Enavant UDCAK9 Ursodeoxycholic Acid Tablets for Dogs & Cats | Liver Support & Bile Acid Therapy | 10 x 15 Tablets

SCHEDULE H PRESCRIPTION VETERINARY MEDICINE — Not to be sold by retail without the prescription of a Registered Veterinary Practitioner. For veterinary use only. Not for human use. UDCA is contraindicated in complete biliary obstruction — confirm biliary patency (bile duct obstruction must be excluded by abdominal ultrasound) before initiating therapy; in complete extrahepatic bile duct obstruction, UDCA cannot be excreted and accumulates as a toxic bile acid load. Use with caution in cats with suspected bile duct obstruction secondary to pancreatitis (triaditis: concurrent pancreatitis, cholangiohepatitis, and IBD). Do not use in animals with known hypersensitivity to bile acids. Monitor liver enzymes (ALT, ALP, GGT, total bilirubin), bile acids, and albumin at baseline, 4 weeks, and every 3 months during long-term therapy. Keep out of reach of children. Store in a cool, dry place away from direct sunlight.

Enavant UDCAK9 Ursodeoxycholic Acid (UDCA IP) Tablets for Dogs & Cats | Liver Support & Bile Acid Therapy | 150mg & 300mg | 10 x 15 Tablets (150 Tablets per Box)

Enavant UDCAK9 is a Schedule H prescription veterinary hepatoprotective containing Ursodeoxycholic Acid IP (UDCA — also known as Ursodiol) in 150mg and 300mg tablet strengths for dogs and cats. UDCA is a naturally occurring tertiary bile acid (constituting only 1–3% of the normal human and canine bile acid pool, but elevated to 40–60% of the total bile acid pool during therapeutic supplementation) that exerts multiple hepatoprotective mechanisms: it replaces toxic hydrophobic bile acids in the bile acid pool with a hydrophilic, non-cytotoxic species; stabilises hepatocyte and cholangiocyte plasma membranes against hydrophobic bile acid-induced detergent disruption; protects mitochondria from bile acid-induced permeability transition pore opening and cytochrome c release; suppresses hepatocyte apoptosis via multiple anti-apoptotic signalling pathways; exerts immunomodulatory activity reducing inflammatory cytokine production and MHC class I aberrant expression on hepatocytes; and stimulates vesicular choleresis improving bile flow and reducing bile stasis. UDCAK9 is indicated for chronic hepatitis, cholangiohepatitis, intrahepatic cholestasis, gallbladder mucocele, and hepatic lipidosis in dogs and cats. Use under veterinary prescription with monitoring of liver function parameters.

Active Ingredient & Mechanisms of Action

• Ursodeoxycholic Acid (UDCA) IP — Hydrophilic tertiary bile acid with hepatoprotective, choleretic, immunomodulatory, anti-apoptotic, and antifibrotic mechanisms: UDCA (3α,7β-dihydroxy-5β-cholan-24-oic acid — the 7β-epimer of chenodeoxycholic acid/CDCA; the β-oriented 7-OH group vs the α-orientation of CDCA confers UDCA its hydrophilicity and distinguishes it from the cytotoxic 7α-OH-bearing primary and secondary bile acids) is a naturally occurring bile acid produced in small quantities by intestinal bacterial 7β-epimerisation of chenodeoxycholic acid; the liver disease state in dogs and cats is characterised by accumulation of toxic hydrophobic bile acids (chenodeoxycholic acid — CDCA, deoxycholic acid — DCA, lithocholic acid — LCA) that cause progressive hepatocyte and cholangiocyte injury via multiple mechanisms: UDCA therapy enriches the bile acid pool with a hydrophilic, low-toxicity species, displacing and diluting the toxic hydrophobic bile acids; mechanisms in detail:
  • (1) Bile acid pool hydrophilicity shift — dilution and displacement of toxic hydrophobic bile acids: oral UDCA is absorbed in the terminal ileum (via the apical sodium-dependent bile acid transporter — ASBT/SLC10A2 — which co-transports bile acids with 2 Na+ ions driven by the Na+ electrochemical gradient maintained by the basolateral Na+/K+-ATPase), transported to the liver via the portal vein bound to albumin and lipoproteins, taken up by hepatocytes via the sinusoidal Na+/taurocholate cotransporting polypeptide (NTCP/SLC10A1) and organic anion transporting polypeptides (OATPs), conjugated with taurine or glycine (dogs predominantly use taurine conjugation — tauroursodeoxycholic acid TUDC; cats, which have limited taurine synthesis, also rely on TUDCA conjugation — note the importance of ensuring adequate taurine intake in cats on restricted-protein diets), and excreted into bile via the canalicular bile salt export pump (BSEP/ABCB11); during long-term UDCA therapy, UDCA constitutes 40–60% of the total bile acid pool, displacing hydrophobic toxic species; UDCA’s high hydrophilicity (lowest hydrophobicity index in the primary-secondary-tertiary bile acid series) means it does not disrupt phospholipid bilayer integrity, does not form mixed micelles with cytotoxic efficiency, and does not activate the hepatocyte plasma membrane Fas death receptor complex (see apoptosis section)
  • (2) Membrane stabilisation of hepatocytes and cholangiocytes against hydrophobic bile acid-induced detergent disruption: hydrophobic bile acids (CDCA, DCA, LCA) intercalate into the hepatocyte plasma membrane phospholipid bilayer (they are amphipathic detergents that partition into biological membranes at micellar concentrations) → increase membrane fluidity → activate membrane receptor signalling cascades (EGFR, Src kinase, PI3K) inappropriately → disturb mitochondrial membrane integrity and promote mitochondrial reactive oxygen species (mtROS) generation; UDCA, due to its hydrophilic character, does not partition into membranes at therapeutic concentrations and instead competes with hydrophobic bile acids for membrane intercalation sites, protecting membrane structural integrity; additionally, UDCA stimulates the insertion of phosphatidylcholine (PC) into the canalicular membrane — PC forms a protective coating over the canalicular membrane that prevents bile acid-induced membrane damage (the phosphatidylcholine flippase MDR3/ABCB4 translocates PC from the inner to the outer canalicular membrane leaflet — deficiency of MDR3/ABCB4 causes progressive familial intrahepatic cholestasis type 3 — PFIC3 in humans); UDCA upregulates MDR3/ABCB4 expression, enhancing biliary PC secretion and canalicular membrane protection
  • (3) Mitochondrial protection — prevention of the mitochondrial permeability transition (MPT): toxic hydrophobic bile acids (particularly CDCA and LCA) enter hepatocyte mitochondria (their amphipathic structure allows membrane partitioning) and open the mitochondrial permeability transition pore (mPTP — a multiprotein complex at the inner mitochondrial membrane contact site, classically described as involving the voltage-dependent anion channel — VDAC — on the outer membrane, the adenine nucleotide translocator — ANT — on the inner membrane, and cyclophilin D — CypD — in the matrix; VDAC and ANT form the mPTP channel pore while CypD is the peptidyl-prolyl isomerase regulatory protein that binds the ANT and lowers the Ca2+ threshold for pore opening; note: the exact molecular composition of the mPTP remains partially uncertain with recent evidence questioning the classical VDAC/ANT/CypD model and implicating the ATP synthase/F1F0-ATPase dimers as the pore-forming component); mPTP opening → mitochondrial inner membrane permeabilisation → dissipation of the mitochondrial membrane potential (ΔΨm) → uncoupling of oxidative phosphorylation (ATP synthesis collapses — energy failure) → mitochondrial swelling → outer mitochondrial membrane (OMM) rupture → release of pro-apoptotic proteins from the mitochondrial intermembrane space (IMS): cytochrome c (activates the intrinsic apoptosis pathway by forming the apoptosome — cytochrome c / Apaf-1 / procaspase-9 heptamer → caspase-9 activation → caspase-3/7 executioner caspase activation), Smac/DIABLO (neutralises XIAP — the X-linked inhibitor of apoptosis protein), and AIF (apoptosis-inducing factor — caspase-independent nuclear chromatin condensation); UDCA prevents bile acid-induced mPTP opening by: (a) activating the prosurvival PI3K/Akt (protein kinase B) → phosphorylation and inactivation of the pro-apoptotic Bcl-2 family member BAD (Bcl-2-associated death promoter) → BAD cannot displace Bcl-2/Bcl-xL from VDAC/Bax, preventing MOMP; (b) activating Akt-mediated phosphorylation and nuclear exclusion of FOXO transcription factors → reduced expression of pro-apoptotic Bcl-2 family members (Bim, PUMA); (c) direct interaction with the inner mitochondrial membrane reducing CypD-mediated sensitisation to Ca2+-triggered pore opening
  • (4) Extrinsic apoptosis pathway inhibition — displacement of death receptors from the plasma membrane DISC: toxic hydrophobic bile acids activate the extrinsic (death receptor) apoptosis pathway in hepatocytes by: (a) clustering and activating the Fas death receptor (CD95/FasR — a type I transmembrane protein of the TNFR superfamily) in the plasma membrane — hydrophobic bile acids increase membrane Fas receptor density and promote ligand-independent Fas oligomerisation → DISC (death-inducing signalling complex) formation → FADD recruitment → procaspase-8 activation → caspase-8 → Bid cleavage to tBid → tBid → mitochondria amplification loop (connecting extrinsic to intrinsic pathway) → caspase-3/7 executioner activation; (b) upregulating DR5 (death receptor 5 — the TRAIL receptor) cell surface expression → TRAIL-mediated apoptosis of bile acid-stressed hepatocytes; UDCA’s membrane-stabilising effect prevents the membrane microdomain (lipid raft) reorganisation that drives Fas/DR5 clustering, reducing ligand-independent death receptor activation in cholestatic hepatocytes; UDCA also stabilises the mitochondrial membrane against tBid-mediated MOMP, reducing cross-talk amplification from the extrinsic to intrinsic pathway
  • (5) Immunomodulatory effects — reduction of MHC class I aberrant hepatocyte expression and inflammatory cytokine suppression: in chronic hepatitis and cholangiohepatitis in dogs and cats, aberrant MHC (major histocompatibility complex) class I overexpression on hepatocytes renders them targets for cytotoxic T-lymphocyte (CTL)-mediated autoimmune attack (CD8+ CTLs recognise viral or auto-antigenic peptides presented by MHC class I on hepatocytes → perforin/granzyme B-mediated hepatocyte lysis); hydrophobic bile acid accumulation upregulates hepatocyte MHC class I expression via NF-κB activation and IFN-γ signalling upregulation; UDCA reduces aberrant MHC class I hepatocyte expression by: suppressing NF-κB p65 nuclear translocation (via IκBα stabilisation) → reduced IL-1β, IL-6, TNF-α, and COX-2 expression; reducing IFN-γ receptor signalling → STAT1 activation reduced → MHC class I gene transcription downregulated; additionally, UDCA activates the glucocorticoid receptor (GR) via a non-genomic mechanism → GR-mediated NF-κB transrepression; the immunomodulatory effects of UDCA are particularly relevant in immune-mediated chronic hepatitis (lymphocytic/lymphoplasmacytic hepatitis in dogs) and feline lymphocytic cholangiohepatitis
  • (6) Choleresis stimulation — bicarbonate-rich hypercholeresis and vesicular choleresis: UDCA stimulates bile flow (choleresis) by two mechanisms: (a) bicarbonate-stimulated hypercholeresis — UDCA (particularly TUDC — the taurine conjugate) activates a Cl−/HCO3− exchanger (AE2 — SLC4A2) on the canalicular and ductular membrane via a Gs-protein/cAMP/PKA-mediated pathway and activation of the Cl− channel CFTR (cystic fibrosis transmembrane conductance regulator) → HCO3− secretion into the bile canaliculus → alkalinisation of the bile acid microenvironment at the canalicular membrane → protonation of anionic bile acids reduced (maintains bile acids in their ionised, membrane-impermeant form → reduces retrograde permeation of bile acids through canalicular and ductular epithelium — the ‘biliary bicarbonate umbrella’ hypothesis); (b) vesicular choleresis — UDCA promotes exocytosis of vesicles from the trans-Golgi network (TGN) containing BSEP/ABCB11 transporters to the canalicular membrane, increasing the density of bile acid export pumps on the canalicular surface → enhanced bile acid secretory capacity; this is mediated via a α-PKC-dependent signalling cascade involving UDCA activation of the EGF receptor transactivation pathway
  • (7) Antifibrotic effects: hepatic stellate cells (HSCs — perisinusoidal Ito cells) are the primary collagen-secreting cells responsible for hepatic fibrosis; in chronic liver injury, HSCs are activated from their quiescent lipocyte state to an activated myofibroblast-like state (expressing α-SMA — alpha-smooth muscle actin) by TGF-β1 (transforming growth factor β1 — the principal pro-fibrogenic cytokine), PDGF-BB (platelet-derived growth factor BB — the primary HSC mitogen and chemoattractant), and reactive oxygen species; activated HSCs secrete type I and III collagen, fibronectin, and tissue inhibitor of metalloproteinases (TIMPs — which inhibit matrix metalloproteinases — MMPs — that normally degrade fibrillar collagen) → progressive periportal and perisinusoidal fibrosis → cirrhosis; UDCA reduces HSC activation by: reducing hydrophobic bile acid load (the primary trigger for Kupffer cell and stellate cell activation in cholestatic liver disease), suppressing TGF-β1 production from injured hepatocytes, and reducing ROS production from mitochondria-stressed hepatocytes that would otherwise paracrinally activate adjacent HSCs

  Indications

  • Chronic hepatitis (lymphocytic/lymphoplasmacytic hepatitis in dogs): the most common inflammatory liver disease in dogs; immune-mediated CD3+ T-lymphocyte and plasma cell infiltration of portal and periportal regions with hepatocyte apoptosis and progressive fibrosis; UDCA reduces hepatocyte MHC class I expression, suppresses inflammatory cytokine production, and protects against hydrophobic bile acid-augmented hepatocyte apoptosis
  • Feline cholangiohepatitis (cholangitis): the most common hepatobiliary disorder in cats; classified as neutrophilic (acute — associated with ascending bacterial infection from the duodenum via the common bile duct, which in cats opens into the duodenum adjacent to the pancreatic duct, facilitating ascending infection and triaditis) and lymphocytic (chronic — immune-mediated); UDCA provides anti-inflammatory and hepatoprotective support; concurrent antibiotic therapy (amoxicillin-clavulanate, metronidazole) is typically required for neutrophilic cholangiohepatitis
  • Intrahepatic cholestasis: impaired bile flow within the liver (canalicular cholestasis) causing accumulation of toxic bile acids, bilirubin, and other biliary constituents within hepatocytes and bile canaliculi; causes in dogs and cats include: hepatocellular disease (hepatitis, hepatic lipidosis, drug-induced liver injury), cholangitis, and primary biliary disorders; UDCA’s choleretic and hepatoprotective mechanisms directly address the pathophysiology
  • Gallbladder mucocele (dogs): abnormal accumulation of inspissated mucus within the gallbladder lumen forming a characteristic kiwi-fruit stellate pattern on ultrasound; associated with hypothyroidism, hyperlipidaemia (Shetland Sheepdog, Cocker Spaniel predisposition), and steroid hepatopathy; UDCA improves bile flow and reduces bile viscosity, potentially slowing mucocele progression; surgical cholecystectomy is indicated for rupture or severe cases
  • Hepatic lipidosis (feline idiopathic hepatic lipidosis — FIHL): the most common severe liver disease in cats; occurs after any period of anorexia (≥3–5 days) in overweight cats → peripheral lipolysis → massive hepatic fatty acid delivery → exceeds hepatic β-oxidation and VLDL export capacity → triglyceride accumulation in hepatocytes (>50% hepatocytes with lipid vacuoles on histology) → hepatocellular dysfunction and intrahepatic cholestasis; UDCA reduces secondary bile acid-mediated cholestatic injury in FIHL; primary treatment is aggressive nutritional support via oesophagostomy or gastrostomy tube feeding
  • Portosystemic shunts (PSS) — supportive therapy: congenital or acquired PSS divert portal blood (containing enteric toxins, bile acids, and ammonia) directly to systemic circulation bypassing hepatic detoxification → hepatic encephalopathy, hyperammonaemia, and bile acid accumulation; UDCA provides hepatoprotective support; definitive treatment is surgical ligation or ameroid constrictor placement
  • Chronic copper-associated hepatopathy (copper storage disease in Bedlington Terriers, Labrador Retrievers, Dalmatians, West Highland White Terriers): UDCA may provide adjunctive hepatoprotection alongside copper chelation therapy (d-penicillamine) and copper-restricted diet

  Dosage & Administration

  • As directed by a Registered Veterinary Practitioner based on body weight and liver function test results
  • Typical dose range: 10–15 mg/kg orally once daily with food (food improves UDCA absorption via stimulation of biliary secretion and mixed micelle formation enhancing intestinal UDCA solubilisation)
  • 150mg tablets: suitable for smaller dogs and cats (approximately 10–15kg at standard dose)
  • 300mg tablets: suitable for medium-to-large dogs (approximately 20–30kg at standard dose)
  • Long-term therapy is typically required for chronic liver disease — do not discontinue without veterinary guidance
  • Monitor liver enzymes (ALT, ALP, GGT), total bilirubin, albumin, bile acids, and body weight at baseline, 4 weeks after initiation, and every 3 months during maintenance therapy

  Safety Information

  • Contraindicated in complete biliary obstruction — confirm biliary patency by abdominal ultrasound before initiation
  • Use with caution in feline triaditis (concurrent pancreatitis + cholangiohepatitis + IBD) — confirm bile duct patency
  • Store in a cool, dry place away from direct sunlight; keep out of reach of children
  • Schedule H prescription drug — veterinary prescription mandatory