What alternative regimen can be used for hepatitis C treatment in a patient taking rifampicin (Rifampin) and isoniazid (Isonicotinic Hydrazide) due to potential drug interactions with sofosbuvir (Sofosbuvir)/velpatasvir (Velpatasvir)?

Alternative Hepatitis C Treatment Regimens for Patients on Rifampicin and Isoniazid

Glecaprevir/pibrentasvir is the recommended alternative regimen for hepatitis C treatment in patients taking rifampicin and isoniazid, as rifampicin is a strong P-gp inducer that significantly reduces sofosbuvir/velpatasvir concentrations, making this combination contraindicated. 1

Drug Interaction Issues

• Rifampicin is a potent P-gp inducer and moderate to strong CYP inducer that significantly decreases concentrations of sofosbuvir and velpatasvir, making this combination not recommended 1
• The FDA label specifically warns against using sofosbuvir/velpatasvir with P-gp inducers and/or moderate to strong CYP inducers such as rifampicin 1
• Isoniazid has fewer direct interactions with DAAs but is used concurrently with rifampicin for TB treatment 2

Recommended Alternative Regimens

First-line Alternative:

• Glecaprevir/pibrentasvir for 8 weeks (no cirrhosis) or 12 weeks (compensated cirrhosis) 2
  • Provides high SVR rates (>95%) across all HCV genotypes 3
  • Pangenotypic coverage makes it suitable without genotype testing 2

Second-line Alternatives:

• Daclatasvir + sofosbuvir (in settings where glecaprevir/pibrentasvir is unavailable) 2

  • Should be used according to 2016 EASL recommendations 2
  • Particularly useful in low- and middle-income countries due to availability of generic versions 2
  • Treatment duration: 12 weeks (no cirrhosis) or 24 weeks/12 weeks + ribavirin (compensated cirrhosis) 2

• Elbasvir/grazoprevir (for genotype 1b only) 2

  • Treatment duration: 12 weeks 2
  • Not pangenotypic, so requires genotype determination 2

Treatment Approach Based on Liver Status

For patients without cirrhosis:

• Glecaprevir/pibrentasvir for 8 weeks 2
• Monitor liver function tests during concurrent TB therapy 2

For patients with compensated cirrhosis:

• Glecaprevir/pibrentasvir for 12 weeks 2
• More careful monitoring of liver function is required 2

Management of TB Treatment During HCV Therapy

• Consider temporarily modifying TB treatment if possible and clinically appropriate 2
• If TB treatment modification is not possible, delay HCV treatment until after completion of rifampicin-containing regimen 1
• For patients who cannot delay HCV treatment, use glecaprevir/pibrentasvir as the preferred alternative 2

Monitoring Recommendations

• Test liver function at baseline and monitor regularly during treatment 2
• If AST/ALT are two or more times normal, monitor liver function weekly for two weeks, then two weekly until normal 2
• If AST/ALT rises to five times normal or bilirubin rises, consider stopping both HCV and TB medications 2
• Monitor for drug-drug interactions throughout treatment 2

Special Considerations

• Treatment efficacy should be assessed by HCV RNA or HCV core antigen detection at week 12 (SVR12) post-treatment 2
• For patients with decompensated cirrhosis, different regimens may be required as glecaprevir/pibrentasvir is not recommended in this population 2
• In settings where newer DAAs are unavailable, generic sofosbuvir and daclatasvir combination remains a viable option 2

Potential Pitfalls

• Never use sofosbuvir/velpatasvir with rifampicin due to significant drug interaction 1
• Ensure adequate monitoring of liver function when treating both TB and HCV concurrently 2
• Be aware that treatment of either condition may need to be sequenced rather than concurrent if drug interactions cannot be managed 2