Navelbine Capsule Drug Interactions

Interactions common to all cytotoxics: Due to the increased thrombotic risk in the case of tumoral disease, the use of anticoagulative treatment is frequent. As the intra-individual variability of the coagulability during diseases is high and there is the risk of interaction between oral anticoagulants and anticancer therapy, if the patient is treated with oral anticoagulants, increasing the frequency of INR (International Normalised Ratio) monitoring is recommended.
Concomitant use contraindicated: Yellow fever vaccine: risk of fatal generalised vaccine disease.
Concomitant use not recommended: Live attenuated vaccines (for yellow fever vaccine, see concomitant use contraindicated as previously mentioned): 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: as with all cytotoxics, exacerbation of convulsions can be observed with phenytoin 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.
Concomitant use to take into consideration: Ciclosporine, tacrolimus: excessive immunodepression with risk of lymphoproliferation.
Interactions specific to vinca-alkaloids: Concomitant use not recommended: Itraconazole: increases neurotoxicity of vinca-alkaloids due to the decrease of their hepatic metabolism.
Concomitant use to take into consideration: Mitomycin C: risk of bronchospams and dyspnoea are increased, in rare case an interstitial pneumonitis was observed.
As vinca-alkaloids are known as substrates for P-glycoprotein, and in the absence of specific study, caution should be exercised when combining Navelbine with strong modulators of this membrane transporter.
Interactions specific to vinorelbine: The combination of Navelbine with other drugs with known bone marrow toxicity is likely to exacerbate the myelosuppressive adverse effects. There is no mutual pharmacokinetic interaction when combining Navelbine with cisplatin over several cycles of treatment. However the incidence of granulocytopenia associated with Navelbine in combination with cisplatin was higher than the one associated with Navelbine single agent.
No clinically significant pharmacokinetic interaction was observed when combining Navelbine 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 this isoenzyme (e.g. ketoconazole, itraconazole) could increase blood concentrations of vinorelbine and combination with strong inducers of this isoenzyme (e.g. rifampicin, phenytoin) could decrease blood concentrations of vinorelbine.
Anti-emetic drugs such as 5HT₃ antagonists (e.g. ondansetron, granisetron) do not modify the pharmacokinetics of Navelbine soft capsules.
An increased incidence of grade 3/4 neutropenia has been suggested when intravenous vinorelbine and lapatinib were associated in one clinical phase I study. In this study, the recommended dose of intravenous form of vinorelbine in a 3-weekly schedule on day 1 and day 8 was 22.5 mg/m² when combined with daily lapatinib 1000 mg. This type of combination should be administered with caution.
Food does not modify the pharmacokinetics of vinorelbine.