Posology : מינונים

4.2   Posology and method of administration
In adult patients
NAVELBINE soft capsule is indicated as a single agent

First three administrations
60mg/m² of body surface area, administered once weekly.
Subsequent administrations
Beyond the third administration, it is recommended to increase the dose of NAVELBINE to 80mg/m² once weekly except in those patients for whom the neutrophil count dropped once below 500/mm3 or more than once between 500 and 1000/mm3 during the first three administrations at 60mg/m².

Neutrophil count during      Neutrophils Neutrophils        Neutrophils         Neutrophils the first                      > 1000       ≥ 500              ≥ 500              < 500 3 administrations of                     and < 1000         and < 1000 60 mg/m2/week                            (1 episode)        (2 episodes) Recommended dose                  80             80              60                 60 starting with the 4th administration

Dose modification
For any administration planned to be given at 80mg/m², if the neutrophil count is below 500/mm3 or more than once between 500 and 1000 / mm3 the administration should be delayed until recovery and the dose reduced from 80 to 60mg/m² per week during the 3 following administrations.
If the neutrophil count is below 1500 /mm3 and/or the platelet count below 100000/mm3, then the treatment should be delayed until recovery.
Neutrophil count            Neutrophils Neutrophils Neutrophils Neutrophils beyond the                    > 1000         ≥ 500           ≥ 500       < 500 4th administration of                     and < 1000      and < 1000
80 mg/m /week
2
(1 episode)     (2 episodes)
Recommended dose                         80                               60 starting with the next administration

It is possible to re-escalate the dose from 60 to 80 mg/m² per week if the neutrophil count did not drop below 500/mm3 or more than once between 500 and 1000/mm3 during 3 administrations given at 60 mg/m² according to the rules previously defined for the first 3 administrations.

The following table gives the dose required for appropriate ranges of body surface area (BSA).

60 mg/m2                  80 mg/m2
BSA (m )2
Dose                    Dose (mg)
(mg)
0.95 to 1.04                            60                          80 1.05 to 1.14                            70                          90 1.15 to 1.24                            70                          100 1.25 to 1.34                            80                          100 1.35 to 1.44                            80                          110 1.45 to 1.54                            90                          120 1.55 to 1.64                           100                          130 1.65 to 1.74                           100                          140 1.75 to 1.84                           110                          140 1.85 to 1.94                           110                          150 ≥ 1.95                               120                          160 Even for patients with BSA 2 m2 the total dose should never exceed 120 mg per week at 60 mg /m2 and 160 mg per week at 80 mg/m2.

Administration
NAVELBINE must be given strictly by the oral route.
NAVELBINE must be swallowed whole with water, without chewing, sucking or dissolving the capsule.
It is recommended to administer the capsule with some food.

Administration in the 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. Age does not modify the pharmacokinetics of vinorelbine, (see section 5.2).

Administration in children
Safety and efficacy in children have not been established and administration is therefore not recommended, (see section 5.1).

Administration in patients with liver insufficiency
NAVELBINE can be administered at the standard dose of 60 mg/m²/week in patients with mild liver impairment (bilirubin < 1.5 x ULN, and ALAT and/or ASAT from 1.5 to 2.5 x ULN). In patients with moderate liver impairment (bilirubin from 1.5 to 3 x ULN, whatever the levels of ALAT and ASAT), NAVELBINE should be administered at a dose of 50 mg/m²/week. The administration of NAVELBINE in patients with severe hepatic impairment is contra-indicated: (see sections 4.3, 4.4, 5.2).

Administration in patients with renal insufficiency
Given the minor renal excretion, there is no pharmacokinetic justification for reducing the dose of NAVELBINE in patients with serious renal insufficiency, (see sections 4.4, 5.2).

Specific instructions must be observed for handling NAVELBINE, (see section 6.6).