Drug Class Description
Vinca alkaloids.

Generic Name
Vinorelbine

Drug Description
Vinorelbine 10 mg/ml as vinorelbine tartrateEach 1ml vial contains 10 mg Vinorelbine as vinorelbine tartrate Each 4ml vial contains 40 mg Vinorelbine as vinorelbine tartrateEach 5ml vial contains 50 mg Vinorelbine as vinorelbine tartrate

Presentation
Concentrate for solution for infusionNAVELBINE is a clear colourless to pale yellow solution

Indications
- As a single agent or in combination for the first line treatment of stage 3 or 4 non small cell lung cancer.- Treatment of advanced breast cancer stage 3 and 4 relapsing after or refractory to an anthracycline containing regimen.

Adult Dosage
Strictly by intravenous injection through an infusion line after appropriate dilution.The use of intrathecal route is contra-indicated.Administration should always be followed by a normal saline infusion to flush the vein.In adults :NAVELBINE is usually given at 25-30mg/m² weekly.NAVELBINE may be administered by slow bolus (5-10 minutes) after dilution in 20-50 ml of sodium chloride 9 mg/ml (0.9%) solution for injection or in 5% glucose solution for injection. Administration should always be followed with at least 250 ml of an isotonic solution to flush the vein.-Advanced 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.Impaired hepatic function:For patients presenting with severe liver impairment (bilirubin> 2xUNL and/or transaminases > 5xUNL), it is suggested that the dose be reduced by 33% and the haematological parameters be closely monitored since the maximum dose which was eva luated in this subset of patients was 20mg/m2.Impaired renal function:For patients with impaired kidney function, there is no need to adjust the dosage.Paediatric patientsNavelbine is not recommended for use in children due to a lack of data on safety and efficacy: see section 5.1: Pharmacodynamic properties

Child Dosage
Not applicable.

Contra Indications
- Known hypersensitivity to vinorelbine or other vinca alkaloids, or to any of the constituents.- Pregnancy- Lactation- Neutrophil count < 1500/mm3 or severe infection current or recent (within 2 weeks)

Special Precautions
Special warningsNAVELBINE must only be administered by the intravenous route.The use of intrathecal route is contra-indicated.NAVELBINE 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 NAVELBINE, close haematological monitoring should be undertaken during treatment (determination of haemoglobin level and the leucocyte, 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 75000/ mm3 then the treatment should be delayed until recovery.If the patient presents signs or symptoms suggestive of infection, a prompt investigation should be carried out.PrecautionsSpecial care should be taken when prescribing for patients with history of ischemic heart disease.The pharmacokinetics of NAVELBINE is not modified in patients presenting with moderate or severe liver impairment.As there is a low level of renal excretion there is no pharmacokinetic rationale for reducing NAVELBINE dose in patients with impaired kidney function.NAVELBINE should not be given concomitantly with radiotherapy if the treatment field includes the liver.All contact with the eye should be strictly avoided, risk of severe irritation and even corneal ulceration if the drug is sprayed under pressure. Immediate washing of the eye with normal saline solution should be undertaken if any contact occurs.

Interactions
The combination of NAVELBINE with other drugs with known bone marrow toxicity is likely to exacerbate the myelosuppressive adverse effects. However the incidence of granulocytopenia associated with NAVELBINE use in combination with cisplatin is higher than associated with NAVELBINE single agent.As CYP 3A4 is mainly involved in the metabolism of NAVELBINE, combination with inducers or inhibitors of this isoenzyme might modify the pharmacokinetics of NAVELBINE.The combination NAVELBINE- cisplatin shows no interaction on pharmacokinetic parameters

Adverse Reactions
Adverse reactions reported as more than isolated cases are listed below, by system organ class and by the MedRA frequency. Additional Adverse reactions from Post Marketing experience has been added according to the MedDRA classification with the frequency Not known.Very common>1/10Common>1/100, <1/10Uncommon>1/1,000, <1/100Rare>1/10,000, <1/1,000Very rare<1/10,000), including isolated reportsNot knownPost marketing reportsThe most commonly reported adverse drug reactions are bone marrow depression with neutropenia, leucopenia and anaemia, neurologic disorders, gastrointestinal toxicity with nausea, vomiting, stomatitis and constipation, Transient elevations of liver function tests, alopecia and local phlebitis.Infections and infestationsCommon: Infection bacterial, viral or fungal at different sites.Uncommon: Septicaemia [very rarely fatal].Not known: Neutropenic sepsis, sometimes fatalBlood and lymphatic system disorders: Very Common: Bone marrow depression resulting mainly in neutropenia reversible within 5 to 7 days and noncumulative over time.- Leucopenia- AnaemiaCommon : Thrombocytopenia.Not known: Febrile neutropeniaImmune system disordersNot known: Systemic allergic reactions as anaphylaxis, anaphylactic shock or anaphylactoïd type reaction .Endocrine disordersNot known: Inappropriate antidiuretic hormone secretion (SIADH)Metabolism and nutrition disordersRare: Severe hyponatraemiaNot known: AnorexiaNervous system disordersVery Common: Neurologic disorders including loss of deep tendon reflexes.- Weakness of the lower extremities has been reported after a prolonged chemotherapy.Uncommon: Severe paresthesias with sensory and motor symptoms. These effectsare generally reversible upon discontinuation of treatment.Cardiac disordersRare: Ischemic heart disease: angina pectoris, myocardial infarction.Very rare: Tachycardia, palpitation and heart rhythm disorders.Vascular disordersUncommon: Hypotension.- Hypertension.- Flushing and peripheral coldness.Rare: Severe hypotension- Collapse.Respiratory system, thoracic and mediastinal disordersUncommon: Dyspnoea and bronchospasm may occur in association with Navelbinetreatment.Rare: Interstitial pneumonopathies have been reported in particular in patients treated with Navelbine in combination with mitomycin.Gastrointestinal disordersVery Common: Stomatitis.- Nausea and vomiting- ConstipationCommon: Diarrhoea.Rare: Paralytic ileus, treatment may be resumed after recovery of normal bowel mobility.- Pancreatitis.Hepatobiliary disordersVery common: Transient elevations of liver function tests without clinical symptoms were reported.Skin and subcutaneous tissue disorders Very common: Alopecia, usually mild in nature, may occurRare: Generalized cutaneous reactionsMusculoskeletal and connective tissue disordersCommon: Arthralgia including jaw pain and myalgia.General disorders and administration site conditionsVery common: Reactions at the injection site may include erythema, burning pain,vein discoloration and local phlebitisCommon: Fatigue, fever, pain at different sites including chest pain and pain at thetumour site.Rare: Local necrosis has been observed. Proper positioning of the cannula in thevein before starting to infuse Navelbine followed by liberal flushing of the vein canlimit these effects.

Manufacturer
Pierre Fabre

Drug Availability
(POM)

Updated
04 March 2010