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Drug Interactions between fluphenazine and mobocertinib

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

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Interactions between your drugs

Major

fluPHENAZine mobocertinib

Applies to: fluphenazine and mobocertinib

GENERALLY AVOID: Mobocertinib can cause concentration-dependent, life-threatening prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In a subset of 250 patients who had electrocardiograms (ECGs) during clinical studies with mobocertinib 160 mg orally once daily, 1.2% of patients had a QTc interval greater than 500 msec and 11% of patients had a change-from-baseline QTc interval greater than 60 msec. Torsades de pointes occurred in 1 patient (0.4%). Clinical trials of mobocertinib did not include patients with baseline QTc greater than 470 msec. From cardiac electrophysiology studies, the largest mean increase in QTc was 23.0 msec following administration of mobocertinib 160 mg once daily. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Avoid use of mobocertinib with concomitant drugs which are known to prolong the QT interval. If concomitant use is unavoidable, monitor the QTc interval more frequently with ECGs.

References

  1. "Product Information. Exkivity (mobocertinib)." Takeda Pharmaceuticals America ORIG-1 (2021):
  2. "Product Information. Exkivity (mobocertinib)." Takeda UK Ltd (2022):
  3. "Product Information. Exkivity (mobocertinib)." Takeda Pharmaceuticals Australia Pty Ltd EXKIVITY PI V1.0 (CC (2022):

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Drug and food interactions

Major

mobocertinib food

Applies to: mobocertinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of mobocertinib. The mechanism may involve inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice. Based on drug interaction studies using model-informed approaches, coadministration of mobocertinib with multiple doses of itraconazole or ketoconazole (strong CYP450 3A4 inhibitors) is predicted to increase the steady-state combined molar AUC (systemic exposure) of mobocertinib and its active metabolites by 374% to 419%, while coadministration with multiple doses of a moderate CYP450 3A4 inhibitor is predicted to increase this value by approximately 100% to 200%. 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. Elevated plasma concentrations of mobocertinib may increase the risk for adverse effects such as QT prolongation, heart failure or reduced ejection fraction, cardiomyopathy, heart block, diarrhea, rash, stomatitis, fatigue, and musculoskeletal pain.

MANAGEMENT: Patients should avoid consumption of grapefruit and grapefruit juice during treatment with mobocertinib.

References

  1. "Product Information. Exkivity (mobocertinib)." Takeda Pharmaceuticals America ORIG-1 (2021):
  2. "Product Information. Exkivity (mobocertinib)." Takeda UK Ltd (2022):

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Moderate

fluPHENAZine food

Applies to: fluphenazine

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.

References

  1. Lutz EG "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA 236 (1976): 2422-3
  2. Freed E "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust 2 (1981): 44-5

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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.

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