VINORELBINE

Vinorelbine must be administered under the supervision of a doctor experienced in the use of chemotherapy. Posology Non-small cell lung cancer. In monotherapy the usual dose given is 25-30 mg/m² once weekly. g. day 1 and 5 every 3 weeks or day 1 and 8 every 3 weeks according to treatment protocol.

4 mg/m² of body surface area. Maximum total dose per administration: 60 mg.

Elderly:

Clinical experience has not detected any significant differences among elderly patients with regard to the response rate, although greater sensitivity in some of these patients cannot be excluded. 5% is excreted unchanged in the urine.

No prospective study relating altered metabolism of the active substance to its pharmacodynamic effects is available in order to establish guidelines for vinorelbine dose reduction in patients with impaired liver or kidney function.

Patient with liver impairment The pharmacokinetics of vinorelbine is not modified in patients presenting with moderate or severe liver impairment. 2) Patient with renal impairment There is no pharmacokinetic basis for reducing the vinorelbine dose in patients with renal dysfunction.

Paediatric population The safety and efficacy in children and adolescents have not been demonstrated and administration is therefore not recommended. Method of administration For intravenous use only. Strictly by intravenous injection through an infusion line, after appropriate dilution.

Use of the intrathecal route is contraindicated. 6. Vinorelbine solution may be administered by slow bolus (6-10 minutes) after dilution in 20-50 ml of normal saline or glucose 50 mg/ml (5%) solution or by a short infusion (20-30 minutes) after dilution in 125 ml of normal saline or glucose 50 mg/ml (5%) solution.

- Administration should always be followed with at least 250 ml of a normal saline infusion to flush the vein.

The undesirable effects reported with more frequency than isolated cases are listed below according to system organ class and frequency. Frequencies are defined as very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), unknown (cannot be calculated on the basis of the data available), according to the MedDRA frequency convention and classed by system organ class.

The adverse drug reactions reported most frequently are: bone marrow depression with neutropenia, anaemia, neurological diseases, gastrointestinal toxicity accompanied by nausea, vomiting, stomatitis and constipation, transitory increases in liver function test results, alopecia and local phlebitis.

Other adverse reactions were added after post-marketing studies, according to the MedDRA classification and with "unknown" frequency. Detailed information on undesirable effects: the effects are reported according to the WHO classification (grade 1=G1; grade 2=G2; grade 3=G3; grade 4=G4; grau 1-4= G1-4; grade1-2=G1-2; grade 3-4=G3-4).

); mild to moderate and normally reversible with the appropriate treatment. Uncommon: severe sepsis accompanied by another visceral failure. Septicaemia. Very rare: sometimes fatal, complicated septicaemia. Unknown: neutropenic septicaemia.

5%), rarely serious. Unknown: febrile neutropenia.

Immune system disorders:

Unknown: systemic allergic reactions, such as anaphylaxis, anaphylactic shock or anaphylactoid reactions. 1%). Common: diarrhoea, usually mild to moderate. Rare: paralytic ileus - treatment may be restarted when normal intestinal transit is resumed.

Pancreatitis has been reported. 7%) including loss of deep tendon reflexes. Weakness of the lower limbs has been reported after prolonged chemotherapy. Uncommon: severe paraesthesia with sensory and motor symptoms. These effects are usually reversible.

Special Warnings Vinorelbine must be administered under the supervision of a doctor experienced in the use of chemotherapy. Vinorelbine must only be administered by the intravenous route . As the inhibition of the haematopoietic system is the main risk associated with the administration of Vinorelbine solution, close blood monitoring is necessary during treatment (determination of haemoglobin levels and platelet, neutrophil and leukocyte counts, on the first day of each new administration).

The dose-limiting adverse reaction is mainly neutropenia. This effect is not cumulative, having its nadir between 7 and 14 days after 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, treatment should be postponed until the values return to normal.

If the patients present signs or symptoms suggestive of infection, a prompt investigation should be carried out. 8). The pharmacokinetics of vinorelbine is not modified in patients who suffer moderate or severe hepatic failure. 2. As there is a low level of renal clearance, there is no pharmacokinetic basis for reducing the Vinorelbine solution dose in patients with impaired renal function.

2. Vinorelbine solution must not be administered simultaneously with radiotherapy when the treatment field includes the liver. This medicinal product is specifically contraindicated when the yellow fever vaccine is administered. The concomitant use of other live attenuated vaccines is not recommended.

5 - Specific interactions of vinorelbine). The concomitant use of phenytoin (and all other cytotoxic agents) and itraconazole (and all other 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 medicinal product is sprayed under pressure.

9%) solution should be undertaken if any contact occurs and an ophthalmologist should be contacted To reduce the risk of bronchospasm, especially if used concomitant with mitomycin C, appropriate precautionary measures should be considered.

1. 6). )