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 of contraindicated or those considered life-threatening which have not yet been classified will be reviewed.
Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level |
---|---|---|---|---|
elbasvir/grazoprevir | bosentan | bosentan is a moderate CYP3A inducer. May lead to decreased plasma concentrations of target drug and decreased virologic response | concurrent administration should be avoided, if possible | major |
etravirine | etravirine is a moderate CYP3A inducer. Concurrent use may result in decreased plasma concentrations of target drug and decreased virologic response | concurrent use is not recommended | major | |
modafinil | modafinil is a moderate CYP3A inducer. Concurrent use may result in decreased plasma concentrations of target drug and decreased virologic response | concurrent use is not recommended | major | |
nafcillin | nafcillin is a moderate CYP3A inducer. May lead to decreased therapeutic effect of target drugs | coadministration is not recommended | major | |
oral ketoconazole | ketoconazole is a strong CYP3A inhibitor. May lead to increased exposure to target drugs. | coadministration is not recommended | major | |
statin therapy (atorvastatin, rosuvastatin) | increased risk of myopathy and rhabdomyolysis | do not exceed 20 mg daily of atorvastatin, and do not exceed 10 mg daily of rosuvastatin | major | |
statin therapy (fluvastatin, lovastatin, simvastatin) | concurrent use may result in increased statin plasma levels | use lowest effective dose and monitor for statin related side effects | moderate | |
strong CYP3A inducers (eg., barbiturates, apalutamide, carbamazepine, efavirenz, encorafenib, enzalutamide, phenytoin, rifampin, mitotane | target drugs are CYP3A substrates. Concurrent administration may result in decreased concentrations of target drug and may decrease virologic response concurrent use is contraindicated. | Concurrent use with moderate CYP3A inducers is not recommended. | Contraindicated | |
strong CYP3A inhibitors (eg., cobicistat, cyclosporine, ritonavir, saquinavir, tipranavir) | target drugs are CYP3A substrates. Concurrent use may increase plasma concentrations of elbasvir resulting in adverse effects | concurrent use is contraindicated | contraindicated | |
OATP1B1 and OATP1B1/3 inhibitors (eg., asciminib, atazanavir, darunavir, elexacaftor, enasidenib, encorafenib, fostemsavir, gemfibrozil, leniolisib, lopinavir, midostaurin, velpatasvir, teriflunomide, tipranavir, trofinetide, voclosporin | grazoprevir is a substrate of OATP1B1/3. Concurrent use may result in increased grazoprevir exposure | concurrent use is contraindicated | contraindicated | |
tacrolimus | tacrolimus concentrations may increase when used concurrently due to changes in liver function while on target drug | frequent monitoring of tacrolimus whole blood concentrations, changes in renal function, and tacrolimus-associated adverse events | moderate | |
glecaprevir/pibrentasvir | atazanavir | increased risk of ALT elevations | coadministration of drugs is contraindicated | contraindicated |
carbamazepine | carbamazepine is a CYP3A4 and P-gp inducer. Concurrent use may lead to decreased efficacy of target drug | coadministration is not recommended | major | |
colchicine | risk of increased colchicine exposure in patients with renal or hepatic impairment | concurrent use is contraindicated for patients with renal or hepatic impairment and/ or use of colchicine for cardiovascular risk reduction | contraindicated in patients with renal or hepatic impairment and/ or using colchicine for cardiovascular risk reduction | |
cyclosporine | cyclosporine inhibits CYP3A4, P-gp, OATP1B1, and BCRP, and it is a substrate of P-gp. Concurrent use may increase serum concentrations of target drug, and it may increase serum concentrations of cyclosporine | do not exceed 100 mg of cyclosporine daily | major | |
dabigatran | dabigatran is a P-gp substrate. Concurrent use may result in increased serum concentrations of dabigatran. | monitor for increased adverse effects associated with dabigatran. Concurrent use is not recommended when dabigatran is used for treatment or risk reduction of DVT, PE following hip replacement and CrCl less than 50 mL/min. concurrent use is not recommended in patients with non-valvular atrial fibrillation and severe renal impairment | moderate | |
darunavir | darunavir is a CYP3A4 inhibitor. Concurrent use may increase serum concentrations of target drug and increase the risk of adverse effects | concurrent use is not recommended | major | |
digoxin | digoxin is a substrate of P-gp. Concurrent use may result in increased serum concentrations of digoxin | measure serum digoxin prior to initiating target drug; reduce digoxin concentrations by decreasing dose by 50% or by modifying dosing frequency | major | |
efavirenz | efavirenz is a CYP3A4 inducer. Concurrent use may decrease concentrations of target drug and decrease therapeutic effect of target drug | concurrent use is not recommended | major | |
elagolix | elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Glecaprevir inhibits P-gp and OATP1B1 | concurrent use is contraindicated | contraindicated | |
ethinyl estradiol containing products | concurrent administration may result in increased risk of ethinyl estradiol associated ALT elevations | concurrent use with products containing more than 20 mcg of ethinyl estradiol is not recommended | major | |
lopinavir; ritonavir | lopinavir inhibits OATP1B1. Ritonavir inhibits CYP3A4 and P-gp. Concurrent use may increase serum concentrations of target drug and ritonavir | concurrent use is not recommended | major | |
rifampin | glecaprevir is a substrate for CYP3A4 and P-glycoprotein (P-gp). Rifampin is a CYP3A4 and P-gp inducer. Coadministration decreases plasma concentrations of glecaprevir by 88% | concurrent use is contraindicated | contraindicated | |
statin therapy (atorvastatin, fluvastatin, lovastatin, pitavastatin. pravastatin, rosuvastatin, simvastatin) | increased risk of myopathy and rhabdomyolysis | concurrent use is not recommended for atorvastatin, lovastatin, and simvastatin. Decrease pravastatin dose by 50%. Do not exceed 10 mg daily of rosuvastatin, and use the lowest effective dose of fluvastatin or pitavastatin | major | |
ledipasvir/sofosbuvir | amiodarone | concurrent use may result in serious symptomatic bradycardia | concurrent administration is not recommended. If it is required cardiac monitoring is recommended | major |
antacids (eg., aluminum and magnesium hydroxide) | concurrent use may decrease concentrations of target drug as solubility decreases as pH increases | separate administrations by at least 4 hours | moderate | |
carbamazepine, phenytoin, phenobarbital | concurrent use may decrease concentrations of target drug resulting in decreased therapeutic effect | coadministration is not recommended | major | |
colchicine | colchicine is a P-gp substrate and ledipasvir is a P-gp inhibitor | concurrent use is contraindicated in patients with renal or hepatic impairment and/ or using colchicine for cardiovascular risk reduction | contraindicated in patients with renal or hepatic impairment and/ or using colchicine for cardiovascular risk reduction | |
digoxin | coadministration may result in increased digoxin concentrations | therapeutic concentration monitoring of digoxin is recommended if used concurrently | moderate | |
H2-receptor antagonists | concurrent use may decrease concentrations of target drug as solubility decreases as pH increases | may be administered simultaneously or 12 hours apart with a dose that does not exceed doses comparable to famotidine 40 mg twice daily | major | |
HIV antiretroviral therapy containing tenofovir DF without HIV protease inhibitor/ritonavir or cobicistat | may increase serum concentrations of tenofovir | monitor for tenofovir related adverse reactions | moderate | |
HIV antiretroviral therapy containing tenofovir DF with HIV protease inhibitor/ritonavir or cobicistat | may increase serum concentrations of tenofovir | consider alternate HCV or antiretroviral therapy. If use is necessary, monitor for tenofovir associated adverse effects | moderate | |
proton pump inhibitors | concurrent use may decrease concentrations of target drug as solubility decreases as pH increases | may administered at the same time under fasting conditions at a maximum dose comparable to omeprazole 20 mg | major | |
rifabutin, rifampin, rifapentine | concurrent use may decrease serum concentrations of target drug | concurrent use is not recommended | major | |
statin therapy (atorvastatin, rosuvastatin) | concurrent use may increase risk of myopathy and rhabdomyolysis | concurrent use with rosuvastatin is not recommended. Monitor for statin related adverse reactions if atorvastatin is used | major | |
tipranavir/ritonavir | concurrent use may decrease serum concentrations of target drug | concurrent use is not recommended | major | |
sofosbuvir/velpatasvir | amiodarone | concurrent use may result in serious symptomatic bradycardia | concurrent administration is not recommended. If it is required cardiac monitoring is recommended | major |
antacids (e.g., aluminum and magnesium hydroxide) | concurrent use may decrease concentrations of target drug as solubility decreases as pH increases | separate administration by at least 4 hours | moderate | |
carbamazepine, phenytoin, phenobarbital | concurrent use may decrease concentrations of target drug resulting in decreased therapeutic effect | coadministration is not recommended | major | |
colchicine | colchicine is a P-gp substrate and velpatasvir is a P-gp inhibitor | concurrent use is contraindicated in patients with renal or hepatic impairment and/or using colchicine for cardiovascular risk reduction | contraindicated in patients with renal or hepatic impairment and/ or using colchicine for cardiovascular risk reduction | |
digoxin | coadministration may result in increased digoxin concentrations | therapeutic concentration monitoring of digoxin is recommended if used concurrently | moderate | |
efavirenz | efavirenz is a CYP3A4 inducer. Concurrent use may decrease concentrations of target drug and decrease therapeutic effect of target drug | concurrent use is not recommended | major | |
elagolix | elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Velpatsavir inhibits OATP1B1. | concurrent use is contraindicated | contraindicated | |
H2-receptor antagonists | concurrent use may decrease concentrations of target drug as solubility decreases as pH increases | may be administered simultaneously or 12 hours apart with a dose that does not exceed doses comparable to famotidine 40 mg twice daily | major | |
HIV antiretroviral therapy containing tenofovir DF | may increase serum concentrations of tenofovir | monitor for tenofovir related adverse reactions | moderate | |
proton pump inhibitors | concurrent use may decrease concentrations of target drug as solubility decreases as pH increases | concurrent use is not recommended. If necessary, target drug should be taken 4 hours before omeprazole 20 mg | major | |
rifabutin, rifampin, rifapentine | concurrent use may decrease serum concentrations of target drug | concurrent use is not recommended | major | |
statin therapy (atorvastatin, rosuvastatin) | concurrent use may increase risk of myopathy and rhabdomyolysis | do not exceed 10 mg of rosuvastatin daily Monitor for statin related adverse reactions if atorvastatin is used | major | |
sofosbuvir/velpatasvir/ voxilaprevir | amiodarone | concurrent use may result in serious symptomatic bradycardia. | concurrent administration is not recommended. If it is required cardiac monitoring is recommended | major |
antacids (eg., aluminum and magnesium hydroxide) | concurrent use may decrease concentrations of target drug as solubility decreases as pH increases | separate administration by at least 4 hours | moderate | |
atazanavir, lopinavir | may increase serum concentrations of target drug | coadministration of drugs is not recommended | major | |
carbamazepine, phenytoin, phenobarbital | concurrent use may decrease concentrations of target drug resulting in decreased therapeutic effect | coadministration is not recommended | major | |
cyclosporine | may increase serum concentrations of voxilaprevir | concurrent use is not recommended | major | |
dabigatran | dabigatran is a P-gp substrate. Concurrent use may result in increased serum concentrations of dabigatran | monitor for increased adverse effects associated with dabigatran. | moderate | |
digoxin | coadministration may result in increased digoxin concentrations | therapeutic concentration monitoring of digoxin is recommended if used concurrently | moderate | |
efavirenz | efavirenz is a CYP3A4 inducer. Concurrent use may decrease concentrations of target drug and decrease therapeutic effect of target drug | concurrent use is not recommended | major | |
H2-receptor antagonists | concurrent use may decrease concentrations of target drug as solubility decreases as pH increases | may be administered simultaneously or staggered with a dose that does not exceed doses comparable to famotidine 40 mg twice daily | major | |
HIV antiretroviral therapy containing tenofovir DF | may increase serum concentrations of tenofovir | monitor for tenofovir related adverse reactions | moderate | |
proton pump inhibitors | concurrent use may decrease concentrations of target drug as solubility decreases as pH increases | omeprazole 20 mg may be administered | major | |
rifampin | concurrent use may decrease serum concentrations and therapeutic effect of target drug | concurrent use is contraindicated | contraindicated | |
rifabutin, rifapentine | concurrent use may decrease serum concentrations and therapeutic effect of target drug | concurrent use is not recommended | major | |
statin therapy (atorvastatin, fluvastatin, lovastatin, pitavastatin. pravastatin, rosuvastatin, simvastatin) | increased risk of myopathy and rhabdomyolysis | concurrent use is not recommended for pitavastatin and rosuvastatin. Pravastatin should not exceed 40 mg daily. Use the lowest effective dose of atorvastatin, fluvastatin, lovastqatin, or simvastatin | major | |
tipranavir/ritonavir | concurrent use may decrease serum concentrations of target drug | concurrent use is not recommended | major |