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Drug interactions between larotrectinib and Simuc-HD

Results for the following 2 drugs:
larotrectinib
Simuc-HD (guaifenesin/hydrocodone/phenylephrine)

Interactions between your drugs

Moderate

HYDROcodone larotrectinib

Applies to: Simuc-HD (guaifenesin / hydrocodone / phenylephrine) and larotrectinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with larotrectinib may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. In study subjects, coadministration of midazolam, a sensitive CYP450 3A4 substrate, with larotrectinib 100 mg twice daily increased midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.7-fold each compared to administration of midazolam alone. The Cmax and AUC of 1-hydroxymidazolam, the main metabolite of midazolam, were both increased by 1.4-fold.

MANAGEMENT: Concomitant use of larotrectinib and sensitive CYP450 3A4 substrates or substrates with narrow therapeutic ranges should generally be avoided. These drugs include, but are not limited to: alfentanil, cisapride, colchicine, cyclosporine, fentanyl, ivacaftor, lovastatin, simvastatin, oral midazolam, triazolam, pimozide, quinidine, sildenafil, ergot derivatives, macrolide immunosuppressants, and vinca alkaloids. If coadministration is required, patients should be monitored carefully for increased adverse reactions of these drugs.

References

  1. "Product Information. Vitrakvi (larotrectinib)." Bayer Pharmaceutical Inc, West Haven, CT.

Drug and food interactions

Major

HYDROcodone food

Applies to: Simuc-HD (guaifenesin / hydrocodone / phenylephrine)

Do not use alcohol or medications that contain alcohol while you are receiving treatment with HYDROcodone. This may increase nervous system side effects such as drowsiness, dizziness, lightheadedness, difficulty concentrating, and impairment in thinking and judgment. In severe cases, low blood pressure, respiratory distress, fainting, coma, or even death may occur. If you are taking certain long-acting formulations of hydrocodone, consumption of alcohol may also cause rapid release of the drug, resulting in high blood levels that may be potentially lethal. Likewise, you should avoid consuming grapefruit and grapefruit juice, as this may increase the blood levels and effects of hydrocodone. Talk to your doctor or pharmacist if you have questions on how to take this or other medications you are prescribed. Do not use more than the recommended dose of HYDROcodone, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medication without first talking to your doctor.

Switch to professional interaction data

Moderate

larotrectinib food

Applies to: larotrectinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of larotrectinib. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of larotrectinib by certain compounds present in grapefruit. When a single 100 mg dose of larotrectinib was coadministered with itraconazole, a potent CYP450 3A4 inhibitor, larotrectinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.8- and 4.3-fold, respectively, compared to administration of larotrectinib alone. The interaction has not been studied with grapefruit juice. 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. Increased exposure to larotrectinib may increase the risk of adverse effects such as neurotoxicity (delirium, dysarthria, dizziness, gait disturbance, paraesthesia, encephalopathy, memory impairment, tremor) and hepatotoxicity (elevations in liver transaminases).

Food does not alter the pharmacokinetics of larotrectinib to a clinically significant extent. When a single 100 mg dose of larotrectinib was administered with a high-fat meal (approximately 900 calories; 58 g carbohydrate, 56 g fat, 43 g protein) in healthy study subjects, larotrectinib peak plasma concentration (Cmax) was reduced by 35% while systemic exposure (AUC) was similar compared to administration in the fasted state.

MANAGEMENT: Larotrectinib may be taken with or without food. Patients should avoid the consumption of grapefruit and grapefruit juice during treatment.

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.

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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