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Drug Interactions between digoxin and Evotaz

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

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Interactions between your drugs

Major

digoxin atazanavir

Applies to: digoxin and Evotaz (atazanavir / cobicistat)

MONITOR CLOSELY: Atazanavir has been shown to prolong the PR interval of the electrocardiogram in some patients. Theoretically, coadministration with other agents that prolong the PR interval (e.g., beta blockers, digoxin, lacosamide, mefloquine, verapamil) may result in elevated risk of conduction disturbances and atrioventricular block. In a pharmacokinetic study, no substantial additive effect on the PR interval was observed during coadministration of atazanavir (400 mg once a day) and atenolol (50 mg once a day). However, an additive effect cannot be excluded because data are limited and atazanavir has not been studied in combination with other agents that prolong the PR interval.

MANAGEMENT: Caution is advised if atazanavir is used concomitantly with other agents that prolong the PR interval, particularly those that are metabolized by CYP450 3A4 (e.g., verapamil), since atazanavir is an inhibitor of that isoenzyme.

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

digoxin cobicistat

Applies to: digoxin and Evotaz (atazanavir / cobicistat)

MONITOR: Coadministration with cobicistat may increase serum digoxin concentrations and the risk of digoxin toxicity. The proposed mechanism is reduced clearance of digoxin due to inhibition of P-glycoprotein-mediated renal tubular secretion by cobicistat. In 22 study subjects, administration of a single 0.5 mg dose of digoxin during treatment with cobicistat 150 mg once daily increased the mean digoxin peak plasma concentration (Cmax) and systemic exposure (AUC) by 41% and 8%, respectively, compared to administration alone.

MANAGEMENT: Caution is advised if digoxin must be used in combination with cobicistat. Pharmacologic response and serum digoxin levels should be monitored more closely whenever cobicistat is added to or withdrawn from therapy, and the digoxin dosage adjusted as necessary. Patients should be advised to notify their physician if they experience potential signs and symptoms of digoxin toxicity such as nausea, anorexia, visual disturbances, slow pulse, or irregular heartbeats.

References (2)
  1. Cerner Multum, Inc. "Australian Product Information."
  2. (2012) "Product Information. Stribild (cobicistat/elvitegravir/emtricitabine/tenofovir)." Gilead Sciences

Drug and food interactions

Moderate

atazanavir food

Applies to: Evotaz (atazanavir / cobicistat)

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
Minor

digoxin food

Applies to: digoxin

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.

References (2)
  1. Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54
  2. Becquemont L, Verstuyft C, Kerb R, et al. (2001) "Effect of grapefruit juice on digoxin pharmacokinetics in humans." Clin Pharmacol Ther, 70, p. 311-6

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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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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