Navelbine 10 mg/ml Concentrate for Solution for Infusion

/ Perrigo

Strictly intravenous administration after appropriate dilution:
Intra-thecal administration of this drug may be fatal: It is recommended to infuse this drug over 6-10 minutes after dilution in 20-50 ml of sodium chloride 9 mg/ml (0.9%) solution for injection or in glucose solution for injection 5%. Administration should always be followed with at least 250 ml of an isotonic solution infusion to flush the vein.
Non-small cell lung cancer and advanced breast cancer: In monotherapy the usual dose given is 25-30 mg/m² once weekly. In combination chemotherapy the usual dose (25-30 mg/m²) is usually maintained, while the frequency of administration is reduced e.g. day 1 and 5 every 3 weeks or day 1 and 8 every 3 weeks according to treatment protocol.
Hormone-resistant prostate cancer: The usual dose given is 30 mg/m2 on days 1 and 8 every 3 weeks with low doses of corticosteroids every day (i.e. hydrocortisone 40 mg/day).
Administration in the elderly: Clinical experience has not identified relevant differences among elderly patients with regard to the response rate, although greater sensitivity in some of these patients cannot be excluded. Age does not modify the pharmacokinetics of Vinorelbine.
Administration in patients with liver insufficiency: The pharmacokinetics of Vinorelbine is not modified in patients presenting moderate or severe liver impairment. Nevertheless as a precautionary measure a reduced dose of 20mg/m2 and close monitoring of hematological parameters is recommended in patient with severe liver impairment.
Administration in patients with renal insufficiency: Given the minor renal excretion, there is no pharmacokinetic justification for reducing the dose of Vinorelbinein patients with renal insufficiency.
Administration in children: Safety and efficacy in children have not been established and administration is therefore not recommended.
For full details see prescribing information.

For the treatment of non small cell lung cancer. For the treatment of advanced breast cancer.
Hormone- refractory prostate cancer, especially in combination with low dose oral corticoid therapy or Estramustin.

– Known hypersensitivity to Vinorelbine or other vinca alkaloids, or to any of the constituent.
– Neutrophil count < 1500/mm3 or severe infection current or recent (within 2 weeks)
–  Platelet count < 100000/mm3.
–  In  combination with yellow fever vaccine.
–  Pregnancy.
–  Lactation.  

This drug should be administered under the supervision of a physician experienced in the use of chemotherapy.
Since inhibition of the hematopoietic system is the main risk associated with, close hematological monitoring should be undertaken during treatment (determination of hemoglobin level and the leukocyte, neutrophil and platelet counts on the day of each new administration).
The dose limiting adverse reaction is mainly neutropenia. This effect is non-cumulative, having its nadir between 7 and 14 days after the administration and is rapidly reversible within 5 to 7 days. 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.
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. The pharmacokinetics of Vinorelbine is not modified in patients presenting moderate or severe liver impairment. For dosage adjustment in this specific patient group,   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 Vinorelbine 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 Vinorelbine 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.
All contact with the eyes should be strictly avoided: there is a risk of severe irritation and even corneal ulceration if the drug is sprayed under pressure. Immediate washing of the eye with sodium chloride 9mg/ml (0.9%) solution for injection should be undertaken if any contact occurs.
Caution must be exercised when combining Vinorelbine 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.
All contact with the eyes should be strictly avoided: there is a risk of severe irritation and even corneal ulceration if the drug is sprayed under pressure. Immediate washing of the eye with sodium chloride 9 mg/ml (0.9%) solution for injection should be undertaken if any contact occurs.
See prescribing information for full details.

Reactions at the injection site may include erythema, burning pain, vein discoloration and local phlebitis, Asthenia, Fatigue, fever, pain at different locations including chest pain and pain at the tumor site.
See prescribing information for full details. 

Due to the increase of thrombotic risk in case of tumoral diseases, the use of anticoagulative treatment is frequent. The high intra-individual variability of the coagulability during diseases, and the eventuality of interaction between oral anticoagulants and anticancer chemotherapy required, if it is decided to treat the patient with oral anticoagulants, to increase frequency of the INR (International Normalised Ratio) monitoring.
See prescribing information for full details.

Contraindicated in pregnancy and lactation.
See prescribing information for full details.

Symptoms: Overdose with Vinorelbine could produce bone marrow hypoplasia sometimes associated with infection, fever and paralytic ileus.
Emergency procedure: General supportive measures together with blood transfusion, growth factors and broad spectrum antibiotic therapy should be instituted as deemed necessary by the physician.
Antidote: There is no known antidote for overdose of this drug.

Storage conditions: After dilution in sodium chloride 9 mg/ml (0.9%) solution for injection or in glucose solution for injection 5%, chemical and physical in-use stability has been demonstrated for 8 days at room temperature (20° C to 5° C) or in the refrigerator (2°C to 8°C) protected from light, in neutral glass bottle, PVC and vinyl acetate bags. From a microbiological point of view, the product should be used immediately. If not used immediately, in -use storage times and conditions prior to use are under the responsibility of the user and would normally not be longer than 24 hours at 2° to 8°C, unless preparation has taken place in controlled and validated aseptic conditions.
See prescribing information for full details.