What are the recommendations for using Vibegron (Beta-3 adrenergic receptor agonist) in patients with elevated liver enzymes (hepatocellular injury)?

Vibegron Use in Patients with Elevated Liver Enzymes

Vibegron can be safely used in patients with mild to moderate hepatic impairment without dose adjustment, but should be avoided in patients with severe hepatic impairment (Child-Pugh C). 1

Pharmacological Considerations

• Vibegron is a selective beta-3 adrenergic receptor agonist that works by relaxing the detrusor smooth muscle during bladder filling, increasing bladder capacity 1, 2
• According to the FDA drug label, vibegron pharmacokinetics are not significantly affected by moderate (Child-Pugh B) hepatic impairment 1
• Unlike some other medications for overactive bladder, vibegron has minimal drug interactions as it does not interact with cytochrome P450 enzymes (CYPs) at clinically relevant concentrations 1, 2

Monitoring Recommendations

• Obtain baseline liver function tests before initiating vibegron therapy, particularly in patients with pre-existing liver disease 3
• For patients with mild to moderate liver enzyme elevations, regular monitoring of liver function is advisable, especially during the first few weeks of treatment 4
• If significant elevation of liver enzymes occurs or worsens during treatment, consider:
  • More frequent monitoring of liver function tests 3
  • Dose reduction if clinically indicated 4
  • Temporary interruption of treatment if liver enzymes exceed 3× baseline 3
  • Discontinuation if liver enzyme elevations persist despite dose adjustment 3

Dosing Considerations

• For patients with normal liver function or mild hepatic impairment: standard dosing of vibegron 75mg once daily 1
• For patients with moderate hepatic impairment (Child-Pugh B): standard dosing can be used, but consider starting at the lower end of the dosing range with more frequent monitoring 4
• Vibegron should not be used in patients with severe hepatic impairment (Child-Pugh C) as its effects in this population have not been studied 1

Clinical Decision Algorithm

1. Assess severity of liver enzyme elevation:

   • Mild elevation (<2× ULN): Proceed with standard dosing with regular monitoring 3
   • Moderate elevation (2-3× ULN): Consider starting at lower dose with more frequent monitoring 3, 4
   • Severe elevation (>3× ULN) or Child-Pugh C: Avoid vibegron 1

2. Monitoring schedule:

   • Baseline liver function tests before starting treatment 3
   • Follow-up testing at 2-4 weeks after initiation 3
   • If stable, continue monitoring every 3 months 3
   • If worsening, increase frequency of monitoring or consider dose adjustment/discontinuation 3

Advantages Over Alternative Treatments

• Vibegron has a favorable side effect profile compared to antimuscarinic agents used for overactive bladder 2, 5
• Clinical trials have shown that vibegron is generally well-tolerated with adverse event rates similar to placebo 6, 5
• The lack of significant drug interactions makes vibegron particularly suitable for patients on multiple medications 2, 5

Potential Pitfalls and Caveats

• While transient elevations in liver enzymes have been observed with other medications, specific data on vibegron's effect on already elevated liver enzymes is limited 3
• Be vigilant for signs of hepatotoxicity (fatigue, nausea, right upper quadrant pain, jaundice) and discontinue medication if these occur 3
• For patients with both hepatic and renal impairment, more cautious monitoring may be necessary, although vibegron pharmacokinetics are not significantly affected by renal impairment 1