5.4 Interactions between medicinal products
Most TKIs are metabolised in the liver, predominantly via the cytochrome enzyme CYP3A4.
Therefore, caution should be exercised when a TKI is administered together with medicinal products that induce or inhibit CYP3A4.
Inhibitors: When a medicinal product causes decreased metabolism with another medicinal product – the exposure of the medicinal product increases (increased concentration and increased risk of adverse reaction).
Inductors: When a medicinal product causes increased metabolism with another medicinal product – the exposure of the medicinal product is reduced (reduced concentration and effect).
| INHIBITORS | INDUCTORS |
|---|---|
| Grapefruit/grapefruit juice | Barbiturates |
| Clarithromycin | Carbamazepine |
| Erythromycin | Phenytoin |
| Fluconazole | Rifampicin |
| Itraconazole | Griseofulvin |
| Ketoconazole | Nevirapi |
| Miconazole | St. John’s Wort |
| Cyclosporine | |
| Indinavir | |
| Ritonavir | |
| Delavirdine | |
| Verapamil | |
| Nefazodone | |
| TAO |
Pazopanib and statins
Concomitant use of Pazopanib and simvastatin increases the incidence of ALT elevations. Therefore, pausing simvastatin (and other statins) is recommended for initiation of Pazopanib.
Pazopanib and medicinal products for modifying gastric pH
Concomitant administration of Pazopanib with proton pump inhibitor (PPI – pantoprazole) or H2-receptor antagonist (Kuracid) may decrease the bioavailability of Pazopanib. If it is necessary to use:
- PPI, it is recommended that Pazopanib be taken without food in the evening with PPI
- H2-receptor antagonist, it is recommended to take Pazopanib at least 1 hour before or 10 hours after the dose of H2-receptor antagonist.
Cabozantinib and MRP2 inhibitors
Co-administration of MRP2 inhibitors (ciclosporin, efavirence, emtricitabine) with Cabozantinib may result in increased Cabozantinib plasma concentrations. Caution should therefore be exercised when using the above medicinal products at the same time.
Tivozanib and Rosuvastatin
Tivozanib inhibits the transporter protein BCRP in vitro, but the clinical relevance of this finding is unknown. Caution should be exercised if tivozanib is co-administered with rosuvastatin.
