Chemical formula: C₄₅H₅₄N₄O₈ Molecular mass: 778.947 g/mol PubChem compound: 44424639
Vinorelbine interacts in the following cases:
As with all cytotoxics, risk of generalised vaccine disease, possibly fatal. This risk is increased in patients already immunodepressed by their underlying disease. It is recommended to use an inactivated vaccine when one exists (e.g. poliomyelitis).
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.
The pharmacokinetics of vinorelbine is not modified in patients presenting with moderate or severe liver impairment. Nevertheless as a precautionary measure a reduced dose of 20mg/m² and close monitoring of haematological parameters is recommended in patients with severe liver impairment.
Patient with renal impairment There is no pharmacokinetic basis for reducing the vinorelbine dose in patients with renal dysfunction.
As vinca-alkaloids are known as substrates for P-glycoprotein, and in the absence of specific study, caution should be exercised when combining Vinorelbine with strong modulators of this membrane transporter.
As CYP3A4 is mainly involved in the metabolism of vinorelbine, combination with strong inhibitors of this isoenzyme (e.g. azole antifungals such as ketoconazole and itraconazole) could increase blood concentrations of vinorelbine and combination with strong inducers of this isoenzyme (e.g. rifampicin, phenytoin) could decrease blood concentrations of vinorelbine.
Men being treated with Vinorelbine are advised not to father a child during and minimally up to 3 months after treatment. Prior to treatment advice should be sought for conserving sperm due to the chance of irreversible infertility as a consequence of treatment with vinorelbine.
Excessive immunodepression with risk of lymphoproliferation.
There is no mutual pharmacokinetic interaction when combining vinorelbine with cisplatin over several cycles of treatment. However, the incidence of granulocytopenia associated with vinorelbine use in combination with cisplatin is higher than associated with vinorelbine single agent.
As with all vinca-alkaloids, increased neurotoxicity of vinca-alkaloids due to the decrease of their hepatic metabolism.
An increased incidence of grade ¾ neutropenia has been suggested when intravenous vinorelbine and lapatinib were associated in one clinical phase I study. In this study, the recommended dose of intravenous form of vinorelbine in a 3-weekly schedule on day 1 and day 8 was 22.5 mg/m² when combined with daily lapatinib 1,000 mg. This type of combination should be administered with caution.
Risk of bronchospasm and dyspnoea are increased, in rare case an interstitial pneumonitis was observed.
As with all cytotoxics, risk of exacerbation of convulsions resulting from the decrease of phenytoin digestive absorption by cytotoxic drug or loss of efficacy of the cytotoxic drug due to increased hepatic metabolism by phenytoin.
There are insufficient data available on the use of vinorelbine in pregnant women. Studies in animals have shown embryotoxicity and teratogenicity. On the basis of the results of animal studies and the pharmacological action of the medicinal product, there is a potential risk of embryonic and foetal abnormalities.
Vinorelbine should therefore not be used during pregnancy, unless the individual awaited benefit clearly outweighs the potential risks. If pregnancy occurs during treatment, the patient should be informed about the risks for the unborn child and be monitored carefully. The possibility of genetic counselling should be considered.
It is unknown whether vinorelbine is excreted in human breast milk. The excretion of vinorelbine in milk has not been studied in animal studies. A risk to the suckling child cannot be excluded therefore breast feeding must be discontinued before starting treatment with vinorelbine.
Women of child-bearing potential must use effective contraception during treatment and up to 3 months after treatment.
Men being treated with Vinorelbine are advised not to father a child during and minimally up to 3 months after treatment. Prior to treatment advice should be sought for conserving sperm due to the chance of irreversible infertility as a consequence of treatment with vinorelbine.
No studies on the effects on the ability to drive and use machines have been performed but on the basis of the pharmacodynamic profile vinorelbine does not affect the ability to drive and use machines. However, caution is necessary in patients treated with vinorelbine considering some adverse effects of the drug.
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 80mg/m²/week).
Adverse reactions reported are listed below, 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: Very common ≥1/10, Common ≥1/100, <1/10, Uncommon ≥1/1,000, <1/100, Rare ≥1/10,000, <1/1,000, Very rare <1/10,000, Not known Post marketing reports.
Pre-marketing experience: The most commonly reported adverse drug reactions are bone marrow depression 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’ and ‘General disorders and administration site conditions’. This information is consistent with the pre-marketing experience.
Very common: Bacterial, viral or 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.
Very common: Bone marrow depression resulting mainly in neutropenia G1-4: 71.5%; G3: 21.8%; G 4: 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%.
Not known: Severe hyponatraemia
Common: Insomnia: G1-2: 2.8%
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%,
Common: Visual disorders G1-2: 1.3%
Uncommon: Heart failure and cardiac dysrhythmia
Not known: Myocardial infarction in patients with cardiac medical history or cardiac risk factors.
Common: Hypertension G1-4: 2.5%; G3-4: 0.3%; Hypotension G1-4: 2.2%; G3-4: 0.6%
Common: Dyspnoea G1-4: 2.8%; G3-4: 0.3%. Cough: G1-2: 2.8%
Very Common: Nausea G1-4: 74.7%; G3-4: 7.3%; Vomiting G1-4: 54.7%; G 3-4: 6.3%; Supportive treatment such as 5HT3 antagonists (ondansetron) may reduce the occurrence of nausea and vomiting; Diarrhoea G1-4: 49.7%; G3-4: 5.7%; Anorexia G1-4: 38.6%; G 3-4: 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 opioid analgesics, 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
Common: Hepatic disorders: G1-2: 1.3%
Common: Skin reactions G1-2: 5.7%
Common: Arthralgia including jaw pain, Myalgia: G1-4: 7%, G3-4: 0.3%
Common: Dysuria G1-2: 1.6%, Other genitourinary disorders G1-2: 1.9%
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%
Very common: Weight loss G1-4: 25%, G3-4: 0.3%
Common: Weight gain G1-2: 1.3%
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).
Common: bacterial, viral or fungal infections at different sites (respiratory tract, urinary tract, gastrointestinal tract, etc.); 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.
Very common: bone marrow depression resulting principally in neutropenia (G3: 24.3%; G4: 27.8%) which is reversible within 5 to 7 days and not cumulative over time; anaemia (G3-4: 7.4%)
Common: thrombocytopenia (G3-4: 2.5%), rarely serious.
Unknown: febrile neutropenia.
Unknown: systemic allergic reactions, such as anaphylaxis, anaphylactic shock or anaphylactoid reactions.
Unknown: syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Rare: severe hyponatraemia
Unknown: anorexia
Very common: stomatitis (G 1-4: 15% with vinorelbine solution as monotherapy); nausea and vomiting (G 3-4: 2.2%); antiemetic therapy can reduce this occurrence; constipation is the principal symptom (G 3-4: 2.7%), which rarely develops into paralytic ileus with vinorelbine solution as monotherapy and with vinorelbine solution in conjunction with other chemotherapy agents (G3-4: 4.1%).
Common: diarrhoea, usually mild to moderate.
Rare: paralytic ileus – treatment may be restarted when normal intestinal transit is resumed. Pancreatitis has been reported.
Very common: neurological alterations (G3-4: 2.7%) 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.
Very common: alopecia, usually mild (G3-4: 4.1% with vinorelbine solution as isolated chemotherapy agent).
Rare: generalised skin reactions have been reported with vinorelbine solution.
Unknown: erythema on the hands and feet.
Rare: ischaemic heart disease (angina pectoris, myocardial infarction).
Very rare: tachycardia, palpitations and altered heart rhythm.
Uncommon: hypotension, hypertension, flushing and peripheral coldness.
Rare: severe hypotension, collapse.
Very common: transitory increases in liver function tests (G1-2), without notification of clinical symptoms (AST 27.6% and ALT 29.3%).
Uncommon: dyspnoea and bronchospasm can occur in association with treatment with vinorelbine solution, as well as with other vinca alkaloids.
Rare: cases of interstitial lung disease have been reported, particularly in patients treated with vinorelbine solution in combination with mitomycin.
Common: arthralgia, including pain in the jaw; myalgia.
Very common: injection site reactions include erythema, burning sensation, venous discolouration and local phlebitis (G3-4: 3.7% with vinorelbine solution as isolated chemotherapy agent).
Common: asthenia, fatigue, fever, pain at different sites including chest pain and pain at the site of the tumour have been reported by patients treated with vinorelbine solution.
Rare: local necrosis has been reported. Correct positioning of the intravenous needle or catheter and a bolus injection followed by flushing of the vein can limit these effects.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
