Clinical examples of interactions between cytokine modulators and small-molecule drugs
| Generic Name Cytokine Modulator | Mechanism of Action | Cytochrome P450 Enzyme Substrate | Type of Study | Clinical Findings | Labeling | Reference |
|---|---|---|---|---|---|---|
| Basiliximab | Binding to IL-2R on activated T cells | Cyclosporine | Retrospective | In pediatric transplant patients, higher whole-blood levels of cyclosporine within first 10 days post-transplant: at day 28-50 20% higher doses required to maintain adequate trough concentrations | No dose adjustments recommended | Strehlau et al., 2000 |
| Basiliximab | Binding to IL-2R on activated T cells | Tacrolimus | Retrospective | In adult transplant patients, 63% increase in tacrolimus blood trough levels on day 3 compared with controls. Decrease in drug levels by day 30. | No dose adjustments recommended | Sifontis et al., 2002 |
| Muronomab | CD3 T cell blocker | Cyclosporine | Retrospective | On day 5, cyclosporine trough levels 48% higher in treated patients compared with the control group. No differences observed on days 7 and 10 | No dose adjustments recommended | Vasquez and Pollak, 1997 |
| Tocilizumab | Anti-IL6R | Omeprazole (CYP2C19) | Prospective | 28% reduction in AUC | Therapeutic monitoring of cytochrome P450 substrates with a narrow therapeutic range should be performed and dose adjustments made as needed | Schmitt et al., 2011, 2012; Hoffmann-La Roche, 2008; http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4371b1-01-FDA.pdf; Zhang et al., 2009 |
| Dextromethorphan (CYP2D6) | No change | |||||
| Simvastatin (CYP3A4) | 57% reduction in AUC | |||||
| Methotrexate (excreted mainly as parent drug via renal transporters) | No change |