Table 1.

Pharmacokinetic (PK) interactions between H2 antagonists (H2A) or proton pump inhibitors (PPI) and tyrosine kinase inhibitors; recommendations and demonstration of the clinical impact of such interactions.

Drug Name:	PK Interactions [31,46]	Recommendations [31,46]	Clinical Impact
Afatinib	NA	NA	NA
Alectinib	±	NA	NA
Axitinib	+	H2A: OK, PPI: OK
Cabozantinib	±	H2A: OK, PPI: OK
Crizotinib	0	H2A: OK, PPI: OK
Dasatinib	++	H2A: OK, PPI: no	NA
Erlotinib	++	H2A: OK, PPI: no	YES [38,39,40]
Gefitinib	+++	H2A: no, PPI: no	YES [38,39,40]
Imatinib	0	H2A: OK, PPI: OK
Lapatinib	+	H2A: no, PPI: no
Lenvatinib	0	H2A: OK, PPI: OK
Nilotinib	+	H2A: OK, PPI: OK
Osimertinib	0	H2A: OK, PPI: OK
Pazopanib	++	H2A: OK, PPI: OK	YES [44]
Regorafenib	0 [47]	H2A: OK, PPI: OK
Sorafenib	0	H2A: OK, PPI: OK	Conflicting results [48,49,50]
Sunitinib	+	H2A: OK, PPI: OK	Conflicting results [40,41,42]
Vandetanib	+	H2A: OK, PPI: OK

Pharmacokinetic interactions: NA: no data available; 0: definitively no interactions; ±: conflicting results; +: possible interactions; ++: clear interactions; +++: major interactions. Recommendations: NA: no data available, OK: concomitant use possible; no: concomitant use strongly discouraged. Clinical impact of concomitant use: NA: no data available; YES: clinical impact demonstrated in clinical series; Conflicting results: clinical series showing different results.