Veterinary Medicine - November 2007 - (Page 740)

Pimobendan update O P E E R - R E V I E W E D Theoretically, pimobendan may increase the rate of intestinal digoxin absorption.10 In our clinical experience, the coadministration of pimobendan with digoxin has neither increased paired serum digoxin concentrations nor resulted in concentrations within the upper 40th percentile of our reference range. We seldom add digoxin to pimobendan therapy except in the face of atrial fibrillation in dogs with advanced dilated cardiomyopathy. Serial Holter recordings in our pa- fects reported during a field study included polyuria, polydipsia, vomiting, azotemia, inappetence, lethargy, diarrhea, dyspnea, pleural effusion, cough, ascites, heart murmur, weakness and ataxia, and syncope.9 Sudden death may also occur.9 A dose-related sinus tachycardia can result,4 and as with any strong inotropic agent, ventricular tachyarrhythmias may develop or worsen while pimobendan is administered. 11 Ventricular tachyarrhythmias are of particular concern CONCLUSION Pimobendan is an inodilator used to treat overt or impending congestive heart failure in dogs. Studies have either demonstrated or suggested a favorable influence when pimobendan is used as adjunctive therapy (e.g. with an ACE inhibitor, furosemide, digoxin) in patients with advanced dilated cardiomyopathy or degenerative mitral valve disease.9,13,14 In our experience with more than 100 dogs, pimobendan is well-tolerated and has few adverse effects. Pimobendan should not be used as a replacement for, but rather as cotherapy with, other cardiac drugs to enhance the quality of life in dogs with overt or impending congestive heart failure. O REFERENCES 1. Lefbon BK. Sildenafil and novel cardiovascular therapies, in Proceedings. Am Coll Vet Intern Med 2005. 2. Hagemeijer F. Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure. Eur Heart J 1993;14:551-566. 3. Fuentes VL. Use of pimobendan in the management of heart failure. Vet Clin North Am Small Anim Pract 2004;34:1145-1155. 4. Chu KM, Shieh SM, Hu OY. Pharmacokinetics and pharmacodynamics of enantiomers of pimobendan in patients with dilated cardiomyopathy and congestive heart failure after single and repeated oral dosing. Clin Pharmacol Ther 1995;57:610-621. 5. Breazile JE, College of Veterinary Medicine, Oklahoma State University, Stillwater, Okla: Personal communication, 2006. 6. Goto Y, Hata K. Mechanoenergetic effect of pimobendan in failing dog hearts. Heart Vessels 1997;12(suppl):103-105. 7. Fox PR, Sisson D, Moise NS. Myocardial diseases of dogs. In: Textbook of canine and feline cardiology. 2nd ed. Philadelphia, Pa: WB Saunders Co, 1999;581-620. 8. Matthew L, Katz S. Calcium sensitizing agents in heart failure. Drugs Aging 1988;12:191-204. 9. Boehringer Ingelheim Vetmedica. Vetmedin (pimobendan) tablets package insert. St. Joseph, Mo., 2007. 10. Aiba T, Ishida K, Yoshinaga M, et al. Pharmacokinetic characterization of transcellular transport and drug interaction of digoxin in CACO-2 cell monolayers. Biol Pharm Bull 2005;28:114-119. 11. Rosenthal SL, Ferguson MJ, Lefbom BK, et al. Association of pimobendan with ventricular arrhythmias in dogs with congestive heart failure, in Proceedings. Am Coll Vet Intern Med 2006. 12. Ruegg JC. Effects of new inotropic agents on Ca++ sensitivity of contractile proteins. Circulation 1986;73:III78-III84. 13. Fuentes VL, Corcoran B, French A, et al. A double-blind, randomized, placebo-controlled study of pimobendan in dogs with dilated cardiomyopathy. J Vet Intern Med 2002;16:255-261. 14. Smith PJ, French AT, Van Israel N, et al. Efficacy and safety of pimobendan in canine heart failure caused by myxomatous mitral valve disease. J Small Anim Pract 2005;46:121-130. We seldom add digoxin except in dogs with atrial fibrillation and advanced dilated cardiomyopathy. tients with atrial fibrillation have shown that pimobendan does not seem to markedly attenuate the effects of digoxin on reducing atrioventricular conduction. In boxers and Doberman pinschers with advanced dilated cardiomyopathy that we have treated with pimobendan, digoxin, an ACE inhibitor, and furosemide, the ventricular response rates have usually been below 140 beats/min for more than 85% of the approximate 24-hour Holter recording time. In addition, the combination of pimobendan with amiodarone or mexiletine or both has been well-tolerated in boxers and Doberman pinschers with advanced dilated cardiomyopathy and severe ventricular arrhythmias. in Doberman pinschers and boxers but could occur in any dog with advanced dilated cardiomyopathy. Pimobendan’s effect on myocytes—conserved energy demand with small increases in intracellular calcium concentration— may reduce the likelihood of a proarrhythmic effect,12 but additional studies are warranted. In our experience in treating patients with advanced dilated cardiomyopathy, pimobendan’s durability as a positive inotropic agent in dogs may not be as good as that reported in human studies. Thus, prematurely administering pimobendan to patients with only mild to moderate myocardial failure caused by dilated cardiomyopathy could result in decreased effectiveness later in the course of the disease. For this reason, we recommend initiating pimobendan for patients with advanced cardiomyopathy. Pimobendan’s efficacy in cats has not been reported. Hypertrophic cardiomyopathy is the most common cardiomyopathy in cats, and pimobendan is contraindicated. PRECAUTIONS Pimobendan has not been evaluated in dogs used for breeding, in pregnant or lactating dogs, in dogs younger than 6 months old, or in dogs with congenital heart defects, diabetes mellitus, or other serious metabolic diseases. Clinical findings or adverse ef- EXTRA See for more on dilated cardiomyopathy and degenerative mitral valve disease in dogs. 740 November 2007 VETERINARY MEDICINE http://www.vetstreamcanis.com/ACI/November/VMD2/dis00923.asp http://www.vetstreamcanis.com/ACI/November/VMD1/dis00918.asp http://www.vetstreamcanis.com/ACI/November/VMD1/dis00918.asp

Table of Contents Feed for the Digital Edition of Veterinary Medicine - November 2007

Veterinary Medicine - November 2007 Contents Leading Off The Veterinary Medicine Interview: Dr. Lila Miller Clinical Exposures Idea Exchange A Challenging Case: Uveitis and Secondary Glaucoma in a Cat Is it Immune-Mediated Neutropenia? Pimobendan Treatment in Dogs with Congestive Heart Failure CE Form Product Preview Advertiser Index Marketplace/Classifieds Mind Over Miller Special Supplement by Lilly: Flea Bite Facts Q&A

Veterinary Medicine - November 2007

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