Adult: As monotherapy after failure of platinum-containing regimen: Initially, 320 mg/m2 via infusion over 20 minutes once every 3 weeks. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline). Elderly: 75-<80 years: 280 mg/m2 via infusion over 20 minutes once every 3 weeks. ≥80 years: 250 mg/m2 via infusion over 20 minutes once every 3 weeks. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Special Patient Group
Patient with performance status of 1 or prior pelvic irradiation: Initially, 280 mg/m2, increase to 320 mg/m2 via infusion over 20 minutes once every 3 weeks for subsequent cycles in the absence of haematological toxicities during the 1st cycle.
Renal Impairment
CrCl (mL/min)
Dosage
20-<40
250 mg/m2 via infusion over 20 minutes once every 3 weeks.
40-60
280 mg/m2 via infusion over 20 minutes once every 3 weeks.
Hepatic Impairment
Mild (Child-Pugh grade A): 250 mg/m2 via infusion over 20 minutes once every 3 weeks. Moderate: (Child-Pugh grade B): 200 mg/m2 via infusion over 20 minutes once every 3 weeks.
Reconstitution
Dilute calculated dose in 100 mL of NaCl 0.9% or glucose 5% solution in an infusion bag.
Contraindications
Within 2 weeks or current severe infection. Baseline absolute neutrophil count (ANC) <1.5 x 109/L for 1st dose; baseline ANC <1 x 109/L for subsequent doses; platelet <100 x 109/L. Lactation. Intrathecal administration. Concomitant use with potent CYP3A4 inhibitors, QTc prolonging agents.
Special Precautions
Patient with risk factors for arrhythmia (e.g. CHF, known or history of QT prolongation, hypokalaemia); history of MI or angina pectoris, history of cardiac disease and other underlying cardiac diseases. Renal and hepatic impairment. Elderly. Pregnancy.
Adverse Reactions
Significant: Haematological toxicities (e.g. neutropenia, leucopenia, anaemia, thrombocytopenia); gastrointestinal toxicities (e.g. grade ≥3 constipation); cardiac disorders (e.g. QT prolongation); posterior reversible encephalopathy syndrome (PRES) manifested by headache, confusion, seizures visual disorders; hyponatraemia, neuropathy. Blood and lymphatic system disorders: Febrile neutropenia. Cardiac disorders: Tachycardia. Ear and labyrinth disorders: Ear pain. Gastrointestinal disorders: Ileus, dysphagia, buccal disorders, dyspepsia, anorexia, nausea, abdominal pain, diarrhoea. General disorders and administration site conditions: Asthenia/fatigue, injection site reaction, pyrexia, chest pain, chills, pain, oedema. Immune system disorders: Hypersensitivity. Infections and infestations: Neutropenic infection, viral/fungal/bacterial infections. Investigations: Weight decreased. Metabolism and nutrition disorders: Decreased appetite, dehydration. Musculoskeletal and connective tissue disorders: Myalgia, muscular weakness, arthralgia, back pain, jaw pain, pain in extremity, bone pain, musculoskeletal pain. Nervous system disorders: Peripheral sensory neuropathy, headache, dizziness, neuralgia, dysgeusia, syncope. Psychiatric disorders: Insomnia. Respiratory, thoracic and mediastinal disorders: Dyspnoea, cough. Skin and subcutaneous tissue disorders: Alopecia, rash, urticaria, pruritus, hyperhidrosis. Vascular disorders: Hyper/hypotension, vein thrombosis, phlebitis. Potentially Fatal: Grade 4 gastrointestinal toxicity (e.g. toxic megacolon or obstruction).
Patient Counseling Information
This drug may cause fatigue and dizziness, if affected, do not drive or operate machinery.
Monitoring Parameters
Verify baseline ANC, platelet and haemoglobin values before initiation of treatment. Monitor Na level during treatment, CBC and LFT.
Overdosage
Symptoms: Bone marrow suppression and risk of severe infection. Management: Closely monitor vital signs. May perform blood transfusion, administer antibiotics and growth factors as required.
Drug Interactions
May enhance the risk of constipation with opioids. Potentially Fatal: Increased concentration with CYP3A4 inhibitors (e.g. ritonavir, ketoconazole). Decreased serum concentration with CYP3A4 inducers (e.g. rifampicin). Increased risk of ventricular arrhythmias with QTc prolonging agents.
Food Interaction
Increased concentration with grapefruit juice. Decreased serum concentration with St John’s wort.
Action
Description: Vinflunine is a fluorinated vinca alkaloid derived from vinorelbine. It binds to tubulin, thereby inhibiting its polymerisation and microtubule formation resulting in treadmilling suppression, disruption of microtubule dynamic, mitotic arrest and apoptosis in M phase (metaphase) of cell cycle. Pharmacokinetics: Distribution: Extensively distributed to tissues. Volume of distribution: Approx 35 L/kg. Plasma protein binding: 67.2 ± 1.1%. Metabolism: Metabolised via formation of multiple esterases into active metabolite 4-O-deacetyl-vinflunine (DVFL) and into inactive metabolites via cytochrome CYP3A4 isoenzyme pathway. Excretion: Mainly via faeces (approx 2/3); urine (approx 1/3). Terminal elimination half-life: Approx 40 hours (vinflunine); approx 120 hours (DVFL).
Chemical Structure
Vinflunine Source: National Center for Biotechnology Information. PubChem Database. Vinflunine, CID=6918295, https://pubchem.ncbi.nlm.nih.gov/compound/Vinflunine (accessed on Jan. 24, 2020)
Storage
Store between 2-8°C. Do not freeze. Protect from light.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling and administration. Any unused portions should be disposed of in accordance with local requirements.
L01CA05 - vinflunine ; Belongs to the class of plant alkaloids and other natural products, vinca alkaloids and analogues. Used in the treatment of cancer.
References
Buckingham R (ed). Vinflunine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/06/2018.Joint Formulary Committee. Vinflunine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/06/2018.
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