Interactions common to all cytotoxics: Concomitant use contraindicated (see Contraindications): Yellow fever vaccine: risk of fatal generalised vaccine disease.
Concomitant use not recommended: Live attenuated vaccines (for yellow fever vaccine, see concomitant use contraindicated in the previous text): risk of generalised vaccine disease, possibly fatal. This risk is increased in patients already immunodepressed by their underlying disease. It is recommended to use an inactivated vaccine when one exists (poliomyelitis).
Phenytoin (and by extrapolation, fosphenytoin): risk of exacerbation of convulsions resulting from the decrease of phenytoin digestive absorption by cytotoxic drug or risk of toxicity enhancement or loss of efficacy of the cytotoxic drug due to increased hepatic metabolism by phenytoin or fosphenytoin.
Interaction with special precaution for use: Oral anticoagulant: There is an increased thrombotic and haemorrhagic risk in case of tumoral diseases. There is an eventuality of interaction between oral anticoagulants and anticancer chemotherapy. Increased frequency of the INR (International Normalised Ratio) monitoring is required.
Concomitant use to take into consideration: Cyclosporine, tacrolimus, everolimus, sirolimus: excessive immuno-depression with risk of lymphoproliferation.
Interaction specific to vinca-alkaloids: Concomitant use not recommended: Itraconazole, posaconazole: increased neurotoxicity of vinca-alkaloids due to the decrease of their hepatic metabolism.
Interaction with special precaution for use: Protease inhibitors: Increase of vinca-alkaloids toxicity due to the decrease of their hepatic metabolism by protease inhibitors. Close clinical monitoring and eventually decrease of chemotherapy dosage is required.
Concomitant use to take into consideration: Mitomycin C: risk of bronchospams and dyspnoea are increased. As vinca-alkaloids are known as substrates for P-glycoprotein, and in the absence of specific study, caution should be exercised when combining vinorelbine with strong modulators of this membrane transporter.
Interactions specific to vinorelbine: The combination of vinorelbine with other drugs with known bone marrow toxicity is likely to exacerbate the myelosuppressive adverse effects.
There is no mutual pharmacokinetic interaction when combining vinorelbine with cisplatin over several cycles of treatment. However, the incidence of granulocytopenia associated with vinorelbine use in combination with cisplatin is higher than associated with vinorelbine single agent.
No clinically significant pharmacokinetic interaction was observed when combining vinorelbine with several other chemotherapeutic agents (paclitaxel, docetaxel, capecitabine and oral cyclophosphamide).
As CYP3A4 is mainly involved in the metabolism of vinorelbine, combination with strong inhibitors of these isoenzymes could increase blood concentration of vinorelbine and combination with strong inducers of this isoenzyme could decrease blood concentrations of vinorelbine.
Anti-emetic drugs such as 5HT3 antagonists (e.g. ondansetron, granisetron) do not modify the pharmacokinetics of vinorelbine Soft-Gelatin Capsules.
Food does not modify the pharmacokinetics of vinorelbine.