Drugs List

Therapeutic Indications

Uses

As a single agent or in combination for:

- The first line treatment of stage 3 or 4 non-small cell lung cancer
- The treatment of advanced breast cancer stage 3 and 4 relapsing after or refractory to an anthracycline containing regimen.

Administration

For oral administration.

To be swallowed whole with water, preferably with food. Capsule should not be sucked, chewed or dissolved.

Contraindications

Neutrophil count below 1,500/cubic millimetre
Platelet count below 100,000/cubic millimetre
Severe current or recent infection (within previous 2 weeks)
Patients requiring long-term oxygen therapy
Current disease that may significantly affect absorption
Previous significant surgical resection of the stomach or small bowel
Severe hepatic impairment (bilirubin greater than 3 x ULN)
Hereditary fructose intolerance
Pregnancy (See Pregnancy)
Breastfeeding (See Lactation)
Children under 18 years of age

Precautions and Warnings

Treatment should be initiated under the supervision of a physician qualified in the use of chemotherapy.

Whilst the doses stated are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Close haematological checks are necessary during treatment (measurement of haemoglobin level, leucocyte, neutrophil and platelet counts before each administration). Treatment limiting toxicity is mainly neutropenia. This effect is non-cumulative, having its nadir between 7 and 14 days after the administration and is rapidly reversible within 5 to 7 days. If neutrophil count is less than 1,500/cubic millimetre and/ or platelet count is less than 100,000/cubic millimetre, delay treatment until recovery (see Dosage - Adult ). A higher incidence of granulocytopenia has been reported in patients receiving combination therapy with vinorelbine and cisplatin than in those receiving vinorelbine monotherapy.
If the patient presents signs or symptoms suggestive of infection, a prompt investigation should be carried out.

Use with caution in hepatic impairment. Moderate hepatic impairment (bilirubin from 1.5 to 3 x ULN) dose reduction is recommended (see Dosage - Hepatic Impairment). Vinorelbine capsules should not be administered concurrently with radiotherapy if the treatment field includes the liver.

Caution is advised when administering vinorelbine to patients with a history of, or current, ischaemic heart disease or a poor performance status.

If vomiting occurs within a few hours of administration, the dose should not be re-administered. Prophylaxis with antiemetics (e.g. metoclopramide or a 5-HT3 antagonist) and administration with food is recommended, and has been shown to reduce the incidence of nausea and vomiting. The incidence of nausea and vomiting is higher with the capsule than the intravenous formulation.

Patients receiving concomitant morphine or opioid analgesics: laxatives and careful monitoring of bowel mobility are recommended. Prescription of laxatives may be appropriate in patients with prior history of constipation.

To avoid the risk of bronchospasm - especially in combination therapy with mitomycin C appropriate prophylaxis may be considered. Outpatients should be informed that in case of dyspnoea a doctor has to be informed.

It is not recommended to use live vaccines during therapy as there is a risk of generalised vaccine disease which may be fatal.

Vinorelbine has genotoxic effects. All patients should ensure adequate contraception during treatment and for 3 months afterwards. Prior to treatment male patients should be advised to consider conserving sperm due to the chance of irreversible infertility as a consequence of treatment with vinorelbine

Vinorelbine capsules should be swallowed whole with water, and preferably with food. If the patient accidentally chews or sucks the capsule, the mouth should be washed out with water or preferably a normal saline solution.

The liquid content of vinorelbine capsules is an irritant and may cause damage if in contact with the skin, mucosa or eyes. If accidental contact does occur, the area should be washed thoroughly with normal saline solution or water.
Damaged capsules should not be taken and should be returned to the pharmacy or doctor for proper disposal.

Vinorelbine capsules contain sorbitol.

The side effects of vinorelbine may affect the patient's ability to drive or operate machinery.

Advise patient to avoid grapefruit products during therapy due to risk of increased plasma concentration of vinorelbine.

Advise patient not to use products containing St John's Wort during therapy due to risk of decreased plasma concentration and clinical effects of Vinorelbine.

Pregnancy and Lactation

Pregnancy

Vinorelbine is contraindicated in pregnancy.

Vinorelbine is suspected to cause serious birth effects when administered during pregnancy. According to Briggs (2008), due to the heavy molecular weight of vinorelbine, it is thought that placental transfer would be inhibited but not prevented.

There have been a small number of cases in which vinorelbine was used and from these, oligohydramnios (attributed to a concomitant cytotoxic) and transient neonatal anaemia have been reported, however the majority of the children had no abnormalities. It is recommended that should vinorelbine treatment occur during pregnancy, genetic counselling should be offered to the patient.

Animal (mice and rabbit) studies have shown embryo- and foetotoxicity with intrauterine growth retardation and delayed ossification.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Contraindicated in breastfeeding.

At the time of writing there are no data on the excretion of vinorelbine into breast milk. Due to the potential for serious adverse reactions in the nursing infant, it should not be given to nursing mothers. Schaefer (2007) advises that breastfeeding should not take place until 30 days after the treatment has stopped, due to the long and variable half life of vinorelbine.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Neutropenia
Fever
Infections
Anaemia
Thrombocytopenia
Nausea
Vomiting
Diarrhoea
Anorexia
Stomatitis
Oesophagitis
Loss of deep tendon reflexes
Motor disturbances
Constipation
Paralytic ileus
Alopecia
Fatigue
Arthralgia
Jaw pain
Myalgia
Tumour pain
Cardiac disorders
Angina pectoris
Myocardial infarction
Skin reactions
Abdominal pain
Dyspnoea
Bronchospasm
Interstitial pneumopathies
Myelosuppression
Leucopenia
Neutropenic sepsis
Febrile neutropenia
Hyponatraemia
Insomnia
Headache
Dizziness
Taste disturbances
Ataxia
Visual disturbances
Hypertension
Hypotension
Cough
Dysphagia
Gastrointestinal bleeding
Hepatic disorders
Dysuria
Pain
Chills
Weight changes
Septicaemia
Hypersensitivity reactions including anaphylaxis
Inappropriate secretion of antidiuretic hormone
Collapse
Flushing
Pancreatitis
Malaise
Granulocytopenia
Neuropathy
Neurological disorders
Sensory disturbances

Drugs List

Therapeutic Indications

Uses

As a single agent or in combination for:

- The first line treatment of stage 3 or 4 non-small cell lung cancer
- The treatment of advanced breast cancer stage 3 and 4 relapsing after or refractory to an anthracycline containing regimen.

Dosage

Treatment should be initiated under the supervision of a physician qualified in the use of chemotherapy.

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For oral administration.

To be swallowed whole with water, preferably with food. Capsule should not be sucked, chewed or dissolved.

Contraindications

Neutrophil count below 1,500/cubic millimetre
Platelet count below 100,000/cubic millimetre
Severe current or recent infection (within previous 2 weeks)
Patients requiring long-term oxygen therapy
Current disease that may significantly affect absorption
Previous significant surgical resection of the stomach or small bowel
Severe hepatic impairment (bilirubin greater than 3 x ULN)
Hereditary fructose intolerance
Pregnancy (See Pregnancy)
Breastfeeding (See Lactation)
Children under 18 years of age

Precautions and Warnings

Treatment should be initiated under the supervision of a physician qualified in the use of chemotherapy.

Whilst the doses stated are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Close haematological checks are necessary during treatment (measurement of haemoglobin level, leucocyte, neutrophil and platelet counts before each administration). Treatment limiting toxicity is mainly neutropenia. This effect is non-cumulative, having its nadir between 7 and 14 days after the administration and is rapidly reversible within 5 to 7 days. If neutrophil count is less than 1,500/cubic millimetre and/ or platelet count is less than 100,000/cubic millimetre, delay treatment until recovery (see Dosage - Adult ). A higher incidence of granulocytopenia has been reported in patients receiving combination therapy with vinorelbine and cisplatin than in those receiving vinorelbine monotherapy.
If the patient presents signs or symptoms suggestive of infection, a prompt investigation should be carried out.

Use with caution in hepatic impairment. Moderate hepatic impairment (bilirubin from 1.5 to 3 x ULN) dose reduction is recommended (see Dosage - Hepatic Impairment). Vinorelbine capsules should not be administered concurrently with radiotherapy if the treatment field includes the liver.

Caution is advised when administering vinorelbine to patients with a history of, or current, ischaemic heart disease or a poor performance status.

If vomiting occurs within a few hours of administration, the dose should not be re-administered. Prophylaxis with antiemetics (e.g. metoclopramide or a 5-HT3 antagonist) and administration with food is recommended, and has been shown to reduce the incidence of nausea and vomiting. The incidence of nausea and vomiting is higher with the capsule than the intravenous formulation.

Patients receiving concomitant morphine or opioid analgesics: laxatives and careful monitoring of bowel mobility are recommended. Prescription of laxatives may be appropriate in patients with prior history of constipation.

To avoid the risk of bronchospasm - especially in combination therapy with mitomycin C appropriate prophylaxis may be considered. Outpatients should be informed that in case of dyspnoea a doctor has to be informed.

It is not recommended to use live vaccines during therapy as there is a risk of generalised vaccine disease which may be fatal.

Vinorelbine has genotoxic effects. All patients should ensure adequate contraception during treatment and for 3 months afterwards. Prior to treatment male patients should be advised to consider conserving sperm due to the chance of irreversible infertility as a consequence of treatment with vinorelbine

Vinorelbine capsules should be swallowed whole with water, and preferably with food. If the patient accidentally chews or sucks the capsule, the mouth should be washed out with water or preferably a normal saline solution.

The liquid content of vinorelbine capsules is an irritant and may cause damage if in contact with the skin, mucosa or eyes. If accidental contact does occur, the area should be washed thoroughly with normal saline solution or water.
Damaged capsules should not be taken and should be returned to the pharmacy or doctor for proper disposal.

Vinorelbine capsules contain sorbitol.

The side effects of vinorelbine may affect the patient's ability to drive or operate machinery.

Advise patient to avoid grapefruit products during therapy due to risk of increased plasma concentration of vinorelbine.

Advise patient not to use products containing St John's Wort during therapy due to risk of decreased plasma concentration and clinical effects of Vinorelbine.

Pregnancy and Lactation

Pregnancy

Vinorelbine is contraindicated in pregnancy.

Vinorelbine is suspected to cause serious birth effects when administered during pregnancy. According to Briggs (2008), due to the heavy molecular weight of vinorelbine, it is thought that placental transfer would be inhibited but not prevented.

There have been a small number of cases in which vinorelbine was used and from these, oligohydramnios (attributed to a concomitant cytotoxic) and transient neonatal anaemia have been reported, however the majority of the children had no abnormalities. It is recommended that should vinorelbine treatment occur during pregnancy, genetic counselling should be offered to the patient.

Animal (mice and rabbit) studies have shown embryo- and foetotoxicity with intrauterine growth retardation and delayed ossification.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Contraindicated in breastfeeding.

At the time of writing there are no data on the excretion of vinorelbine into breast milk. Due to the potential for serious adverse reactions in the nursing infant, it should not be given to nursing mothers. Schaefer (2007) advises that breastfeeding should not take place until 30 days after the treatment has stopped, due to the long and variable half life of vinorelbine.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

Effects on the ability to drive and operate machinery have not been established but vinorelbine may cause neuromotor and neurosensory disorders so caution should be exercised.

Counselling

Vinorelbine capsules should be swallowed whole with water, and preferably with food.

If vomiting occurs within a few hours of a dose, the dose should not be re-administered.

All patients should use effective contraception during and for 3 months following treatment.

Advise men regarding sperm storage and the risk of infertility.

Advise the patients that the side effects of vinorelbine may affect their ability to drive or operate machinery.

Patients should be advised to report any signs or symptoms of infection or dyspnoea to their doctor immediately.

Advise patient to avoid grapefruit products during therapy.

Advise patient not to use products containing St John's Wort during therapy.

Side Effects

Neutropenia
Fever
Infections
Anaemia
Thrombocytopenia
Nausea
Vomiting
Diarrhoea
Anorexia
Stomatitis
Oesophagitis
Loss of deep tendon reflexes
Motor disturbances
Constipation
Paralytic ileus
Alopecia
Fatigue
Arthralgia
Jaw pain
Myalgia
Tumour pain
Cardiac disorders
Angina pectoris
Myocardial infarction
Skin reactions
Abdominal pain
Dyspnoea
Bronchospasm
Interstitial pneumopathies
Myelosuppression
Leucopenia
Neutropenic sepsis
Febrile neutropenia
Hyponatraemia
Insomnia
Headache
Dizziness
Taste disturbances
Ataxia
Visual disturbances
Hypertension
Hypotension
Cough
Dysphagia
Gastrointestinal bleeding
Hepatic disorders
Dysuria
Pain
Chills
Weight changes
Septicaemia
Hypersensitivity reactions including anaphylaxis
Inappropriate secretion of antidiuretic hormone
Collapse
Flushing
Pancreatitis
Malaise
Granulocytopenia
Neuropathy
Neurological disorders
Sensory disturbances

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Pharmacological Properties

Reference Sources

British National Formulary, 62nd Edition (2011) Pharmaceutical Press, London.

Drugs in Pregnancy and Lactation: A Reference Guide for Fetal and Neonatal Risk, 8th Edition. ed. Briggs, Freeman & Yaffe; Lippincott Williams & Wilkins, Philadelphia 2008.

Drugs during Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd Edition, ed. Schaefer, Peters & Miller, Elsevier Academic Press, London 2007.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Navelbine 20mg soft capsules. Pierre Fabre Ltd. Revised September 2010
Summary of Product Characteristics: Navelbine 30mg soft capsules. Pierre Fabre Ltd. Revised September 2010
Summary of Product Characteristics: Navelbine 80mg soft capsules. Pierre Fabre Ltd. Revised September 2010