Sofosbuvir et velpatasvir : interactions médicamenteuses

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Coadministration of amiodarone with VOSEVI is not recommended. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

…↑ pitavastatin Coadministration with VOSEVI may increase the concentration of pitavastatin and is not recommended, due to an increased risk of myopathy, including rhabdomyolysis. atorvastatin fluvastatin lovastatin simvastatin ↑ atorvastatin ↑ fluvastatin ↑ lovastatin ↑ simvastatin Coadministration with VOSEVI may increase the concentrations of atorvastatin,… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, have been reported in patients treated with HCV NS3/4A protease inhibitor-containing regimens, including treatment with VOSEVI. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

…↑ pitavastatin Coadministration with VOSEVI may increase the concentration of pitavastatin and is not recommended, due to an increased risk of myopathy, including rhabdomyolysis. atorvastatin fluvastatin lovastatin simvastatin ↑ atorvastatin ↑ fluvastatin ↑ lovastatin ↑ simvastatin Coadministration with VOSEVI may increase the concentrations of atorvastatin,… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

The use of OATP inhibitors which may substantially increase exposure of voxilaprevir (e.g., cyclosporine) with VOSEVI is not recommended [see Clinical Pharmacology (12.3) ]. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

P-glycoprotein The concomitant use of colchicine capsules and inhibitors of P-glycoprotein (e.g. clarithromycin, ketoconazole, cyclosporine, etc.) should be avoided due to the potential for serious and life-threatening toxicity [see Warnings and Precautions (5.3) and Clinical Pharmacology (12) ] . (notice Colchicine, Interactions médicamenteuses)

Avoid use of PRADAXA Capsules and P-gp inhibitors in patients with severe renal impairment (CrCl 15-30 mL/min) [see Drug Interactions (7.1) and Use in Specific Populations (8.6) ] . (notice Dabigatran, Mises en garde et précautions)

Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, have been reported in patients treated with HCV NS3/4A protease inhibitor-containing regimens, including treatment with VOSEVI. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, have been reported in patients treated with HCV NS3/4A protease inhibitor-containing regimens, including treatment with VOSEVI. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Coadministration of amiodarone with VOSEVI is not recommended; if coadministration is required, cardiac monitoring is recommended [see Warnings and Precautions (5.3) ]. digoxin ↑ digoxin Therapeutic concentration monitoring of digoxin is recommended when coadministered with VOSEVI. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

The effect on voxilaprevir is unknown. efavirenz ↓ velpatasvir ↓ voxilaprevir Coadministration of VOSEVI with efavirenz-containing regimens is not recommended. tenofovir disoproxil fumarate (tenofovir DF) ↑ tenofovir Monitor for tenofovir-associated adverse reactions in patients receiving VOSEVI concomitantly with a regimen containing tenofovir DF. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

The effect on voxilaprevir is unknown. efavirenz ↓ velpatasvir ↓ voxilaprevir Coadministration of VOSEVI with efavirenz-containing regimens is not recommended. tenofovir disoproxil fumarate (tenofovir DF) ↑ tenofovir Monitor for tenofovir-associated adverse reactions in patients receiving VOSEVI concomitantly with a regimen containing tenofovir DF. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

The effect on voxilaprevir is unknown. efavirenz ↓ velpatasvir ↓ voxilaprevir Coadministration of VOSEVI with efavirenz-containing regimens is not recommended. tenofovir disoproxil fumarate (tenofovir DF) ↑ tenofovir Monitor for tenofovir-associated adverse reactions in patients receiving VOSEVI concomitantly with a regimen containing tenofovir DF. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

The effect on voxilaprevir is unknown. efavirenz ↓ velpatasvir ↓ voxilaprevir Coadministration of VOSEVI with efavirenz-containing regimens is not recommended. tenofovir disoproxil fumarate (tenofovir DF) ↑ tenofovir Monitor for tenofovir-associated adverse reactions in patients receiving VOSEVI concomitantly with a regimen containing tenofovir DF. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

The effect on voxilaprevir is unknown. efavirenz ↓ velpatasvir ↓ voxilaprevir Coadministration of VOSEVI with efavirenz-containing regimens is not recommended. tenofovir disoproxil fumarate (tenofovir DF) ↑ tenofovir Monitor for tenofovir-associated adverse reactions in patients receiving VOSEVI concomitantly with a regimen containing tenofovir DF. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Strong CYP3A inhibitor and P-gp inhibitor : Avoid coadministration. (notice Évérolimus, Interactions médicamenteuses)

…with VOSEVI may increase the concentration of pitavastatin and is not recommended, due to an increased risk of myopathy, including rhabdomyolysis. atorvastatin fluvastatin lovastatin simvastatin ↑ atorvastatin ↑ fluvastatin ↑ lovastatin ↑ simvastatin Coadministration with VOSEVI may increase the concentrations of atorvastatin, fluvastatin, lovastatin, and simvastatin. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…pitavastatin Coadministration with VOSEVI may increase the concentration of pitavastatin and is not recommended, due to an increased risk of myopathy, including rhabdomyolysis. atorvastatin fluvastatin lovastatin simvastatin ↑ atorvastatin ↑ fluvastatin ↑ lovastatin ↑ simvastatin Coadministration with VOSEVI may increase the concentrations of atorvastatin, fluvastatin,… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, have been reported in patients treated with HCV NS3/4A protease inhibitor-containing regimens, including treatment with VOSEVI. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Coadministration of VOSEVI with BCRP substrates (e.g., methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan) is not recommended [see Clinical Pharmacology (12.3) ]. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Coadministration of VOSEVI with BCRP substrates (e.g., methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan) is not recommended [see Clinical Pharmacology (12.3) ]. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Coadministration of VOSEVI with BCRP substrates (e.g., methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan) is not recommended [see Clinical Pharmacology (12.3) ]. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, have been reported in patients treated with HCV NS3/4A protease inhibitor-containing regimens, including treatment with VOSEVI. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Use of VOSEVI with P-gp inducers and/or moderate to strong CYP inducers is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…Coadministration with VOSEVI may increase the concentration of pitavastatin and is not recommended, due to an increased risk of myopathy, including rhabdomyolysis. atorvastatin fluvastatin lovastatin simvastatin ↑ atorvastatin ↑ fluvastatin ↑ lovastatin ↑ simvastatin Coadministration with VOSEVI may increase the concentrations of atorvastatin, fluvastatin, lovastatin,… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Coadministration of VOSEVI with BCRP substrates (e.g., methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan) is not recommended [see Clinical Pharmacology (12.3) ]. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Coadministration of VOSEVI with BCRP substrates (e.g., methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan) is not recommended [see Clinical Pharmacology (12.3) ]. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Avoid concomitant use of VOTRIENT with strong inhibitors of P-gp or BCRP. (notice Pazopanib, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Coadministration of VOSEVI with rosuvastatin is not recommended. pitavastatin ↑ pitavastatin Coadministration with VOSEVI may increase the concentration of pitavastatin and is not recommended, due to an increased risk of myopathy, including rhabdomyolysis. atorvastatin fluvastatin lovastatin simvastatin ↑ atorvastatin ↑ fluvastatin ↑ lovastatin ↑ simvastatin… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antimycobacterials: rifampin ↓ sofosbuvir ↓ velpatasvir ↑ voxilaprevir (single dose) ↓ voxilaprevir (multiple dose) Coadministration with rifampin is contraindicated [see Contraindications (4) ]. rifabutin rifapentine ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

VOSEVI is contraindicated with rifampin [see Drug Interactions (7.3) , and Clinical Pharmacology (12.3) ]. (notice Sofosbuvir et velpatasvir, Contre-indications)

Antimycobacterials: rifampin ↓ sofosbuvir ↓ velpatasvir ↑ voxilaprevir (single dose) ↓ voxilaprevir (multiple dose) Coadministration with rifampin is contraindicated [see Contraindications (4) ]. rifabutin rifapentine ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

• Potent Inhibitors of P-gp: Avoid another dose of NURTEC ODT within 48 hours when administered with a potent P-gp inhibitor. (notice Rimégépant, Interactions médicamenteuses)

Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, have been reported in patients treated with HCV NS3/4A protease inhibitor-containing regimens, including treatment with VOSEVI. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Coadministration of VOSEVI with BCRP substrates (e.g., methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan) is not recommended [see Clinical Pharmacology (12.3) ]. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…with VOSEVI may increase the concentration of pitavastatin and is not recommended, due to an increased risk of myopathy, including rhabdomyolysis. atorvastatin fluvastatin lovastatin simvastatin ↑ atorvastatin ↑ fluvastatin ↑ lovastatin ↑ simvastatin Coadministration with VOSEVI may increase the concentrations of atorvastatin, fluvastatin, lovastatin, and simvastatin. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

• Avoid concomitant use with strong CYP3A4/P-gp inducers or strong CYP3A4/P-gp inhibitors that decrease or increase sirolimus concentrations ( 7.4 , 12.3 ). (notice Sirolimus, Interactions médicamenteuses)

Coadministration of VOSEVI with BCRP substrates (e.g., methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan) is not recommended [see Clinical Pharmacology (12.3) ]. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Effect of Other Drugs on TALZENNA Effect of P-gp Inhibitors Breast Cancer Avoid coadministration of TALZENNA with the following P-gp inhibitors: itraconazole, amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil. (notice Talazoparib, Interactions médicamenteuses)

The effect on voxilaprevir is unknown. efavirenz ↓ velpatasvir ↓ voxilaprevir Coadministration of VOSEVI with efavirenz-containing regimens is not recommended. tenofovir disoproxil fumarate (tenofovir DF) ↑ tenofovir Monitor for tenofovir-associated adverse reactions in patients receiving VOSEVI concomitantly with a regimen containing tenofovir DF. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Coadministration of VOSEVI with BCRP substrates (e.g., methotrexate, mitoxantrone, imatinib, irinotecan, lapatinib, rosuvastatin, sulfasalazine, topotecan) is not recommended [see Clinical Pharmacology (12.3) ]. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Therefore, the concomitant use of P-gp inhibitors or inducers should be avoided. (notice Vincristine, Interactions médicamenteuses)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (notice Afatinib, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Antacids (e.g., aluminum and magnesium hydroxide) Separate antacid and VOSEVI administration by 4 hours. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticoagulants: dabigatran etexilate ↑ dabigatran Clinical monitoring of dabigatran is recommended when coadministered with VOSEVI. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticoagulants: dabigatran etexilate ↑ dabigatran Clinical monitoring of dabigatran is recommended when coadministered with VOSEVI. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Anticoagulants: dabigatran etexilate ↑ dabigatran Clinical monitoring of dabigatran is recommended when coadministered with VOSEVI. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…following drugs can be coadministered with dolutegravir without a dose adjustment: atazanavir/ritonavir, darunavir/ritonavir, elbasvir/grazoprevir, methadone, midazolam, omeprazole, oral contraceptives containing norgestimate and ethinyl estradiol, prednisone, rifabutin, rilpivirine, sofosbuvir/velpatasvir, and tenofovir [see Clinical Pharmacology ( 12.3 )] . (notice Dolutégravir, Interactions médicamenteuses)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticoagulants: dabigatran etexilate ↑ dabigatran Clinical monitoring of dabigatran is recommended when coadministered with VOSEVI. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Table 2: Established and Other Potentially Clinically Relevant Interactions Affecting VIBERZI OATP1B1 Inhibitors Clinical Impact: Increased exposure to eluxadoline when coadministered with cyclosporine [ see Clinical Pharmacology ( 12.3 ) ] Intervention: Administer VIBERZI at a dose of 75 mg twice daily [see Dosage and Administration ( 2 )] and monitor patients… (notice Éluxadoline, Interactions médicamenteuses)

Anticoagulants: dabigatran etexilate ↑ dabigatran Clinical monitoring of dabigatran is recommended when coadministered with VOSEVI. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Concentrations of fidaxomicin and OP-1118 may also be decreased at the site of action (i.e., gastrointestinal tract) via P-gp inhibition; however, concomitant P-gp inhibitor use had no attributable effect on safety or treatment outcome of fidaxomicin-treated adult patients in controlled clinical trials. (notice Fidaxomicine, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Anticoagulants: dabigatran etexilate ↑ dabigatran Clinical monitoring of dabigatran is recommended when coadministered with VOSEVI. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Anticoagulants: dabigatran etexilate ↑ dabigatran Clinical monitoring of dabigatran is recommended when coadministered with VOSEVI. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Drug Interactions Effects of Other Drugs on Loperamide Concomitant use of loperamide hydrochloride capsules with inhibitors of CYP3A4 (e.g., itraconazole) or CYP2C8 (e.g., gemfibrozil) or inhibitors of P-glycoprotein (e.g., quinidine, ritonavir) can increase exposure to loperamide. (notice Lopéramide, Interactions médicamenteuses)

Antacids (e.g., aluminum and magnesium hydroxide) Separate antacid and VOSEVI administration by 4 hours. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

P-Glycoprotein (P-gp) Inhibitors Clinical Impact: The concomitant use of P-gp inhibitors can increase the exposure to morphine by two-fold and can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. (notice Morphine, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

P-glycoprotein (P-gp) Inhibitors (e.g., amiodarone, captopril, cyclosporine, quercetin, quinidine, verapamil) Clinical Impact Increase in plasma naldemedine concentrations [see Clinical Pharmacology (12.3) ] Intervention Monitor for potential naldemedine-related adverse reactions [see Adverse Reactions (6.1) ] . (notice Naldémédine, Interactions médicamenteuses)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Pravastatin may be administered with VOSEVI at a dose that does not exceed pravastatin 40 mg. rosuvastatin ↑ rosuvastatin Coadministration of VOSEVI with rosuvastatin may significantly increase the concentration of rosuvastatin which is associated with increased risk of myopathy, including rhabdomyolysis. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Clinical Effect/Recommendation Acid Reducing Agents: ↓ velpatasvir Velpatasvir solubility decreases as pH increases. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

• Concomitant P-glycoprotein (P-gp) inhibitors (e.g., cyclosporine): Caution should be exercised when concomitant use of XIFAXAN and a P-glycoprotein inhibitor is needed. (notice Rifaximine, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Anticoagulants: dabigatran etexilate ↑ dabigatran Clinical monitoring of dabigatran is recommended when coadministered with VOSEVI. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (notice Sofosbuvir et velpatasvir, Mises en garde et précautions)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Frequent monitoring of relevant laboratory parameters (e.g., International Normalized Ratio [INR] in patients taking warfarin, blood glucose levels in diabetic patients) or drug concentrations of concomitant medications such as cytochrome P450 substrates with a narrow therapeutic index (e.g., certain immunosuppressants) is recommended to ensure safe and effective… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Dapagliflozin or dapagliflozin 3-O-glucuronide did not meaningfully inhibit P-gp, OCT2, OAT1, or OAT3 active transporters. (notice Dapagliflozine, Interactions médicamenteuses)

Digoxin Quinidine is an inhibitor of P-glycoprotein. (notice Dextrométhorphane et quinidine, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Effects of Other Drugs on HALAVEN No drug-drug interactions are expected with CYP3A4 inhibitors, CYP3A4 inducers or P-glycoprotein (P-gp) inhibitors. (notice Éribuline, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Potential for Other Drugs to Affect VOSEVI Sofosbuvir, velpatasvir, and voxilaprevir are substrates of drug transporters P-gp and BCRP while GS-331007 (predominant circulating metabolite of sofosbuvir) is not. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

P-glycoprotein Substrates Lomitapide is an inhibitor of P-glycoprotein (P-gp). (notice Lomitapide, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Substrates and Inhibitors of P-glycoprotein It has been shown in vitro that mefloquine is a substrate and an inhibitor of P-glycoprotein. (notice Méfloquine, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Quinine inhibits P-gp and has the potential to affect the transport of drugs that are P-gp substrates. (notice Quinine, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Strong P-glycoprotein (P-gp) Inhibitors In vitro studies indicated that silodosin is a P‑gp substrate. (notice Silodosine, Interactions médicamenteuses)

Mechanism and Clinical Effect(s) Vepdegestrant is a P-gp inhibitor. (notice Vepdégestrant, Interactions médicamenteuses)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir: methadone, tacrolimus (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir: methadone, tacrolimus (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir: methadone, tacrolimus (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir:… (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

…drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir: methadone, tacrolimus (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)