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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 - Cmax: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 - Cmax: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 - Cmax: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 - Cmax: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 - Cmax:--
(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 - Cmax: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 - Cmax: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 - Cmax: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 - Cmax: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 - Cmax: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 - Cmax:--
(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 - Cmax:--
(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 - Cmax: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 - Cmax: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 - Cmax: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 - Cmax: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 - Cmax: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 - Cmax: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 - Cmax:--
(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 - Cmax: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 - Cmax: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 - Cmax: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 - Cmax: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%↓; 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.

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