SLENTROL TREATMENT PLAN A MEDICALLY APPROPRIATE APPROACH TO WEIGHT MANAGEMENT FOR OBESE DOGS A dog’s weight can be influenced by factors such as breed, size, genetics, and diet. SLENTROL is a once-daily medication for the management of canine obesity with a treatment plan specifically designed to allow adjustments based on the individual needs of each dog. The plan provides steady, sustained weight loss over time, during which time owners can develop new and fundamentally better feeding behaviors and exercise regimens for their dogs. Achieving reliable weight reduction in a gradual and safe manner is the preferred, medically responsible way to lose weight. SLENTROL helps dogs lose weight and maintain desired weight in 2 treatment phases. Weight-Loss Phase This phase is designed to achieve a safe and dependable target weight loss of 0.1% per day, equal to approximately 3% per month. Dose is adjusted monthly, as needed, until desired weight is achieved. Weight-Management Phase This phase is designed to stabilize the desired weight and is recommended for a period of at least 3 months. During this time, the veterinarian and owner work together to further establish appropriate feeding and activity levels for the dog. Post-Treatment—after SLENTROL is completed Appropriate feeding and exercise habits established during treatment with SLENTROL are a necessary component of long-term success. The partnership between veterinarians and owners that began in the treatment phases should continue to keep the dog at or close to the desired weight. DOSE VOLUME (mL) IS USED FOR ALL DOSING. SLENTROL TREATMENT PLAN AT A GLANCE The 2 treatment phases of SLENTROL and the plan for post-treatment are outlined here in brief. By utilizing a treatment plan based on a medically appropriate rate of weight loss, veterinarians have the opportunity to: Achieve a healthier weight for obese canine patients Enable owners to better understand the benefits of weight loss and how to sustain it WEIGHT- WEIGHT- POST- LOSS PHASE MANAGEMENT TREATMENT PHASE GOAL: GOAL: GOAL: Achieve desired Stabilize at desired Maintain desired weight at a safe rate weight (within 5%) weight through diet of 0.1% per day/ and exercise 3% per month SLENTROL should not be used in cats, dogs receiving long-term corticosteroid therapy, or in dogs with liver disease. The most common side effect is vomiting. In addition, dogs may experience diarrhea, lethargy, or anorexia. The client should be made aware that if any of these signs persist for more than 2 days the dog should be re-evaluated. SLENTROL is not for use in humans under any circumstances. WEIGHT-LOSS PHASE SETTING THE DOSE FOR THE 1st MONTH All dogs receive a standardized dose regimen (based on mL/lb or mL/kg) to help them adjust to the medication. A dose of 0.0045 mL/lb (0.01 mL/kg) is given for the first 14 days (for example, 0.45 mL for a 100-lb dog). Owners should be instructed to double the dose volume for days 15-28. INITIATION There is a maximum daily Days 1-14 Days 15-28 dosage of 0.09 mL/lb (0.2 mL/kg) based on 0.0045 mL/lb (0.01 mL/kg) Double initial dose volume current body weight. SETTING THE DOSE: 2nd and FOLLOWING MONTHS Use this calculation at every monthly “weigh-in” until desired weight has been reached. When the dog weighs in at desired weight, go directly to Step 1 of Weight-Management Phase. NOTE: If dog has gained weight, dose volume will increase—go to Step 3 below. CALCULATION Step 1 Step 2 Calculate actual % weight loss Calculate target % weight loss for previous period Weight at last visit current weight 100 Days since last visit 0.1 Weight at last visit (0.1 is target percent per day) DOSE ADJUSTMENT Step 3 Actual % weight loss < target % weight loss OR weight gain or 1st-time adjustment: double dose volume No change in dose volume 2nd and all further adjustments: increase dose 50% (1.5 times previous dose volume) WEIGHT-MANAGEMENT PHASE A weight-management phase is strongly recommended for a minimum of 3 months. This transition phase stabilizes desired weight, during which time owners should continue to receive counsel on: Dietary choices Food quantity Exercise levels These recommendations prepare the dog for a lifetime of healthy weight, and are an essential element of the SLENTROL Treatment Plan. SETTING THE DOSE FOR THE 1st MONTH Phase begins once desired weight has been achieved or if sufficient weight has been lost. Calculation below is for 1st month only, using a new target of 0.14% per day. CALCULATION Step 1 Step 2 Calculate actual % weight change Calculate target % weight change for previous period Weight at last visit current weight 100 Days since last visit 0.14 Weight at last visit (0.14 is new target percent per day) DOSE ADJUSTMENT Step 3 Actual % target % Weight gain weight change > weight change All other weight loss or or Increase dose 50% Decrease dose 50% No change in dose volume (1.5 times previous dose volume) (0.5 times previous dose volume) There is a maximum daily dosage of 0.09 mL/lb (0.2 mL/kg) based on current body weight at visit. SLENTROL should not be used in cats, dogs receiving long-term corticosteroid therapy, or in dogs with liver disease. The most common side effect is vomiting. In addition, dogs may experience diarrhea, lethargy, or anorexia. The client should be made aware that if any of these signs persist for more than 2 days the dog should be re-evaluated. SLENTROL is not for use in humans under any circumstances. SETTING THE DOSE FOR THE 2nd and FOLLOWING MONTHS The goal for the rest of this phase is to keep the dog within 5% of desired weight or the weight achieved at the end of the weight-loss phase. Controlling the weight establishes a constant baseline, while the owner continues lifestyle adjustments meant to maintain the healthy weight post-treatment. The safety of SLENTROL use in dogs has not been evaluated beyond one year. CALCULATION Step 1 Step 2 Calculate upper limit of 5% range Calculate lower limit of 5% range 1.05 desired weight 0.95 desired weight TITRATION Step 3 Current weight > upper limit Current weight < lower limit Within range or or Increase dose 25% Decrease dose 25% No change in dose volume (1.25 times previous dose volume) (0.75 times previous dose volume) POST-TREATMENT Dogs will experience an increase in appetite within 1-2 days after cessation of therapy with SLENTROL. Maintaining the desired weight long term can only be achieved with appropriate changes in diet and exercise. Encourage owners to: Continue feeding a nutritionally complete dog food, in portions established during the Weight-Management Phase Keep activity and exercise at a level that allows the dog to expend energy in direct proportion to the amount of calories consumed SLENTROL should be prescribed as part of an overall weight-management program; successful implementation requires active, ongoing communication between veterinarian and owner. WEIGHT MANAGEMENT PHASE A 3-month weight management phase is recommended to successfully maintain the weight loss achieved with treatment. During the weight management phase, the veterinarian and the pet owner should establish the optimal level of food intake and physical activity needed. SLENTROL administration should be continued during the weight management phase until the dog owner can establish the food intake and physical activity (dirlotapide) needed to stabilize body weight at the dog’s desired weight. Oral solution for use in dogs only. To dose for weight management, body weight should continue to be assessed at monthly intervals. • First dose adjustment CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. • If the dog lost ≥1% body weight per week in the last month of the weight loss phase, the dose volume DESCRIPTION: SLENTROL (dirlotapide) is a solution formulated at a concentration of 5 mg/mL of dirlotapide (number of mL administered each day) should be decreased by 50% resulting in a decrease of the for oral administration to dogs. Dirlotapide is a selective microsomal triglyceride transfer protein inhibitor dose volume to 0.5 times the dose administered the previous month. that blocks the assembly and release of lipoprotein particles into the bloodstream (via the lymphatic system) • If the dog lost between 0 and 1% the dose should remain the same. 1 in dogs. The empirical formula is C40H33F3N4O3 and the molecular weight is 674.73. The chemical name • If the dog gained weight, the dose should be increased by 50% resulting in an increase of the dose is (S)-N-{2-[Benzyl(methyl)amino]-2-oxo-1-phenylethyl}-1-methyl-5-[4'-(trifluoromethyl)[1,1'-biphenyl]-2- volume to 1.5 times the dose administered the previous month. carboxamido]-1H-indole-2-carboxamide. • Subsequent dose adjustments The chemical structure of dirlotapide is: In subsequent months the dose volume should be increased or decreased by 25% to maintain a constant weight. Ph H H N • If the dog is within -5% to +5% of the body weight at the end of the weight loss phase, the dose N CH3 N volume (number of mL administered each day) should remain unchanged. O N O O • If the dog lost >5% body weight, then the dose should be decreased by 25%. Ph CH3 • If the dog gained >5% body weight, then the dose should be increased by 25%. Based on the dog’s current body weight a daily dose of 0.2 mL/kg (0.09 mL/lb) should not be exceeded.