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Drug Interactions between mirtazapine and pexidartinib

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

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Interactions between your drugs

Moderate

mirtazapine pexidartinib

Applies to: mirtazapine and pexidartinib

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of mirtazapine, which is partially metabolized by the isoenzyme. In healthy study subjects, administration of mirtazapine (30 mg once daily) with the potent CYP450 3A4 inducer carbamazepine (400 mg twice daily) decreased mean steady-state mirtazapine peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 40% and 60%, respectively, compared to administration with placebo. In another study consisting of patients with unipolar depression receiving mirtazapine 45 mg daily, the addition of carbamazepine reportedly decreased mirtazapine plasma concentrations by approximately 47% after 3 weeks. Likewise, when mirtazapine 30 mg once daily was given with phenytoin 200 mg once daily in healthy, nonsmoking male volunteers, steady-state mirtazapine Cmax and AUC decreased by 33% and 47%, respectively, compared to mirtazapine given alone. Mirtazapine had no significant effect on the pharmacokinetics of either carbamazepine or phenytoin.

MANAGEMENT: The possibility of diminished therapeutic response to mirtazapine should be considered during coadministration with CYP450 3A4 inducers, particularly potent ones like carbamazepine, enzalutamide, lumacaftor, mitotane, phenobarbital, phenytoin, rifampin, and St. John's wort. Pharmacologic response to mirtazapine should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the dosage adjusted as necessary.

References (4)
  1. (2001) "Product Information. Remeron (mirtazapine)." Organon
  2. Timmer CJ, Sitsen JMA, Delbressine LP (2000) "Clinical pharmacokinetics of mirtazapine." Clin Pharmacokinet, 38, p. 461-74
  3. Spaans E, Van Den Heuvel MW, Schnabel PG, et al. (2002) "Concomitant use of mirtazapine and phenytoin: a drug-drug interaction study in healthy male subjects." Eur J Clin Pharmacol, 58, p. 423-9
  4. Sitsen JM, Maris FA, Timmer CJ (2001) "Drug-drug interaction studies with mirtazapine and carbamazepine in healthy male subjects." Eur J Drug Metab Pharmacokinet, 26, p. 109-21

Drug and food interactions

Major

pexidartinib food

Applies to: pexidartinib

ADJUST DOSING INTERVAL: The presence of food may increase the absorption and toxicity of pexidartinib. Administration of pexidartinib with a high-fat meal increased peak plasma concentration (Cmax) and systemic exposure (AUC) by 100% and prolonged the time to reach peak plasma concentration (Tmax) by 2.5 hours.

GENERALLY AVOID: Grapefruit or grapefruit juice may increase the plasma concentration and risk of adverse effects of pexidartinib, including potentially fatal hepatotoxicity. The mechanism is inhibition of CYP450 3A4-mediated metabolism of pexidartinib by certain compounds present in grapefruits. Concomitant administration of itraconazole, a strong CYP450 3A4 inhibitor, increased pexidartinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 48% and 70%, respectively.

MANAGEMENT: Pexidartinib should be administered on an empty stomach, at least one hour before or two hours after a meal or snack. Consumption of grapefruit or grapefruit juice should generally be avoided during pexidartinib therapy. If concomitant use is unavoidable, the dose of pexidartinib should be reduced according to the manufacturer's recommendations. If concomitant use of grapefruit or grapefruit juice is discontinued, the dose of pexidartinib may be increased (after 3 plasma half-lives of a strong CYP450 3A4 inhibitor) to the dose that was used prior to consumption of grapefruit or grapefruit juice.

References (1)
  1. (2019) "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc.
Moderate

mirtazapine food

Applies to: mirtazapine

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals 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

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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.

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