Drug Interactions between docetaxel and Tazverik
This report displays the potential drug interactions for the following 2 drugs:
- docetaxel
- Tazverik (tazemetostat)
Interactions between your drugs
DOCEtaxel tazemetostat
Applies to: docetaxel and Tazverik (tazemetostat)
GENERALLY AVOID: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of docetaxel, which is a substrate of the isoenzyme. Rifampin and hyperforin, a component of St. John's wort, have been shown to significantly induce the in vitro metabolism of docetaxel in human hepatocyte cultures. However, clinical pharmacokinetic studies are lacking.
MANAGEMENT: Coadministration of docetaxel with potent CYP450 3A4 inducers such as carbamazepine, dexamethasone, enzalutamide, phenobarbital, phenytoin, rifamycins, and St. John's wort should generally be avoided unless the benefit outweighs the potential risk of docetaxel underexposure. Alternative agents with no or minimal CYP450 3A4 induction potential are recommended whenever possible. If concomitant use is required, close monitoring for signs of reduced therapeutic efficacy is advised. Other known inducers include aminoglutethimide, barbiturates, bexarotene, bosentan, dabrafenib, efavirenz, etravirine, nafcillin, nevirapine, somatrem, somatropin, and various other anticonvulsants, although the extent to which they interact with docetaxel is unknown.
References
- (2001) "Product Information. Taxotere (docetaxel)." Rhone Poulenc Rorer
- Aronson JK, Grahame-Smith DG (1981) "Clinical pharmacology: adverse drug interactions." Br Med J, 282, p. 288-91
- McInnes GT, Brodie MJ (1988) "Drug interactions that matter: a critical reappraisal." Drugs, 36, p. 83-110
- Baker SD (1997) "Drug interactions with the taxanes." Pharmacotherapy, 17(5 Pt 2), s126-32
- Komoroski BJ, Parise RA, Egorin MJ, Strom SC, Venkataramanan R (2005) "Effect of the St. John's wort constituent hyperforin on docetaxel metabolism by human hepatocyte cultures." Clin Cancer Res, 11(19 Pt 1), p. 6972-9
Drug and food interactions
DOCEtaxel food
Applies to: docetaxel
GENERALLY AVOID: Coadministration with inhibitors of CYP450 3A4, such as grapefruit juice, may significantly increase the plasma concentrations of docetaxel, which is a substrate of the isoenzyme. Current data suggest that consumption of large quantities of grapefruit juice inhibit both intestinal and hepatic CYP450 3A4 due to certain compounds present in grapefruit. In a pharmacokinetic study consisting of 7 cancer patients, mean dose-normalized docetaxel systemic exposure (AUC) increased by 2.2-fold and clearance decreased by 49% when intravenous docetaxel was given at a reduced dosage of 10 mg/m2 in combination with the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally once daily for 3 days) compared to docetaxel administered alone at 100 mg/m2. In addition, a case report of a 52-year-old woman with esophageal squamous cell carcinoma receiving a twice weekly chemotherapy regimen including intravenous docetaxel (40 mg/m2) reported that docetaxel AUC increased by 65% compared with the AUC target of 1.96 mg*h/L and clearance decreased by 63%, with a 71% reduction in the patient's neutrophil count. In the absence of other CYP450 3A4 inhibitors, these effects were attributed to daily consumption of 250 mL of grapefruit juice, which the patient had been consuming for at least 3 months. Two weeks after the patient ceased the grapefruit juice, the docetaxel AUC was closer to the target value and the neutrophil count reduction was less than 35%.
MANAGEMENT: The use of docetaxel in combination with grapefruit and grapefruit juice should generally be avoided. If concomitant use is required, a reduced dosage of docetaxel should be considered, particularly if used with large amounts of grapefruit juice, and therapeutic drug monitoring of docetaxel considered per local treatment protocols. Patients should be closely monitored for the development of docetaxel toxicity such as myelosuppression, stomatitis, neurotoxicity (e.g., paraesthesia, dysesthesia, pain), myalgia, asthenia, fluid retention, nausea, vomiting, and diarrhea.
References
- (2001) "Product Information. Taxotere (docetaxel)." Rhone Poulenc Rorer
- Aronson JK, Grahame-Smith DG (1981) "Clinical pharmacology: adverse drug interactions." Br Med J, 282, p. 288-91
- McInnes GT, Brodie MJ (1988) "Drug interactions that matter: a critical reappraisal." Drugs, 36, p. 83-110
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Yong WP, Wang LZ, Tham LS, et al. (2008) "A phase I study of docetaxel with ketoconazole modulation in patients with advanced cancers." Cancer Chemother Pharmacol, 62, p. 243-51
- Cerner Multum, Inc. "Australian Product Information."
- Engels FK, Mathot RA, Loos WJ, van Schaik RH, Verweij J (2006) "Influence of high-dose ketoconazole on the pharmacokinetics of docetaxel." Cancer Biol Ther, 5, p. 833-9
- Valenzuela B, Rebollo J, Perez T, Brugarolas A, Perez-Ruixo JJ (2011) "Effect of grapefruit juice on the pharmacokinetics of docetaxel in cancer patients: a case report." Br J Clin Pharmacol
- Starr SP, Hammann F, Gotta V, et al. (2016) "Pharmacokinetic interaction between taxanes and amiodarone leading to severe toxicity." Br J Clin Pharmacol, 450, p. 22-27
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
- (2020) "Product Information. Tazverik (tazemetostat)." Epizyme, Inc
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
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
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