velbine, concentrate for infusion:
Some undesirable effects were observed with Navelbine, concentrate for solution for infusion during pre- and post-marketing experience which were not reported with Navelbine soft capsule.
In order to provide the complete information and to further the safety of use of Navelbine soft capsule, these effects are presented below:
Infections and infestations
Uncommon:
Septicaemia [very rarely fatal]
Immune system disorders
Not known:
Systemic allergic reactions were reported as anaphylaxis, anaphylactic shock or anaphylactoïd type reaction.
Endocrine disorders
Not known:
Inappropriate antidiuretic hormone secretion (SIADH).
Vascular disorders
Uncommon:
Flushing and peripheral coldness
Rare :
Severe hypotension, collapse.
Respiratory system, thoracic and mediastinal disorders
Uncommon:
Bronchospasm may occur as with other vinca alkaloids.
Rare:
Interstitial pneumonopathy has been reported in particular in patients treated with Navelbine in combination with mitomycin.
Gastrointestinal disorders
Rare:
Pancreatitis.
4.9 Overdose
Symptoms
Overdosage with Navelbine soft capsules could produce bone marrow hypoplasia sometimes associated with infection, fever, paralytic ileus and hepatic disorders.
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. A close monitoring of hepatic function recommended.
Antidote
There is no known antidote for overdosage of Navelbine.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Vinca alkaloïds and analogues (ATC Code: L01C A04)
Navelbine is a antineoplastic drug of the vinca alkaloid family but unlike all the other vinca alkaloids, the catharantine moiety of vinorelbine has been structurally modified. At the molecular level, it acts on the dynamic equilibrium of tubulin in the microtubular apparatus of the cell. It inhibits tubulin polymerization and binds preferentially to mitotic microtubules, affecting axonal microtubules at high concentrations only. The induction of tubulin spiralization is less than that produced by vincristine.
Navelbine blocks mitosis at G2-M, causing cell death in interphase or at the following mitosis.
Safety and efficacy of Navelbine in paediatric patients have not been established. Clinical data from two single-arm Phase II studies using intravenous vinorelbine in 33 and 46 paediatric patients with recurrent solid tumours, including rhabdomyosarcoma, other soft tissue sarcoma, Ewing sarcoma, liposarcoma, synovial sarcoma, fibrosarcoma, central nervous system cancer, osteosarcoma, neuroblastoma at doses of 30 to 33.75mg/m2 D1 and D8 every 3 weeks or once weekly for 6 weeks every 8 weeks showed no meaningful clinical activity. The toxicity profile was similar to that reported in adult patients (see section 4.2).
5.2 Pharmacokinetic properties
Pharmacokinetic parameters of vinorelbine were eva luated in blood.
Absorption
After oral administration, vinorelbine is rapidly absorbed and the Tmax is reached between 1.5 to 3 h with a blood concentration peak (Cmax) of approximately 130 ng/ml after a dose of 80 mg/m².
Absolute bioavailability is |
