top of page

Spironolactone

Grade

MMVD

Recommendations by ACVIM Stage

We recommend following ACVIM and similar consensus guidelines for disease staging and the use of ACEi in canine heart failure.

Stage C (Home-Based Treatment)

Once an acute patient is adequately stabilised, Spironolactone is administered in addition to Pimobendan with various additional medications, such as Furosemide or Torasemide, to help stabilise the patient.


  • Pimobendan: 0.25 – 0.3 mg/kg PO every 8-12 hours. Some AVCIM consensus panellists propose a third daily dose as patients near end-stage disease.

  • Furosemide: 2 mg/kg, PO, q6-12h, up to 8 mg/kg daily.

  • Spironolactone: 2 mg/kg PO every 12 to 24 hours (Keene et al., 2019).

  • Benazepril is administered at 0.5 mg/kg PO, q24h (or 0.25 mg/kg PO, q12h).

Stage D

Stage D patients have heart failure refractory to stage C treatment protocols. Few clinical trials have addressed drug efficacy and safety in this patient population. Pimobendan is administered at 0.25 – 0.3 mg/kg PO every 12 hours, potentially a third daily dose., in addition to some or all of the following medicines


  • Pimobendan: 0.25 – 0.3 mg/kg PO every 12 hours, potentially a third daily dose.

  • Furosemide:  6- 8 mg/kg/day in divided doses, or Torasemide is substituted where patients are no longer considered adequately responsive to Furosemide.

  • Torsemide  0.1-0.2 mg/kg, q12-24h, replaces previous Furosemide dosing with subsequent upward titration (Torsemide is commenced at 5%-10% of the last Furosemide dose in mg/kg).

  • Spironolactone: 2 mg/kg PO every 12 to 24 hours (Keene et al., 2019).

  • Benazepril: 0.5 mg/kg PO, q12-24h

Additional Medications and Procedures

These are clinician and patient-specific. Examples include cavitary centesis (abdominal paracentesis, thoracentesis), which may be required to relieve respiratory distress or discomfort. We refer clinicians to current ACVIM MMVD recommendations. 

Administration

  • Tablets should be administered with food.

Formulations

  • UK Availability: Available in sole agent form as 10, 50, or 100 mg Tablets or as combined Benazepril Hydrochloride, Spironolactone 2.5 mg/20 mg, 5 mg/40 mg, 10 mg/80 mg chewable tablets for dogs


Therapeutics

​

About Spironolactone

Spironolactone, a potassium-sparing mineralocorticoid-receptor antagonist diuretic, is indicated in ACVIM MMVD Stages C cases and above. 

Sole Use

  • Uncommon, usually used as part of polypharmacy cardiology protocols. 

Multimodal Use 

  • ACVIM Consensus Guidelines: Because Spironolactone is generally deployed in the late stages of MMVD (Stages C and D), it is usually used multimodally alongside additional medicines  (e.g., Pimobendan, ACE inhibitors, Furosemide, Torasemide and Digoxin). 

Treatment Goals

Potassium-sparing diuresis. An aldosterone antagonist for adjunctive treatment for heart failure or ascites alongside furosemide in patients with CHF.


  • Symptom Control: Spironolactone treatment aims to relieve and manage pulmonary oedema, pleural effusion and ascites —reduction of the effects of oedema where patients are hypokalaemic or likely to become hypokalaemic. 

  • QALYs | Survival Time: Extended survival times with good quality of life allow a calculation of quality-adjusted life years (QALYs). QUALYs are a standardised calculation derived from a systematic review of suitable efficacy studies. These are not yet available for Spironolactone for this indication. Improved quality of life of patients with MMVD is currently a subjective, case-by-case judgement.

Treatment Endpoints

  • Spironolactone therapy is seldom withdrawn until patients experience death or euthanasia.

Efficacy Profile 

  • Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary endpoint (i.e., cardiac-related death, euthanasia, or severe worsening) in dogs with moderate to severe MR caused by MMVD (Bernay et al., 2010).

Adverse Effects  

  • One randomized, double-blinded, prospective study found no increased risk of adverse effects when administered alongside ACE inhibitors, furosemide ± digoxin (Lefebvre et al., 2013). 

  • Reversible prostatic atrophy is often observed in entire male dogs. 

  • Vomiting and diarrhoea may commonly occur

Contraindications

  • Hypoadrenocorticism, hyperkalaemia or hyponatraemia, anuria, acute kidney injury, or significant renal impairment(SPC Data).

  • Do not administer spironolactone in conjunction with NSAIDs to dogs with renal insufficiency (SPC Data).

Monitoring

  • Electrolyte monitoring is advisable. Monitor renal output and function.

Reproductive Safety

  • Pregnancy: Developmental toxicity in laboratory animals. Use with caution in pregnant patients (SPC Data).

  • Lactation:  Use with caution in nursing patients.

  • Male Fertility: Possible adverse effect

  • Female Fertility: Possible adverse effect

Alternative Products and Protocols

  • ACVIM Consensus Guidelines: Because Spironolactone is generally deployed in the late stages of MMVD (Stages C and D), it is usually used multimodally alongside additional medicines  (e.g., Pimobendan, ACE inhibitors, Furosemide, Torasemide and Digoxin). 


Evidence

​

1 Species-Specific Evidence Review

  1. Acierno, M.J., Brown, S., Coleman, A.E., Jepson, R.E., Papich, M., Stepien, R.L., Syme, H.M., 2018. ACVIM consensus statement: Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J Vet Intern Med 32, 1803–1822. https://doi.org/10.1111/jvim.15331

  2. Bernay, F., Bland, J.M., Häggström, J., Baduel, L., Combes, B., Lopez, A., Kaltsatos, V., 2010. Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease. J Vet Intern Med 24, 331–341. https://doi.org/10.1111/j.1939-1676.2009.0467.x

  3. Borgarelli, M., Ferasin, L., Lamb, K., Bussadori, C., Chiavegato, D., D’Agnolo, G., Migliorini, F., Poggi, M., Santilli, R.A., Guillot, E., Garelli-Paar, C., Toschi Corneliani, R., Farina, F., Zani, A., Dirven, M., Smets, P., Guglielmini, C., Oliveira, P., Di Marcello, M., Porciello, F., Crosara, S., Ciaramella, P., Piantedosi, D., Smith, S., Vannini, S., Dall’Aglio, E., Savarino, P., Quintavalla, C., Patteson, M., Silva, J., Locatelli, C., Baron Toaldo, M., 2020. DELay of Appearance of sYmptoms of Canine Degenerative Mitral Valve Disease Treated with Spironolactone and Benazepril: the DELAY Study. Journal of Veterinary Cardiology 27, 34–53. https://doi.org/10.1016/j.jvc.2019.12.002

  4. Guyonnet, J., Elliott, J., Kaltsatos, V., 2010. A preclinical pharmacokinetic and pharmacodynamic approach to determine a dose of spironolactone for treatment of congestive heart failure in dog. J Vet Pharmacol Ther 33, 260–267. https://doi.org/10.1111/j.1365-2885.2009.01130.x

  5. Hezzell, M.J., Boswood, A., López-Alvarez, J., Lötter, N., Elliott, J., 2017. Treatment of dogs with compensated myxomatous mitral valve disease with spironolactone-a pilot study. J Vet Cardiol 19, 325–338. https://doi.org/10.1016/j.jvc.2017.06.001

  6. 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

  7. Lefebvre, H. p., Ollivier, E., Atkins, C. e., Combes, B., Concordet, D., Kaltsatos, V., Baduel, L., 2013. Safety of Spironolactone in Dogs with Chronic Heart Failure because of Degenerative Valvular Disease: A Population-Based, Longitudinal Study. Journal of Veterinary Internal Medicine 27, 1083–1091. https://doi.org/10.1111/jvim.12141

  8. Syme, H., 2011. Hypertension in small animal kidney disease. Vet Clin North Am Small Anim Pract 41, 63–89. https://doi.org/10.1016/j.cvsm.2010.11.002

  9. Thomason, J.D., Rapoport, G., Fallaw, T., Calvert, C.A., 2014. The influence of enalapril and spironolactone on electrolyte concentrations in Doberman pinschers with dilated cardiomyopathy. Vet J 202, 573–577. https://doi.org/10.1016/j.tvjl.2014.09.004

  10. Webster, C.R.L., Center, S.A., Cullen, J.M., Penninck, D.G., Richter, K.P., Twedt, D.C., Watson, P.J., 2019. ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs. J Vet Intern Med 33, 1173–1200. https://doi.org/10.1111/jvim.15467

2 Condition-Specific Evidence Review

  1. Beaumier, A., Rush, J.E., Yang, V.K., Freeman, L.M., 2018. Clinical findings and survival time in dogs with advanced heart failure. J Vet Intern Med 32, 944–950. https://doi.org/10.1111/jvim.15126

3 Substance-Specific Evidence Review

  1. Ovaert, P., Elliott, J., Bernay, F., Guillot, E., Bardon, T., 2010. Aldosterone receptor antagonists--how cardiovascular actions may explain their beneficial effects in heart failure. J Vet Pharmacol Ther 33, 109–117. https://doi.org/10.1111/j.1365-2885.2009.01122.x

SPC Datasheets Accessed

  1. Prilactone Next® 10mg, 50mg and 100mg chewable tablets for dogs [WWW Document], n.d. URL https://www.noahcompendium.co.uk/ (accessed 9.4.23).

Expert Opinion

  1. 1317822 Canine: Extrapolation of pharmacological properties in man and veterinary species. Some material employed in collating the data displayed here was taken from veterinary product datasheets or extrapolated from pharmacology texts.


Monograph Details

​

bottom of page