Vinorelbine Alvogen Adverse Reactions

The overall reported frequency of undesirable effects was determined from clinical studies in 316 patients (132 patients with non-small cell lung cancer and 184 patients with breast cancer) who received the recommended regimen of vinorelbine (first three administrations at 60 mg/m²/week followed by 80 mg/m²/week).
Adverse reactions reported are listed as follows, by system organ and by frequency.
Additional adverse reactions from Post Marketing experience have been added according to the MedDRA classification with the frequency Not known.
The reactions were described using the NCI common toxicity criteria as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
Undesirable effects reported with vinorelbine soft capsule: Pre-marketing experience: The most epression with neutropenia, anaemia and thrombocytopenia, gastrointestinal toxicity with nausea, vomiting, diarrhoea, stomatitis and constipation. Fatigue and fever were also reported very commonly.
Post-marketing experience: Vinorelbine soft capsule is used as single agent or in combination with other chemotherapeutic agents such as cisplatin, or capecitabine.
The most commonly system organ classes involved during post-marketing experience are: 'Blood and lymphatic system disorders', 'Gastrointestinal disorders', 'Infections and infestations' and 'General disorders and administration site conditions'. This information is consistent with the pre-marketing experience.
Infections and infestations: Very common: Bacterial, viral commonly reported adverse drug reactions are bone marrow dor fungal infections without neutropenia at different sites G1-4: 12.7%; G3-4: 4.4%.
Common: Bacterial, viral or fungal infections resulting from bone marrow depression and/or immune system compromise (neutropenic infections) are usually reversible with an appropriate treatment; Neutropenic infection G3-4: 3.5%.
Not known: Neutropenic sepsis; Complicated septicaemia and sometimes fatal.
Blood and lymphatic system disorders: Very common: Bone marrow depression resulting mainly in neutropenia G1-4: 71.5%; G3: 21.8%; G4: 25.9%, is reversible and is the dose limiting toxicity; Leucopenia G1-4: 70.6%; G3: 24.7%; G4: 6%; Anemia G1-4: 67.4%; G3-4: 3.8%; Thrombocytopenia G1-2: 10.8%.
Common: G4 Neutropenia associated with fever over 38°C including febrile neutropenia: 2.8%.
Metabolism and nutrition disorders: Not known: Severe hyponatraemia.
Psychiatric disorders: Common: Insomnia: G1-2: 2.8%.
Nervous system disorders: Very common: Neurosensory disorders G1-2: 11.1% were generally limited to loss of tendon reflexes and infrequently severe.
Common: Neuromotor disorders G1-4: 9.2%: G3-4: 1.3%; Headache: G1-4: 4.1%, G3-4: 0.6%; Dizziness: G1-4: 6%; G3-4: 0.6%; Taste disorders: G1-2: 3.8%.
Uncommon: Ataxia grade 3: 0.3%.
Eye disorders: Common: Visual disorders G1-2: 1.3%.
Cardiac disorders: Uncommon: Heart failure and cardiac dysrhythmia.
Not known: Myocardial infarction in patients with cardiac medical history or cardiac risk factors.
Vascular disorders: Common: Hypertension G1-4: 2.5%; G3-4: 0.3%; Hypotension G1-4: 2.2%; G3-4: 0.6%.
Respiratory system, thoracic and mediastinal disorders: Common: Dyspnoea G1-4: 2.8%; G3-4: 0.3%; Cough: G1-2: 2.8%.
Gastrointestinal disorders: Very Common: Nausea G1-4: 74.7%, G3-4: 7.3%; Vomiting G1-4: 54.7%, G3-4: 6.3%; Supportive treatment (such as oral setrons) may reduce the occurrence of nausea and vomiting; Diarrhoea G1-4: 49.7%, G3-4: 5.7%; Anorexia G1-4: 38.6%, G3-4: 4.1%. Stomatitis G1-4: 10.4%, G3-4: 0.9%; Abdominal pain: G1-4: 14.2%; Constipation G1-4: 19%, G3-4: 0.9%. Prescription of laxatives may be appropriate in patients with prior history of constipation and/or who receive concomitant treatment with morphine or morphine like medicinal products; Gastric disorders: G1-4: 11.7%.
Common: Oesophagitis G1-3: 3.8%; G3: 0.3%; Dysphagia: G1-2: 2.3%.
Uncommon: Paralytic ileus G3-4: 0.9% [exceptionally fatal] treatment may be resumed after recovery of normal bowel mobility.
Not known: Gastrointestinal bleeding.
Hepatobiliary disorders: Common: Hepatic disorders: G1-2: 1.3%.
Skin and subcutaneous tissue disorders: Very common: Alopecia usually mild in nature G1-2: 29.4% may occur.
Common: Skin reactions G1-2: 5.7%.
Musculoskeletal and connective tissue disorders: Common: Arthralgia including jaw pain, Myalgia: G1-4: 7%, G3-4: 0.3%.
Renal and urinary disorders: Common: Dysuria G1-2: 1.6%; Other genitourinary disorders G1-2: 1.9%.
General disorders and administration site conditions: Very common: Fatigue/malaise G1-4: 36.7%; G3-4: 8.5%; Fever G1-4: 13.0%, G3-4: 12.1%.
Common: Pain including pain at the tumour site G1-4: 3.8%, G3-4: 0.6%; Chills: G1-2: 3.8%.
Investigations: Very common: Weight loss G1-4: 25%, G3-4: 0.3%.
Common: Weight gain G1-2: 1.3%.
Undesirable effects with vinorelbine, concentrate for infusion: Some undesirable effects were observed with vinorelbine, concentrate for infusion during pre- and post-marketing experience which were not reported with vinorelbine soft capsule.
In order to provide the complete information and to further the safety of use of Vinorelbine Alvogen soft capsule, these effects are presented as follows: Infections and Infestations: Uncommon: Septicemia (very rarely fatal).
Immune system disorders: Not known: Systemic allergic reactions were reported as anaphylaxis, anaphylactic shock or anaphylactoid 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 vinorelbine in combination with mitomycin.
Gastrointestinal disorders: Rare: Pancreatitis.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.