Special warnings: Vinorelbine Soft-Gelatin Capsule 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 setron (e.g. ondansetron, granisetron) may reduce the occurrence of this.
Vinorelbine Soft-Gelatin capsule is associated with a higher incidence of nausea/vomiting than the IV formulation. A primary prophylaxis with antiemetics is recommended.
Due to sorbitol content, patient 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 (see Dosage & Administration).
For dose escalation from 60 to 80 mg/m2 per week, after the third administration, see Dosage & 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 re-escalate the dose from 60 to 80 mg/m2 per week (see Dosage & Administration).
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 Dosage & Administration.
If patients present signs or symptoms suggestive of infection, a prompt investigation should be carried out.
Use of this medicine with live attenuated vaccines is not recommended (for yellow fever vaccine, see Contraindications).
Caution is recommended when vinorelbine is used with strong inhibitors or inducers of cytochrome CYP3A4. Hence, the use of this medicine with phenytoin, fosphenytoin, itraconazole or posaconazole is not recommended.
Special precautions for use: Special care should be taken when prescribing for patients: With history of ischaemic heart disease; With poor performance status.
Vinorelbine should not be given concomitantly with radiotherapy if the treatment field includes the liver.
Oral vinorelbine was studied in patients with liver impairment at the following doses: 60 mg/m2 in 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 patients with moderate liver impairment (bilirubin from 1.5 to 3 x ULN, whatever the levels of ALAT and ASAT).
Safety and pharmacokinetics of vinorelbine were not modified in these patients at the tested doses.
Oral vinorelbine was not studied in patients with severe hepatic impairment, therefore its use is contraindicated in these patients.
As there is a low level of renal excretion there is no pharmacokinetic rationale for reducing the dose of vinorelbine 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 does not affect the ability to drive and use machines. However, caution is necessary in patient treated with vinorelbine considering some adverse effects of the drug.
Use in Pregnancy: Vinorelbine is suspected to cause serious birth effects when administered during pregnancy. Vinorelbine is contraindicated in pregnancy.
In case of a vital indication a medical consultation concerning the risk of harmful effects for the child should be performed for the therapy of a pregnant patient. If pregnancy occurs anyhow during treatment, genetic counselling should be offered.
Women of child-bearing potential: Women of child-bearing potential must use effective contraception during treatment and up to 3 months after treatment.
Use in Lactation: It is unknown whether vinorelbine is excreted in human breast milk. The excretion of vinorelbine in milk has not been studied in animal studies. A risk to the suckling cannot be excluded therefore breast feeding must be discontinued before starting treatment with vinorelbine
Fertility: Men being treated with vinorelbine are advised not to father a child during and up to 3 months after treatment. Prior to treatment advice should be sought for conserving sperm due to the chance of irreversible infertility as a consequence of treatment with vinorelbine.