Vetmedin (pimobendan) Chewable Tablets for Dogs - Drugs.com (2023)

Vetmedin (pimobendan) chewable tablets indications

VETMEDIN (pimobendan) is indicated for the treatment of signs of mild, moderate, or severe congestive heart failure in dogs due to clinical myxomatous mitral valve disease (MMVD) or dilated cardiomyopathy (DCM). VETMEDIN is indicated for use with concomitant therapy in congestive heart failure (e.g. furosemide, etc.) as appropriate on a case-by-case basis.

dosage and application

VETMEDIN should be administered orally at a total daily dose of 0.23 mg/lb (0.5 mg/kg) body weight using an appropriate combination of whole tablets or half tablets. The total daily dose should be divided into 2 servings, which need not necessarily be equal, and the servings should be taken approximately 12 hours apart (ie morning and evening). The tablets are marked and the calculated dose should be given in increments of half a tablet.

contraindications

VETMEDIN should not be administered in hypertrophic cardiomyopathy, aortic stenosis or other clinical conditions in which an increase in cardiac output is inappropriate for functional or anatomical reasons.

Hints

Only for use in dogs with clinical evidence of heart failure. At 3 and 5 times the recommended dose administered for 6 months, pimobendan elicited an exaggerated hemodynamic response in the normal canine heart, which was associated with cardiac pathology (cfanimal safety).

Human clues:It is not intended for human use. Keep this and all other medicines out of the sight and reach of children. In case of accidental ingestion by humans, consult a doctor.

Precautions

The safety of VETMEDIN in dogs with asymptomatic heart disease or heart failure caused by etiologies other than MMVD or MCD has not been established. The safe use of VETMEDIN in dogs under 6 months of age, dogs with congenital heart defects, dogs with diabetes mellitus or other serious metabolic diseases, breeding dogs or pregnant or lactating bitches has not been studied.

side effects

Clinical findings/side effects were recorded in a 56-day field study in dogs with congestive heart failure (CHF) due to MMVD (256 dogs) or DCM (99 dogs). The dogs were treated with VETMEDIN (175 dogs) or the active control enalapril maleate (180 dogs). The dogs in both treatment groups received additional cardiac background therapy (cfefficiencydetails and difference in digoxin administration between treatment groups).

The VETMEDIN group had the following prevalence (percentage of dogs with at least one occurrence) of common adverse reactions/new clinical findings (absent in one dog prior to the start of study treatments): anorexia (38%), lethargy (33%). . , diarrhea (30%), dyspnea (29%), azotemia (14%), weakness and ataxia (13%), pleural effusion (10%), syncope (9%), cough (7%), sudden death (6% ), ascites (6%) and heart murmur (3%). The prevalence was similar in the active control group. The prevalence of renal failure was higher in the active control group (4%) than in the VETMEDIN group (1%).

Adverse reactions/new clinical findings were observed in both treatment groups and were possibly related to CHF, CHF treatment, or both. The following adverse reactions/new clinical findings are listed by body system and not by order of prevalence: CHF death, sudden death, chordae-tendineae rupture, left atrial rupture, generalized arrhythmias, tachycardia, syncope, weak pulse, irregular pulse, increased pulmonary edema, Dyspnea, respiratory rate increased, cough, nausea, pleural effusion, ascites, hepatic congestion, decreased appetite, vomiting, diarrhea, melena, weight loss, lethargy, depression, weakness, collapse, tremor, ataxia, convulsions, restlessness, restlessness, pruritus, increased water intake, increased urination, urinary accidents, azotemia, dehydration, abnormal serum electrolytes, protein and glucose levels, mild increase in serum liver enzymes, and mildly decreased platelet count.

See Table 1 for CHF mortality (including euthanasia, natural causes, and sudden death) and new arrhythmia development (absent in one dog prior to the start of study treatments) by treatment group and treatment type. Heart disease (MMVD or DCM) in the 56-day field study.

Table 1: Death from CHF and new arrhythmias in the 56-day field study

^ANew arrhythmias included supraventricular premature beats and tachycardia, atrial fibrillation, atrioventricular block, sinus bradycardia, ventricular premature beats and tachycardia, and bundle branch block.

After the 56-day blinded field study, 137 dogs in the VETMEDIN group were allowed to continue in an open-label extended-use study without restriction of concomitant VETMEDIN therapy. Adverse reactions/new clinical findings in the long-term study were consistent with those reported in the 56-day study with the following exception: one dog in the long-term study developed acute cholestatic liver failure after 140 days on VETMEDIN and furosemide. .

In foreign post-marketing drug experience reports, the following additional suspected adverse reactions have been reported in dogs treated with a capsule formulation of pimobendan: bleeding, petechiae, anemia, hyperactivity, agitated behavior, erythema, rash, salivation, constipation, and diabetes mellitus.

To report suspected adverse reactions, request a Safety Data Sheet (SDS), or obtain technical assistance, contact Boehringer Ingelheim Animal Health USA Inc. by phone at 1-888-637-4251. For more information on reporting animal adverse drug experiences, contact the FDA at 1-888-FDA-VETS or at http://www.fda.gov/reportanimalae.

Clinical Pharmacology

Pimobendan undergoes oxidative demethylation to a pharmacologically active metabolite, which is then conjugated with sulfate or glucuronic acid and excreted mainly in the faeces. The mean protein binding of pimobendan and the active metabolite in canine plasma is >90%. After a single oral dose of VETMEDIN 0.25 mg/kg tablets, the mean (±1 SD) maximum plasma concentrations (Cmax) of pimobendan and the active metabolite were 3.09 (0.76) ng/mL and 3.66 (1 .21) ng/mL. Cmax values ​​for individual dogs were observed for pimobendan and the active metabolite 1 to 4 hours after dosing (mean: 2 and 3 hours, respectively). The total body clearance of pimobendan was approximately 90 mL/min/kg and the terminal elimination half-lives of pimobendan and the active metabolite were approximately 0.5 hours and 2 hours, respectively. Plasma levels of pimobendan and the active metabolite were below measurable levels 4 and 8 hours after oral administration, respectively. The steady-state volume of distribution of pimobendan is 2.6 l/kg, indicating that the active substance is readily distributed to tissues. Food decreased the bioavailability of an aqueous solution of pimobendan, but the effect of food on the absorption of pimobendan from VETMEDIN tablets is unknown.

In healthy dogs fitted with left ventricular (LV) pressure transducers, pimobendan increased LV dP/dtmax (a measure of the contractility of the heart) in a dose-dependent manner between 0.1 and 0.5 mg/kg orally. The effect was still present 8 hours after administration. There was a lag between peak blood levels of pimobendan and the active metabolite and the peak physiological response (peak LV dP/dtmax). Blood levels of pimobendan and the active metabolite began to decline before maximal contractility was observed. Repeated oral administration of pimobendan did not result in signs of tachyphylaxis (decreased positive inotropic effect) or drug accumulation (increased positive inotropic effect). Laboratory studies indicate that the beneficial inotropic effect of pimobendan may be attenuated by concomitant use of a β-adrenergic blocker or calcium channel blocker.

efficiency

In a 56-day, double-blind, multi-site field study, 355 dogs with New York Heart Association modifications were evaluated. (NYHA) Class II, III, or IV CHF due to MMVD or DCM were randomized to active control (malapril maleate) or VETMEDIN (pimobendan) treatment groups. Of the 355 dogs, 52% were male and 48% were female; 72% were diagnosed with MMVD and 28% with DCM; 34% had class II, 47% class III and 19% class IV CHF. The dogs' ages and weights ranged from 1 to 17 years and 3.3 to 191 pounds, respectively. The most common breeds were crossbreeds, Doberman Pinschers, Cocker Spaniels, Miniature Poodles, Maltese, Chihuahuas, Miniature Schnauzers, Dachshunds and Cavalier King Charles Spaniels. All 180 dogs (130 MMVD, 50 DCM) in the active control group received enalapril maleate (0.5 mg/kg once or twice daily) and all but 2 received furosemide. Per protocol, all DCM dogs in the active control group received digoxin. All 175 dogs (126MMVD, 49 DCM) in the VETMEDIN group received pimobendan (0.5 mg/kg/day divided into 2 portions, not necessarily equal, and the portions were administered approximately 12 hours apart), and all but 4 received furosemide. Digoxin was optional for treatment of supraventricular tachyarrhythmias in both treatment groups, as was the addition of a β-adrenergic blocker when digoxin was ineffective at controlling heart rate. After the initial in-clinic treatment on Day 1, dog owners should maintain the intended product and concomitant medication for up to 56 ± 4 days.

Efficacy determination (treatment success) for each case was based on improvement in at least 2 of the following 3 primary endpoints: Modified NYHA score, Masked Vet Radiologist Pulmonary Edema Score, and Investigator Overall Clinical Efficacy Score (based on physical evidence). physical examination, radiography, electrocardiography and clinical pathology). Posture, pleural effusion, cough, activity level, change in furosemide dose, heart size, body weight, survival, and owner observations were secondary assessments that provided information supporting the product's efficacy and safety.

Based on protocol adherence and the completeness of each individual case, 265 cases (134 VETMEDIN, 131 active control) were evaluated on day 29 for treatment success. See Table 2 for efficacy results.

Table 2: Efficacy results from the 56-day field study

At the end of the 56-day study, dogs in the VETMEDIN group were enrolled in an unmasked field study to monitor safety with long-term use without concomitant medication restrictions.

VETMEDIN has been safely used in dogs receiving concomitant furosemide, digoxin, enalapril, atenolol, spironolactone, nitroglycerin, hydralazine, diltiazem, dewormers (including heartworm prophylaxis), antibiotics (metronidazole, cephalexin, amoxicillin clavulanate, fluoroquinolones). . Products, famotidine, theophylline, levothyroxine sodium, diphenhydramine, hydrocodone, metoclopramide, and butorphanol, and in dogs on a low-sodium diet.

!The modified NYHA classification was formerly used to classify dogs with heart disease.

A dog with NYHA Class II Modified Heart Failure will have visible fatigue, shortness of breath, coughing, etc. when normal exercise is exceeded.

A dog with NYHA Class III modified heart failure is comfortable at rest, but physical capacity is minimal.

A dog with NYHA Class IV modified heart failure is unable to exercise and disabling clinical signs are present even at rest.

Pleasant taste:In a laboratory study, the palatability of VETMEDIN was evaluated in 20 adult beagle dogs administered twice daily for 14 days. Ninety percent (18 of 20 dogs) voluntarily consumed more than 70% of the 28 pills offered. Including two dogs that consumed only 4% and 7% of the pills offered, the average voluntary intake was 84.2%.

Animal Safety:In a laboratory study, 6 healthy beagle dogs per treatment group received VETMEDIN chewable tablets at 0 (control), 1, 3 and 5 times the recommended dose for 6 months. See Table 3 for cardiac pathology results. The cardiac pathology/histopathology observed in the 3X and 5X dose groups is typical of positive vasodilator and inotropic drug toxicity in normal canine hearts and is associated with exaggerated hemodynamic responses to these drugs. None of the dogs developed signs of heart failure and there were no deaths.

Table 3: Incidence of cardiac pathology/histopathology in the 6-month safety study

^AMost macroscopic and histopathologic findings occurred in these three dogs.

Mitral valve regurgitation murmurs were recorded three times (Day 65) in one dog and five times (Days 135 and 163) in two dogs. These murmurs (grade II-III or VI) were not associated with clinical symptoms.

Indirect blood pressure was not affected by VETMEDIN at the package insert dose (1X). Mean diastolic blood pressure decreased in the 3X group (74 mmHg) compared to the control group (82 mmHg). Mean systolic blood pressure decreased in the 5X group (117 mmHg) compared to the control group (124 mmHg). None of the dogs showed clinical signs of hypotension.

On 24-hour Holter monitoring, the mean heart rate increased in the 5X group (101 bpm) compared to the control group (94 bpm). With the exception of escape beats, the 3X and 5X groups had a slightly higher number of isolated ectopic ventricular (LV) complexes. The maximum number of non-escape EVs recorded at baseline or in a control dog was 4 EVs/24 hours. At week 4 or week 20, three dogs in the 3X group had peak values ​​of 33, 13, and 10 VE/24 hours and two dogs in the 5X group had peak values ​​of 22 and 9 VE/24 hours. One dog in the 1X group with no VE at baseline had 6 VE/24 hours at week 4 and again at week 20. Second degree atrioventricular block occurred in one dog in the 3X group at weeks 4 and 20 and in one dog each to the 1X and 5X groups at week 20. None of the dogs showed clinical signs on the electrocardiogram associated with these changes.

Treatment was associated with small differences in mean platelet count (decrease in the 3X and 1X groups), potassium (increase in the 5X group), glucose (decrease in the 1X and 3X groups), and peak glucose in the glucose curves . (Magnification in the 5X group). All individual values ​​of these variables were within the normal range. Three dogs in the 1X group and one in the 5X group had mild elevations in alkaline phosphatase (less than twice normal). Soft stools and vomiting were infrequent and self-limiting.

Storage information:Store at 20° to 25°C (68° to 77°F), ranges between 15° to 30°C (59° to 86°F) are acceptable.

as delivered

is not present^®(Pimobendan) Kautabletten:

Available in oblong chewable tablets of 1.25, 2.5, 5 and 10 mg: 50 tablets per bottle.

NDC 0010-4480-01 - 1.25 mg - 50 pills

NDC 0010-4481-01 - 2.5 mg - 50 pills

NDC 0010-4482-01 - 5 mg - 50 pills

NDC 0010-4479-01 – 10 mg – 50 pills

FDA approved under NADA # 141-273

Marketed by:

Boehringer Ingelheim Animal Health EE. UU., Inc., Duluth, GA 30096

is not present^®is a registered trademark of Boehringer Ingelheim Vetmedica GmbH, used under license.

© 2021 Boehringer Ingelheim Animal Health USA Inc. All rights reserved.

159637-003

448005-02

Reviewed on 10/2021

US-PET-0379-2022

NPC:1028166.6