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Drug Interactions between Evotaz and Quinaglute Dura-Tabs

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

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Interactions between your drugs

Major

quiNIDine atazanavir

Applies to: Quinaglute Dura-Tabs (quinidine) and Evotaz (atazanavir / cobicistat)

MONITOR CLOSELY: Coadministration with atazanavir may increase the plasma concentrations of amiodarone, systemic lidocaine, and quinidine. The proposed mechanism is atazanavir inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of these antiarrhythmic agents. The interaction has not been studied but could conceivably lead to serious and/or life-threatening reactions including cardiac arrhythmias and other toxicities.

MANAGEMENT: Caution is advised if atazanavir must be used with amiodarone, systemic lidocaine, or quinidine. Pharmacologic response and plasma antiarrhythmic drug levels should be monitored more closely whenever atazanavir is added to or withdrawn from therapy, and the antiarrhythmic dosage adjusted as necessary. According to some authorities, use of the fixed combination atazanavir-cobicistat or atazanavir-ritonavir with amiodarone or quinidine is considered contraindicated.

References

  1. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."
  4. (2015) "Product Information. Evotaz (atazanavir-cobicistat)." Bristol-Myers Squibb
View all 4 references

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Major

quiNIDine cobicistat

Applies to: Quinaglute Dura-Tabs (quinidine) and Evotaz (atazanavir / cobicistat)

MONITOR CLOSELY: Coadministration with cobicistat may significantly increase the plasma concentrations of certain antiarrhythmic agents such as amiodarone, bepridil, disopyramide, flecainide, propafenone, and quinidine. The mechanism involves inhibition of CYP450 2D6 (flecainide, propafenone) and/or 3A4 (amiodarone, bepridil, disopyramide, quinidine) metabolism, as cobicistat is a potent inhibitor of both isoenzymes. The interaction has not been specifically studied, but could conceivably lead to serious and/or life-threatening reactions including cardiac arrhythmias and other toxicities if levels are significantly increased. The use of these antiarrhythmic agents has been associated with dose-related prolongation of the QT interval, thus elevated plasma levels may potentiate the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes as well as cardiac arrest and sudden death.

MANAGEMENT: Caution is advised if cobicistat must be used concomitantly with antiarrhythmic agents that are primarily metabolized by CYP450 2D6 and/or 3A4. Pharmacologic response and plasma antiarrhythmic drug levels should be monitored more closely whenever cobicistat is added to or withdrawn from therapy, and the antiarrhythmic dosage adjusted as necessary.

References

  1. (2012) "Product Information. Stribild (cobicistat/elvitegravir/emtricitabine/tenofov)." Gilead Sciences

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Drug and food interactions

Moderate

quiNIDine food

Applies to: Quinaglute Dura-Tabs (quinidine)

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

References

  1. Ace LN, Jaffe JM, Kunka RL (1983) "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos, 4, p. 183-90
  2. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  3. Ha HR, Chen J, Leuenberger PM, Freiburghaus AU, Follah F (1995) "In vitro inhibition of midazolam and quinidine metabolism by flavonoids." Eur J Clin Pharmacol, 48, p. 367-71
  4. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
View all 4 references

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

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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.

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

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