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Drug Interactions between quinidine and tucatinib

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

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Interactions between your drugs

Moderate

quiNIDine tucatinib

Applies to: quinidine and tucatinib

GENERALLY AVOID: Coadministration with tucatinib may increase the plasma concentrations of CYP450 3A4 substrates. The mechanism involves tucatinib-mediated inhibition of CYP450 3A isoenzymes. When a single 2 mg dose of midazolam, a CYP450 3A substrate, was administered with tucatinib (300 mg twice daily), midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3-fold and 5.7-fold, respectively. Increased exposure to the CYP450 3A substrate may increase the risk of toxicity.

MANAGEMENT: Concomitant use of tucatinib with CYP450 3A substrates, particularly those with a narrow therapeutic index, should be avoided. If coadministration is required, a reduction in the dosage of the CYP450 3A substrate in accordance with product labeling is recommended.

References (1)
  1. (2020) "Product Information. Tukysa (tucatinib)." Seattle Genetics Inc

Drug and food interactions

Moderate

quiNIDine food

Applies to: 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 (4)
  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

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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