Vinorelbine


Generic Medicine Info
Indications and Dosage
Intravenous
Advanced breast cancer
Adult: For stage 3 and 4 cases relapsing after or refractory to anthracycline-containing regimen: As single agent: 25-30 mg/m2 once weekly. As part of combination chemotherapy: Maintain 25-30 mg/m2, while frequency of administration is reduced (e.g. day 1 and 5 every 3 weeks or day 1 and 8 every 3 weeks) according to treatment protocol. After dilution, doses may be given via slow bolus inj or infusion over 6-10 minutes, or infusion over 20-30 minutes followed by flushing with at least 250 mL normal saline. Alternatively, via inj (after dilution) over 6-10 minutes into the side port of a free-flowing IV line then flush with at least 75-125 mL of compatible infusion solution. Dose modification may be required according to individual neutrophil and/or platelet counts, safety and tolerability. Dosage recommendations may vary among individual products and local treatment protocols. Refer to detailed product or country-specific guidelines.

Intravenous
Non-small cell lung cancer
Adult: For the 1st-line treatment of stage 3 or 4 cases: As single agent: 25-30 mg/m2 once weekly. As part of combination chemotherapy: Maintain 25-30 mg/m2, while frequency of administration is reduced (e.g. day 1 and 5 every 3 weeks or day 1 and 8 every 3 weeks) according to treatment protocol. After dilution, doses may be given via slow bolus inj or infusion over 6-10 minutes, or infusion over 20-30 minutes followed by flushing with at least 250 mL normal saline. Alternatively, via inj (after dilution) over 6-10 minutes into the side port of a free-flowing IV line then flush with at least 75-125 mL of compatible infusion solution. Dose modification may be required according to individual neutrophil and/or platelet counts, safety and tolerability. Dosage recommendations may vary among individual products and local treatment protocols. Refer to detailed product or country-specific guidelines.

Oral
Advanced breast cancer
Adult: For stage 3 and 4 cases relapsing after or refractory to anthracycline-containing regimen: As single agent: Initially, 60 mg/m2 (Max initial dose: 120 mg/m2) once weekly for 3 weeks. If the 1st 3 administrations are tolerated, subsequent doses are increased to 80 mg/m2 once weekly up to Max 160 mg/m2 once weekly. Dose modification may be required according to individual neutrophil and/or platelet counts, safety and tolerability. In combination regimens: Dosage and schedule recommendations may vary depending on local treatment protocols. Refer to detailed product or country-specific guidelines.

Oral
Non-small cell lung cancer
Adult: For the 1st-line treatment of stage 3 or 4 cases: As single agent: Initially, 60 mg/m2 (Max initial dose: 120 mg/m2) once weekly for 3 weeks. If the 1st 3 administrations are tolerated, subsequent doses are increased to 80 mg/m2 once weekly up to Max 160 mg/m2 once weekly. Dose modification may be required according to individual neutrophil and/or platelet counts, safety and tolerability. In combination regimens: Dosage and schedule recommendations may vary depending on local treatment protocols. Refer to detailed product or country-specific guidelines.
Hepatic Impairment
Oral
Moderate (bilirubin 1.5-3 times the upper limit of normal [ULN] independent of AST/ALT concentration): Reduce dose to 50 mg/m2 weekly. Severe: Contraindicated.

Intravenous
Severe (bilirubin >2 times the ULN and/or transaminase >5 times the ULN): Reduce dose to 20 mg/m2. Alternatively, in serum total bilirubin 2.1-3 mg/dL: Give 50% of starting dose; serum total bilirubin >3 mg/dL: Administer 25% of starting dose.
Reconstitution
IV: Slow bolus inj: Dilute in 20-50 mL 0.9% NaCl or 5% dextrose solutions for inj. Inj or infusion over 6-10 minutes: Dilute in a 50 mL infusion bag of 0.9% NaCl or 5% dextrose solution for inj; alternatively, dilute in an IV bag with 5% dextrose inj, 0.9% NaCl inj, 0.45% NaCl inj, 5% dextrose + 0.45% NaCl inj, Ringer's inj or lactated Ringer's inj to a final concentration of 0.5-2 mg/mL. Infusion over 20-30 minutes: Dilute in 125 mL 0.9% NaCl solution. Dilution preparation and stability recommendations may vary according to individual products or between countries (refer to detailed product guidelines).
Incompatibility
IV: May precipitate when diluted in alkaline solutions.
Contraindications
Current or recent (within 2 weeks) severe infection or neutrophil count <1,500 cells/mm3, platelet count <100,000 cells/mm3. Oral: Disease significantly affecting absorption, previous significant stomach or small bowel surgical resection; patients who require long-term oxygen therapy. Severe hepatic impairment (oral). Pregnancy and lactation. Co-administration with yellow fever vaccine.
Special Precautions
Patient with history of ischaemic heart disease, poor performance status, compromised bone marrow reserve. Premedication with antiemetics is recommended (oral). Consider initiation of prophylactic bowel regimen (e.g. adequate dietary intake, hydration, stool softener use); may give laxatives in patients with history of constipation or those receiving opioid analgesics. Do not give with radiotherapy if the treatment field includes the liver. Not recommended to be used concurrently with other live attenuated vaccines, phenytoin, and itraconazole. Avoid extravasation or eye contamination. Hepatic impairment.
Adverse Reactions
Significant: Drug-induced hepatic injury (e.g. elevated AST and bilirubin levels); sensory and motor neuropathies; pulmonary toxicity (e.g. severe acute bronchospasm); nausea and vomiting (oral); severe irritation, local tissue necrosis or thrombophlebitis (if extravasation occurs).
Eye disorders: Visual impairment.
Gastrointestinal disorders: Diarrhoea, stomatitis, abdominal pain, gastric disorders, oesophagitis, dysphagia, taste disorders.
General disorders and administration site conditions: Fatigue, malaise, fever, chills, pain (including pain at tumour site); inj site reactions (e.g. burning pain, erythema, vein discolouration).
Hepatobiliary disorders: Hepatic disorders.
Infections and infestations: Bacterial, viral, or fungal infections; neutropenic infection.
Investigations: Weight loss or gain.
Metabolism and nutrition disorders: Anorexia.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, jaw pain.
Nervous system disorders: Headache, dizziness, neuromotor disorders, loss of tendon reflexes; weakness of lower extremities (prolonged therapy).
Psychiatric disorders: Insomnia.
Renal and urinary disorders: Dysuria, other genitourinary symptoms.
Respiratory, thoracic and mediastinal disorders: Dyspnoea, cough.
Skin and subcutaneous tissue disorders: Alopecia (mild).
Vascular disorders: Arterial hypertension or hypotension.
Potentially Fatal: Severe myelosuppression (e.g. neutropenia, febrile neutropenia, anaemia, leucopenia, thrombocytopenia) leading to serious infection or septic shock; severe gastrointestinal toxicity (e.g. paralytic ileus, constipation, intestinal obstruction, perforation or necrosis); interstitial pneumonitis, acute respiratory distress syndrome (ARDS).
IV/Parenteral/PO: D
Monitoring Parameters
Obtain CBC with differential and platelet count before each dose and after treatment; LFTs and pulmonary status prior to and periodically during therapy. Evaluate pregnancy status before treatment initiation in females of reproductive potential. Assess for new-onset or worsening pulmonary or neuropathy symptoms; signs and symptoms of constipation, ileus, and infection.
Overdosage
Symptoms: Bone marrow hypoplasia which may be associated with fever, infection, paralytic ileus, and hepatic disorders. Management: Supportive treatment. Administer broad spectrum antibiotics, growth factors or blood transfusion as necessary. Closely monitor hepatic function.
Drug Interactions
May increase the risk of neurotoxicity with itraconazole. Phenytoin may enhance the hepatic metabolism of vinorelbine. May decrease the absorption of phenytoin which may lead to convulsions. May increase the incidence of granulocytopenia with cisplatin. May exacerbate myelosuppressive effects with other agents with known bone marrow toxicity. May increase the risk of dyspnoea and bronchospasm with mitomycin C. May cause excessive immunodepression and risk of lymphoproliferation with immunosuppressants (e.g. tacrolimus, ciclosporin). Strong CYP3A4 inducers (e.g. rifampicin) may reduce blood concentrations of vinorelbine. May elevate blood concentrations with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir). May increase incidence of grade 3 or 4 neutropenia with lapatinib.
Potentially Fatal: Increased risk of generalised vaccine disease when given with yellow fever vaccine, or other live attenuated vaccines.
Action
Description: Vinorelbine is a semisynthetic vinca alkaloid antineoplastic agent. It binds to tubulin and blocks microtubule assembly, thereby disrupting mitotic spindle formation and arresting the cells at metaphase stage, specifically for the M phase. It also interferes with nucleic acid and protein synthesis by inhibiting the utilisation of glutamic acid.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Bioavailability: 40% (oral). Time to peak plasma concentration: 1.5-3 hours (oral).
Distribution: Extensively distributed, particularly in pulmonary tissues. Plasma protein binding: 13.5%. Strongly binds to blood cells particularly in platelets (78%) and lymphocytes (4.8%).
Metabolism: Metabolised in liver most likely by carboxylesterases to 4-O-deacetylvinorelbine (active metabolite), and by CYP3A4 isoenzyme into inactive metabolites.
Excretion: Mainly via faeces (approx 46%); urine (approx 18%, 10-12% as unchanged drug). Terminal elimination half-life: Triphasic: Approx 28-44 hours.
Chemical Structure

Chemical Structure Image
Vinorelbine

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5311497, Vinorelbine. https://pubchem.ncbi.nlm.nih.gov/compound/Vinorelbine. Accessed Oct. 26, 2021.

Storage
Store between 2-8°C. Do not freeze. Protect from light. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
MIMS Class
Cytotoxic Chemotherapy
ATC Classification
L01CA04 - vinorelbine ; Belongs to the class of plant alkaloids and other natural products, vinca alkaloids and analogues. Used in the treatment of cancer.
References
Anon. Vinorelbine Tartrate. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 30/09/2021.

Anon. Vinorelbine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 30/09/2021.

Buckingham R (ed). Vinorelbine Tartrate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/09/2021.

Joint Formulary Committee. Vinorelbine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/09/2021.

Navelbine 10 mg/mL and 50 mg/mL Solution for Injection in Vial (Orient Europharma [M] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 30/09/2021.

Navelbine 10 mg/mL Concentrate for Solution for Infusion (Pierre Fabre Limited). MHRA. https://products.mhra.gov.uk. Accessed 30/09/2021.

Navelbine 20 and 30mg Soft Capsule (Orient Europharma [M] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 30/09/2021.

New Zealand Medical & Scientific Ltd. Navelbine 10 mg/mL Solution for Injection data sheet 21 August 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 30/09/2021.

New Zealand Medical & Scientific Ltd. Navelbine 20 mg, 30 mg Soft Capsules data sheet 21 August 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 30/09/2021.

Vinorelbine 80 mg Soft Capsules (Consilient Health Limited). MHRA. https://products.mhra.gov.uk. Accessed 30/09/2021.

Vinorelbine Injection, Solution (Sagent Pharmaceuticals). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 30/09/2021.

Disclaimer: This information is independently developed by MIMS based on Vinorelbine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2022 MIMS. All rights reserved. Powered by MIMS.com
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