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Pimobendan

Grade

Congestive Heart Failure

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Dosing

  • 1-2 mg/kg, PO, q12-24h (Ozawa et al., 2022) 

Associated Recommendations

Because rabbit cardiology remains subjective, we give no firm recommendations on using Pimobendan in rabbits with any stage of CHF. There is no community consensus on diagnosing or staging any rabbit cardiac presentation. Therefore, we can't identify specific cardiac cohorts, offer defined therapeutic protocols and strategies, or assess treatment outcomes and efficacy for cohort-targeted treatment regimes.

Therapeutics

Therapeutics

Rabbit CHF Staging Proposal 

Assess patients using consensus-derived protocols before treatment if and when they become available. 

Baseline Patient Values

Record baseline values for therapeutic monitoring for comparison during subsequent monitoring sessions and the potential for inclusion in future studies (Keene et al., 2019). Typically, these include:


  • Heart rate, rhythm and sound

  • Respiratory rate (resting and sleeping) and sound 

  • Mucous membrane characteristics 

  • Signs associated with oedema

  • Thirst, urine output, weight 

  • Blood pressure (where available)

  • The results of any cardiac imaging (where available)

Normal Reference Values

  • Respiration: The normal resting respiratory rate is 32 to 60 breaths/min (reference values for resting and sleeping respiratory rates in rabbit CHF are not yet available). 

  • Cardiac Function: Normal resting heart rate is 130 to 325 bpm. Assess pulse using the central auricular or femoral artery. Murmurs, arrhythmias, and pulse deficits should be absent. 

  • Blood Pressure: Mean arterial pressure 80-90 mmHg Systolic: 90–130 mm Hg, Diastolic: 80–90 mm Hg 

  • CRT: Normal capillary refill time is > 2 seconds, and normal mucous membranes are pink


Where possible, parameters should be assessed before handling (Paul-Murphy and Ramer, 1998; Reusch, 2005; Quesenberry, 2021; Varga-Smith, 2022). 

Condition Monitoring

All CHF Patients benefit from regular physical assessments and reviews of the baseline values and vital signs described above (Keene et al., 2019; Porciello et al., 2016).


Suitability

Pharmacological principles lead some experts to propose potential benefits from Pimobendan use in rabbit patients with CHF, but no efficacy literature is available (Chitty, 2015; Müller and Mancinelli, 2022; Ozawa et al., 2021; Schnellbacher et al., 2012; Ozawa et al., 2022).


Pimobendan has demonstrated potential efficacy in managing various species with CHF of varying causes, comorbidities, and stages. However, the potential benefits in rabbit CHF patients remain unknown. Pimobendan is indicated in all canine MMVD Stages B2 cases and above. Substantial evidence supports beneficial use (Keene et al., 2019; Apple et al., 2016; Boswood et al., 2016; Häggström et al., 2013a, 2013b, 2008; Iwanuk et al., 2019a,  2019b; Lombard et al., 2006). 

Treatment Goals

  • To maintain or improve patient comfort at each stage of CHF.

  • To prolong the length, quality of life, and rate of stage progression of CHF patients at each disease stage.

Treatment End Point

  • Until further data becomes available, the duration of Pimobendan treatment is unlimited.

Significant Adverse Effects

  • Tachycardia: In rare cases, a slight positive chronotropic effect (rise in heart rate) and vomiting can occur. However, these effects are dose-dependent in dogs and can be avoided by reducing the dose (Canine Data from SPC).

  • GIT Distress: In rare canine cases, transient diarrhoea, anorexia or lethargy have been observed (Canine Data from SPC).

  • Hemostasis: Although a relationship with pimobendan has not been established, in very rare canine cases, signs of effects on primary haemostasis (petechiae on mucous membranes, subcutaneous haemorrhages) may be observed during treatment. These signs disappear when the treatment is withdrawn (Canine Data from SPC).

Significant Contraindications

  • Outflow Compromise: e.g. aortic or pulmonary valve stenosis or hypertrophic obstructive cardiomyopathy (Canine Data from SPC).

  • Uncontrolled Arrhythmias: Other treatments are likely more beneficial (Canine Data from SPC).

  • Hepatic Impairment: Consider suitability, as Pimobendan is metabolised mainly via the live (Canine Data from SPC).

Significant Interactions

  • In dogs, Pimobendan-induced increase in cardiac contractility is attenuated by the calcium antagonists verapamil and diltiazem and by the β-antagonist propranolol (SPC Data).

Reproductive Safety

  • Pregnancy: There is no evidence of teratogenic or foetotoxic effects. Use only according to the benefit/risk assessment (Canine Data from SPC).

  • Lactation: Pimobendan is excreted into milk. Use only according to the benefit/risk assessment (SPC data).

  • Male Fertility: Pimobendan has not been evaluated in dogs used for breeding (SPC data).

  • Female Fertility: Pimobendan has not been evaluated in dogs used for breeding (SPC data).

  • Neonates: No data located.

Overdose

  • Acute: Positive chronotropic effect, vomiting, apathy, ataxia, heart murmurs or hypotension are possible. Remove further dose administration and apply temporary symptomatic treatment. Symptomatic treatment should be initiated.

  • Chronic: Mitral valve thickening and left ventricular hypertrophy have been observed in dogs administered 3-5X therapeutic dose range 3-5 months or more.

Alternative Medicines

  • We make no recommendations at this time. We refer clinicians to current ACVIM CHF/MMVD recommendations for cats and dogs.

Alternative Protocols

  • We make no recommendations at this time. at this time. We refer clinicians to current ACVIM CHF/MMVD recommendations for cats and dogs.

Evidence

Evidence-Base

1 Species-Specific Evidence Review

  1. Chitty, J., 2015. Cardiovascular disease in rabbits. Companion Animal 20, 74–78. https://doi.org/10.12968/coan.2015.20.2.74

  2. Fitzgerald, B.C., Dias, S., Martorell, J., 2018. Cardiovascular Drugs in Avian, Small Mammal, and Reptile Medicine. Veterinary Clinics of North America: Exotic Animal Practice, Therapeutics 21, 399–442. https://doi.org/10.1016/j.cvex.2018.01.015

  3. Müller, K., Mancinelli, E., 2022. Cardiology in Rabbits and Rodents–Common Cardiac Diseases, Therapeutic Options, and Limitations. Veterinary Clinics of North America: Exotic Animal Practice 25, 525–540. https://doi.org/10.1016/j.cvex.2022.01.006

  4. Ozawa, S., Guzman, D.S.-M., Keel, K., Gunther-Harrington, C., 2021. Clinical and pathological findings in rabbits with cardiovascular disease: 59 cases (2001–2018). Journal of the American Veterinary Medical Association 259, 764–776. https://doi.org/10.2460/javma.259.7.764

  5. Ozawa, S.M., Guzman, D.S.-M., Hawkins, M.G., Diao, S.M., Masri, A.E., Gunther-Harrington, C.T., Knych, H.K., 2022. Pharmacokinetics of pimobendan following oral administration to New Zealand White rabbits (Oryctolagus cuniculus). Am J Vet Res 83, 356–363. https://doi.org/10.2460/ajvr.21.03.0032

  6. Schnellbacher, R., Olson, E.E., Mayer, J., 2012. Emergency Presentations Associated with Cardiovascular Disease in Exotic Herbivores. Journal of Exotic Pet Medicine, Emergency Presentation of Exotic Mammal Herbivores 21, 316–327. https://doi.org/10.1053/j.jepm.2012.09.007

  7. van Meel, J.C., Diederen, W., 1989. Hemodynamic profile of the cardiotonic agent pimobendan. J Cardiovasc Pharmacol 14 Suppl 2, S1-6.

2 Condition-Specific Evidence Review

  1. Chitty, J., 2015. Cardiovascular disease in rabbits. Companion Animal 20, 74–78. https://doi.org/10.12968/coan.2015.20.2.74

  2. DeFrancesco, T.C., 2013. Management of Cardiac Emergencies in Small Animals. Veterinary Clinics of North America: Small Animal Practice 43, 817–842. https://doi.org/10.1016/j.cvsm.2013.03.012

  3. Fitzgerald, B.C., Dias, S., Martorell, J., 2018. Cardiovascular Drugs in Avian, Small Mammal, and Reptile Medicine. Veterinary Clinics of North America: Exotic Animal Practice, Therapeutics 21, 399–442. https://doi.org/10.1016/j.cvex.2018.01.015

  4. Müller, K., Mancinelli, E., 2022. Cardiology in Rabbits and Rodents–Common Cardiac Diseases, Therapeutic Options, and Limitations. Veterinary Clinics of North America: Exotic Animal Practice 25, 525–540. https://doi.org/10.1016/j.cvex.2022.01.006

  5. Ozawa, S., Guzman, D.S.-M., Keel, K., Gunther-Harrington, C., 2021. Clinical and pathological findings in rabbits with cardiovascular disease: 59 cases (2001–2018). Journal of the American Veterinary Medical Association 259, 764–776. https://doi.org/10.2460/javma.259.7.764

  6. Pariaut, R., 2009. Cardiovascular Physiology and Diseases of the Rabbit. Veterinary Clinics of North America: Exotic Animal Practice 12, 135–144. https://doi.org/10.1016/j.cvex.2008.08.004

  7. Schnellbacher, R., Olson, E.E., Mayer, J., 2012. Emergency Presentations Associated with Cardiovascular Disease in Exotic Herbivores. Journal of Exotic Pet Medicine, Emergency Presentation of Exotic Mammal Herbivores 21, 316–327. https://doi.org/10.1053/j.jepm.2012.09.007

3 Substance-Specific Evidence Review

  1. Beaufrère, H., Pariaut, R., 2009. Pimobendan. Journal of Exotic Pet Medicine, Parasites 18, 311–313. https://doi.org/10.1053/j.jepm.2009.09.010

  2. Ozawa, S.M., Guzman, D.S.-M., Hawkins, M.G., Diao, S.M., Masri, A.E., Gunther-Harrington, C.T., Knych, H.K., 2022. Pharmacokinetics of pimobendan following oral administration to New Zealand White rabbits (Oryctolagus cuniculus). Am J Vet Res 83, 356–363. https://doi.org/10.2460/ajvr.21.03.0032

  3. van Meel, J.C., Diederen, W., 1989. Hemodynamic profile of the cardiotonic agent pimobendan. J Cardiovasc Pharmacol 14 Suppl 2, S1-6.

4 Efficacy Evidence Review

  1. No Data Located

Supplementary Information

5.1 UK SPC Links

  1. Cardisan 1.25 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A013008 (accessed 12.22.23).

  2. Cardisan 2.5 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A013007 (accessed 12.22.23).

  3. Cardisan 5 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A013009 (accessed 12.22.23).

  4. Cardisan 10 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A013010 (accessed 12.22.23).

  5. Cardisan 15 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A013011 (accessed 12.22.23).

  6. Cardisure Flavoured 1.25 mg Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A011500 (accessed 12.22.23).

  7. Cardisure flavoured 2.5 mg Tablets For dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008038 (accessed 12.22.23).

  8. Cardisure Flavoured 5 mg Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008039 (accessed 12.22.23).

  9. Fortekor Plus 5mg/10mg Tablets [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009422 (accessed 12.22.23).

  10. Pimocard 1.25 mg Flavoured Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008358 (accessed 12.22.23).

  11. Pimocard 2.5 mg Flavoured Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008359 (accessed 12.22.23).

  12. Pimocard 10 mg Flavoured Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008361 (accessed 12.22.23).

  13. Pimotab 1.25 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010358 (accessed 12.22.23).

  14. Pimotab 2.5 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010359 (accessed 12.22.23).

  15. Pimotab 5 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010360 (accessed 12.22.23).

  16. Pimotab 10 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010361 (accessed 12.22.23).

  17. Pimotab 15 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010362 (accessed 12.22.23).

  18. Vetmedin 0.75 mg/ml Solution for Injection for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008883 (accessed 12.22.23).

  19. Vetmedin Chew 1.25 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009246 (accessed 12.22.23).

  20. Vetmedin Chew 2.5 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009247 (accessed 12.22.23).

  21. Vetmedin Chew 5 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009248 (accessed 12.22.23).

  22. Vetmedin Chew 10 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009249 (accessed 12.22.23).

  23. Zelys 1.25 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009706 (accessed 12.22.23).

  24. Zelys 5 mg chewable tablets for dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009707 (accessed 12.22.23).

5.2 Additional Material Consulted

  1. Booth, D., 2011. Small Animal Clinical Pharmacology and Therapeutics - 2nd Edition [WWW Document]. URL https://shop.elsevier.com/books/small-animal-clinical-pharmacology-and-therapeutics/boothe/978-0-7216-0555-5 (accessed 1.24.24).

  2. Maddison, G., 2008. Small Animal Clinical Pharmacology E-Book: 2nd edition | Edited by Jill E. Maddison | ISBN: 9780702037252 [WWW Document]. Elsevier Asia Bookstore. URL https://www.asia.elsevierhealth.com/small-animal-clinical-pharmacology-e-book-9780702037252.html (accessed 1.23.24).

  3. Plumb, 2024. Benazepril [WWW Document]. URL https://app.plumbs.com/drug/PGVZkcnorQPROD?source=search&searchQuery=benaze (accessed 1.24.24).

  4. Quesenberry, K.E. (Ed.), 2021. Ferrets, rabbits, and rodents: clinical medicine and surgery, Fourth edition. ed. Elsevier, St. Louis, Missouri.

  5. Varga-Smith, M., 2022. Textbook of Rabbit Medicine - 9780702084034 | Elsevier Health [WWW Document]. Elsevier UK. URL https://www.uk.elsevierhealth.com/textbook-of-rabbit-medicine-9780702084034.html (accessed 1.23.24).

5.3 Conference Proceedings

  1. van Zeeland YR.A, Schoemaker NJ. Diagnosis and treatment of cardiovascular disease in small mammals. Proc Conf Annu  Assoc Exot Mam Vet; 2018:607–616.

5.4 Expert Opinion(s)

  1. McArthur, S. and Mancinelli, E. (2024). Extrapolating pharmacological properties in man and veterinary species. Expert opinions derived from clinical experience, personal communications and the reputable texts listed in 5.2 were employed in data collation.

Monograph Details

Monograph Details

Analysis Criteria

  • Species: Rabbit

  • Active Substance: Pimobendan

  • Indication: CHF (Congestive Heart Failure)

  • VCI Dosing Suggestion: CHF: 1-2 mg/kg PO, q12-24h (Ozawa et al., 2022)

Collaboration Resources

Consensus Team

  • Monograph Authors: S McArthur; E Mancinelli (last updated 09/03/2024)

  • Monograph Editors: TBA (last updated 09/03/2024)

Monograph Contact

  • For permissions and further information about the Veterinary Consensus Initiative (VCI), please get in touch with us via Stuart McArthur B Vet Med MRCVS; Email: stuart.mcarthur@me.com

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