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Drug Interactions between Novantrone and Quin-G

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

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Interactions between your drugs

Moderate

quiNIDine mitoXANTRONE

Applies to: Quin-G (quinidine) and Novantrone (mitoxantrone)

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of mitoxantrone, which is a substrate of the efflux transporter also known as ABCB1 or MDR1. The interaction has been studied with cyclosporine, a potent P-gp inhibitor. In a pharmacokinetic study of 38 children with de novo acute myeloid leukemia, mitoxantrone 6 mg/m2 administered daily in combination with cyclosporine resulted in a 42% decrease in mean mitoxantrone clearance and 12% increase in systemic exposure (AUC) compared to mitoxantrone 10 mg/m2 administered daily without cyclosporine. There were no differences in the rates of stomatitis or infection between the two groups, but an increased incidence of hyperbilirubinemia was observed in the cyclosporine group, which rapidly reversed upon conclusion of treatment. Therefore, it appears a 40% dose reduction of mitoxantrone given with cyclosporine produced statistically similar systemic exposure and toxicity as mitoxantrone given alone.

MANAGEMENT: Caution is advised if mitoxantrone is prescribed in combination with a P-gp inhibitor. Patients should be closely monitored for increased adverse effects including cardiotoxicity and myelosuppression.

References

  1. "Multum Information Services, Inc. Expert Review Panel"
  2. "Product Information. Novantrone (mitoxantrone)." Immunex Corporation PROD (2001):

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Drug and food interactions

Moderate

quiNIDine food

Applies to: Quin-G (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.

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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