What are the contraindications for initiating Ozempic (semaglutide) and Maviret (glecaprevir/pibrentasvir) in a patient with Hepatitis C?

Concurrent Use of Ozempic and Maviret for Weight Loss and Hepatitis C Treatment

Ozempic (semaglutide) and Maviret (glecaprevir/pibrentasvir) can be safely administered together as there are no significant drug-drug interactions between these medications that would affect treatment outcomes or patient safety.

Drug Interaction Analysis

Maviret (Glecaprevir/Pibrentasvir)

• Maviret is a direct-acting antiviral (DAA) combination used to treat hepatitis C
• Glecaprevir is primarily metabolized by CYP3A4 and is a substrate of P-glycoprotein (P-gp) and OATP1B1 1
• Pibrentasvir is primarily eliminated via biliary excretion, with minimal renal excretion 1

Ozempic (Semaglutide)

• Semaglutide is a GLP-1 receptor agonist used for weight loss and type 2 diabetes
• Semaglutide is not significantly metabolized by CYP enzymes
• It does not inhibit or induce CYP enzymes or act as a substrate for P-gp

Key Considerations

1. No Direct Interaction: The European Association for the Study of the Liver (EASL) guidelines do not list GLP-1 receptor agonists like semaglutide among medications contraindicated with Maviret 1

2. Metabolism Pathways: The medications use different metabolic pathways:

   • Maviret components are metabolized primarily through CYP3A4 and hepatic transporters
   • Semaglutide undergoes protein degradation with minimal hepatic metabolism

3. Potential Benefits: Weight loss from Ozempic may actually benefit hepatitis C treatment outcomes by improving liver health

Important Monitoring Considerations

While these medications can be used together, certain monitoring is recommended:

1. Hepatic Function:

   • Monitor liver function tests regularly during treatment
   • Semaglutide can be used in mild to moderate hepatic impairment
   • Maviret is generally well-tolerated in compensated liver disease

2. Glucose Levels:

   • Hepatitis C treatment with DAAs like Maviret can improve hepatic function and affect glycemic control 1
   • Monitor for potential hypoglycemia during and after DAA therapy, especially as the patient will also be on Ozempic
   • Dose adjustments of Ozempic may be needed as HCV treatment progresses

3. Gastrointestinal Effects:

   • Both medications can cause gastrointestinal side effects
   • Nausea is common with both Ozempic and Maviret
   • Start Ozempic at the lowest dose and titrate up slowly to minimize GI effects

Treatment Duration and Efficacy

• Maviret is typically administered for 8 weeks in treatment-naïve patients without cirrhosis 1, 2
• Longer treatment duration (12 weeks) may be needed for treatment-experienced patients or those with cirrhosis 3, 4
• Maviret has shown high sustained virologic response (SVR) rates of 95-99% across various HCV genotypes 2, 5

Contraindications to Consider

While Ozempic and Maviret can be used together, be aware of these contraindications:

1. For Maviret:

   • Severe hepatic impairment (Child-Pugh C) 1
   • Co-administration with atazanavir-containing regimens 1
   • Ethinylestradiol-containing contraceptives (can cause ALT elevations) 1

2. For Ozempic:

   • Personal or family history of medullary thyroid carcinoma
   • Multiple Endocrine Neoplasia syndrome type 2
   • History of serious hypersensitivity to semaglutide

Practical Recommendations

1. Timing of Administration:

   • Maviret: Take once daily with food
   • Ozempic: Administer weekly subcutaneously, regardless of meals
   • No specific timing separation is required between the two medications

2. Monitoring Schedule:

   • Baseline: Complete liver function tests, HCV RNA, glucose levels
   • During treatment: Monitor liver enzymes at weeks 4 and 8
   • Post-treatment: Check HCV RNA at 12 weeks after completing Maviret to confirm SVR

3. Patient Education:

   • Inform patient about potential overlapping side effects (nausea, headache, fatigue)
   • Advise on the importance of adherence to both medications for optimal outcomes
   • Instruct on glucose monitoring, especially if the patient has diabetes

By following these guidelines, patients can safely and effectively receive concurrent treatment with Ozempic for weight loss and Maviret for hepatitis C infection.