4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions. The following drug-drug interactions are considered clinically relevant for DAAs. Only those drug-drug interactions classified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level |
|---|---|---|---|---|
| elbasvir | Strong CYP3A4 inducers (e.g. phenytoin, carbamazepine, St John’s wort, phenobarbital) | Concurrent use may decrease elbasvir plasma concentration | Use is contraindicated | 1-severe (CP), contraindicated (DrugReax) |
| glecaprevir/ pibrentasvir | Strong or moderate dual CYP3A4 and p-glycoprotein inducers (e.g. rifampin, isoniazid) | Concurrent use may decrease glecepravir plasma concentration | Coadministration should be avoided | 1-severe (CP), major (DrugReax) |
| grazoprevir | OTAP1B1/3 inhibitors (e.g. cyclosporine, eltrombopag) | Concurrent use can increase grazoprevir concentrations and elevate ALT. | Use is contraindicated | 1-severe (CP), contraindicated (DrugReax) |
| grazoprevir | Protease inhibitors (e.g. saquinavir, ritonavir, darunavir) | Concurrent use can increase grazoprevir concentrations and elevate ALT. | Use is contraindicated | 1-severe (CP), contraindicated (DrugReax) |
| ledipasvir | Proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs) (e.g. omeprazole, ranitidine) | Increased pH in stomach reduces ledipasvir solubility | Use cautiously; take H2RA simultaneously or 12 hours apart from ledipasvir; PPI dose should not exceed equivalent of omeprazole 20 mg/ day. H2RA should not exceed equivalent of famotidine 40 mg twice daily | 2-Major (CP), Major (DrugReax) |
| ledipasvir | p-glycoprotein inducers (e.g. rifampin, St John’s wort) | Concurrent use can decrease ledipasvir concentrations, potentially resulting in loss of antiviral efficacy | Avoid coadministration of ledipasvir with potent p-glycoprotein inducers | 2-Major (CP), Contraindicated (DrugReax) |
| sofosbuvir | rifampin | Concurrent use can decrease sofosbuvir concentrations | Avoid coadministration; contraindicated | 2-Major (CP), contraindicated (DrugReax) |
| sofosbuvir | p-glycoprotein inducers (carbamazepine, phenytoin) | Concurrent use can decrease sofosbuvir concentrations | Avoid coadministration | 2-Major (CP), Major (DrugReax) |
| sofosbuvir | amiodarone | Concurrent use may increase severe bradycardia risk | Avoid coadministration | 2-Major (CP), Major (DrugReax) |
| velpatasvir | Strong or moderate dual CYP3A4 and CYP2B6 inducers (e.g., primidone, phenobarbital) | Concurrent use can decrease velpatasvir concentrations | Avoid coadministration | 2-major (CP), major (DrugReax) |
| velpatasvir | PPIs and H2RAs (e.g. omeprazole, ranitidine) | Increased pH in stomach reduces velpatasvir solubility | Use cautiously; take H2RA simultaneously or 12 hours apart from velpatasvir; PPI dose should not exceed equivalent of omeprazole 20 mg/ day and should be taken 4 hours after administration of velpatasvir; H2RA should not exceed equivalent of famotidine 40 mg/ twice daily | 2-Major (CP), Major (DrugReax) |
| voxilaprevir | Strong or moderate dual CYP3A4 and CYP2B6 inducers (e.g. primidone, phenobarbital) | Concurrent use can decrease voxilaprevir concentrations | Avoid coadministration | 2-major (CP), major (DrugReax) |
| voxilaprevir | Strong or moderate dual CYP3A4 and p-glycoprotein inducers (e.g. phenytoin, St. John’s wort) | Concurrent use can decrease voxilaprevir concentrations | Avoid coadministration | 2-major (CP), major (DrugReax) |
| voxilaprevir | Cyclosporine (P-glycoprotein inhibitor) | Concurrent use can increase voxilaprevir concentrations | Avoid coadministration | 2-major (CP), major (DrugReax) |
Legend:
- *CP= Clinical Pharmacology