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Drug Interactions between Quinora and Venclexta

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

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Interactions between your drugs

Major

quiNIDine venetoclax

Applies to: Quinora (quinidine) and Venclexta (venetoclax)

GENERALLY AVOID: Coadministration with P-glycoprotein (P-gp) inhibitors may increase the plasma concentrations of venetoclax, which is a substrate of this efflux transporter. Administration of venetoclax with a single dose of rifampin, a P-gp inhibitor when given acutely, increased venetoclax Cmax by 106% and AUC by 78%. Increased venetoclax exposure may potentiate the risk of tumor lysis syndrome, particularly at initiation of therapy and during the dosage ramp-up phase, as well as other adverse effects such as diarrhea, nausea, vomiting, neutropenia, anemia, and thrombocytopenia.

MANAGEMENT: Concomitant use of venetoclax with P-gp inhibitors should generally be avoided. If coadministration is required, the manufacturer recommends that venetoclax dosage be reduced by at least 50%. The dosage used prior to initiating the P-gp inhibitor may be resumed 2 to 3 days after discontinuation of the inhibitor.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Venclexta (venetoclax)." AbbVie US LLC (2016):

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Drug and food interactions

Major

venetoclax food

Applies to: Venclexta (venetoclax)

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of venetoclax. Relative to fasting conditions, venetoclax systemic exposure (AUC) increased by approximately 3.4-fold when administered with a low-fat meal and by 5.1- to 5.3-fold when administered with a high-fat meal.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of venetoclax. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased venetoclax exposure may potentiate the risk of tumor lysis syndrome, particularly at initiation of therapy and during the dosage ramp-up phase, as well as other adverse effects such as diarrhea, nausea, vomiting, neutropenia, anemia, and thrombocytopenia.

MANAGEMENT: Venetoclax should be administered with a meal and water at approximately the same time each day. Patients should avoid consumption of grapefruit products, Seville oranges, and starfruit during treatment with venetoclax.

References

  1. "Product Information. Venclexta (venetoclax)." AbbVie US LLC (2016):

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Moderate

quiNIDine food

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

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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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