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Drug Interactions between lefamulin and Provigil

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

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Interactions between your drugs

Major

modafinil lefamulin

Applies to: Provigil (modafinil) and lefamulin

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may significantly decrease the plasma concentrations of lefamulin, which is a substrate of both the isoenzyme and efflux transporter. When oral lefamulin was administered with oral rifampin, a potent CYP450 3A4/P-gp inducer, mean lefamulin peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 57% and 72%, respectively. Coadministration of intravenous lefamulin with oral rifampin reduced mean lefamulin Cmax and AUC by 8% and 28%, respectively. Reduced therapeutic efficacy may occur.

MANAGEMENT: Concomitant use of lefamulin with potent or moderate inducers of CYP450 3A4 and/or P-gp should be avoided unless the benefit outweighs the risks. Monitor for reduced efficacy of lefamulin if coadministration is necessary.

References

  1. (2019) "Product Information. Xenleta (lefamulin)." Nabriva Therapeutics US, Inc.

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Drug and food interactions

Moderate

lefamulin food

Applies to: lefamulin

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of lefamulin. When a single 600 mg oral dose of lefamulin was administered with a high-calorie, high-fat breakfast (800 to 1000 calories; approximately 50% from fat), lefamulin peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 23% and 18%, respectively.

GENERALLY AVOID: Grapefruit juice may increase the oral bioavailability of lefamulin. The proposed mechanism is 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, but pharmacokinetic data are available for the potent CYP450 3A4 inhibitor, ketoconazole. When oral lefamulin was administered with oral ketoconazole, mean lefamulin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 58% and 165%, respectively. 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 lefamulin may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Lefamulin tablets should be taken at least one hour before or two hours after a meal. Patients should preferably avoid or limit the consumption of grapefruit and grapefruit juice during treatment with lefamulin.

References

  1. (2019) "Product Information. Xenleta (lefamulin)." Nabriva Therapeutics US, Inc.

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Minor

modafinil food

Applies to: Provigil (modafinil)

Administration with food may delay the absorption of modafinil (the racemate) and armodafinil (the R-enantiomer) without significantly affecting their overall bioavailability. According to the product labeling, modafinil's absorption may be delayed by approximately one hour if taken with food. Similarly, the time to reach peak plasma concentration (Tmax) of armodafinil may be delayed by approximately 2 to 4 hours in the fed state.

References

  1. (2001) "Product Information. Provigil (modafinil)." Cephalon, Inc
  2. (2007) "Product Information. Nuvigil (armodafinil)." Cephalon Inc

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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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