From the Guidelines
Carvedilol can be used in patients with liver disease, but its use requires careful consideration of the patient's condition, particularly in those with decompensated cirrhosis or refractory ascites, due to its potential hypotensive effects. For patients with mild to moderate liver impairment, starting with a lower dose (typically 6.25–12.5 mg) and titrating slowly based on blood pressure and heart rate response is recommended 1. In severe liver disease, carvedilol should be used with extreme caution as drug clearance is significantly reduced, potentially leading to higher blood levels and increased side effects. Regular monitoring of liver function tests is essential during treatment. Carvedilol is particularly beneficial in patients with cirrhosis and portal hypertension, as it reduces portal pressure and may decrease the risk of variceal bleeding through non-selective beta-blockade and alpha-1 blockade, which reduces hepatic venous pressure gradient 1.
Some key considerations for the use of carvedilol in liver disease include:
- Monitoring for hypotension, bradycardia, and worsening ascites
- Avoiding use in patients with systolic blood pressure <90 mmHg, severe hyponatraemia, low mean arterial pressure, or increasing serum creatinine
- Reducing or temporarily discontinuing the dose in patients with refractory ascites and signs of systemic circulatory dysfunction
- Considering alternative treatments, such as endoscopic band ligation (EBL) or covered TIPS placement, in patients who cannot tolerate carvedilol or have contraindications to its use 1.
Overall, the decision to use carvedilol in patients with liver disease should be based on a careful evaluation of the potential benefits and risks, taking into account the patient's individual condition and the latest evidence-based guidelines.
From the FDA Drug Label
Compared to healthy subjects, patients with severe liver impairment (cirrhosis) exhibit a 4 to 7 fold increase in Carvedilol Tablet levels. Carvedilol Tablet is contraindicated in patients with severe liver impairment
Patients with severe hepatic impairment
Carvedilol is contraindicated in patients with severe liver disease. In patients with severe liver impairment, Carvedilol levels are increased 4 to 7 fold compared to healthy subjects 2. Severe liver impairment is a contraindication for Carvedilol use 2.
From the Research
Carvedilol in Liver Disease
- Carvedilol is a non-selective beta-blocker (NSBB) that has been shown to be effective in reducing portal pressure and improving survival in patients with liver cirrhosis and portal hypertension 3, 4.
- The use of carvedilol in patients with cirrhosis and portal hypertension is supported by international guidelines, which recommend its use in primary prophylaxis against variceal haemorrhage in those with high-risk varices 3.
- Carvedilol has been shown to be more effective than traditional NSBBs, such as propranolol, in lowering portal pressure and reducing the risk of hepatic decompensation 4, 5.
- The safety of carvedilol in patients with decompensated cirrhosis and ascites has been debated, but studies have shown that it is not harmful and may even improve survival in these patients 6, 5.
- A randomized controlled trial found that treatment with carvedilol improved survival and reduced the risk of acute kidney injury and spontaneous bacterial peritonitis in patients with acute-on-chronic liver failure 7.
Benefits of Carvedilol
- Reduces portal pressure and improves survival in patients with liver cirrhosis and portal hypertension 3, 4.
- More effective than traditional NSBBs in lowering portal pressure and reducing the risk of hepatic decompensation 4, 5.
- Improves survival in patients with decompensated cirrhosis and ascites 6.
- Reduces the risk of acute kidney injury and spontaneous bacterial peritonitis in patients with acute-on-chronic liver failure 7.
Target Dose and Safety
- The target dose of carvedilol to treat portal hypertension should be 12.5 mg/day 4.
- Carvedilol is safe to use in patients with ascites and gastroesophageal varices, as long as no impairment of the systemic hemodynamic or renal dysfunction occurs, with maintained arterial blood pressure as a suitable safety surrogate 4.
- Severe adverse events were higher in the carvedilol group, although drug-associated adverse events were not different 5.