Types of Drug-Drug Interactions

The table below shows the effects of acid-reducing agents (protein pump inhibitors) on select kinase inhibitors, together with recommendations for coadministration. Click here to print these pages for use in the clinic.

Kinase inhibitor	Recommendations
Afatinib	Tmax (hour): 2-5 PPI: N.A. Time of intake of kinase inhibitor and PPI: N.A. Effect on kinase inhibitor exposure - AUC: N.A. Effect on kinase inhibitor exposure - C_max:N.A. (FDA/EMA) recommendations: PPIs can be used concomitantly* Refs.: 1,2
Axitinib	Tmax (hour): 2-4 PPI: Rabeprazole 20mg q.d. Time of intake of kinase inhibitor and PPI: Concomitantly Effect on kinase inhibitor exposure - AUC: 15%¯ Effect on kinase inhibitor exposure - C_max:42%¯ (FDA/EMA) recommendations: PPIs can be used concomitantly Refs.: 1,2
Bosutinib	Tmax (hour): 6 PPI: Lansoprazole 60mg q.d., Time of intake of kinase inhibitor and PPI: Concomitantly Effect on kinase inhibitor exposure - AUC: 26%↓ Effect on kinase inhibitor exposure - C_max:46%↓ (FDA/EMA) recommendations: Avoid combination Refs.: 3
Cabozantinib	Tmax (hour): 2-5 PPI: Omeprazole 40 mg q.d. Time of intake of kinase inhibitor and PPI: PPI 1 hour before cabozantinib Effect on kinase inhibitor exposure - AUC: 7%↓ Effect on kinase inhibitor exposure - C_max:10%↓ (FDA/EMA) recommendations: PPIs can be used concomitantly Refs.: 1,2
Crizotinib	Tmax (hour): 4-6 PPI: Esomeprazole 40 mg Time of intake of kinase inhibitor and PPI: Concomitantly Effect on kinase inhibitor exposure - AUC: 10%↓ Effect on kinase inhibitor exposure - C_max:-- (FDA/EMA) recommendations: PPIs can be used concomitantly Refs.: 1,2
Dabrafenib	Tmax (hour): 2 PPI: N.a. Time of intake of kinase inhibitor and PPI: N.A. Effect on kinase inhibitor exposure - AUC: N.A. Effect on kinase inhibitor exposure - C_max:N.A. (FDA/EMA) recommendations: Avoid combination* Refs.: 1,2
Dasatinib	Tmax (hour): 0,5-3 PPI: Omeprazole 40mg q.d. Time of intake of kinase inhibitor and PPI: Concomitantly Effect on kinase inhibitor exposure - AUC: 43%↓ Effect on kinase inhibitor exposure - C_max:42%↓ (FDA/EMA) recommendations: Avoid combination Refs.: 1,2,4
Erlotinib	Tmax (hour): 4 PPI: Omeprazole 40mg q.d. Time of intake of kinase inhibitor and PPI: Concomitantly Effect on kinase inhibitor exposure - AUC: 46%↓ Effect on kinase inhibitor exposure - C_max:61%↓ (FDA/EMA) recommendations: Avoid combination Refs.: 1,2
Gefitinib	Tmax (hour): 3-7 PPI: N.A. Time of intake of kinase inhibitor and PPI: N.A. Effect on kinase inhibitor exposure - AUC: N.A. Effect on kinase inhibitor exposure - C_max:N.A. (FDA/EMA) recommendations: Avoid combination Refs.**: 1,2
Ibrutinib	Tmax (hour): 1-2 PPI: N.A. Time of intake of kinase inhibitor and PPI: N.A. Effect on kinase inhibitor exposure - AUC: N.A. Effect on kinase inhibitor exposure - C_max:N.A. (FDA/EMA) recommendations: Avoid combination* Refs.: 1,2
Imatinib	Tmax (hour): 2-4 PPI: Omeprazole 40mg q.d. Time of intake of kinase inhibitor and PPI: Concomitantly Effect on kinase inhibitor exposure - AUC: -- Effect on kinase inhibitor exposure - C_max:-- (FDA/EMA) recommendations: PPIs can be used concomitantly Refs.: 1,2
Lapatinib	Tmax (hour): 3-4 PPI: Esomeprazole 40mg q.d. Time of intake of kinase inhibitor and PPI: PPI 12 hours before Lapatinib Effect on kinase inhibitor exposure - AUC: 27%↓ Effect on kinase inhibitor exposure - C_max:-- (FDA/EMA) recommendations: Avoid combination Refs.: 1,2
Nilotinib	Tmax (hour): 3 PPI: Esomeprazole 40mg q.d. Time of intake of kinase inhibitor and PPI: Concomitantly Effect on kinase inhibitor exposure - AUC: 34%↓ Effect on kinase inhibitor exposure - C_max:27%↓ (FDA/EMA) recommendations: PPIs can be used concomitantly Refs.: 5-7
Nintedanib	Tmax (hour): 2-4 PPI: N.A. Time of intake of kinase inhibitor and PPI: N.A. Effect on kinase inhibitor exposure - AUC: N.A. Effect on kinase inhibitor exposure - C_max:N.A. (FDA/EMA) recommendations: PPIs can be used concomitantly* Refs.: 1,2
Pazopanib	Tmax (hour): 3,5 PPI: Esomeprazole 40 mg q.d. Time of intake of kinase inhibitor and PPI: Concomitantly* Effect on kinase inhibitor exposure - AUC: 40%↓ Effect on kinase inhibitor exposure - C_max:42%↓ (FDA/EMA) recommendations: PPIs can be used concomitantly Refs.**: 1,2
Ponatinib	Tmax (hour): 4 PPI: Lansoprazole 60mg q.d. Time of intake of kinase inhibitor and PPI: Concomitantly Effect on kinase inhibitor exposure - AUC: -- Effect on kinase inhibitor exposure - C_max:25%↓ (FDA/EMA) recommendations: PPIs can be used concomitantly Refs.: 8
Regorafenib	Tmax (hour): 3-4 PPI: N.A. Time of intake of kinase inhibitor and PPI: N.A. Effect on kinase inhibitor exposure - AUC: N.A. Effect on kinase inhibitor exposure - C_max:N.A. (FDA/EMA) recommendations: Avoid combination Refs.: 1,2
Ruxolitinib	Tmax (hour): 1 PPI: N.A. Time of intake of kinase inhibitor and PPI: N.A. Effect on kinase inhibitor exposure - AUC: N.A. Effect on kinase inhibitor exposure - C_max:N.A. (FDA/EMA) recommendations: PPIs can be used concomitantly* Refs.: 1,2
Sorafenib	Tmax (hour): 3 PPI: Esomeprazole 40 mg q.d. Time of intake of kinase inhibitor and PPI: Concomitantly Effect on kinase inhibitor exposure - AUC: -- Effect on kinase inhibitor exposure - C_max:-- (FDA/EMA) recommendations: PPIs can be used concomitantly Refs.: 1,2
Sunitinib	Tmax (hour): 6-12 PPI: N.A. Time of intake of kinase inhibitor and PPI: N.A. Effect on kinase inhibitor exposure - AUC: N.A. Effect on kinase inhibitor exposure - C_max:N.A. (FDA/EMA) recommendations: PPIs can be used concomitantly* Refs.: 1,2
Trametinib	Tmax (hour): 1,5 PPI: N.A. Time of intake of kinase inhibitor and PPI: N.A. Effect on kinase inhibitor exposure - AUC: N.A. Effect on kinase inhibitor exposure - C_max:N.A. (FDA/EMA) recommendations: PPIs can be used concomitantly* Refs.: 1,2
Vandetanib	Tmax (hour): 6 PPI: Omeprazole 40 mg q.d. Time of intake of kinase inhibitor and PPI: Concomitantly Effect on kinase inhibitor exposure - AUC: -- Effect on kinase inhibitor exposure - C_max:15%↓ (FDA/EMA) recommendations: PPIs can be used concomitantly Refs.: 9
Vemurafenib	Tmax (hour): 4 PPI: N.A. Time of intake of kinase inhibitor and PPI: N.A. Effect on kinase inhibitor exposure - AUC: N.A. Effect on kinase inhibitor exposure - C_max:N.A. (FDA/EMA) recommendations: PPIs can be used concomitantly* Refs.: 1,2

* Based only on “in vitro” and basic chemical data; ** Based on a study with ranitidine 450mg bid., 13 hours and 1 hour before gefitinib (AUC 47%↓; C_max 71%↓); *** Esomeprazole (evening) concomitantly with pazopanib (in the morning).

References

Food and Drug Administration. 2015. (last accessed July 2015)
European Medicines Agency. 2015. (last accessed July 2015)
Abbas R, Hug BA, Leister C et al. A phase I ascending single-dose study of the safety, tolerability, and pharmacokinetics of bosutinib (SKI-606) in healthy adult subjects. Cancer Chemother Pharmacol 2012; 69: 221-227.
Eley T, Luo FR, Agrawal S et al. Phase I study of the effect of gastric acid pH modulators on the bioavailability of oral dasatinib in healthy subjects. J Clin Pharmacol 2009; 49: 700-709.
Yin OQ, Bedoucha V, McCulloch T et al. Effects of famotidine or an antacid preparation on the pharmacokinetics of nilotinib in healthy volunteers. Cancer Chemother Pharmacol 2013; 71: 219-226.
Yin OQ, Gallagher N, Fischer D et al. Effect of the proton pump inhibitor esomeprazole on the oral absorption and pharmacokinetics of nilotinib. J Clin Pharmacol 2010; 50: 960-967.
Yin OQ, Giles FJ, Baccarani M et al. Concurrent use of proton pump inhibitors or H2 blockers did not adversely affect nilotinib efficacy in patients with chronic myeloid leukemia. Cancer Chemother Pharmacol 2012; 70: 345-350.
Narasimhan NI, Dorer DJ, Davis J et al. Evaluation of the effect of multiple doses of lansoprazole on the pharmacokinetics and safety of ponatinib in healthy subjects. Clin Drug Investig 2014; 34: 723-729.
Johansson S, Read J, Oliver S et al. Pharmacokinetic evaluations of the co-administrations of vandetanib and metformin, digoxin, midazolam, omeprazole or ranitidine. Clin Pharmacokinet 2014; 53: 837-847.

References

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