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Drug Interactions between selexipag and Tykerb

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

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Interactions between your drugs

Moderate

lapatinib selexipag

Applies to: Tykerb (lapatinib) and selexipag

MONITOR: Coadministration with inhibitors of CYP450 2C8 may increase exposure to the active metabolite of selexipag. According to the prescribing information, selexipag is hydrolyzed to its active metabolite in the liver and intestine by carboxylesterases, and the active metabolite subsequently undergoes oxidative metabolism catalyzed primarily by CYP450 2C8 and to a lesser extent by CYP450 3A4. Coadministration of selexipag with the moderate to potent CYP450 2C8 inhibitor clopidogrel, given at 300 mg loading dose or 75 mg once daily maintenance dose, had no relevant effect on exposure to selexipag but increased exposure to the active metabolite by approximately 2.2- and 2.7-fold following the loading and maintenance doses, respectively. The interaction has not been studied with other, less potent CYP450 2C8 inhibitors.

MANAGEMENT: Caution is advised when selexipag is prescribed with CYP450 2C8 inhibitors. Dosage adjustments as well as clinical and laboratory monitoring of selexipag may be appropriate whenever a CYP450 2C8 inhibitor is added to or withdrawn from therapy. Patients should be monitored for potentially increased side effects such as diarrhea, nausea, vomiting, flushing, anemia, and decreased appetite.

References

  1. (2001) "Product Information. Plavix (clopidogrel)." Bristol-Myers Squibb
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."
  4. (2016) "Product Information. Uptravi (selexipag)." Actelion Pharmaceuticals US Inc
View all 4 references

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Drug and food interactions

Moderate

lapatinib food

Applies to: Tykerb (lapatinib)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lapatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

ADJUST DOSING INTERVAL: Food can significantly increase the oral bioavailability of lapatinib. According to the manufacturer, lapatinib peak plasma concentration (Cmax) was approximately 2.5- and 3-fold higher and systemic exposure (AUC) 3- and 4-fold higher when administered with a low fat meal (5% fat; 500 calories) or with a high-fat meal (50% fat; 1000 calories), respectively, compared to fasting. Dividing the daily dose also resulted in an approximately 2-fold higher systemic exposure at steady state compared to the same total dose administered once daily.

MANAGEMENT: Patients treated with lapatinib should preferably avoid the consumption of grapefruit or grapefruit juice. The manufacturer recommends that lapatinib be administered at least one hour before or one hour after a meal. The lapatinib dose is administered once daily and should not be divided.

References

  1. (2007) "Product Information. Tykerb (lapatinib)." Novartis Pharmaceuticals

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Minor

selexipag food

Applies to: selexipag

Food prolongs the gastrointestinal absorption of selexipag. When taken with food, the time to peak concentration (Tmax) was delayed and peak plasma concentration (Cmax) was approximately 30% lower. Selexipag systemic exposure (AUC) and that of its active metabolite did not significantly change, however. Selexipag may be taken with or without food. Tolerability may be improved when taken with food.

References

  1. (2016) "Product Information. Uptravi (selexipag)." Actelion Pharmaceuticals US 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.

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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