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Benazepril

Grade

Congestive Heart Failure

  • Anecdotal: 0.25 – 0.5 mg/kg, PO, q12-24h (Müller and Mancinelli, 2022).

Major species extrapolation  (MSE) and anecdotal expert opinion in textbooks inform all dosing suggestions identified.

Benazepril Therapeutic Monitoring

  • Electrolyte Monitoring: Like major pet species, as well as the assessments outlined below, rabbits receiving Benazepril benefit from the assessment of serum creatinine and electrolyte concentrations 3-14 days after beginning an ACEi (SPC Data; Keene et al., 2019).

Recommendations by Disease Stage

Today, as rabbit cardiology remains subjective, we give no firm recommendations on using Benazepril in rabbits with any stage of CHF. 


There is no community consensus on diagnosing or staging any rabbit cardiac presentation. Therefore, we can't yet reliably identify specific rabbit cardiac cohorts, offer defined therapeutic protocols and strategies, or assess treatment outcomes and efficacy for cohort-targeted treatment regimes.

Rabbit CHF Staging Proposal 

All patients should be assessed using consensus-derived protocols before treatment.  Staging congestive heart failure (CHF) still requires collaborative development for rabbits. Therefore, to assist with this, we offer this platform and organisation as collaborative tools for the collecting and sharing of presentation findings, proposed staging and treatment outcomes for rabbit CHF cases.

Baseline Patient Values

Baseline values for therapeutic monitoring should be recorded for comparison during subsequent monitoring sessions and the potential for inclusion in future studies Keene et al., 2019).  Typically, they 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. Pulse may be assessed 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


If possible, parameters should be assessed before handling stress  (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. 


As the CHF progresses, knowledge of how these parameters become modified will help us gather disease staging criteria for rabbits  (Keene et al., 2019; Porciello et al., 2016).

Therapeutics

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About Benazepril and Rabbit CHF Recommendations

Pharmacological principles lead some experts to propose potential benefits from Benazepril use in rabbit patients with CHF. However, the dosing information located is generally based upon major species extrapolation. A variety of review publications refer to the anecdotal use of benazepril. However, no convincing efficacy literature is presented (Chitty, 2015; Fitzgerald et al.,  2018; Müller and Mancinelli, 2022; Ozawa et al., 2021; Beaufrère and Pariaut, 2009; Ozawa et al., 2022; van Meel and  Diederen, 1989).

Evidence-Base and Efficacy Profile

Benazepril has demonstrated varying efficacy in managing CHF with species, causes, comorbidities, and disease stages of chronic heart conditions. Potential benefits in rabbit CHF patients remain unknown.  Benazepril is indicated as an adjuvant treatment to Pimobendan in some canine MMVD  Stages B2 cases and above, but only weak evidence supports beneficial use (Keene et al., 2019). 


No efficacy data is available to support benficial therapeutic use of any cardiac medication in rabbits.  

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 Benazepril treatment is unlimited in rabbit CHF cases where there is a benefit, so it is usually lifelong, i.e. until death or euthanasia.

Alternative Products

  • No recommendations can be made at this time. We refer clinicians to current ACVIM CHF/MMVD recommendations for cats and dogs.

Alternative Protocols

  • No recommendations can be made at this time. We refer clinicians to current ACVIM CHF/MMVD recommendations for cats and dogs.

Evidence

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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. Li, J., Wanchun, C., 1997. Benazepril on tissue angiotensin-converting enzyme and cellular proliferation in restenosis after experimental angioplasty. J Cardiovasc Pharmacol 30, 790–797. https://doi.org/10.1097/00005344-199712000-00014

  3. 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

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

  5. Reusch, B., 2005. Investigation and management of cardiovascular disease in rabbits. In Practice 27, 418–425. https://doi.org/10.1136/inpract.27.8.418

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. Keene, B.W., Atkins, C.E., Bonagura, J.D., Fox, P.R., Häggström, J., Fuentes, V.L., Oyama, M.A., Rush, J.E., Stepien, R., Uechi, M., 2019. ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. J Vet Intern Med 33, 1127–1140. https://doi.org/10.1111/jvim.15488

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

  6. Reusch, B., 2005. Investigation and management of cardiovascular disease in rabbits. In Practice 27, 418–425. https://doi.org/10.1136/inpract.27.8.418

3 Substance-Specific Evidence Review

  1. Li, J., Wanchun, C., 1997. Benazepril on tissue angiotensin-converting enzyme and cellular proliferation in restenosis after experimental angioplasty. J Cardiovasc Pharmacol 30, 790–797. https://doi.org/10.1097/00005344-199712000-00014

  2. Yamamoto, S., Takemori, E., Hasegawa, Y., Kuroda, K., Nakao, K., Inukai, T., Sakonjyo, H., Nishimura, T., Nishimori, T., 1991. General pharmacology of the novel angiotensin converting enzyme inhibitor benazepril hydrochloride. Effects on cardiovascular, visceral and renal functions and on hemodynamics. Arzneimittelforschung 41, 913–923. https://pubmed.ncbi.nlm.nih.gov/1796919/

4 Efficacy Evidence Review

  1. No Data Located

Supplementary Information 

1 UK SPC Links

  1. Arixil Vet 5 mg Film-coated Tablet for Dogs and Cats [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009988 (accessed 1.1.24).

  2. Arixil Vet 20 mg Film-coated Tablet for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009989 (accessed 1.1.24).

  3. Banacep Vet 5 mg Film-coated Tablet for Dogs and Cats [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A006998 (accessed 1.1.24).

  4. Banacep Vet 20 mg Film-coated Tablet for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008086 (accessed 1.1.24).

  5. Benazecare Flavour 5 mg Tablets for Dogs and Cats [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A006679 (accessed 1.1.24).

  6. Benazecare Flavour 20 mg Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A006680 (accessed 1.1.24).

  7. BenazeVet 2.5 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010811 (accessed 1.1.24).

  8. BenazeVet 5 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010803 (accessed 1.1.24).

  9. BenazeVet 20 mg Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A010804 (accessed 1.1.24).

  10. Benefortin Flavour 2.5 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008272 (accessed 1.1.24).

  11. Benefortin Flavour 5 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008273 (accessed 1.1.24).

  12. Benefortin Flavour 20 mg Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008274 (accessed 1.1.24).

  13. Cardalis 2.5 mg/20 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008282 (accessed 1.1.24a).

  14. Cardalis 2.5 mg/20 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008282 (accessed 1.1.24b).

  15. Cardalis 5 mg/40 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008569 (accessed 1.1.24).

  16. Cardalis 10 mg/80 mg Chewable Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008570 (accessed 1.1.24).

  17. Fortekor 2.5 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A005871 (accessed 1.1.24).

  18. Fortekor Flavour 5 mg Tablets for Cats and Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A007625 (accessed 1.1.24).

  19. Fortekor Flavour 20 mg Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A007630 (accessed 1.1.24).

  20. Fortekor Plus 5mg/10mg Tablets [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A009422 (accessed 1.1.24).

  21. Kelapril 5 mg, Film-coated Tablets for Dogs and Cats [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008293 (accessed 1.1.24).

  22. Kelapril 20 mg, Film-coated Tablets for Dogs [WWW Document], n.d. URL https://www.vmd.defra.gov.uk/productinformationdatabase/product/A008294 (accessed 1.1.24).

 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).

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.

4 Expert Opinion

  1. McArthur, S. (2024)  Extrapolation of pharmacological properties in man and veterinary species. Additional material employed in collating the data displayed is expert opinion derived from clinical experience or reputable texts.

Monograph Details

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