Expert Advice | Alanine Transaminase | Obesity

EXPERT ADVICE MAKING THE CONNEcTION wITH YOUR ClIENTS

A guide to talking about canine obesity and SLENTROL

LESS WEIGHT. MORE LIVING.

This guide was created to help you and your staff have effective conversations with owners of obese dogs about the need for treatment and the availability of SLENTROL (dirlotapide). you can establish your own success story for your clinic and the dogs you help to achieve healthy weight. The information in this piece is a compilation of best practices and recommendations given by veterinary professionals who participated in a SLENTROL Leader’s Exchange called SCALE (SLENTROL Champion and Local Expert). . *  A detailed description of SCALE can be found at the end of this guide.The SLENTROL Conversation PEER pERSpEcTIVES Discussing canine obesity and the need for dogs to lose unhealthy weight can often be difficult to manage with dog owners. * The next 3 sections include their perspectives on important client challenges: • Overcoming conversation obstacles • Talking with clients about SLENTROL • Handling client concerns By building on the experiences of your peers.

Keep your assessment objective and break the news the same way you would tell a client a dog has periodontal disease Expert tips • Use your practice-management software program to print out weight charts for your patients. HURDLE 1 Breaking the news that your client’s dog is obese How to overcome • When discussing associated conditions. leverage obesity as the possible common factor. Your clients may not realize the impact a few pounds can make on their dog’s health Sound bite: “Those 7 pounds are an extra 20% added to your dog’s weight. Read how your peers overcome conversation hurdles with the following time-efficient tips and sample sound bites. These are great tools to show clients that their dog’s weight has progressively increased Sound bite: “Your dog has gained about 5 pounds each year. such as arthritis. he/she’ll be 20 pounds overweight next year!” • Put the weight into perspective. This will help you save time and stress the importance of treatment with clients • Treat obesity with the same urgency as any other serious canine health condition. That’s like a person gaining an extra 30 pounds!” . If this continues.Overcoming CONVERSATION HURDlES Speaking with clients about their dog’s unhealthy weight can often be difficult.

respiratory disorders.” .” “hefty. There are other pathophysiological factors that affect a dog’s ability to lose weight and can be the reason previous weight-loss attempts have failed9-13 Sound bite: “When dogs become obese.HURDLE 2 Convincing clients that there is a need to treat obesity How to overcome • Avoid trivializing the problem by using light descriptions to address dogs’ weight. such as “chunky. requires treatment just like any other canine disease1 Expert tips • Relate canine obesity to human health issues. which is increasingly being thought of as a disease. high blood pressure. but may not know that dogs are also prone to many of the same risks2-8 Sound bite: “Just like in humans. and even cause or worsen other serious medical conditions. Tell your clients that obesity. Changes in their bodies can lower their metabolism. That means diet and exercise sometimes won’t be enough to help your dog lose weight. that extra weight on your dog is associated with some serious conditions like arthritis. increase their appetite. Most people understand that obesity is dangerous to human health.” • Help your clients understand that obesity sometimes cannot be treated by diet and exercise alone.” or “pudgy” • Research shows that dog owners who are told about the health risks of canine obesity are more motivated to take action. their bodies begin to work against them. and more.

if you are concerned that your clients will be offended. follow through with your recommendation and prescribe SLENTROL • Use your clients’ frustration with diet and exercise to transition to SLENTROL Sound bite: “You’ve already tried cutting back your dog’s food. but don’t place blame or forget to empathize with your clients’ frustration Expert tips • If you and your clients decide to try diet and exercise before SLENTROL. keep in mind that they want what’s best for their dog just like you do. However. 1 month). and have your clients come in to assess their dog’s weight during that time.HURDLE 3 Being firm with your treatment recommendations How to overcome • Assert your role as the veterinary professional. etc • Tone of voice should remain neutral and professional • alk about obesity the same way you would discuss any other important canine disease . general health.” Talking to an overweight client? Just use a little TACT Discussing canine obesity with overweight owners can be a sensitive issue. Now it’s time to cut back your dog’s appetite. You ultimately know what’s best for your canine patients • Acknowledge the failure of previous weight-loss attempts. As the veterinary professional. If there is no improvement in weight. you are the trusted expert when it comes to canine health. and your clients look to you to provide the best care for their dog. associated conditions. Keeping your obesity conversations on a clinical level can be easy by using TACT: T • Address obesity as a major concern for the dog’s health • Concentrate on the dog and his or her weight. place a time limit on the trial (eg.

and provides suggested sound bites to translate that data into client-friendly language. Important SLENTROL facts Sound bites for presenting these facts to your clients SLENTROL works • SLENTROL is proven to safely help dogs lose weight —— Weight loss at a significant rate averaging 3% per month —— Excellent safety profile established in worldwide studies “Helping your dog lose weight can be difficult.”14 Mode oF action • SLENTROL decreases appetite and reduces food intake “SLENTROL works by cutting back your dog’s appetite. lethargy. The client should be made aware that if any of these signs persist for more than 2 days the dog should be re-evaluated.”15 SLENTROL should not be used in cats. dogs receiving long-term corticosteroid therapy. or in dogs with liver disease. . That’s why I’m recommending SLENTROL. That’s a good. “And unlike other weight-loss drugs. you won’t have to worry that your dog is hungry. SLENTROL is not a stimulant and isn’t associated with bad side effects like oily discharge or excess gas. SLENTROL is not for use in humans under any circumstances. or anorexia. which means your dog eats less. In addition. And it’s safe—dogs on SLENTROL lose about 3% of their weight each month. The most common side effect is vomiting.talking to YoUr clients ABOUT SlENTROl When introducing SLENTROL to clients. The chart below outlines the most important facts your clients need to know about SLENTROL. It’s the dependable option that’s proven to help dogs lose weight. By reducing your dog’s appetite. dogs may experience diarrhea. keeping it simple is key. steady rate that will help make sure your dog loses fat and not muscle.

healthy feeding and exercise still play an important part in this process.” . “I know you want what’s best for your dog. and to do that. These monthly check-ins will help me make sure he/she is losing weight at an appropriate rate. or climbing stairs.Important SLENTROL facts Sound bites for presenting these facts to your clients Your clients’ role • As part of the SLENTROL Treatment Plan. “Now remember. While your dog is on SLENTROL. like running. you can really make a difference in his/her quality of life. playing. the monthly check-in appointments give veterinarians and clients time to work together to develop healthier feeding and exercise habits “I want to make sure your dog gets the most successful results with SLENTROL. I can work with you to establish healthy habits that will help maintain the weight loss after he/she completes the treatment. you’ll need to come in for monthly dose assessments. By helping your dog lose weight with SLENTROL.” Quality oF liFe • In a survey of SLENTROL users16 —— 61% of dogs were able to run more —— 47% of dogs played more —— 37% of dogs were able to climb stairs better than before “Losing weight can help your dog with things that he/she used to enjoy. “We’ll check your dog’s weight and then adjust the dose if needed.

That’s why I check your dog’s BCS. See how he/she has gained weight over the past few years? That might be the real reason your dog has been progressively less active. The Body Condition Score (BCS) chart gives clients an official guide that shows them how to recognize what is a healthy weight for their dogs. you can show the increase in weight over the years parallels the decrease in activity Sound bite: “How active would you say your dog is now? How does that compare to his/her activity level from last year or the year before? That drop in activity may not be due to age.” . Keep a BCS chart 1in the exam room and ask your clients to try to identify their dog’s score. or Body Condition Score. By using weight charts. IF YoUr clients saY: “My dog isn’t obese! How to respond: He’s just a little chunky. It shows you how to recognize the signs of too 3 much weight on a dog. Many owners may not realize their dog is less active or they believe drops in activity level are due to age. Take a look at this chart. Based on this scale. Take a look at your dog’s weight chart.” OBSTACLE 1 • Most dog owners will not know if their dogs are overweight or obese. what kind of score would you give your dog?” OBSTACLE OBSTACLE • Ask your clients to compare their dog’s current activity level with those of previous years. at every exam.Handling clIENT cONcERNS Every veterinarian encounters owners who don’t recognize that their dog is obese and have difficulty accepting a recommendation of SLENTROL. Then tell them your assessment and how it was determined OBSTACLE OBSTACLE 2 OBSTACLE 3 Sound bite: “Sometimes it’s hard to know when those extra pounds have 2 added up. Get your clients on board by checking out how your peers are addressing 5 of the top client concerns. Help them realize that weight gain can be the real cause.

Staying committed to the plan now can help their dog’s overall health and can lead to a better quality of life OBSTACLE OBSTACLE 2 OBSTACLE 3 2 Sound bite: “As in any weight-loss plan. And don’t worry that you have to do this on your own. Just wait and see what a difference a healthy weight can make in your dog’s life. you will be able to help your dog become healthier and more active. it takes commitment to achieve success. With just a few months 3of your time.” OBSTACLE OBSTACLE .” How to respond: • Remind them that you are recommending SLENTROL to help the health of their dog OBSTACLE 1 • Discuss treatment with SLENTROL as a short-term commitment that will 1 achieve long-term goals. Together we can establish a healthy feeding and exercise regimen that will keep the weight off even after treatment. I’ll be here to help you every month. But think of the long-term benefits for your dog.IF YoUr clients saY: “It looks like this plan will be too much work and take a lot of my time.

However.IF YoUr clients saY: “I don’t want to use a diet drug on my dog. firmly recommend a weight check every month to see how the dog is progressing. Clearly outline all your reasons for prescribing SLENTROL. With SLENTROL. respect their decision and design a diet and exercise program for their dog. Focus on SLENTROL as the dependable option that can help dogs lose 3 weight.” How to respond: • Truly believing in your recommendation to use SLENTROL can help ease owner apprehension. that weight may be making your dog’s arthritis even worse. In fact. If your patients already have a condition because of their obesity. have the SLENTROL conversation again . Losing weight can help take some of the burden off his/her joints. If the plan is not working after a few months. and put a strain on his/her lungs and joints.16 OBSTACLE OBSTACLE Sound bite: “Excess weight can affect your dog’s health. Give examples of other canine patients you’ve put on SLENTROL 1 and how successful they have been on the treatment OBSTACLE OBSTACLE 1 OBSTACLE 2 OBSTACLE 3 • Highlight the medical risks associated with obesity and how these risks can impact 2 their dog’s health.” • If your clients still do not believe in using a medication. emphasize how obesity may have caused it or is making it worse. you have a proven and dependable way to help your dog achieve a healthy weight. and how it may lead to improvements in their quality of life2-8.

” OBSTACLE . 3 SLENTROL is proven to help dogs lose weight at a safe and dependable pace. Assure them that SLENTROL is FDA approved and has been studied extensively in both the United States and Europe OBSTACLE OBSTACLE 2 • Remind them that you are recommending SLENTROL to help their dog lose unhealthy weight.IF YoUr clients saY: “A medication for obesity How to respond: doesn’t sound safe for my dog. I’ll be able to monitor your dog’s progress each month when you bring him/her in for dose assessments. Plus. Unless we get the weight off. he/she will be at risk for some very serious medical conditions. Restating the reasons why you are prescribing SLENTROL can help reassure them of your recommendation 2 OBSTACLE 1 OBSTACLE 3 Sound bite: “Your dog’s weight isn’t safe for his/her health. Then address them with data from the trials.” OBSTACLE 1 • Ask your clients to tell you their specific concerns.

IF YoUr clients saY: “This is going to cost too much. He/She may be at risk of developing serious conditions that can require long-term medication or even surgery. included 99 veterinarians who implemented a SLENTROL program in their practices and have multiple patients on product. UT. After hearing the dangers of obesity. This piece is based on the discussions that occurred during the meeting. in Salt Lake City. which took place January 25-26. many owners will put their dog’s health first and want to take the best option available OBSTACLE OBSTACLE 1 OBSTACLE 2 • Give owners the big picture: starting treatment can improve their dog’s quality of life and may even help avoid future problems with their health. By helping him/her lose weight.” OBSTACLE About SCALE The SCALE Leader’s Exchange. 2 this approach can help your clients realize that accepting your Taking recommendation for SLENTROL may save them money in the long run OBSTACLE 1 OBSTACLE 3 Sound bite: “Think of what can happen if your dog doesn’t lose that unhealthy 3 weight. you may be able to avoid these future problems and save more money in the long run. 2008. .” How to respond: • Educate owners on the health risks associated with obesity and the benefits of using SLENTROL. Veterinarians exchanged ideas on best practices by sharing their clinical experiences with SLENTROL and participating in roundtable discussions.

remove the bottle cap and insert the supplied oral dosing syringe through the membrane into the bottle. WEIGHT LOSS PHASE Initial assessment and dosing in first month Assess the dog prior to initiation of therapy with SLENTROL to determine the desired weight and to assess the animal’s general health (See Precautions). If the dog has lost weight. the dose volume should be increased. the veterinarian and the pet owner should establish the optimal level of food intake and physical activity needed. administered once daily for the next 14 days (days 15 to 28 of treatment).009 mL/lb) of body weight. Invert the bottle and withdraw the appropriate volume required using the graduation marks on the side of the oral dosing syringe. If the dog has gained weight since the last visit. as necessary. Go directly to the First (or Subsequent) Dose Adjustment Section below. Monthly weight loss rate achieved • If the Actual % weight loss is the same or greater than the Target % weight loss.5 times the dose administered the previous month.Oral solution for use in dogs only. the dose may be withdrawn until the appetite returns (usually 1-2 days) and then resume dosing at the same volume. body weight should continue to be assessed at monthly intervals.09 mL/lb) should not be exceeded. the following dose adjustment instructions apply: • First dose adjustment • The dose volume (number of mL administered each day) should be increased by 100%. Based on the dog’s current body weight a daily dose of 0. Reverting to previous food intake or physical activity levels at this point can contribute to a re-gain of some or all of the weight loss that has been achieved.01 mL/kg (0. to maintain a target percent weight loss of ≥ 0. Subsequent Monthly Dose Adjustments for Weight Loss Dogs should be weighed monthly and the dose volume adjusted every month. • Subsequent dose adjustments In subsequent months the dose volume should be increased or decreased by 25% to maintain a constant weight. In subsequent months of therapy. Wipe the oral dosing syringe clean after each use with a clean dry cloth or disposable towel. Only perform a 100% dose increase once during treatment after day 14. When SLENTROL is discontinued. determine if an adjustment in dose is required using the following calculations: (Number of weeks between visits) X 0. The chemical name is (S )-N-{2-[Benzyl(methyl)amino]-2-oxo-1phenylethyl}-1-methyl-5-[4’-(trifluoromethyl)[1. based on the amount of weight lost (expressed as a percent) during the previous month of therapy.2 mL/kg (0.7 % per week = Target % weight loss ( Weight at last visit – Weight at current visit Weight at last visit ) X 100 = Actual % loss Example – in 4 weeks (28 days) the Target weight loss would be 4 X 0. The initial dosage of SLENTROL is 0. the recommended dosing regimen prescribed for SLENTROL varies for each individual dog and the dose volume must be specifically calculated each month. The dose should not exceed a maximum daily dose of 0. • Dose adjustments are determined at monthly intervals.73. Note: All dose adjustments are based solely on volume (mL). the dose volume (number of mL administered each day) should remain the same for the next month of dosing until the next scheduled assessment. Based on the dog’s current body weight a daily dose of 0. The monthly adjustments should continue in this way until the desired weight determined at the start of therapy is reached. for the first 14 days. the dose volume (number of mL administered each day) should be decreased by 50% resulting in a decrease of the dose volume to 0.2 mL/kg (0. During the first month of therapy. compare the Actual % weight loss to the Target % weight loss and use the following guidelines.0045 mL/lb) body weight. • If the dog lost >5% body weight. • Subsequent dose adjustments • If additional dose increases are necessary in the following months. • If the dog gained weight.7% per week) with the Actual % weight loss for that dog.8% of the total body weight Compare the Target % weight loss (of ≥ 0. INFORMATION FOR OWNER OR PERSON TREATING ANIMAL: Successful implementation of any weight loss program for dogs requires active. Dirlotapide is a selective microsomal triglyceride transfer protein inhibitor that blocks the assembly and release of lipoprotein particles into the bloodstream (via the lymphatic system) in dogs. Dose Preparation and Administration: To prepare for oral administration. • If the dog gained >5% body weight. With regard to dosing it is important to note that: • Initial body weight is used to calculate the dose that is first administered.7% per week. When the desired weight is reached. the dose volume (number of mL administered each day) should be increased by 50%. CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.1’-biphenyl]-2-carboxamido]-1H-indole-2-carboxamide. resulting in an increase of the dose volume to 1.0 times the dose administered during the previous month of dosing. Monthly weight loss not achieved • If the Actual % weekly weight loss is less than the Target % weight loss of 0. To dose for weight management. To determine if a dose adjustment is necessary. then the dose should be decreased by 25%.1 The empirical formula is C40H33F3N4O3 and the molecular weight is 674. or at least 2. the dose volume of SLENTROL should be doubled to 0. • If the dog lost between 0 and 1% the dose should remain the same. The safety of SLENTROL use in dogs has not been evaluated beyond 1 year.09 mL/lb). The chemical structure of dirlotapide is: INDICATIONS: SLENTROL (dirlotapide) Oral Solution is indicated for the management of obesity in dogs.02 mL/kg (0. the dosing regimen for SLENTROL consists of two fixed dose rates (number of mL administered per unit of body weight) in all dogs. SLENTROL administration should be continued during the weight management phase until the dog owner can establish the food intake and physical activity needed to stabilize body weight at the dog’s desired weight. resulting in an increase of the dose volume to 2. orally.7% weekly. The dog will need to be weighed at the start of treatment and then at monthly intervals so that the dosing regimen can be adjusted according to the prescribing instructions below. SLENTROL can be administered directly into the dog’s mouth or on a small amount of food. DOSAGE AND ADMINISTRATION: SLENTROL should be prescribed as part of an overall weight management program that incorporates a complete and balanced canine diet and physical activity.09 mL/lb) should not be exceeded.7% per week. It can be given with a meal or at a different time of day. the dose volume (number of mL administered each day) should remain unchanged.5 times the dose administered the previous month. After the first 14 days of treatment. During the weight management phase. WEIGHT MANAGEMENT PHASE A 3-month weight management phase is recommended to successfully maintain the weight loss achieved with treatment. DESCRIPTION: SLENTROL (dirlotapide) is a solution formulated at a concentration of 5 mg/mL of dirlotapide for oral administration to dogs. begin the weight management phase. administered once daily. • First dose adjustment • If the dog lost ≥1% body weight per week in the last month of the weight loss phase. If a dog’s food consumption is greatly reduced for several consecutive days. during any part of treatment. the daily amount of food offered and physical activity should be continued as established during the weight management phase.5 times the dose administered the previous month of dosing. then the dose should be increased by 25%. on-going . • Subsequent dose adjustments are made by adjusting the volume of solution administered. Do not introduce water into the oral dosing syringe or the SLENTROL solution. based on the dog’s current body weight. • If the dog is within -5% to +5% of the body weight at the end of the weight loss phase. the dose should be increased by 50% resulting in an increase of the dose volume to 1.2 mL/kg (0.

The cause of death was not conclusive but did not appear to be related to the dirlotapide therapy. ADVERSE REACTIONS: The adverse reactions associated with treatment with SLENTROL include vomiting. It is important that the prescribing veterinarian maintains an active veterinarian-client-patient relationship with the dog and the dog owner/caretaker during all phases of therapy and proactively communicates about their role in making the program successful in the short as well as the long-term. Two dogs in the SLENTROL treatment group developed corneal ulcers. γ-glutamyl transferase (GGT).4% 2.7% 3. d Pre = % of dogs with values above the laboratory reference range at pre-treatment. The fecal and biliary routes are the predominant routes of elimination. abnormal skin and ear findings. Dirlotapide is available systemically.6%).4% 3. loose stools/diarrhea.7% 6.9% 4. EFFECTIVENESS: . was found dead by the owner 7 days after stopping dirlotapide therapy. and vomiting. however. The SLENTROL-treated dogs generally had an increased frequency and duration of vomiting and diarrhea compared to the control dogs. If vomiting is severe or lasts longer than 2 days. flatulence. Dirlotapide and its metabolites are secreted in the bile and may undergo enterohepatic circulation. In the post-treatment period.2% 9. SLENTROL is not recommended for use in dogs currently receiving long-term corticosteroid therapy.8% 16. Reverting to previous food intake or physical activity levels at this point can contribute to a re-gain of some or all of the weight loss that has been achieved. The incidence of these findings were similar in both control and SLENTROL treated groups and most dogs had similar lesions noted pre-treatment. During weight stabilization. Dirlotapide in circulation is highly protein bound.When SLENTROL is discontinued.8% Post e 6. lethargy. alkaline phosphatase (ALP). Although systemic blood levels do not directly correlate with effectiveness (effectiveness has been linked to drug concentrations in the gut).5% 17.8% 12. there were other abnormal findings. A 5 year old Dachshund developed a hepatopathy after 82 days of treatment and was withdrawn from the study for vomiting. If vomiting does occur it is recommended to continue dosing at the same dose volume.4% 14. should be managed prior to use of SLENTROL. the daily amount of food offered and physical activity should be continued as established during the weight management phase.0% 4.6% ALT = serum alanine aminotransferase activity. continue SLENTROL and monitor as needed. long-term weight management requires changes that extend beyond the period of drug therapy. headache. ALT activity levels continued to rise after all clinical observations resolved. SLENTROL has not been evaluated in dogs less than 1 year of age. and large inter-individual variability has been observed in multiple studies and at various dose levels. CLINICAL PHARMACOLOGY: SLENTROL (dirlotapide) is a selective microsomal triglyceride transfer protein inhibitor that blocks the assembly and release of lipoproteins into the bloodstream.6% Pre d 4. if total inappetence or anorexia is observed for more than one day. but may not be limited to: • SLENTROL is not a cure for obesity.8%) were the most frequent adverse reactions associated with treatment with SLENTROL. For a copy of the Material Safety Data Sheet (MSDS) for SLENTROL oral solution call 1-800-733-5500. • Almost 1 in 4 of dogs placed on SLENTROL therapy experienced occasional episodes of vomiting and diarrhea. The vomiting occurred most often during the first month of treatment or within a week of a dose increase. SLENTROL mainly acts locally in the gut to reduce appetite. INFORMATION FOR OWNER OR PERSON TREATING ANIMAL: Successful implementation of any weight loss program for dogs requires active. If the elevation in alanine aminotransferase (ALT) activity is mild. Some dogs treated with SLENTROL displayed a mild to moderate elevation in serum hepatic transaminase activity early in treatment that decreased over time while treatment continued. including hyperadrenalcorticalism (Cushing’s disease). anorexia (1. A decrease in appetite and associated begging behavior can be expected with SLENTROL treatment.6% 14.7% SLENTROL n = 170 Post e 9. and resolved with continued SLENTROL treatment. and lameness/arthritis. In most cases these episodes lasted for one or two days. The dog continued to receive SLENTROL until additional seizures occurred 11 and 12 days later. or total bilirubin. The mechanism of action for producing weight loss is not completely understood. consult your veterinarian and have your dog evaluated. One SLENTROL-treated and one control dog developed signs consistent with pancreatitis. The investigator referred the case to a neurologist and the seizures continued approximately twice weekly. Many control and SLENTROL-treated dogs had dental disease. drug accumulation (at higher doses). Dogs with ALP activity > 325 IU/L were excluded from the study. The safety of SLENTROL use in dogs has not been evaluated beyond 1 year. Adverse reactions associated with humans ingesting dirlotapide include: abdominal distention.3% 7. Caution should be taken when considering any weight loss program in growing dogs. and it seemed to increase with dose and with repeated dosing. Vomiting was usually mild in severity. Hepatic transaminases generally returned to normal when treatment was discontinued (See Precautions for further information). SLENTROL may cause eye-irritation. diarrhea. One treated dog developed inappropriate urination and defecation and another treated dog developed polyuria and polydipsia. a 6 year old spayed female Chihuahua. these signs should be reported to the prescribing veterinarian.6%). flush the eyes immediately with clean water. Keep this and all drugs out of reach of children. increase fecal fat and produce weight loss in the management of obesity in dogs. To maintain the weight lost when treated with SLENTROL. However. The mean elimination half-life ranged between 5 and 18 hours. These adverse reactions were mainly observed during the first month of treatment or during the week after a dose increase. Weight gain will occur if the amount of food offered is not limited at the time SLENTROL is discontinued. abdominal pain. Do not use in dogs with liver disease. Non-linear pharmacokinetics with less-than-proportional exposure.6% 1. If accidental eye exposure occurs. but absorption in dogs is highly variable. on-going communication between the dog owner/caretaker and the veterinary professional treating the pet. Pre-existing endocrine disease. the time of day or method of administration (with or without food) may be changed.6% 24. including treatment with SLENTROL. Absorbed SLENTROL is metabolized in the liver. The control dogs received corn oil. and ataxia (1. WARNINGS: Not for use in humans. PRECAUTIONS: Safety in breeding.1% 2. the adjustments in dietary management as well as physical activity that were begun as part of the overall weight loss program must be continued by the owner after drug therapy is discontinued.4% 0% 11.6%). nausea.9% 9. and anorexia. b AST = serum aspartate aminotransferase activity.1%) and lethargy (4. When drug therapy such as SLENTROL is included in the program. increased serum transaminases. The neurologist found no lesions that support the causality of the seizures. vomiting (16. Vomiting continued for a few days after stopping treatment and the dog was hospitalized due to the anorexia.9% 9. All dogs should undergo a thorough history and physical examination that includes laboratory tests to screen for underlying conditions. but it seems to result from reduced fat absorption and a satiety signal from lipid-filled enterocytes. c ALP = serum alkaline phosphatase activity. SLENTROL increases the risk of producing hepatic lipidosis during weight loss in obese cats. Elevations in hepatic transaminase activity usually decrease when SLENTROL is discontinued. • SLENTROL decreases the food intake of the dog. A 5 year old Beagle with no medical history of seizures in the SLENTROL treatment group had a seizure on Day 52 of the study. SLENTROL may produce a mild to moderate elevation in serum hepatic transaminase activity. The safety of SLENTROL use in dogs has not been evaluated beyond 1 year. increased hepatic enzymes. e Post = % of dogs with values above the laboratory reference range after 4 months of treatment. To report a suspected adverse reaction call Pfizer Animal Health at 1-800-366-5288. CONTRAINDICATIONS: SLENTROL should not be used in cats. Treatment Vomiting Diarrhea Lethargy Anorexia Constipation Dehydration Adverse Reactions During Weight Loss: Percentage of Patients with Reported Signs Control SLENTROL n = 88 n = 170 21. Serum Chemistry Results: Percentage of Dogs Serum Analyte ALT a > 120 IU/L AST b > 60 IU/L ALP c > 125 IU/L Cholesterol > 320 mg/dL a Control n = 88 Pre d 3.2% In addition to the adverse reactions listed above. this discussion may include.4% 9. Other adverse reactions included diarrhea (1. discontinue treatment with SLENTROL. and anorexia. pregnant. they seem to correlate with the systemic toxicity observed for this drug. of short duration. or lactating dogs has not been established. • Successful. If there is a marked elevation in ALT activity above the normal reference range or there is a simultaneous increase in aspartate aminotransferase (AST).4% 0% 1. The decreased appetite experienced when dogs are treated with dirlotapide is only temporary and lasts no longer than 1-2 days beyond the cessation of therapy.

Microsomal triglyceride transfer protein: role in the assembly of intestinal lipoproteins.2 mL/kg (1 mg/kg) current body weight. Individual Responses: After 14 days of treatment. vomiting. had a consistently elevated ALT and also had an elevated alkaline phosphatase prior to treatment. antiparasitics. All treatment-related clinical chemistry changes had reverted to normal at the end of the 1-month recovery phase.24 mg/lb (0. The increases in ALT activity diminished during 3 months of continued treatment and were generally within normal limits for the 1. 0. J. Prothrombin times were similar in the SLENTROL-treated and the control dogs and there were no clinical signs of abnormal hemostasis observed during the 12-month study. low blood urea nitrogen and low serum creatinine compared to control dogs. primarily during the first 28 days of treatment. Polyphagia was reported as an abnormal clinical finding in 8 of 106 dogs when SLENTROL was discontinued. SLENTROL was not tested concomitantly with long-acting steroid products. SLENTROL administration also resulted in a decrease in body weight. from 23 veterinary clinics. there were also mild increases in gamma-glutamyltransferase activity (GGT) and alkaline phosphatase (ALP) activity in the first month of treatment. M. and body weight.5 and 2. J. Histopathology revealed accumulation of lipid vacuoles in the apical third of enterocytes in the small intestine in all treated dogs and minimal to mild periportal fatty change in the liver in five treated dogs. low serum albumin and globulins. Vet.0 uM/L (~5-fold pre-treatment value). Some treated dogs had ocular lesions at the end of the study including retinal degeneration and cataracts. SLENTROL administration produced reductions in food intake.5. 2 LaFlamme.correlate with the systemic toxicity observed for this drug. or total bilirubin. two of six dogs (one male and one female) had AST elevations > 100 U/L in combination with ALT elevations >500 U/L and a mild increase in bile acids. Vomiting generally occurred within 4 hours of dosing and had the highest incidence during the first three days of treatment. Daily oral treatment with SLENTROL was safe and effectively stabilized body weight ± 5%. SLENTROL was discontinued and body weight measured for an additional 2 months. Tetrick.A. 1. short-acting oral steroid preparations. Vomiting was dose-related and was observed in all treatment groups. At the end of treatment the final mean dosage was 0. Mean ALT activity and AST activity were increased at doses of 1.0001) 11.11 to 0. SLENTROL dosage was adjusted monthly (50% first adjustment and 25% subsequently) to maintain the desired body weight ± 5%. The alkaline phosphatase levels mildly decreased in the treated dogs. The control dogs received corn oil. and returned to normal concentrations during a one-month post treatment period. plasma vitamin A and E concentrations of the SLENTROL-treated dogs were significantly below the vitamin A and E concentrations of the control dogs.to 12-fold higher than controls for AST and ALT activity. 5. and then adjusted monthly for 4 months. The weight management period was designed to educate the owner on the optimal amount of food necessary and exercise required to maintain the dog’s desired body weight. doubled at 14 days. excluded from the totals. Canine Practice. range 0. P. and it seemed to increase with dose and with repeated dosing. anthelmintics.5 mg/kg/day group and ~5.56 mg/kg) based on current body weight. References 1 Wetterau. Decreases in plasma concentrations of vitamins A and E were observed early in treatment for all SLENTROL-treated groups. and mean decreases in serum total protein and albumin. 171-184. Clinical Chemistry: Dogs treated with SLENTROL revealed a dose-related decrease in serum cholesterol and high-density lipoprotein (HDL) concentration. no other changes in other liver function indicators accompanied these mild elevations in hepatic transaminases. conducted at 14 different US veterinary clinics. an amount that has been shown to provide a health benefit in obese dogs3.5 and 2. 2001. and total bilirubin were not changed during 12 months of SLENTROL treatment. Development and validation of a body condition scoring system for dogs.05 mg/kg). Patent No. In the remaining dogs elevated hepatic transaminase enzymes were not accompanied by increases in other liver function indicators such as ALP. ALT activity tended to gradually increase as the SLENTROL dose increased during the first 6 months of weight loss and then decreased during the next 6 months despite continued SLENTROL treatment at the weight stabilization dosage. ophthalmic. These elevations decreased over time with continued treatment. HOW SUPPLIED: SLENTROL is available in 20. At the completion of the weight management phase. respectively. The control used was medium chain triglyceride oil. One dog.26 mg/kg. Enterocytes in the villus tips of the small intestine contained lipid vacuoles. Clinical Chemistry & Histopathology: Changes in serum chemistry included a significant dose-related decrease in mean serum cholesterol and high-density lipoprotein. 1997. these lesions were considered incidental to the Labrador breed. and topical steroid preparations. Am. Acute Tolerance: In a separate 14-day acute tolerance study the safety of SLENTROL (dirlotapide) was evaluated following daily oral administration of 0.5 mg/kg once daily for 90 days. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity. Clinical Observations: Diarrhea.S. Pathology: On gross necropsy. 22:10-15. Clinical Observations: Vomiting and loose stools were the most frequent clinical signs observed. Clinical Chemistry: Serum cholesterol concentrations were significantly decreased during the first 6 months of treatment at the weight loss dosage and were at the low normal or below the laboratory reference range (135 to 270 mg/dL). 6. The dosage was adjusted monthly to produce ≥ 1% weekly body weight loss for 6 months and then adjusted to maintain body weight constant (retraining or weight stabilization phase) for the next 6 months. up to a maximum dosage of 0. when adjusted monthly by 50% the first month and then by 25% monthly. Plasma vitamin A concentration was low after one month and the median values did not decline any further.12 mg/lb with a range of 0. and large inter-individual variability has been observed in multiple studies and at various dose levels. 50 and 150 mL bottles containing 5 mg/mL of dirlotapide in solution. The incidence of loose stools was lower than the incidence of vomiting. Mean and individual values were usually within the published normal range. EFFECTIVENESS: The effectiveness of SLENTROL for the management of obesity was confirmed in two controlled. Excessive salivation was noted in approximately 4 of 48 SLENTROL-treated dogs.to 6-fold higher than control values in the 2. or other products known to affect appetite. GGT. and otic. Diarrhea was mild and observed intermittently throughout the study. Effect of weight reduction on clinical signs of lameness in dogs with hip osteoarthritis. SLENTROL-treated dogs lost a statistically significant (P ≤ 0. ANIMAL SAFETY: Margin of Safety: In a controlled laboratory margin of safety study in neutered.05 mg/lb to 0. and food intake in the treated dogs. participated in the study. primarily during the first month after treatment was discontinued (n = 51). Assoc.023 mg/lb (0. In the female. 216(7):1089-1091. In one field study evaluated for weight loss only. as needed based on individual body weight changes. Gamma glutamyl transferase. Clinical Observations: Vomiting was observed in all groups.5 mg/kg/day groups. STORAGE INFORMATION: Store in original container at room temperature 15° to 30° C (59° to 86° F). Intest. with a body condition score (BCS) ≥ 8 on a 9-point scale 2. A mild increase in mean ALT and AST activity was observed. multi-site field studies using client-owned dogs. Plasma vitamin A and E concentrations appeared to increase during the weight stabilization phase (second 6 months of treatment) and returned to concentrations similar to the control dogs when SLENTROL treatment was discontinued. one high-dose female had an elevation in both ALT activity (257 U/L (~9-fold pre-treatment value) and AST activity (99 U/L (~4-fold pre-treatment value) and one mid-dose female had mild increases in ALT activity (102 U/L (~3-fold pre-treatment value). body condition score. Other clinical pathology changes included low total proteins.Y.R. Kluwer Academic/Plenum Publishers. U.351 NADA #141-260. Other abnormal clinical pathology values included sporadic findings that were similar in the control dogs. Non-linear pharmacokinetics with less-than-proportional exposure. Approved by FDA 820 600 000 October 2006 . Dogs regained approximately 3% of their body weight in 2 months. albumin. Lipid Metab. and excessive salivation were observed more frequently in SLENTROL-treated dogs than in control-treated dogs. Based on the available safety data. Mean serum triglyceride concentration was not changed.. N. Fat Soluble Vitamins: During the first 6 months of treatment.to 4-fold and ~10. New York.8% body weight and 39% lost ≥ 13% body weight. AST: 23 to 66 U/L). 3 Impellizeri. SLENTROL was evaluated in dogs receiving 135 other commonly used veterinary products such as vaccines. SLENTROL (dirlotapide) was administered orally at 0. Most episodes were of short duration and most dogs had only one or two episodes of diarrhea during the 12 months of treatment. organ weights. SLENTROL was effective in producing ≥ 0. which remained well within the published reference range for these analytes (ALT: 2 to 102 U/L. obese Beagle dogs. 2000. Except in this dog.7% weekly (≥ 0. Med. More than 65 different pure breeds and mixed breed dogs were represented in the 276 dogs receiving SLENTROL during the clinical field studies. Vomiting tended to occur within 3 hours of dosing and was more frequent during the first two to four weeks of treatment. collars. 1-Year use-dose study: In a separate long-term laboratory study. J.0 and 10 mg/kg body weight in normal weight Beagle dogs. Plasma vitamin E concentrations were lowest after 6 months of SLENTROL treatment but adipose tissue levels of vitamin E appeared to be increased compared to control dogs after 12 months of treatment. At 1 month. 63 dogs that completed 4 months of SLENTROL treatment for weight loss were evaluated for weight management during a 3 month retraining phase. drug accumulation (at higher doses).5.A. the mucosal surface of the small intestine appeared pale (presumably unabsorbed fat) primarily in the high dose groups.5 mg/kg/day. mean values of the mid and high dose-groups (versus control values) were ~2. D. The control used was medium chain triglyceride oil.5 mg/kg) group. 2.. and calcium. were not progressive with continued treatment. antimicrobials. total proteins.1% daily) weight loss at an initial dosage 0.009 mL/lb medium chain triglyceride oil (control) or 0. Other effects included decreased blood urea nitrogen. Individual Responses: A total of 10 of 48 dogs had sporadic mild to moderate ALT measurements that exceeded the upper limit of the reference range at some point during 12 months (maximum of 366 U/L) of SLENTROL treatment. Sporadic episodes of loose stools occurred throughout the 3-month dosing period in all dose groups.P. In a separate study. the efficacy and safety of SLENTROL (dirlotapide) was evaluated following daily oral administration of an initial dosage of 0. a non-dose-dependent mild to moderate elevation in serum hepatic transaminase enzymes.1 mg/kg (dirlotapide) for 12 months in seventy-two obese Labrador Retrievers. anabolic steroids. Individual Responses: In the high dose (2. The mean elimination half-life ranged between 5 and 18 hours. The ALT elevations were not sustained despite continued treatment during the 6 months of weight stabilization. shampoos. and was also similar between the treated and control groups. Vomiting was also mild and the majority was observed during the first month of treatment. dips. occurred intermittently throughout the study. AST activity (71 U/L (~2-fold pre-treatment value) in combination with a moderate increase in bile acids (57. Vomiting and lethargy still occurred during the weight management phase. AST activity was marginally elevated in 1 of 48 dogs (maximum 84 U/L in a SLENTROL-treated dog and 116 U/L in a control dog) during 12 months of treatment. Muir. Two hundred and fifty eight (88 control and 170 SLENTROL) obese dogs. 21 in the US and 2 in Canada.720. globulin.

© 2008 Pfizer Inc. 3. 2002. Klausner JS. J Nutr. NY. Senard JM.30:30-34. Hickman MA. Adipokine gene expression in dog adipose tissues and dog white adipocytes differentiated in primary culture. Data on file. 2006. Pfizer Inc.MAKING THE CONNECTION TO SLENTROL Pfizer Animal Health is here to help you achieve success with SLENTROL. Pfizer market research SL1007.63:7-10. NY. Obesity-induced hypertension in the dog. 2002.37:474-481. Eisele I. Correlation between plasma leptin concentration and body fat content in dogs. Kealy RD. Muir P. All rights reserved. 4. White RAS. www. 6. Combined results from US studies 1962C-60-03-671 and 1962C-60-02-636 and EU studies 5962C-85-03-280 and 5962C-85-02-263. Verwaerde P. 1987. Horm Metab Res. Deremer S. Study 1560C-60-05-712. Armstrong PJ. J Am Vet Med Assoc. 2000. J Am Vet Med Assoc. Saito M. 10. Smith GK. Trayhurn P. 11.216:1089-1091. 12. Adipose tissue and adipokines—energy regulation from the human perspective. 2006. Moorehead C.9(pt 2): III-64-III-68. 8.35:191-196. Pfizer Inc. 9. New York. Honjoh T. 2008. et al.com LESS WEIGHT. Prevalence and risk factors for obesity in adult dogs from private US veterinary practices. Compendium Cont Ed Vet. Ask your PAH Therapeutic Specialist for these materials and make the connection to success! Ready resources for SLENTROL Health care team support • SLENTROL detailer • Pathophysiology of obesity in-clinic presentation • Expert Advice: Implementing a Weight-Management Program workshop SLENTROL client support • Healthy Start Kit • Reminder cards • SLENTROL Reminders program • SLENTROL in-clinic brochure References: 1. Am J Vet Res. et al. Wood IS. Rocchini AP. Hypertension. NY. Wood IS. Trayhurn P. 7. 14. Lawler DF. Printed in USA/April 2008.136(suppl):1935-1939. J Am Vet Med Assoc. Effect of weight reduction on clinical signs of lameness in dogs with hip osteoarthritis.4:177-186. Impellizeri JA. Paster ER. Trayhurn P. German AJ. Study 7B61P-60-01-201. MORE LIVING. Pfizer Inc. Data on file. 15. Ballam JM. Data on file. et al. J Hypertens. New York. Kirk CA. Nakadomo F.220:1315-1320. Pfizer Inc. 2006. Williams JM. Bing C.SLENTROL. Tracheal collapse in the dog—is there really a role for surgery? A survey of 100 cases. Tetrick MA. Changes in short-term variability of blood pressure and heart rate during the development of obesity-associated hypertension in high-fat fed dogs. New York. Ishioka K. Wentz E. 2.17:1135-1143. 1999. Lund EM. Adipokines and their importance in obese cats. 16. SLE0408055 . 13. Inflammation in obesity: down to the fat? Compendium Cont Ed Pract Vet. Intern J Appl Res Vet Med. 1994. J Small Anim Pract. New York. Galinier M. Hunter L. Effects of diet restriction on life span and age-related changes in dogs. 5. Data on file. NY. 2006. Sagawa MM. 2005. Powers MY. Lifelong diet restriction and radiographic evidence of osteoarthritis of the hip joint in dogs. The list below summarizes resources that are available to support you and your staff in having the SLENTROL conversation with your clients.229:690-693.28:33-36.

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