Erlotinib - Overall Recommendations

Erlotinib CAN be Co-Administered with the Following Agents

• Gemcitabine¹
• CYP3A4 substrates, including paclitaxel¹

Erlotinib CAN be Co-Administered with the Following Agents, IF Administered with Caution

• Ciprofloxacin (inhibits both CYP3A4 and CYP1A2)^1,2
• Potent CYP1A2 inhibitors (e.g. fluvoxamine)¹
• Anticoagulants^1,2
• Statins¹
• P-glycoprotein inhibitors (e.g. cyclosporine, verapamil)¹
• Capecitabine¹

Erlotinib CANNOT be Co-Administered with the Following Agents

• Potent CYP3A4 inhibitors (e.g. ketoconazole)^1,2
• Potent CYP3A4 inducers (e.g. rifampicin)^1,2
• Proton pump inhibitors (other drugs that alter gastric pH should also be avoided)^1,2
• Platinum-based chemotherapy²

Additional Important Information when Prescribing Erlotinib

If co-administration of erlotinib and strong CYP3A4 inhibitors is necessary and toxicity occurs, use with caution and reduce the erlotinib dose in 50-mg decrements.^2-4

If co-administration of a CYP3A4 inducer is necessary, increase the erlotinib dose in 50-mg increments at 2-week intervals as tolerated, to a maximum of 450 mg.²

In smokers, increase the erlotinib dose by 50-mg increments at 2-week intervals to a maximum of 300 mg; immediately reduce to the recommended dose upon cessation of smoking.²

Co-administration of erlotinib and medicines that alter gastric pH:^1,2

• avoid concomitant use of proton pump inhibitors, as separation of doses may not eliminate the interaction
• if an H2-receptor antagonist (e.g. ranitidine) is required, erlotinib must be taken ≥2 hours before or 10 hours after the H2-receptor antagonist
• if needed, antacids should be taken ≥4 hours before or 2 hours after erlotinib.

Prothrombin time and INR should be regularly monitored in patients taking warfarin or other coumarin-derived anticoagulants.^1,2

Erlotinib is not recommended in combination with platinum-based chemotherapy.² Erlotinib increases platinum concentrations; although the magnitude of this increase is not considered clinically relevant, in clinical practice factors such as renal impairment may lead to increased exposure to carboplatin.¹

References

1. European Medicines Agency. Erlotinib (TARCEVA). Summary of Product Characteristics. 2015.
2. Food and Drug Administration. Erlotinib (TARCEVA) Prescribing information. 2015.
3. van Leeuwen RW, van Gelder T, Mathijssen RH, Jansman FG. Drug-drug interactions with tyrosine-kinase inhibitors: a clinical perspective. Lancet Oncol 2014; 15: e315-326.
4. Teo YL, Ho HK, Chan A. Metabolism-related pharmacokinetic drug-drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations. Br J Clin Pharmacol 2015; 79: 241-253.