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Drug Interactions between irinotecan and Tazverik

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

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Interactions between your drugs

Moderate

irinotecan tazemetostat

Applies to: irinotecan and Tazverik (tazemetostat)

MONITOR: Coadministration with inducers of the CYP450 3A4 isoenzyme may decrease the plasma concentrations of irinotecan and its pharmacologically active metabolite, SN-38. Irinotecan is partially metabolized by CYP450 3A4, and induction of this process results in less of the drug available in the plasma for conversion to SN-38 via carboxylesterases. The interaction has been reported with St. John's wort and the enzyme-inducing anticonvulsants carbamazepine, phenobarbital, and phenytoin. An approximately 40% reduction in SN-38 systemic exposure (AUC) has been reported in the presence of St. John's wort and greater than 60% reductions have been reported in the presence of enzyme-inducing anticonvulsants. However, all of these agents are known to be potent inducers of CYP450 3A4 as well as other enzymatic pathways (e.g., UDP-glucuronosyl transferase, or UGT; carboxylesterases) and drug transporters (e.g., multispecific organic anion transporter, or MRP2; P-glycoprotein) that may be involved in the clearance of irinotecan and/or SN-38. The extent, if any, to which irinotecan may interact with less potent CYP450 3A4 inducers is unknown.

MANAGEMENT: The antitumour activity of irinotecan may be reduced in patients treated with CYP450 3A4 inducers. Pharmacologic response to irinotecan should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the irinotecan dosage adjusted as necessary.

References

  1. (2001) "Product Information. Camptosar (irinotecan)." Pharmacia and Upjohn
  2. De Bruijn P, De Jonge MJ, Mathijssen RH, Sparreboom A, Verweij J (2002) Modulation of irinotecan(CPT-11)metabolism by St. John's wort in cancer patients. http:aacr02.agora.com/planner/displayabstract.asp?presentationid=2603
  3. Murry DJ, Cherrick I, Salama V, et al. (2002) "Influence of phenytoin on the disposition of irinotecan: a case report." J Pediatr Hematol Oncol, 24, p. 130-3
  4. Mathijssen RH, Verweij J, De Bruijn P, Loos WJ, Sparreboom A (2002) "Effects of St. John's Wort on Irinotecan Metabolism." J Natl Cancer Inst, 94, p. 1247-9
  5. Kuhn JG (2002) "Influence of anticonvulsants on the metabolism and elimination of irinotecan. A North American Brain Tumor Consortium preliminary report." Oncology (Williston Park, 16(8 Suppl 7), p. 33-40
  6. Friedman HS, Petros WP, Friedman AH, et al. (1999) "Irinotecan therapy in adults with recurrent or progressive malignant glioma." J Clin Oncol, 17, p. 1516-25
  7. Santos A, Zanetta S, Cresteil T, et al. (2000) "Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans." Clin Cancer Res, 6, p. 2012-20
  8. Yonemori K, Takeda Y, Toyota E, Kobayashi N, Kudo K (2004) "Potential interactions between irinotecan and rifampin in a patient with small-cell lung cancer." Int J Clin Oncol, 9, p. 206-9
  9. Innocenti F, Undevia SD, Ramirez J, et al. (2004) "A phase I trial of pharmacologic modulation of irinotecan with cyclosporine and phenobarbital." Clin Pharmacol Ther, 76, p. 490-502
  10. Di YM, Li CG, Xue CC, Zhou SF (2008) "Clinical drugs that interact with St. John's wort and implication in drug development." Curr Pharm Des, 14, p. 1723-42
  11. Crews KR, Stewart CF, Jones-Wallace D, et al. (2002) "Altered irinotecan pharmacokinetics in pediatric high-grade glioma patients receiving enzyme-inducing anticonvulsant therapy." Clin Cancer Res, 8, p. 2202-9
  12. Radomski KM, Gajjar AJ, Kirstein MN, et al. (2000) "Irinotecan clearance is increased by concomitant administration of enzyme inducers in a patient with glioblastoma multiforme." Pharmacotherapy, 20, p. 353
  13. Minami H, Lad TE, Nicholas MK, Vokes EE, Ratain MJ (1999) "Pharmacokinetics and pharmacodynamics of 9-aminocamptothecin infused over 72 hours in phase II studies." Clin Cancer Res, 5, p. 1325-30
  14. Zamboni WC, Gajjar AJ, Heideman RL, et al. (1998) "Phenytoin alters the disposition of topotecan and N-desmethyl topotecan in a patient with medulloblastoma." Clin Cancer Res, 4, p. 783-9
  15. (2015) "Product Information. Onivyde (irinotecan liposomal)." Merrimack Pharmaceuticals
View all 15 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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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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