Vivaldis Pimoben Cardiac Tablet for Dogs | Pimobendan + Benazepril | CHF, MMVD & DCM Management | 1.25/2.5mg & 5/10mg | 3 Strips (30 Tablets)

Vivaldis Pimoben (Pimobendan + Benazepril) is a Schedule H prescription cardiac veterinary medicine. This product must only be administered as directed by a licensed veterinarian following a confirmed cardiac diagnosis. Do not self-administer or adjust doses without veterinary guidance. Cardiac disease in dogs requires accurate diagnosis (thoracic radiography, echocardiography, and clinical staging per ACVIM consensus guidelines) before initiating therapy — do not begin treatment based on symptoms alone. Regular veterinary monitoring including repeat echocardiography, blood pressure measurement, and renal function (serum creatinine, BUN, electrolytes) is mandatory during chronic pimobendan + benazepril therapy. Pimobendan must not be used in dogs with hypertrophic obstructive cardiomyopathy (HOCM), aortic stenosis, or other conditions where increased cardiac output is contraindicated. Benazepril requires dose reduction in dogs with significant pre-existing renal insufficiency — baseline renal function must be assessed before initiation. Not for use in cats without specific veterinary guidance. Keep out of reach of children. Store in a cool, dry place away from direct sunlight.

Vivaldis Pimoben Cardiac Tablet for Dogs | Pimobendan + Benazepril | CHF, MMVD & DCM Management | 1.25/2.5mg & 5/10mg | 3 Strips (30 Tablets)

Vivaldis Pimoben is a prescription veterinary cardiac medicine manufactured by Vivaldis Animal Health (India), combining pimobendan and benazepril hydrochloride in a single tablet for the management of congestive heart failure (CHF), myxomatous mitral valve disease (MMVD — the most prevalent cardiac disease of dogs, particularly small and toy breeds), and dilated cardiomyopathy (DCM — the primary cardiac disease of large and giant breeds). The combination of a positive inotrope/vasodilator (pimobendan) with an ACE inhibitor (benazepril) represents the dual-pillar pharmacological approach to canine CHF management endorsed by the ACVIM (American College of Veterinary Internal Medicine) cardiac consensus guidelines. Available in two dose strengths: 1.25mg pimobendan/2.5mg benazepril per tablet (for small and toy breeds) and 5mg pimobendan/10mg benazepril per tablet (for medium, large, and giant breeds). Each pack contains 3 strips of 10 tablets (30 tablets total).

Canine Cardiac Disease: The Two Primary Indications

• Myxomatous Mitral Valve Disease (MMVD) — the dominant canine cardiac disease and the primary indication for pimobendan: MMVD (also termed chronic valvular heart disease [CVHD], endocardiosis, or mitral valve insufficiency [MVI]) is the most prevalent cardiovascular disease in dogs, accounting for approximately 75–80% of all canine cardiac disease; prevalence increases steeply with age: approximately 10% of dogs over 5 years, 30% over 10 years, and over 90% of cavalier King Charles spaniels (CaKCS) over 10 years (CaKCS are the breed with the highest MMVD prevalence and earliest onset — driven by a complex polygenic susceptibility); pathophysiology: MMVD is characterised by progressive myxomatous degeneration of the mitral valve leaflets and chordae tendineae: (a) myxomatous transformation — the valve leaflets undergo myxomatous degeneration (accumulation of dermatan sulfate and chondroitin sulfate proteoglycans in the spongiosa layer; disruption of the collagen fibril architecture of the fibrosa layer; depletion of valvular interstitial cells [VICs — the fibroblast-like cells maintaining valve matrix integrity] and their replacement by myofibroblast-activated VICs secreting matrix metalloproteinases [MMP-1, MMP-2, MMP-13 — collagenases] and TGF-β1 → uncontrolled extracellular matrix remodelling); (b) chordal rupture: progressive chordal weakening (loss of collagen fibril tensile strength from MMP-mediated proteolysis) → chordae tendineae rupture → acute severe mitral regurgitation → acute pulmonary oedema; (c) mitral regurgitation progression: the incompetent mitral valve allows systolic backflow from the left ventricle (LV) into the left atrium (LA) → LA volume overload → LA dilatation → increased LA pressure → pulmonary venous hypertension → pulmonary oedema (the primary life-threatening consequence of MMVD CHF); LV volume overload from the regurgitant fraction → eccentric LV hypertrophy (the Frank-Starling mechanism: increased LV preload → sarcomere lengthening → increased stroke volume to compensate for the regurgitant fraction; over time, the compensatory eccentric hypertrophy becomes maladaptive → LV dilatation → systolic dysfunction → reduced forward cardiac output); ACVIM staging: Stage A — at-risk breed, no murmur; Stage B1 — murmur present, no cardiac remodelling (no LA or LV enlargement on echo); Stage B2 — murmur present, significant cardiac remodelling (LA:Ao ≥16.6mm/m BSA or normalised LA:Ao ≥1.6, and/or LV enlargement); Stage C — current or prior CHF (pulmonary oedema); Stage D — refractory CHF; the landmark EPIC trial (Boswood et al., JAVMA 2016) demonstrated that pimobendan initiated at Stage B2 (pre-CHF with cardiac remodelling) significantly delayed onset of CHF by a median of 15 months — establishing pimobendan as the standard of care for Stage B2 MMVD in dogs
• Dilated Cardiomyopathy (DCM) — the systolic dysfunction disease of large breeds: DCM is characterised by primary myocardial failure: diffuse, progressive loss of cardiomyocyte contractility leading to ventricular dilatation and systolic dysfunction without a primary valve lesion; breed predispositions: Dobermann Pinscher (the highest DCM prevalence — autosomal dominant with incomplete penetrance; Dobermann DCM is the most studied; approximately 45% of Dobermanns have DCM or preclinical DCM by Holter/echo screening), Irish Wolfhound, Great Dane, Boxer (arrhythmogenic right ventricular cardiomyopathy [ARVC] variant — fibro-fatty myocardial replacement in the RV; distinct from DCM but managed similarly), Cocker Spaniel (taurine-deficiency associated DCM in a subset); pathophysiology: (a) primary myocardial failure: the cardiomyocyte sarcomere generates insufficient force per cross-bridge cycle (the Fm − maximum isometric force) → reduced stroke volume and reduced ejection fraction (EF < 25% in severe DCM; normal canine EF: 25–45% by M-mode); (b) compensatory neurohormonal activation: reduced forward cardiac output → baroreceptor unloading (the aortic and carotid sinus baroreceptors detect reduced pulse pressure) → sympathetic nervous system (SNS) activation (noradrenaline release from cardiac sympathetic fibres → β1-adrenergic receptor stimulation of the SA node [chronotropy] and LV myocardium [inotropy]) and RAAS activation (reduced renal perfusion pressure → juxtaglomerular apparatus renin secretion → angiotensinogen → angiotensin I [Ang I] → pulmonary ACE [angiotensin-converting enzyme − a Zn2+-dependent dipeptidyl carboxypeptidase] → angiotensin II [Ang II] → AT1R → aldosterone release from the adrenal zona glomerulosa → renal Na+/water retention → increased preload − initially compensatory, ultimately causing pulmonary oedema and ascites); (c) chronic RAAS and SNS activation → maladaptive cardiac remodelling (Ang II and aldosterone drive cardiac fibrosis: cardiac fibroblast activation → collagen I/III deposition → interstitial fibrosis → further impairs myocardial compliance and conduction; β1-adrenergic receptor downregulation from chronic noradrenaline exposure → “receptor desensitisation” → progressive loss of inotropic reserve)

Active Ingredients & Mechanisms of Action

• Pimobendan — the dual-mechanism positive inotrope and vasodilator (calcium sensitiser + PDE3 inhibitor): pimobendan (4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-3(2H)-pyridazinone; MW 334.37 g/mol) is unique among positive inotropes in having two simultaneous and complementary mechanisms: (a) calcium sensitisation of cardiac troponin C — the primary and cardioprotective mechanism: the cardiac sarcomere generates force via the cross-bridge cycle: Ca2+ released from the sarcoplasmic reticulum (SR) during systole binds cardiac troponin C (cTnC — the calcium sensor of the troponin complex [cTnC/cTnI/cTnT] within the thin filament); Ca2+-cTnC binding → conformational change in cTnI (troponin I: the inhibitory subunit that holds actin-myosin cross-bridge formation in check at diastole) → displacement of the cTnI inhibitory region from actin → tropomyosin shifts → myosin head access to actin binding sites → acto-myosin cross-bridge formation → force generation; pimobendan binds the N-terminal regulatory domain of cTnC (at the hydrophobic patch exposed by Ca2+ binding) and stabilises the Ca2+-cTnC open conformation → the cross-bridge remains active at lower intracellular Ca2+ concentrations (increased Ca2+ sensitivity of the myofilament) → the same systolic Ca2+ transient produces more contractile force; critically: pimobendan does NOT increase intracellular Ca2+ and does NOT increase the systolic Ca2+ peak — this is its key cardioprotective advantage over catecholamines (which increase Ca2+ via β1-AR/PKA/LTCC and chronically accelerate cardiomyocyte Ca2+ overload → cardiomyocyte apoptosis and arrhythmia) and over older PDE inhibitors used alone (which raise cAMP → PKA → LTCC opening → increased Ca2+ influx); pimobendan’s calcium sensitisation mechanism increases contractility without increasing myocardial oxygen demand in proportion to the force increase (since the Ca2+ transient is unchanged) − a favourable energetic profile for the failing heart; (b) PDE3 inhibition — the vasodilatory and supplementary inotropic mechanism: pimobendan is a phosphodiesterase 3 (PDE3) inhibitor; PDE3 (the cGMP-inhibited cAMP phosphodiesterase; PDE3A — the cardiac isoform; PDE3B — the adipocyte/hepatocyte isoform) hydrolyses cAMP → 5’-AMP; PDE3 inhibition → cAMP accumulation in: (i) cardiomyocytes → PKA activation → phosphorylation of phospholamban (PLB; the SR Ca2+-ATPase [SERCA2a] inhibitory protein; PLB phosphorylation at Ser16 by PKA disinhibits SERCA2a → enhanced SR Ca2+ reuptake during diastole → improved diastolic relaxation [lusitropy]) and phosphorylation of the L-type voltage-gated Ca2+ channel (LTCC/Cav1.2 − PKA phosphorylation of LTCC at Ser1928 → increased open probability → increased Ca2+ influx during the plateau phase of the action potential → increased Ca2+-induced Ca2+-release [CICR] from the SR → supplementary inotropic effect); (ii) vascular smooth muscle cells (VSMCs) → cAMP → PKA → phosphorylation of myosin light chain kinase (MLCK) → MLCK inactivation → reduced myosin light chain phosphorylation → VSMC relaxation → arterial and venous vasodilation; arterial vasodilation (afterload reduction) → reduced LV afterload → the LV empties against less resistance → improved forward stroke volume; venous vasodilation (preload reduction) → reduced venous return → reduced LV filling pressure → reduced pulmonary capillary wedge pressure → relief of pulmonary oedema; (c) pimobendan’s active metabolite — ODMT (O-desmethyl pimobendan): pimobendan undergoes hepatic N-demethylation (CYP3A4/5 and CYP2C19 mediated) → ODMT, which has comparable PDE3 inhibitory activity to pimobendan and significantly greater calcium sensitisation potency at cTnC; ODMT is the dominant circulating active species in dogs (ODMT:pimobendan AUC ratio approximately 2:1 in dogs − the metabolite contributes the majority of the cardiac effect)
• Benazepril — the ACE inhibitor for RAAS suppression, afterload/preload reduction, and anti-fibrotic cardiac protection: benazepril (3-[[1-(ethoxycarbonyl)-3-phenyl-(1S)-propyl]amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-(3S)-benzazepine-1-acetic acid; a prodrug — MW 424.49 g/mol) is a prodrug ACE inhibitor: (a) bioactivation: benazepril is a prodrug ester; hepatic esterases cleave the ester bond → benazeprilat (the active diacid; MW 396.47 g/mol); benazeprilat is a potent, competitive ACE inhibitor (Ki ≈0.6 nM); the prodrug format is required because the diacid benazeprilat has poor oral bioavailability (the negatively charged carboxylate groups prevent GI absorption − the ester prodrug is lipid-soluble → absorbed → first-pass hepatic hydrolysis → active benazeprilat); (b) ACE inhibition mechanism: ACE (angiotensin-converting enzyme; kininase II; a Zn2+-dependent dipeptidyl carboxypeptidase [zinc coordinated by His383, His387, and Glu411 in the active site; the catalytic water molecule activated by the Zn2+ → nucleophilic attack on the C-terminal dipeptide of Ang I]) cleaves the C-terminal His-Leu dipeptide from angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu − the decapeptide; renin cleaves angiotensinogen [a 452 amino acid α2-globulin] at the Leu10-Val11 bond to release Ang I) → angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe − the octapeptide); benazeprilat’s two carboxylate groups chelate the active site Zn2+ with high affinity (the ‘chelation trick’ of all carboxylate ACE inhibitors: Phe at benazeprilat P1’ position and phenylpropyl at P2 position provide Van der Waals contacts with the S1’ and S2 subsites of ACE, contributing nanomolar affinity beyond the Zn2+ chelation) → competitive inhibition of Ang I → Ang II conversion; (c) RAAS suppression consequences: reduced Ang II → (i) reduced AT1R stimulation in VSMCs → vasorelaxation (Ang II is a potent vasoconstrictor via IP3 → VSMC intracellular Ca2+ release → MLCK activation; Ang II also potentiates noradrenaline release from sympathetic terminals via pre-synaptic AT1R) → reduced systemic vascular resistance (SVR) → afterload reduction; (ii) reduced aldosterone secretion from the adrenal zona glomerulosa → reduced renal Na+/water retention → reduced plasma volume → reduced preload; (iii) reduced AT1R-mediated cardiac fibroblast activation → reduced TGF-β1 secretion → reduced collagen I/III deposition in the cardiac interstitium → anti-fibrotic cardiac protection (the long-term structural benefit of ACE inhibitors in CHF: slowing of the cardiac fibrosis that accelerates CHF progression); (d) bradykinin potentiation — the additional vasodilatory mechanism: ACE is identical to kininase II (the enzyme that degrades bradykinin [BK — Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg, a nonapeptide] by cleaving the C-terminal Phe-Arg and then Ser-Pro dipeptides); ACE inhibition → reduced bradykinin degradation → bradykinin accumulates → BK2 receptor (B2R) stimulation on endothelial cells → phospholipase C (PLC) → IP3 → endothelial intracellular Ca2+ rise → eNOS (endothelial nitric oxide synthase; Ca2+-calmodulin-activated) → L-arginine + O2 → NO + L-citrulline → NO diffuses to adjacent VSMC → soluble guanylyl cyclase (sGC) → cGMP → PKG → MLCK phosphorylation/inactivation → vasodilation; bradykinin also stimulates prostacyclin (PGI2) synthesis in endothelial cells (PLC → arachidonic acid release → COX-1 → PGG2/PGH2 → prostacyclin synthase → PGI2 → IP receptor on VSMCs → cAMP → vasodilation + anti-platelet aggregation); bradykinin potentiation contributes to both the vasodilatory efficacy and to the characteristic ACE inhibitor cough in humans (bradykinin sensitises airway C-fibres − this is less prominent in dogs and cats); (e) benazepril in dogs with concurrent renal disease: benazepril is the preferred ACE inhibitor in dogs with concurrent renal insufficiency because benazeprilat has dual elimination (renal and biliary/faecal excretion in roughly equal proportions in dogs − the unique dual-excretion property of benazepril among ACE inhibitors; most other ACE inhibitors are primarily renally eliminated and accumulate in renal failure); in dogs with significant CKD, benazeprilat’s biliary elimination maintains therapeutic levels without the accumulation-related hypotension and hyperkalaemia risk of renally eliminated ACE inhibitors

Indications

• Congestive heart failure (CHF) in dogs — ACVIM Stage C and D MMVD and DCM
• Pre-CHF MMVD with cardiac remodelling — ACVIM Stage B2 (pimobendan is indicated at Stage B2 based on the EPIC trial)
• Dilated cardiomyopathy (DCM) — symptomatic and pre-symptomatic (Dobermann, Irish Wolfhound, Great Dane, and other large/giant breed DCM)
• Mitral valve insufficiency (MVI) with left atrial and/or left ventricular enlargement, with or without pulmonary oedema

Dosage & Administration

• Administer strictly as directed by a licensed veterinarian; dosage is based on the dog’s body weight, cardiac staging, and response to treatment
• Pimobendan is typically dosed at 0.2–0.3mg/kg twice daily (approximately 12 hours apart), ideally administered 1 hour before feeding (pimobendan’s oral bioavailability is significantly reduced when given with food − Cmax reduced by approximately 30–50% in the fed state); the veterinarian will specify the exact timing
• Dose strengths: 1.25mg/2.5mg tablets (pimobendan/benazepril) — for small and toy breeds; 5mg/10mg tablets — for medium, large, and giant breeds; the appropriate strength is selected by the veterinarian based on body weight
• Regular veterinary monitoring: repeat echocardiography, chest radiography, blood pressure, and renal function (serum creatinine, BUN, K+) every 3–6 months or as directed

Safety & Precautions

• Prescription veterinary medicine — use only as directed by a licensed veterinarian
• Do not use in dogs with hypertrophic obstructive cardiomyopathy (HOCM), aortic stenosis, subaortic stenosis, or any condition where increased cardiac output or vasodilation is contraindicated
• Monitor renal function and serum electrolytes (particularly K+ — ACE inhibitors reduce aldosterone → reduced renal K+ excretion → hyperkalaemia risk, especially with concurrent potassium supplementation or potassium-sparing diuretics)
• Use with caution in hypotensive dogs or dogs receiving other vasodilators or diuretics — the combination of pimobendan (vasodilator) + benazepril (vasodilator) + furosemide (diuretic) is the standard triple therapy for CHF but requires monitoring for hypotension
• Not for use in cats without specific veterinary direction
• Keep out of reach of children; store in a cool, dry place away from direct sunlight