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Drug Interactions between Tazverik and zolpidem

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

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Interactions between your drugs

Moderate

zolpidem tazemetostat

Applies to: zolpidem and Tazverik (tazemetostat)

MONITOR: Coadministration with CYP450 inducers may decrease the plasma concentrations of zolpidem, which is primarily metabolized by CYP450 3A4 and, to a lesser extent, by CYP450 1A2. In eight healthy female volunteers, administration of a single 20 mg dose of zolpidem following pretreatment with the potent CYP450 inducer rifampin (600 mg/day for 5 days) decreased mean zolpidem peak plasma concentration (Cmax) and systemic exposure (AUC) by 58% and 73%, respectively, compared to administration following placebo. These changes were associated with significant reductions in the pharmacodynamic effects of zolpidem. In another study with 18 healthy volunteers, administration of a single 5 mg dose of zolpidem following daily dosing of carbamazepine 400 mg for 15 days resulted in a 41% decrease in mean Cmax and 57% decrease in mean AUC of zolpidem compared to administration of zolpidem alone.

MANAGEMENT: The potential for diminished pharmacologic effects of zolpidem should be considered during coadministration with CYP450 inducers, particularly potent ones like carbamazepine, enzalutamide, lumacaftor, mitotane, phenobarbital, phenytoin, rifamycins, and St. John's wort. Alternative treatments or a dosage adjustment for zolpidem may be required if an interaction is suspected.

References

  1. (2001) "Product Information. Ambien (zolpidem)." sanofi-aventis
  2. Villikka K, Kivisto KT, Luurila H, Neuvonen PJ (1997) "Rifampin reduces plasma concentrations and effects of zolpidem." Clin Pharmacol Ther, 62, p. 629-34
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Vlase L, Popa A, Neag M, Muntean D, Baldea I, Leucuta SE (2010) "Pharmacokinetic Interaction Between Zolpidem and Carbamazepine in Healthy Volunteers." J Clin Pharmacol
View all 4 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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Moderate

zolpidem food

Applies to: zolpidem

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of zolpidem. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Administration of zolpidem with food may delay the onset of hypnotic effects. In 30 healthy subjects, administration of zolpidem 20 minutes after a meal resulted in decreased mean peak plasma drug concentration (Cmax) and area under the concentration-time curve (AUC) by 25% and 15%, respectively, compared to fasting. The time to reach peak plasma drug concentration (Tmax) was prolonged by 60%, from 1.4 to 2.2 hours.

MANAGEMENT: Patients receiving zolpidem should be advised to avoid the consumption of alcohol. For faster sleep onset, zolpidem should not be administered with or immediately after a meal.

References

  1. (2001) "Product Information. Ambien (zolpidem)." sanofi-aventis
  2. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84

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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.