etic rationale for reducing the dose of Navelbine in patients with impaired kidney function: see sections 4.2, 5.2.
4.5 Interaction with other medicinal products and other forms of interaction
Concomitant use contraindicated
Yellow fever vaccine: as with all cytotoxics, risk of fatal generalised vaccine disease: see section 4.3.
Concomitant use not recommended
Live attenuated vaccines: (for yellow fever vaccine, see concomitant use contraindicated) as with all cytotoxics, 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 (e.g. poliomyelitis): see section 4.4
Phenytoin: as with all cytotoxics, 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.
Itraconazole: as with all vinca-alkaloids, increased neurotoxicity of vinca-alkaloids due to the decrease of their hepatic metabolism.
Concomitant use to take into consideration
Cisplatin: There is no mutual pharmacokinetic interaction when combining Navelbine with cisplatin over several cycles of treatment. However, the incidence of granulocytopenia associated with Navelbine use in combination with cisplatin is higher than associated with Navelbine single agent.
Mitomycin C: risk of bronchospasm and dyspnoea are increased, in rare case an interstitial pneumonitis was observed.
Ciclosporin, tacrolimus: excessive immunodepression with risk of lymphoproliferation.
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.
The combination of NAVELBINE with other drugs with known bone marrow toxicity is likely to exacerbate the myelosuppressive adverse effects.
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. azole antifungals such as ketoconazole and 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 (see section 4.4).
Anticoagulant treatment: as with all cytotoxics, the frequency of INR (International Normalised Ratio) monitoring should be increased due to the potential interaction with oral anticoagulants and increased variability of coagulation in patients with cancer.
Food does not modify the pharmacokinetics of vinorelbine.
4.6 Fertility, pregnancy and lactation
Pregnancy
Navelbine is suspected to cause serious birth effects when administered during pregnancy: see section 5.3.
Navelbine is contra-indicated in pregnancy: see section 4.3.
In case of a vital indication for treatment with Navelbine during pregnancy a medical consultation concerning the risk o |
