n) may reduce the occurrence of this: see section 4.5. Navelbine soft capsule is associated with a higher incidence of nausea/vomiting than the intravenous formulation. Primary prophylaxis with antiemetics and administration of the capsules with some food is recommended as this has also been shown to reduce the incidence of nausea and vomiting: see section 4.2.
Patients receiving concomitant morphine or opioid analgesics: laxatives and careful monitoring of bowel mobility are recommended. Prescription of laxatives may be appropriate in patients with prior history of constipation.
Due to sorbitol content, patients with rare hereditary problems with fructose intolerance should not take the capsules.
Close haematological monitoring must be undertaken during treatment (determination of haemoglobin level and the leucocyte, neutrophil and platelet counts on the day of each new administration).
Dosing should be determined by haematological status:
- If the neutrophil count is below 1500 /mm3 and/or the platelet count is below 100000/mm3, then the treatment should be delayed until recovery.
- For dose escalation from 60 to 80 mg/m2 per week, after the third administration: see section 4.2.
- For the administrations given at 80mg/m², if the neutrophil count is below 500/mm3 or more than once between 500 and 1000 /mm3, then the treatment should be delayed until recovery. The administration should not only be delayed but also reduced to 60mg/m² per week. It is possible to reescalate the dose from 60 to 80 mg/m2 per week: see section 4.2.
During clinical trials where treatments were initiated at 80 mg/m2, a few patients developed excessive neutropenic complications including those with a poor performance status. Therefore it is recommended that the starting dose should be 60 mg/m2 escalating to 80 mg/m2 if the dose is tolerated as described in section 4.2.
If patients present signs or symptoms suggestive of infection, a prompt investigation should be carried out.
Special precautions for use
Special care should be taken when prescribing for patients with:
- history of ischemic heart disease: see section 4.8
- poor performance status
Navelbine should not be given concomitantly with radiotherapy if the treatment field includes the liver.
This product is specifically contra-indicated with yellow fever vaccine and its concomitant use with other live attenuated vaccines is not recommended: see section 4.3.
Caution must be exercised when combining Navelbine and strong inhibitors or inducers of CYP3A4 (see section 4.5), and its combination with phenytoin (like all cytotoxics) and with itraconazole (like all vinca alkaloids) is not recommended.
Oral Navelbine was studied in patients with liver impairment at the following doses:
- 60 mg/m² in 7 patients with mild liver impairment (bilirubin < 1.5 x ULN, and ALAT and/or ASAT from 1.5 to 2.5 x ULN);
- 50 mg/m² in 6 patients with moderate liver impairment (bilirubin from 1.5 to 3 x ULN, whatever the levels of ALAT and ASAT).
Total clearance of vinorelbine was neither modified between mild and moderate liver impairment nor was it altered in hepatically impaired patients when compared with clearance in patients with normal liver function.
Oral Navelbine was not studied in patients with severe hepatic impairment therefore its use is contra-indicated in these patients: see sections 4.2, 4.3, 5.2.
As there is a low level of renal excretion there is no pharmacokin |
