Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction
Effects of other medicinal products on pemigatinib

Strong CYP3A4 inhibitors
A strong CYP3A4 inhibitor (itraconazole 200 mg once daily) increased pemigatinib AUC geometric mean by 88 % (90 % CI of 75 %, 103 %), which may increase the incidence and severity of adverse reactions with pemigatinib. Patients who are taking 13.5 mg pemigatinib once daily should have their dose reduced to 9 mg once daily and patients who are taking 9 mg pemigatinib once daily should have their dose reduced to 4.5 mg once daily (see section 4.2).

CYP3A4 inducers
A strong CYP3A4 inducer (rifampin 600 mg once daily) decreased pemigatinib AUC geometric mean by 85 % (90 % CI of 84 %, 86 %), which may decrease the efficacy of pemigatinib. Concurrent use of strong CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbital, rifampicin) should be avoided during treatment with pemigatinib (see section 4.4). Concomitant use of pemigatinib with St John’s wort is contra-indicated (see section 4.3). If needed, other enzyme inducers (e.g. efavirenz) should be used under close surveillance.

Proton pump inhibitors
Pemigatinib geometric mean ratios (90 % CI) for Cmax and AUC were 65.3 % (54.7, 78.0) and 92.1 % (88.6, 95.8), respectively, when co-administered in healthy subjects with esomeprazole (a proton pump inhibitor) relative to pemigatinib alone. Co-administration of a proton pump inhibitor (esomeprazole) did not result in a clinically important change in pemigatinib exposure.
However, in more than one third of patients given PPIs, a significant reduction of the exposure of pemigatinib was observed. PPIs should be avoided in patients receiving pemigatinib (see section 4.4).

H2-receptors antagonists
Co-administration of ranitidine did not result in a clinically important change in pemigatinib exposure.

Effects of pemigatinib on other medicinal products
Effect of pemigatinib on CYP2B6 substrates
In vitro studies indicate that pemigatinib induces CYP2B6. Co-administration of pemigatinib with CYP2B6 substrates (e.g. cyclophosphamide, ifosfamide, methadone, efavirenz) may decrease their exposure. Close clinical surveillance is recommended when pemigatinib is administered with these medicinal products or any CYP2B6 substrate having a narrow therapeutic index.

Effect of pemigatinib on P-gp substrates
In vitro, pemigatinib is an inhibitor of P-gp. Co-administration of pemigatinib with P-gp substrates (e.g. digoxin, dabigatran, colchicine) may increase their exposure and thus their toxicity. Pemigatinib administration should be separated by at least 6 hours before or after administration of P-gp substrates with a narrow therapeutic index.