Acid-Reducing Agents - All Kinase Inhibitors

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

Tmax

(hour)

PPI Time of intake of kinase inhibitor and PPI Effect on kinase inhibitor exposure - AUC Effect on kinase inhibitor exposure - Cmax (FDA/EMA) recommendations Refs.
Afatinib 2-5 N.A. N.A. N.A. N.A. PPIs can be used concomitantly* 1,2
Axitinib 2-4 Rabeprazole 20mg q.d. Concomitantly 15%¯ 42%¯ PPIs can be used concomitantly 1,2
Bosutinib 6 Lansoprazole 60mg q.d., Concomitantly 26%↓ 46%↓ Avoid combination 3
Cabozantinib 2-5 Omeprazole 40 mg q.d. PPI 1 hour before cabozantinib 7%↓ 10%↓ PPIs can be used concomitantly 1,2
Crizotinib 4-6 Esomeprazole 40 mg Concomitantly 10%↓ -- PPIs can be used concomitantly 1,2
Dabrafenib 2 N.a. N.A. N.A. N.A. Avoid combination* 1,2
Dasatinib 0,5-3 Omeprazole 40mg q.d. Concomitantly 43%↓ 42%↓ Avoid combination 1,2,4
Erlotinib 4 Omeprazole 40mg q.d. Concomitantly 46%↓ 61%↓ Avoid combination 1,2
Gefitinib 3-7 N.A. N.A. N.A. N.A. Avoid combination** 1,2
Ibrutinib 1-2 N.A. N.A. N.A. N.A. Avoid combination* 1,2
Imatinib 2-4 Omeprazole 40mg q.d. Concomitantly -- -- PPIs can be used concomitantly 1,2
Lapatinib 3-4 Esomeprazole 40mg q.d. PPI 12 hours before Lapatinib 27%↓ -- Avoid combination 1,2
Nilotinib 3 Esomeprazole 40mg q.d. Concomitantly 34%↓ 27%↓ PPIs can be used concomitantly 5-7
Nintedanib 2-4 N.A. N.A. N.A. N.A. PPIs can be used concomitantly* 1,2
Pazopanib 3,5 Esomeprazole 40 mg q.d. Concomitantly*** 40%↓ 42%↓ PPIs can be used concomitantly 1,2
Ponatinib 4 Lansoprazole 60mg q.d. Concomitantly -- 25%↓ PPIs can be used concomitantly 8
Regorafenib 3-4 N.A. N.A. N.A. N.A. Avoid combination 1,2
Ruxolitinib 1 N.A. N.A. N.A. N.A. PPIs can be used concomitantly* 1,2
Sorafenib 3 Esomeprazole 40 mg q.d. Concomitantly -- -- PPIs can be used concomitantly 1,2
Sunitinib 6-12 N.A. N.A. N.A. N.A. PPIs can be used concomitantly* 1,2
Trametinib 1,5 N.A. N.A. N.A. N.A. PPIs can be used concomitantly* 1,2
Vandetanib 6 Omeprazole 40 mg q.d. Concomitantly -- 15%↓ PPIs can be used concomitantly 9
Vemurafenib 4 N.A. N.A. N.A. N.A. PPIs can be used concomitantly* 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%↓; Cmax 71%↓); *** Esomeprazole (evening) concomitantly with pazopanib (in the morning).

References

  1. Food and Drug Administration. 2015. (last accessed July 2015)
  2. European Medicines Agency. 2015. (last accessed July 2015)
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
Last update: 21 July 2015