Interactions : אינטראקציות

7         DRUG INTERACTIONS
7.1       Effect of Other Drugs on ZYKADIA
Strong CYP3A Inhibitors
A strong CYP3A4/P-gp inhibitor (ketoconazole) increased the systemic exposure of ceritinib [see Clinical Pharmacology (12.3)] which may increase the incidence and severity of adverse reactions of ZYKADIA.
Avoid concurrent use of strong CYP3A inhibitors during treatment with ZYKADIA. If concurrent use of strong CYP3A inhibitors is unavoidable, reduce the ZYKADIA dose [see Dosage and Administration (2.4)].
Do not consume grapefruit and grapefruit juice as they may inhibit CYP3A.
Strong CYP3A Inducers
A strong CYP3A4/P-gp inducer (rifampin) decreased the systemic exposure of ceritinib [see Clinical Pharmacology (12.3)], which may decrease the efficacy of ZYKADIA. Avoid concurrent use of strong CYP3A inducers during treatment with ZYKADIA.
7.2       Effect of ZYKADIA on Other Drugs
CYP3A Substrates
Ceritinib increased the systemic exposure of a sensitive CYP3A substrate (midazolam) [see Clinical Pharmacology (12.3)]. Avoid coadministration of ZYKADIA with sensitive CYP3A substrates. If concomitant 
ZYK API FEB22 V5
use is unavoidable, consider dose reduction of the sensitive CYP3A substrate(s). If ZYKADIA is coadministered with other CYP3A substrates, refer to the CYP3A substrate labeling for dosage recommendation with strong CYP3A inhibitors.
CYP2C9 Substrates
Ceritinib increased the systemic exposure of a CYP2C9 substrate (warfarin) [see Clinical Pharmacology (12.3)]. Increase the frequency of INR monitoring if coadministration with warfarin is unavoidable as the anti- coagulant effect of warfarin may be enhanced.
Avoid coadministration of ZYKADIA with CYP2C9 substrates for which minimal concentration changes may lead to serious toxicities. If concomitant use of such CYP2C9 substrates is unavoidable, consider dose reduction for the coadministered CYP2C9 substrates. 7.3          Drugs That Prolong QT Interval ZYKADIA causes concentration-dependent increases in the QTc interval. When possible, avoid coadministration of ZYKADIA with other products with a known potential to prolong the QTc interval [see Warnings and Precautions (5.4), Clinical Pharmacology (12.2)].
7.4      Drugs That Cause Bradycardia
ZYKADIA can cause bradycardia. When possible, avoid coadministration of ZYKADIA with other products known to cause bradycardia [see Warnings and Precautions (5.6), Clinical Pharmacology (12.2)].