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Drug Interactions between idarubicin and quinine

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

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Interactions between your drugs

Moderate

IDArubicin quiNINE

Applies to: idarubicin and quinine

MONITOR: Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of daunorubicin and idarubicin, both of which are substrates of the efflux transporter also known as ABCB1 or MDR1. The interaction has been studied with cyclosporine, a potent P-gp inhibitor, in attempt to overcome multidrug resistance in MDR1-overexpressing tumors. In a randomized study to test whether cyclosporine can enhance the antileukemia effect of anthracyclines, cyclosporine was found to significantly reduce the frequency of resistance to induction chemotherapy consisting of sequential cytarabine and daunorubicin (31% vs. 47%). The addition of cyclosporine also increased relapse-free and overall survival, particularly in patients with moderate or high P-gp expression. Pharmacokinetically, steady-state mean serum concentrations of daunorubicin and its active metabolite, daunorubicinol, were significantly higher (approximately 2-fold and 4-fold, respectively) in patients receiving cyclosporine. Although there was no significant difference in the frequency or severity of stomatitis or renal toxicity (as measured by creatinine elevation), grade 4 hyperbilirubinemia and grade 3 nausea occurred more frequently in patients receiving cyclosporine than in controls (31% vs. 4% and 11% vs. 3%, respectively). In a pharmacokinetic study of 27 patients with acute myelogenous leukemia receiving induction chemotherapy with idarubicin and cytarabine, the systemic exposure (AUC) to idarubicin and idarubicinol was increased by 77% and 182%, respectively, in patients administered cyclosporine 10 mg/kg daily compared to controls due to a 40% reduction in total body clearance. The interaction was also reported in another study in which increases in the AUC of idarubicin and idarubicinol were associated with increased levels of toxicity.

MANAGEMENT: Caution is advised if daunorubicin or idarubicin 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. (2001) "Product Information. Cerubidine (daunorubicin)." Wyeth-Ayerst Laboratories
  3. (2001) "Product Information. Idamycin (idarubicin)." Pharmacia and Upjohn
  4. (2001) "Product Information. Daunoxome (daunorubicin liposomal)." Nexstar Pharmaceuticals Inc
View all 4 references

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Drug and food interactions

Minor

quiNINE food

Applies to: quinine

Coadministration with grapefruit juice does not appear to affect the pharmacokinetics of quinine in a clinically relevant manner. Although grapefruit juice is an inhibitor of CYP450 3A4 and quinine is metabolized by this pathway to its major metabolite, 3-hydroxyquinine, a study of ten healthy volunteers found no significant differences in quinine peak plasma concentration (Cmax), time to reach Cmax (Tmax), terminal elimination half-life, systemic exposure (AUC), or apparent oral clearance (Cl/F) when a single 600 mg oral dose of quinine sulfate was administered in combination with 200 mL of orange juice (control), half-strength grapefruit juice, and full-strength grapefruit juice twice daily for 6 days each, separated by a 2-week washout period. Relative to the control period, the apparent renal clearance of quinine was markedly increased by 81% during treatment with half-strength grapefruit juice. However, since renal clearance accounts for approximately 6% of the total clearance of quinine, this change would likely have minimal clinical impact. The lack of a significant interaction is probably due to the fact that grapefruit juice primarily inhibits intestinal rather than hepatic CYP450 3A4, and quinine is not known to undergo significant presystemic metabolism as evidenced by its relatively high oral bioavailability (76% to 88%). Nevertheless, excessive consumption of grapefruit juice and tonic water (which contains quinine) was suspected as the cause of torsade de pointes arrhythmia in a patient with a history of asymptomatic long QT syndrome. Treatment with magnesium sulfate and metoprolol had no effect, but the arrhythmia resolved spontaneously 48 hours after discontinuation of the drinks. Based on current data, moderate grapefruit juice consumption is probably safe for the majority of patients taking quinine.

References

  1. Ho PC, Chalcroft SC, Coville PF, Wanwimolruk S (1999) "Grapefruit juice has no effect on quinine pharmacokinetics." Eur J Clin Pharmacol, 55, p. 393-8
  2. Hermans K, Stockman D, Van den Branden F (2003) "Grapefruit and tonic: a deadly combination in a patient with the long QT syndrome." Am J Med, 114, p. 511-2
  3. (2006) "Product Information. Qualaquin (quinine)." AR Scientific Inc
  4. Zhang H, Coville PF, Walker RJ, Miners JO, Birkett DJ, Wanwimolruk S (1997) "Evidence for involvement of human CYP3A in the 3-hydroxylation of quinine." Br J Clin Pharmacol, 43, p. 245-52
  5. Mirghani RA, Yasar U, Zheng T, et al. (2002) "Enzyme kinetics for the formation of 3-hydroxyquinine and three new metabolites of quinine in vitro; 3-hydroxylation by CYP3A4 is indeed the major metabolic pathway." Drug Metab Dispos, 30, p. 1368-71
View all 5 references

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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.

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