Verapamil and Liver Function Tests
Verapamil can cause hepatotoxicity with elevated liver enzymes, requiring periodic monitoring of liver function tests, though this adverse effect is uncommon in routine clinical use. 1
Hepatotoxicity Risk and Monitoring
Incidence and Pattern of Liver Injury
- Verapamil causes elevations of transaminases with or without concomitant elevations in alkaline phosphatase and bilirubin. 1
- These elevations are sometimes transient and may disappear even with continued verapamil treatment. 1
- Several cases of hepatocellular injury related to verapamil have been proven by rechallenge, with approximately half presenting clinical symptoms including malaise, fever, and/or right upper quadrant pain in addition to elevated SGOT, SGPT, and alkaline phosphatase. 1
- Case reports document mixed cytotoxic-cholestatic liver injury with transaminases elevated up to six-fold and alkaline phosphatase up to four-fold, accompanied by jaundice, pruritus, and upper abdominal pain. 2
Mandatory Monitoring Requirements
- Periodic monitoring of liver function in patients receiving verapamil is prudent. 1
- When used as a moderate CYP3A inhibitor (such as in combination with tolvaptan for ADPKD), verapamil necessitates consideration for dose adjustment or holding the interacting medication if liver enzymes increase. 3
Clinical Context: Drug Interactions Affecting LFTs
Verapamil as CYP3A Inhibitor
- Verapamil acts as a moderate CYP3A inhibitor, reducing clearance of other drugs by 50-80%. 3
- When combined with drugs metabolized by CYP3A4 (such as tolvaptan), this interaction can increase the risk of liver enzyme elevations, requiring downtitration or holding of the affected medication. 3
- All calcium-channel blockers, including verapamil, are metabolized in the liver by cytochrome P450 3A4. 3
Hepatoprotective Effects in Specific Contexts
Ischemia-Reperfusion Injury
- In experimental models, verapamil at therapeutic concentrations significantly protects against warm liver ischemia-reperfusion injury by attenuating late hepatocyte injury (beyond 1 hour of reperfusion). 4
- Verapamil significantly increased bile flow and reduced plasma ALT and LDH at 24 hours after liver ischemia-reperfusion compared to controls. 4
- Low concentrations (20 micromol/l) of verapamil improved metabolic liver efficiency during extracorporeal liver perfusion, suggesting potential hepatoprotective effects. 5
Cirrhosis and Portal Hypertension
- In patients with advanced cirrhosis and portal hypertension, verapamil (100 mg oral) did not improve hepatic intrinsic clearance or liver function parameters. 6
- Verapamil caused systemic vasodilation but provided no beneficial effect on portal pressure, hepatic blood flow, or hepatic vascular resistance in cirrhotic patients. 6
Common Pitfalls and Clinical Caveats
When to Suspect Verapamil-Induced Hepatotoxicity
- Monitor for clinical symptoms including malaise, fever, right upper quadrant pain, jaundice, or pruritus in addition to routine LFT monitoring. 1
- Hepatotoxicity can occur even without symptoms, emphasizing the importance of periodic biochemical monitoring. 1
- Re-challenge with verapamil after hepatotoxicity has been documented to reproduce liver injury, confirming causality. 2
Populations Requiring Enhanced Monitoring
- Patients with hepatic insufficiency have delayed verapamil metabolism with elimination half-life prolonged up to 14-16 hours and may require only one-third of the normal oral daily dose. 1
- Approximately 90% of verapamil is bound to plasma proteins, and the volume of distribution is increased in hepatic insufficiency with plasma clearance reduced to about 30% of normal. 1