the diabetic state or other underlying conditions in thedogs: hematuria, vomiting, diarrhea, pancreatitis, non-specific hepatopathy/pancreatitis, development ofcataracts, and urinary tract infections. In a 21-day field safety and effectiveness study, 40 dogs, already well controlled on vetsulin , wereadministered vetsulin using a VetPen insulin pen loaded with a pre-filled 2.7 mL vetsulin cartridge and 29gauge/12 mm pen needles. All dogs enrolled in the study were evaluated for safety. Loss of diabetic controlwas reported in 10 dogs, 3 of which were withdrawn from the study. Four dogs’ loss of control resolvedafter dose adjustment while still using the insulin pen. For the remaining 3 dogs, the loss of diabetic controlwas reported at the end of the study and outcome was not documented. Two dogs had injection sitereactions: edema in one dog and two instances of crusting in another. Poor appetite and weight loss wasreported in one dog.

CatsIn a field effectiveness and safety study, safety data was reported for 78 cats receiving vetsulin .Hypoglycemia (defined as blood glucose 50 mg/dL) was reported in 61 cats (88 total incidences). Fifteenof the occurrences (involving 13 cats) were associated with clinical signs described as lethargy, diarrhea,decreased appetite/anorexia, vomiting, and hypothermia. One cat had seizures following accidentaloverdosing by the owner and again during the subsequent dose adjustment period. The cat responded tosupportive therapy and had no further hypoglycemic episodes. In all cases of hypoglycemia, the clinicalsigns resolved following symptomatic treatment and/or dose adjustment. Polyneuropathy was reported in4 cats. Two injection site reactions were reported: one as a mildly thickened subcutaneous tissue reactionand the second as a mild bruising. The following clinical observations occurred in the field study following treatment with vetsulin and maybe directly attributed to the drug or may be secondary to the diabetic state or other underlying conditions inthe cats: vomiting, lethargy, diarrhea, decreased appetite/anorexia, pancreatitis, dermal events, respiratorydisease, urinary tract disorder, renal disease, dehydration, weight loss, polydipsia, polyuria, behavioralchange, and ocular discharge/conjunctivitis. In a smaller field effectiveness and safety study, 14 cats weretreated with vetsulin . Hypoglycemia was reported in 6 cats (8 total occurrences). Lethargy not associatedwith hypoglycemia was reported in 4 cats (6 total occurrences). The following clinical observations occurredin the field study following treatment with vetsulin and may be directly attributed to the drug or may besecondary to the diabetic state or other underlying conditions in the cats: foul odor to stool, diarrhea, dullcoat, rapid, shallow breathing, stiff gate in rear, gallop rhythm, and pruritus with alopecia. During the 1998-2007 period, the following adverse events in 50 cats treated with porcine insulin zincsuspension were reported to Intervet International and Intervet Inc: Death, seizures, lack of effectiveness/dysregulation, hypoglycemia, allergic or skin reaction, lethargy, vomiting/diarrhea, injection pain,hyperthermia, nystagmus, PU/PD, and abnormal behavior.In a 21-day field safety and effectiveness study, 36 cats, already well controlled on vetsulin , wereadministered vetsulin using a VetPen insulin pen loaded with a pre-filled 2.7 mL vetsulin cartridge and29 gauge/12 mm pen needles. Loss of diabetic control was reported in three cats all of which resolved afterdose adjustment while still using the insulin pen. Hypoglycemia was reported in one cat. The cat recoveredwith supportive care and dose adjustment. To report suspected adverse drug experiences, call Merck at 1-800-224-5318.For additional information about adverse drug experience reporting for animal drugs, contact FDA at1-888-FDA-VETS, or NERAL PHARMACOLOGYvetsulin is a mixture of amorphous and crystalline insulin resulting in immediate and prolonged insulinactivity. In dogs, vetsulin may show two peaks of activity. In a laboratory study, 12 healthy adult Beagleswere administered vetsulin at a dose of 0.5 IU/kg. The onset of activity varied from 0.5 to 2 hours; the time to peak activity varied from 1 to 10 hours; and the duration of activityvaried from 10 to 24 hours. In diabetic dogs, vetsulin has two peaks of activity following subcutaneousadministration (the first occurs at 2 to 6 hours

dog to dog but can be dramatic and, in most cases, improvement can be seen within a few days. If Vetsulin is not given as directed, signs of diabetes will . If your pet is conscious, rub approximately 1 tablespoon of corn syrup or honey on your pet's gums. When it is able to swallow, give corn syrup or honey by mouth until your pet is .