Navelbine Capsule Special Precautions

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 physician 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, never repeat the administration of this dose. Supportive treatment such as 5HT₃ antagonists (e.g. ondansetron, granisetron) may reduce the occurrence of this.
Navelbine soft capsule is associated with a higher incidence of nausea/vomiting than the i.v formulation. Primary prophylaxis with antiemetics and administration of the capsule with some food is recommended as this has also been shown to reduce the incidence of nausea and vomiting.
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, patient with rare hereditary problems with fructose intolerance should not take the capsules.
This medicinal product contains small amounts of ethanol (alcohol), less than 100 mg per dose.
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. For the administrations given at 80 mg/m², if the neutrophil count is below 500/mm³ or more than once between 500 and 1000/mm³, the administration should not only be delayed but also reduced to 60 mg/m² per week. It is possible to reescalate the dose from 60 to 80 mg/m² per week.
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.
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 ischaemic heart disease; with 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. Caution must be exercised when combining Navelbine and strong inhibitors or inducers of CYP3A4, and its combination with phenytoin (like all cytotoxics) and with itraconazole (like all vinca alkaloids) is not recommended. Oral Navelbine has been studied in patients with hepatic disorder at the following dosages: 60 mg/m² in patients with mild hepatic disorder (bilirubin <1.5 x ULN, and ALT and/or AST from 1.5 to 2.5 x ULN); 50 mg/m² in patients with moderate hepatic disorder (bilirubin between 1.5 and 3 x ULN, independent of ALT and AST level). Total clearance of vinorelbine was neither modified between mild and moderate liver impairment nor was it altered in hepatically impaired patients when compared with the clearance in patients with normal liver function. Oral Navelbine has not been studied in patients with severe hepatic impairment, therefore the use in these patients is contra-indicated. 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.
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 has no effect on the ability to drive and use machines. However, caution is necessary in patients treated with vinorelbine considering some adverse effects of the drug.