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Drug Interactions between tazemetostat and Tussadur-HD

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

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Interactions between your drugs

Moderate

HYDROcodone tazemetostat

Applies to: Tussadur-HD (guaifenesin / hydrocodone / pseudoephedrine) and tazemetostat

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of opioids that are metabolized by the isoenzyme such as butorphanol, fentanyl, hydrocodone, methadone, and oxycodone. Reduced efficacy or withdrawal symptoms may occur in patients maintained on their narcotic pain regimen following the addition of a CYP450 3A4 inducer. Conversely, discontinuation of the inducer may increase opioid plasma concentrations and potentiate the risk of overdose and fatal respiratory depression.

MANAGEMENT: Pharmacologic response to the opioid should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the opioid dosage adjusted as necessary.

References

  1. Holmes VF (1991) "Rifampin-induced methadone withdrawal in AIDS." J Clin Psychopharmacol, 10, p. 443-4
  2. Liu S-J, Wang RI (1984) "Case report of barbiturate-induced enhancement of methadone metabolism and withdrawal syndrome." Am J Psychiatry, 141, p. 1287-8
  3. Bell J, Seres V, Bowron P, Lewis J, Batey R (1988) "The use of serum methadone levels in patients receiving methadone maintenance." Clin Pharmacol Ther, 43, p. 623-9
  4. Finelli PF (1976) "Phenytoin and methadone tolerance." N Engl J Med, 294, p. 227
  5. Tong TG, Pond SM, Kreek MJ, et al. (1981) "Phenytoin-induced methadone withdrawal." Ann Intern Med, 94, p. 349-51
  6. Kreek MJ, Garfield JW, Gutjahr CL, Giusti LM (1976) "Rifampin-induced methadone withdrawal." N Engl J Med, 294, p. 1104-6
  7. Bending MR, Skacel PO (1977) "Rifampicin and methadone withdrawal." Lancet, 1, p. 1211
  8. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  9. (2001) "Product Information. OxyContin (oxycodone)." Purdue Frederick Company
  10. Raistrick D, Hay A, Wolff K (1996) "Methadone maintenance and tuberculosis treatment." BMJ, 313, p. 925-6
  11. Altice FL, Friedland GH, Cooney EL (1999) "Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone." AIDS, 13, p. 957-62
  12. Otero MJ, Fuertes A, Sanchez R, Luna G (1999) "Nevirapine-induced withdrawal symptoms in HIV patients on methadone maintenance programme: an alert." AIDS, 13, p. 1004-5
  13. Pinzani V, Faucherre V, Peyriere H, Blayac JP (2000) "Methadone withdrawal symptoms with nevirapine and efavirenz." Ann Pharmacother, 34, p. 405-7
  14. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  15. (2006) "Product Information. Ionsys (fentanyl)." Ortho McNeil Pharmaceutical
  16. (2007) "Product Information. Diskets (methadone)." Cebert Pharmaceuticals Inc
  17. Cerner Multum, Inc. "Australian Product Information."
  18. (2013) "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc
  19. (2017) "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation
View all 19 references

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Drug and food interactions

Major

HYDROcodone food

Applies to: Tussadur-HD (guaifenesin / hydrocodone / pseudoephedrine)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including hydrocodone. 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.

GENERALLY AVOID: Consumption of alcohol while taking some sustained-release formulations of hydrocodone may cause rapid release of the drug, resulting in high systemic levels of hydrocodone that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. In study subjects, the rate of absorption of hydrocodone from an extended-release formulation was found to be affected by coadministration with 40% alcohol in the fasted state, as demonstrated by an average 2.4-fold (up to 3.9-fold in one subject) increase in hydrocodone peak plasma concentration and a decrease in the time to peak concentration. Alcohol also increased the extent of absorption by an average of 1.2-fold (up to 1.7-fold in one subject).

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of hydrocodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of hydrocodone by certain compounds present in grapefruit. Increased hydrocodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.

MANAGEMENT: Patients taking sustained-release formulations of hydrocodone should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as hydrocodone should not be combined with alcohol. Patients should also avoid consumption of grapefruit or grapefruit juice during treatment with hydrocodone.

References

  1. (2013) "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc

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

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Moderate

pseudoephedrine food

Applies to: Tussadur-HD (guaifenesin / hydrocodone / pseudoephedrine)

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
View all 7 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.