Interactions : אינטראקציות

7.          DRUG INTERACTIONS

7.1         Effect of Other Drugs on NERLYNX
Table 10 includes drug interactions that affect the pharmacokinetics of neratinib.
Table 10:      Drug Interactions That Affect Neratinib
Gastric Acid Reducing Agents
Concomitant use of NERLYNX with a proton pump inhibitor, H2-receptor antagonist, or antacid may decrease neratinib plasma concentration. Decreased Clinical Impact        neratinib AUC may reduce NERLYNX activity. Lansoprazole (PPI) resulted in a decrease of neratinib Cmax by 71% and AUC by 65% [see Clinical Pharmacology (12.3)].
Avoid concomitant use [see Dosage and
•   PPIs
Administration (3.3)].
Take NERLYNX at least 2 hours before the next dose of the H2-receptor antagonist or
Prevention or         •   H2-receptor antagonists
10 hours after the H2-receptor antagonist
Management
[see Dosage and Administration (3.3)].
Separate NERLYNX dosing by 3 hours
•   Antacids                          after antacids [see Dosage and Administration (3.3)].
Strong CYP3A4 Inhibitors
•    Concomitant use of NERLYNX with a strong CYP3A4 inhibitor
(ketoconazole) increased neratinib Cmax by 221% and AUC by 381% [see
Clinical Pharmacology (12.3)].
Clinical Impact
•    Concomitant use of NERLYNX with other strong CYP3A4 inhibitors may increase neratinib concentrations.
•    Increased neratinib concentrations may increase the risk of toxicity.
Prevention or             Avoid concomitant use of NERLYNX with strong CYP3A4 inhibitors.
Management
Moderate CYP3A4 and P-gp Dual Inhibitors
Clinical Impact            •    Simulated concomitant use of NERLYNX with a moderate CYP3A4 and P- gp dual inhibitor (verapamil) suggest the neratinib Cmax and AUC may increase by 203% and 299%, respectively [see Clinical Pharmacology
(12.3)].
•    Concomitant use of NERLYNX with other moderate CYP3A4 and P-gp dual inhibitors may increase neratinib concentrations.
•    Increased neratinib concentrations may increase the risk of toxicity.
Prevention or             Avoid concomitant use of NERLYNX with other moderate CYP3A4 and P-gp Management                dual inhibitors.
Strong or Moderate CYP3A4 Inducers
•    Concomitant use of NERLYNX with a strong CYP3A4 inducer (rifampin) reduced neratinib Cmax by 76% and AUC by 87% [see Clinical Pharmacology (12.3)].
Clinical Impact
•    Concomitant use of NERLYNX with other strong or moderate CYP3A4 inducers may decrease NERLYNX concentrations.
•    Decreased neratinib AUC may reduce NERLYNX activity.
Prevention or             Avoid concomitant use of NERLYNX with strong or moderate CYP3A4 Management                inducers.


AUC=Area Under Curve; Cmax=Maximum Concentration
* These examples are a guide and not considered a comprehensive list of all possible drugs that may fit this category. The healthcare provider should consult appropriate references for comprehensive information.

7.2          Effect of NERLYNX on Other Drugs
P-glycoprotein (P-gp) Substrates
Concomitant use of NERLYNX with digoxin, a P-gp substrate, increased digoxin concentrations [see Clinical Pharmacology (12.3)]. Increased concentrations of digoxin may lead to increased risk of adverse reactions including cardiac toxicity. Refer to the digoxin prescribing information for dosage adjustment recommendations due to drug interactions. NERLYNX may inhibit the transport of other P-gp substrates (e.g., dabigatran, fexofenadine).