Special Warning : אזהרת שימוש

4.4       Special warnings and precautions for use

Special warnings
NAVELBINE should be prescribed by a physician who is experienced in the use of chemotherapy with facilities for monitoring cytotoxic drugs.

If the patient chews or sucks the capsule by error, the liquid is an irritant. Proceed to mouth rinses with water or preferably a normal saline solution.

In the event of the capsule being cut or damaged, the liquid content is an irritant, and so may cause damage if in contact with skin, mucosa or eyes. Damaged capsules should not be swallowed and should be returned to the pharmacy or to the doctor in order to be properly destroyed. If any contact occurs, immediate thorough washing with water or preferably with normal saline solution should be undertaken.
In the case of vomiting within a few hours after drug intake, do not re-administer. Supportive treatment such as 5HT3 antagonists (e.g., ondansetron, granisetron) 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.

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 re-escalate 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.
This medicinal product contains 5.36 mg sorbitol in each 20 mg capsule and 8.11 mg sorbitol in each 30 mg capsule.
The additive effect of concomitantly administered product containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.
The content of sorbitol in medicinal products for oral use may affect the bioavailability of other medicinal products for oral use administered concomitantly.
This medicinal product contains 5 mg alcohol (ethanol) in each 20 mg capsule and 7.5 mg alcohol (ethanol) in each 30 mg capsule.
The amount in each capsule of this medicine is equivalent to less than 1 ml beer or 1 ml wine.
The small amount of alcohol in this medicinal product will not have any noticeable effects.
This medicinal product contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.
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 pharmacokinetic rationale for reducing the dose of NAVELBINE in patients with impaired kidney function (see sections 4.2, 5.2).

Effects on Driving

4.7   Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed but, on the basis of the pharmacodynamic profile, vinorelbine does not affect the ability to drive and use machines. However, caution is necessary in patients treated with vinorelbine considering some adverse effects of the drug, (see section 4.8).