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Drug Interactions between atazanavir and sofosbuvir / velpatasvir / voxilaprevir

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

atazanavir voxilaprevir

Applies to: atazanavir and sofosbuvir / velpatasvir / voxilaprevir

GENERALLY AVOID: Coadministration with atazanavir/ritonavir or lopinavir/ritonavir may significantly increase the plasma concentrations of voxilaprevir. The proposed mechanism is inhibition of organic anion transporting polypeptide (OATP) 1B1-mediated hepatic uptake of voxilaprevir by atazanavir, lopinavir, and ritonavir. Inhibition of P-glycoprotein-mediated intestinal efflux and CYP450 3A4-mediated metabolism of voxilaprevir may also contribute. When a single 400 mg/100 mg/100 mg dose of sofosbuvir/velpatasvir/voxilaprevir was administered with a single 300 mg dose of atazanavir plus 100 mg dose of ritonavir to 15 healthy study subjects, mean voxilaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 4.4- and 4.3-fold, respectively. Mean velpatasvir Cmax and AUC were also increased by approximately 1.3- and 1.9-fold, respectively, while mean sofosbuvir Cmax and AUC were increased by 1.3- and 1.4-fold, respectively. No data are available for sofosbuvir/velpatasvir/voxilaprevir administered with lopinavir/ritonavir, but a similar interaction should be expected.

MANAGEMENT: Concomitant use of sofosbuvir/velpatasvir/voxilaprevir with atazanavir- or lopinavir-containing regimens is not recommended.

References (1)
  1. (2017) "Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir)." Gilead Sciences
Moderate

velpatasvir voxilaprevir

Applies to: sofosbuvir / velpatasvir / voxilaprevir and sofosbuvir / velpatasvir / voxilaprevir

MONITOR: Coadministration with inhibitors of organic anion transporting polypeptides (OATP) 1B1 and/or 1B3 may increase the plasma concentrations of voxilaprevir, which is a substrate of the hepatic uptake transporters. When a single 100 mg dose of voxilaprevir was administered with a single 600 mg dose of the potent OATP 1B1/1B3 inhibitor cyclosporine (n=24), mean voxilaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 19.0- and 9.4-fold, respectively. Inhibition of P-glycoprotein (P-gp)- and breast cancer resistance protein (BCRP)-mediated intestinal transport and CYP450 3A4-mediated metabolism of voxilaprevir may also contribute to the overall interaction with cyclosporine. The safety of such high levels of voxilaprevir has not been established.

MANAGEMENT: Caution and monitoring are advised when voxilaprevir is used with OATP 1B1 or 1B3 inhibitors.

References (1)
  1. (2017) "Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir)." Gilead Sciences

Drug and food interactions

Moderate

atazanavir food

Applies to: atazanavir

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.

References (1)
  1. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
Moderate

voxilaprevir food

Applies to: sofosbuvir / velpatasvir / voxilaprevir

ADJUST DOSING INTERVAL: Administration with food enhances the oral bioavailability of sofosbuvir, velpatasvir, and voxilaprevir. Relative to fasting conditions, mean sofosbuvir systemic exposure (AUC) increased by 64% to 144%, mean velpatasvir AUC increased by 40% to 166%, and mean voxilaprevir AUC increased by 112% to 435% when the combined sofosbuvir/velpatasvir/voxilaprevir formulation is administered with food.

MANAGEMENT: Sofosbuvir/velpatasvir/voxilaprevir should be administered with food.

References (1)
  1. (2017) "Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir)." Gilead Sciences

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Protease inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'protease inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'protease inhibitors' category:

  • atazanavir
  • sofosbuvir/velpatasvir/voxilaprevir

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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