Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Consilient Health Limited, 5<sup>th</sup> Floor, Beaux Lane House, Mercer Street Lower, Dublin 2, Ireland
As a single agent or in combination for:
As a single agent, the recommended regimen is:
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 Vinorelbine 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 the first 3 administrations of 60 mg/m²/week | Neutrophils >1,000 | Neutrophils ≥500 and <1,000 (1 episode) | Neutrophils ≥500 and <1,000 (2 episodes) | Neutrophils <500 |
|---|---|---|---|---|
| Recommended dose starting with the 4th administration | 80 | 80 | 60 | 60 |
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.
| Neutrophil count beyond the 4th administration of 80 mg/m²/week | Neutrophils >1,000 | Neutrophils ≥500 and <1,000 (1 episode) | Neutrophils ≥500 and <1,000 (2 episodes) | Neutrophils <500 |
|---|---|---|---|---|
| Recommended dose starting with the next administration | 80 | 60 |
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.
For combination regimens, the dose and schedule will be adapted to the treatment protocol.
Based on clinical studies, the oral dose of 80 mg/m² was demonstrated to correspond to 30 mg/m² of the iv form and 60 mg/m² to 25 mg/m².
This has been the base for combination regimens alternating iv and oral forms improving patient convenience.
Capsules of different strengths (20, 30, 80 mg) are available in order to choose the adequate combination for the right dosage.
The following table gives the dose required for appropriate ranges of body surface area (BSA).
| 60 mg/m² | 80 mg/m² | |
|---|---|---|
| BSA (m²) | Dose (mg) | Dose (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.
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).
Safety and efficacy in children have not been established and administration is therefore not recommended (see section 5.1).
Vinorelbine can be administered at the standard dose of 60 mg/m²/week in patients with mild hepatic disorder (bilirubin <1.5 x ULN, and ALT and/or AST between 1.5 and 2.5 x ULN).
In patients with moderate hepatic disorder (bilirubin between 1.5 and 3 x ULN, independent of ALT and AST level), Vinorelbine needs to be administered at a dose of 50 mg/m²/week.
The administration of Vinorelbine in patients with severe hepatic disorder is not recommended because there is insufficient data in this population in order to determine the pharmacokinetics, efficacy and safety (see sections 4.4, 5.2).
Given the minor renal excretion, there is no pharmacokinetic justification for reducing the dose of Vinorelbine in patients with serious renal insufficiency (see sections 4.4, 5.2).
Vinorelbine must be given strictly by the oral route.
Vinorelbine must be swallowed whole with water, without chewing, sucking or dissolving the capsule.
It is recommended to administer the capsule with some food.
Overdosage with Vinorelbine soft capsules could produce bone marrow hypoplasia sometimes associated with infection, fever, paralytic ileus and hepatic disorders.
General supportive measures together with blood transfusion, growth factors, and broad spectrum antibiotic therapy should be instituted as deemed necessary by the physician.
A close monitoring of hepatic function is recommended.
There is no known antidote for overdosage of Vinorelbine.
Shelf life: 2 years.
Store in a refrigerator (2°C-8°C).
Carton box containing a PVC/PVDC-Aluminium blister with child-resistant safety paper layer.
Carton box containing an OPA/Aluminium/PVC-Aluminium blister.
Pack size: 1 or 4 blisters containing 1 soft capsule each. Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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