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Drug Interactions between alfentanil and tazemetostat

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

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Interactions between your drugs

Moderate

ALfentanil tazemetostat

Applies to: alfentanil and tazemetostat

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of alfentanil, which appears to be extensively metabolized by the isoenzyme. Clinical data are limited, however. In nine healthy male volunteers, intravenous administration of a single 20 mcg/kg dose of alfentanil with the potent CYP450 3A4 inducer rifampin increased alfentanil clearance by nearly 3-fold and decreased elimination half-life by 40% compared to controls. Another study also reported substantially increased clearance rates of alfentanil in seven patients receiving long-term therapy with inducer drugs compared to six patients not receiving those drugs (mean clearance 6.94 mL/min/kg vs. 3.47 mL/min/kg; half-life 50.6 hrs vs. 90.7 hrs).

MANAGEMENT: Patients who are currently receiving or have recently received drugs that induce CYP450 3A4 should be monitored for potentially decreased response to alfentanil, and the dosage adjusted as necessary.

References (4)
  1. Kharasch ED, Thummel KE (1993) "Human alfentanil metabolism by cytochrome P450 3A3/4. An explanation for the interindividual variability in alfentanil clearance?" Anesth Analg, 76, p. 1033-9
  2. Koehntop DE, Noormohamed SE, Fletcher CV (1994) "Effects of long-term drugs on alfentanil clearance in patients undergoing renal transplantation." Pharmacotherapy, 14, p. 592-9
  3. Labroo RB, Thummel KE, Kunze KL, Podoll T, Trager WF, Kharasch ED (1995) "Catalytic role of cytochrome P4503A4 in multiple pathways of alfentanil metabolism." Drug Metab Dispos, 23, p. 490-6
  4. Kharasch ED, Russell M, Mautz D, Thummel KE, Kunze KL, Bowdle A, Cox K (1997) "The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions." Anesthesiology, 87, p. 36-50

Drug and food interactions

Major

tazemetostat food

Applies to: 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)
  1. (2020) "Product Information. Tazverik (tazemetostat)." Epizyme, Inc
Moderate

ALfentanil food

Applies to: alfentanil

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

References (9)
  1. Linnoila M, Hakkinen S (1974) "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther, 15, p. 368-73
  2. Sturner WQ, Garriott JC (1973) "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA, 223, p. 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. (1991) "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol, 41, p. 147-52
  4. Levine B, Saady J, Fierro M, Valentour J (1984) "A hydromorphone and ethanol fatality." J Forensic Sci, 29, p. 655-9
  5. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL (1985) "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol, 19, p. 398-401
  6. Carson DJ (1977) "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet, 1, p. 894-7
  7. Rosser WW (1980) "The interaction of propoxyphene with other drugs." Can Med Assoc J, 122, p. 149-50
  8. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM (1982) "Distalgesic and ethanol-impaired function." Lancet, 2, p. 384
  9. Kiplinger GF, Sokol G, Rodda BE (1974) "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther, 212, p. 175-80

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

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