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Drug Interactions between eliglustat and Tykerb

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

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Interactions between your drugs

Moderate

lapatinib eliglustat

Applies to: Tykerb (lapatinib) and eliglustat

GENERALLY AVOID: Coadministration with weak inhibitors of CYP450 3A4 may increase the plasma concentrations of eliglustat, which is primarily metabolized by CYP450 2D6 and, to a lesser extent, CYP450 3A4. Eliglustat at substantially elevated plasma concentrations is predicted to cause prolongation of the PR, QTc and QRS cardiac intervals, which may increase the risk of bradycardia, atrioventricular block, cardiac arrest, and serious ventricular arrhythmias such as torsade de pointes. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that the potent CYP450 3A4 inhibitor ketoconazole may increase eliglustat systemic exposure (AUC) by 4.4-, 5.4- and 6.2-fold in CYP450 2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs) and poor metabolizers (PMs), respectively, while the moderate CYP450 3A4 inhibitor fluconazole may increase eliglustat AUC by 3.2-, 2.9- and 3.0-fold, respectively. No data are available for use with other, less potent inhibitors.

MANAGEMENT: Concomitant use of eliglustat with weak CYP450 3A4 inhibitors such as chloramphenicol, cyclosporine, danazol, dasatinib, ethinyl estradiol, fluvoxamine, goldenseal, isoniazid, ivacaftor, lapatinib, lomitapide, nifedipine, nilotinib, palbociclib, pazopanib, suvorexant, ticagrelor, and zafirlukast is not recommended in CYP450 2D6 poor metabolizers. No dosage adjustment for eliglustat is necessary when used with weak CYP450 3A4 inhibitors in extensive or intermediate metabolizers.

References (1)
  1. (2014) "Product Information. Cerdelga (eliglustat)." Genzyme Corporation

Drug and food interactions

Major

eliglustat food

Applies to: eliglustat

GENERALLY AVOID: Grapefruit juice may significantly increase the systemic exposure to eliglustat. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because eliglustat is predicted to cause prolongation of the PR, QTc, and QRS cardiac intervals at substantially elevated plasma concentrations, consumption of grapefruit juice during treatment may increase the risk of bradycardia, atrioventricular block, cardiac arrest, and serious ventricular arrhythmias such as torsade de pointes.

MANAGEMENT: Patients treated with eliglustat should avoid consumption of grapefruit and grapefruit juice.

References (1)
  1. (2014) "Product Information. Cerdelga (eliglustat)." Genzyme Corporation
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)
  1. (2007) "Product Information. Tykerb (lapatinib)." Novartis Pharmaceuticals

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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