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Drug Interactions between atazanavir and Viekira XR

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

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Interactions between your drugs

Major

atazanavir paritaprevir

Applies to: atazanavir and Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir)

ADJUST DOSE: Coadministration of atazanavir plus ritonavir in combination with ombitasvir/paritaprevir/ritonavir plus dasabuvir may significantly increase the plasma concentrations of paritaprevir. The mechanism may involve inhibition of both CYP450 3A4-mediated metabolism and P-glycoprotein-mediated transport by atazanavir and ritonavir. In 12 study subjects, administration of once daily morning doses of ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg) plus twice daily doses of dasabuvir concomitantly with atazanavir 300 mg plus ritonavir 100 mg once daily in the evening (12 hours after morning doses of ombitasvir/paritaprevir/ritonavir plus dasabuvir) resulted in increases of approximately 2.2-, 3.2- and 12-fold in mean paritaprevir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin), respectively. Mean ritonavir Cmax, AUC and Cmin also increased by approximately 1.6-, 3.2- and 24.7-fold, respectively, presumably due to dose-related increases from the additional dose of ritonavir per day. The mean Cmax and AUC of ombitasvir and dasabuvir were reduced slightly, by less than 20%, while the AUC and Cmin of atazanavir were increased by 19% and 68%, respectively.

MONITOR CLOSELY: Coadministration of atazanavir with ombitasvir/paritaprevir/ritonavir plus dasabuvir may increase the risk of hyperbilirubinemia. Both atazanavir and paritaprevir can cause elevations in indirect (unconjugated) bilirubin, the former by inhibition of UGT1A1 and the latter by inhibition of OATP1B1/1B3. In 63 subjects with HCV/HIV-1 coinfection, elevations in total bilirubin (mostly indirect) greater than two times the upper limit of normal occurred in 34 (54%) of subjects receiving ombitasvir/paritaprevir/ritonavir plus dasabuvir with ribavirin, 15 of whom were also receiving atazanavir at the time of bilirubin elevation. Nine of these patients also had adverse events of ocular icterus, jaundice, or hyperbilirubinemia. None of the subjects with hyperbilirubinemia had concomitant elevations of aminotransferases.

MANAGEMENT: When coadministered with ombitasvir/paritaprevir/ritonavir plus dasabuvir, atazanavir 300 mg should be given in the morning without ritonavir. The ritonavir component of the HIV antiretroviral regimen should be restarted after completion of treatment with ombitasvir/paritaprevir/ritonavir plus dasabuvir.

References (1)
  1. (2022) "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC
Moderate

ritonavir atazanavir

Applies to: Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir) and atazanavir

ADJUST DOSE: Coadministration with ritonavir may significantly increase the plasma concentrations of atazanavir. The mechanism is ritonavir inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of atazanavir. In 28 study subjects, ritonavir (100 mg once a day for 10 days) increased the mean steady-state peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and trough plasma concentration (Cmin) of atazanavir (300 mg once a day) by 86%, 238% and over 1000%, respectively, compared to administration of atazanavir alone. Compared with historical data from standard therapeutic dosing of atazanavir alone at 400 mg once a day, administration of atazanavir/ritonavir at 300 mg/100 mg once a day increased atazanavir mean Cmax, AUC and Cmin by 18%, 103% and 671%, respectively.

MANAGEMENT: Patients requiring the combination should be prescribed atazanavir 300 mg with ritonavir 100 mg as a single daily dose with food.

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

Drug and food interactions

Moderate

ritonavir food

Applies to: Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir)

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References (1)
  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
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

paritaprevir food

Applies to: Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir)

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of ombitasvir, paritaprevir, ritonavir, and dasabuvir. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a moderate-fat meal (approximately 600 Kcal; 20% to 30% calories from fat) increased the mean systemic exposure (AUC) by 82%, 211%, 49%, and 30%, respectively. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a high-fat meal (approximately 900 Kcal; with 60% calories from fat) increased the mean AUC by 76%, 180%, 44%, and 22%, respectively.

MANAGEMENT: Ombitasvir/paritaprevir/ritonavir plus dasabuvir should always be administered with a meal. The fat or calorie content does not matter.

References (1)
  1. (2022) "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC

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
  • Viekira XR (dasabuvir/ombitasvir/paritaprevir/ritonavir)

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.


Report options

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.