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Drug Interactions between quinine and Tazverik

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

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Interactions between your drugs

Moderate

quiNINE tazemetostat

Applies to: quinine and Tazverik (tazemetostat)

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of quinine, which is primarily metabolized by the isoenzyme. The interaction has been studied with rifampin, a potent CYP450 3A4 inducer, and treatment failures have been reported. In patients with uncomplicated Plasmodium falciparum malaria who received quinine sulfate 10 mg/kg concomitantly with rifampin 15 mg/kg/day for 7 days, the median quinine systemic exposure (AUC) between days 3 and 7 of therapy was 75% lower than that observed in patients who received quinine monotherapy. Likewise, in nine healthy subjects who received a single 600 mg oral dose of quinine sulfate following pretreatment with rifampin 600 mg/day for 2 weeks, the mean quinine peak plasma concentration (Cmax) and AUC decreased by 55% and 85%, respectively. The extent to which other, less potent inducers of CYP450 3A4 may interact with quinine is unknown.

MANAGEMENT: Caution is advised if quinine is used in combination with CYP450 3A4 inducers such as carbamazepine, phenobarbital, phenytoin, and St. John's wort. The possibility of diminished therapeutic efficacy should be considered. rifampin

References

  1. Twum-Barima Y, Carruthers SG (1981) "Quinidine-rifampin interaction." N Engl J Med, 304, p. 1466-9
  2. (2001) "Product Information. Rifadin (rifampin)." Hoechst Marion Roussel
  3. Wanwimolruk S, Kang W, Coville PF, Viriyayudhakorn S, Thitiarchakul S (1995) "Marked enhancement by rifampicin and lack of effect of isoniazid on the elimination of quinine in man." Br J Clin Pharmacol, 40, p. 87-91
  4. Pukrittayakamee S, Prakongpan S, Wanwimolruk S, Clemens R, Looareesuwan S, White NJ (2003) "Adverse effect of rifampin on quinine efficacy in uncomplicated falciparum malaria." Antimicrob Agents Chemother, 47, p. 1509-1513
  5. Fabre C, Criddle J, Nolder D, Klein JL (2005) "Recrudescence of imported falciparum malaria after quinine therapy: potential drug interaction with phenytoin." Trans R Soc Trop Med Hyg, 99, p. 871-3
  6. (2006) "Product Information. Qualaquin (quinine)." AR Scientific Inc
View all 6 references

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Drug and food interactions

Major

tazemetostat food

Applies to: Tazverik (tazemetostat)

GENERALLY AVOID: Consumption of grapefruit or grapefruit juice during tazemetostat therapy may significantly increase the plasma concentrations of tazemetostat. The proposed mechanism is inhibition of the CYP450 3A4-mediated metabolism of tazemetostat by certain compounds in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). According to the product labeling, coadministration of tazemetostat (400 mg twice daily) with the moderate CYP450 3A4 inhibitor fluconazole increased the tazemetostat steady state exposure (AUC 0 to 8 hours) by 3.1-fold and peak plasma concentration by 2.3-fold. 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. Clinically, this interaction may result in an increased risk of the frequency or severity of adverse reactions due to tazemetostat such as hemorrhage, pleural effusion, skin infection, dyspnea, pain, and respiratory distress.

MANAGEMENT: The manufacturer advises that patients treated with tazemetostat should avoid consumption of grapefruit or grapefruit juice.

References

  1. (2020) "Product Information. Tazverik (tazemetostat)." Epizyme, Inc

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.