Vinorelbine

Registered South African indications:

• Advanced inoperable non-small cell lung cancer
• Metastatic breast cancer
  - After failed first-line monotherapy with anthracyclines or who relapsed within 6 months of anthracycline-based adjuvant therapy

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other vinca-alkaloids
• Pregnancy (cap)
• Breastfeeding
• Severe hepatic impairment (cap)
• Intra-thecal administration (inj)
• Disease significantly affecting absorption (cap)
• Previous significant surgical resection of stomach or small bowel (cap)
• Neutrophil count <1500/mm³
• Severe infection current or recent (within 2 weeks)
• Platelet count <100 000/mm³ 
• Long term oxygen therapy (cap)
• Women of childbearing potential not using effective contraception (inj)
• Coadministration of yellow fever vaccine

Cautions

• Pregnancy (inj)
• Men of childbearing potential
• Mild to moderate hepatic impairment
• Severe hepatic impairment (inj)
• Elderly
• Chewing or sucking capsule (cap)
• History of constipation (cap)
• History of ischemic heart disease
• Avoid contact with skin, mucosa or eyes
• Poor performance status (cap)
• Patients of Japanese descent
• Previous history of bronchospasm, especially in combination therapy with mitomycin C
• Fructose intolerance (cap)
• May affect ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj, cap

Used for the treatment of

• Advanced non-small cell lung cancer (additional agent may be required)
• Breast cancer
  - As a single agent to patients with stage 4 metastatic breast cancer, where treatment with anthracycline- and taxane containing chemotherapy has failed or is not appropriate (inj)
  - Treatment of advanced breast cancer stage 3 and 4 relapsing or refractory to an anthracycline containing regimen (cap)

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Consult specialist for dosages and regimens

Not established for use in children

Pregnancy

• Contraindicated (cap)
  Caution; positive evidence of risk (inj)
• There is 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 foetal abnormalities
• In case of a vital indication for treatment with vinorelbine during pregnancy, a medical consultation concerning the risk of harmful effects for the child should be conducted. If pregnancy occurs during treatment, genetic counselling should be offered
• Women of childbearing potential must use effective contraception during treatment and up to 3 months after treatment

Breastfeeding

• Contraindicated 
• 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 breastfeeding child can not be excluded, therefore breastfeeding must be discontinued before starting treatment with vinorelbine

Fertility

• Men being treated with vinorelbine are advised not to father a child during and up to six months (minimum 3 months) following cessation of 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

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Caution; dose adjustment recommended (inj)
  Severe: Contraindicated (cap)

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Neurologic disorders
• Loss of deep tendon reflexes
• Weakness of the lower extremities
• Severe paraesthesia with sensory and motor symptoms (inj)
• Fatigue
• Headache (cap)
• Dizziness (cap)
• Ataxia (cap)
• Insomnia (cap)

Cardiovascular Disorders

• Ischaemic heart diseases
• Angina pectoris
• Transitory electrocardiogram changes
• Myocardial infarction (sometimes fatal)
• Tachycardia
• Palpitation
• Heart rhythm disorders
• Hypotension
• Hypertension
• Flushing (inj)
• Peripheral coldness (inj)
• Collapse
• Heart failure (cap)

Respiratory Disorders

• Dyspnoea
• Bronchospasm (inj)
• Interstitial lung disease (sometimes fatal) (inj)
• Cough (cap)

Gastrointestinal Disorders

• Constipation
• Paralytic ileus
• Nausea and vomiting
• Stomatitis
• Oesophagitis
• Diarrhoea
• Pancreatitis (inj)
• Gastrointestinal bleeding (cap)

Hepatobiliary Disorders

• Transient elevations of hepatic function tests

Genitourinary Disorders

• Increased creatinine
• Dysuria (cap)

Endocrine and Metabolic Disorders

• Inappropriate antidiuretic hormone secretion (SIADH)
• Severe hyponatraemia
• Anorexia
• Weight gain

Musculoskeletal Disorders

• Myalgia
• Arthralgia
• Jaw pain

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Generalised cutaneous reactions
  - Rash
  - Pruritis
  - Urticaria
• Palmar-plantar erythrodysesthesia syndrome (inj)
• Injection site reactions
  - Erythema
  - Burning pain
  - Vein discolouration
  - Local phlebitis
• Injection site necrosis (inj)

Immune, Blood and Lymphatic System Disorders

• Infection bacterial, viral or fungal at different localisation (respiratory, urinary, gastrointestinal tract)
• Severe sepsis with other visceral failure
• Septicaemia (including complicated septicaemia, sometimes fatal)
• Neutropenic sepsis (potential fatal outcome)
• Bone marrow depression
• Neutropenia
• Anaemia
• Thrombocytopenia  
• Febrile neutropenia
• Pancytopenia
• Systemic allergic reactions (inj)
  - Anaphylaxis
  - Anaphylactic shock
  - Anaphylactoid type reaction
• Fever
• Leucopenia (cap)

Sensory Disorders

• Taste disorders (cap)
• Visual impairment (cap)

Other

• Pain, including chest pain and tumour site pain

• Radiotherapy (if the treatment field includes the liver)
• Live-attenuated vaccines
• Yellow fever vaccine
• CYP3A4 inducers
• Phenobarbital
• Rifampicin
• Carbamazepine
• CYP3A4 inhibitors
• Ketoconazole
• HIV protease inhibitors
• Erythromycin
• Clarithromycin
• Telithromycin
• Nefazodone
• Phenytoin
• Cisplatin 
• Mitomycin C
• Ciclosporin
• Tacrolimus
• Itraconazole
• P-glycoprotein modulators
• Agents with known bone marrow toxicity
• Anticoagulants
• St John's wort

• Full blood count
• Hepatic function

Specific cases may require

• International normalised ratio (INR)
• Pregnancy test

Injection 10mg/vial, Injection 50mg/5ml - EML (Tertriary)

Vinorelbine is a cytostatic drug of the Vinca alkaloid family. Vinorelbine inhibits tubulin polymerisation and binds preferentially to mitotic microtubules, only affecting axonal microtubules at high concentration. The induction of tubulin spiralization is less than that produced by vincristine. Vinorelbine blocks mitosis at G2-M, causing cell death in interphase or at the following mitosis.

Capsule 20mg

• Navelbine (Pierre Fabre) originator
• Navilin 20 (Eurolab)

Capsule 30mg

• Navelbine (Pierre Fabre) originator
• Navilin 30 (Eurolab)

Injection (per ml) 10mg

• Aspen vinorelbin (Pharmacare)
• Carcyt (Tema)
• Cipla vinorelbine (Cipla)
• Navelbine (Pierre Fabre)
• Sandoz vinorelbine (Sandoz)
• Teva Vinorelbine (Sandoz)
• Vinorel (Pharmaplan)
• Vinorelbin "Ebewe" (Key Oncologics)

Injection (per ml) 50mg

• Cipla vinorelbine (Cipla)
• Carcyt (Tema Medical)
• Sandoz vinorelbine (Sandoz)
• Vinorel (Pharmaplan)
• Vinorelbin "Ebewe" (Key Oncologics)

Injection (per 5ml) 50mg

• Aspen vinorelbin (Pharmacare)
• Carcyt (Tema Medical)
• Navelbine (Pierre Fabre)
• Teva Vinorelbine (Teva)
• Vinorelbine pierre fabre (Tema) - Discontinued (13/12/19)