Navelbine Drug Interactions

Interactions common to all cytotoxics: Concomitant use contraindicated: Yellow fever vaccine: Risk of fatal generalised vaccine disease.
Concomitant use not recommended: Live attenuated vaccines (see Concomitant use contraindicated for the yellow fever vaccine): Risk of generalised, potentially fatal, vaccine disease. This risk is increased in subjects who are already immunodepressed due to the underlying disease.
Use an inactivated vaccine when this exists (poliomyelitis).
Phenytoin (and, by extrapolation, fosphenytoin): Risk of seizures due to reduced gastrointestinal absorption of phenytoin alone due to the cytotoxic or loss of efficacy of the cytotoxic agent due to an increase in its hepatic metabolism by phenytoin or fosphenytoin.
Concomitant use requiring precautions: Vitamin K antagonists: Increased risk of thrombosis and haemorrhage in tumour disease. In addition, possible interaction between the VKA and chemotherapy. More frequent monitoring of the INR (International Normalised Ratio).
Macrolides (clarithromycin, erythromycin, telithromycin): Risk of increased toxicity of the anti-mitotic agent due to a reduction in its hepatic metabolism by clarithromycin, erythromycin or telithromycin. Close clinical and laboratory monitoring. Possibly, use an alternative antibiotic.
Cobicistat: Increased neurotoxicity of the antimitotic due to a reduction in its hepatic metabolism by cobicistat. Close clinical monitoring and possible adjustment of dosage of the anti-mitotic agent.
Concomitant use to take into consideration: Immunosuppressants (ciclosporin, everolimus, sirolimus, tacrolimus): Excessive immunosuppression with risk of lymphoproliferative syndrome.
Interactions specific to the vinca alkaloids: Concomitant use not recommended: Itraconazole, posaconazole, ketoconazole: Increased neurotoxicity of the anti-mitotic agent due to a reduction in its hepatic metabolism by itraconazole, ketoconazole or posaconazole.
Concomitant use requiring precautions: Protease inhibitors: Increased toxicity of the antimitotic due to a reduction in its hepatic metabolism by the protease inhibitor. Close clinical monitoring and possible adjustment of dosage of the antimitotic agent.
Concomitant use to take into consideration: Mitomycin C: Risk of increased pulmonary toxicity of mitomycin and the vinca alkaloids.
As the vinca alkaloids are recognised to be substrates for glycoprotein P and in the absence of specific studies, precautions are required when vinorelbine is used in combination with potent membrane transport modulators.
Interactions specific to vinorelbine: Combination of vinorelbine with other medicinal products known to have bone marrow toxicity is liable to worsen the myelosuppressive adverse effects.
There are no mutual pharmacokinetic interactions when vinorelbine is used in combination with cisplatin during several treatment cycles. The incidence of granulocytopenias however was greater with combination of vinorelbine with cisplatin than when vinorelbine was used in monotherapy.
No clinically significant pharmacokinetic interactions have been seen during combination of vinorelbine with several other anticancer agents (paclitaxel, docetaxel, capecitabine and oral ciclophosphamide).
As CYP3A4 is mostly involved in the metabolism of vinorelbine, combination with potent inhibitors of this isoenzyme may increase blood vinorelbine concentration and combination with potent inducers of this isoenzyme may reduce the blood concentration of vinorelbine.
Anti-emetics such as the 5HT3 antagonists (for example: ondansetron, granisetron) do not result in changes in the pharmacokinetics of vinorelbine soft-gelatin capsule.
In a phase I clinical study examining a combination of intravenous vinorelbine and lapatinib, an increased incidence of grade 3/4 neutropenia was suggested. In this study the recommended dose of intravenous vinorelbine was 22.5 mg/m² on days 1 and 8 every 3 weeks in combination with 1000 mg of lapatinib administered daily. This type of combination must therefore be administered with caution.
Interaction with foods: Simultaneous ingestion of food does not change exposure to vinorelbine.