Consumer medicine information

Velabine

Vinorelbine

BRAND INFORMATION

Brand name

Velabine

Active ingredient

Vinorelbine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Velabine.

SUMMARY CMI

VELABINE

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I taking VELABINE capsules?

VELABINE contains the active ingredient vinorelbine tartrate. VELABINE is used to treat lung cancer and advanced breast cancer. For more information, see Section 1. Why am I taking VELABINE capsules? in the full CMI.

2. What should I know before I take VELABINE capsules?

Do not use if you have ever had an allergic reaction to VELABINE capsules or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I take VELABINE capsules? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with VELABINE capsules and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take VELABINE capsules?

Swallow your VELABINE capsules whole with a full glass of water, without chewing or sucking the capsule.

More instructions can be found in Section 4. How do I take VELABINE capsules? in the full CMI.

5. What should I know while taking VELABINE capsules?

Things you should do
  • Keep all appointments with your doctor to check on your progress and monitor side effects.
  • If you become pregnant while taking VELABINE capsules, tell your doctor immediately.
Things you should not do
  • You should not breast-feed while you are being treated with VELABINE capsules.
  • Men being treated with VELABINE capsules are advised not to father a child during and up to a minimum of 3 months after treatment.
  • Do not use if you have or have had an infection or high temperature in the last 2 weeks
  • Do not use if you are currently receiving radiation therapy.
  • Do not use if you have recently had a yellow fever vaccination or plan to have one.
  • Do not use if you have severe liver problems, if you have a reduced number of platelets of red blood, cells, if you have stomach or intestinal disorders or if you have any condition requiring long-term oxygen therapy.
Driving or using machines
  • Be careful driving or operating machinery until you know how VELABINE capsules affect you.
Drinking alcohol
  • Fatigue and dizziness are common side effects of VELABINE capsules. Drinking alcohol may make these symptoms worse.
Looking after your medicine
  • Store VELABINE capsules in the refrigerator (2 to 8°C). Do not freeze it.

For more information, see Section 5. What should I know while taking VELABINE capsules? in the full CMI.

6. Are there any side effects?

Common side effects include nausea, vomiting, diarrhoea, loss of appetite, unusual tiredness, weakness, sleepiness, drowsiness or lack of energy, unusual hair loss, constipation, aching muscles, skin reactions, fever, jaw pain, painful swollen joints, weight loss, weight gain and high or low blood pressure. Serious side effects include difficulty breathing, chest pain, fast or irregular heartbeat, rash, itching or hives on the skin, swelling of the feet and ankles, face, lips, tongue or other parts of the body.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

VELABINE

Active ingredient: Vinorelbine tartrate

Consumer Medicine Information (CMI)

This leaflet provides important information about taking VELABINE capsules. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about taking VELABINE capsules.

Where to find information in this leaflet:

1. Why am I taking VELABINE capsules?
2. What should I know before I take VELABINE capsules?
3. What if I am taking other medicines?
4. How do I take VELABINE capsules?
5. What should I know while taking VELABINE capsules?
6. Are there any side effects?
7. Product details

1. Why am I taking VELABINE capsules?

VELABINE capsules contain the active ingredient vinorelbine tartrate. Vinorelbine belongs to a family of medicines called vinca alkaloids.

VELABINE capsules belong to a group of medicines called antineoplastic or cytotoxic medicines. You may also hear of these medicines being called chemotherapy.

VELABINE capsules are used to treat lung cancer and advanced breast cancer. VELABINE capsules may be used on its own or in combination with other medicines to treat cancer. VELABINE capsules work by stopping cancer cells from growing and multiplying causing the cells to die.

VELABINE capsules are not recommended for use in children and adolescents aged less than 18 years as there is no information on its effects in these age groups.

2. What should I know before I take VELABINE capsules?

Warnings

Do not take VELABINE capsules if:

  • you are allergic to vinorelbine; or to the other vinca alkaloids, (vinblastine, vincristine, vindesine, vinflunine); or to any of the ingredients listed at the end of this leaflet.
    Symptoms of an allergic reaction to VELABINE capsules may include shortness of breath, wheezing, difficulty breathing or a tight feeling in your chest, swelling of the face, lips, tongue or other parts of the body, rash, itching, hives or flushed, red skin.
  • you are currently receiving radiation therapy to your liver.
  • you have or have had (within the last two weeks), a severe infection. Your doctor may decide to delay your treatment until the infection has gone.
  • you plan to have a yellow fever vaccine or have just had one.
  • you are currently receiving radiation therapy to your liver.
  • you have or have had any of the following medical conditions:
    - severe liver problems
    - a low white blood cell and/or platelet count which you may notice as signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers
    - surgery on your stomach or small bowel
    - stomach or intestinal disorders
    - any condition requiring long-term oxygen therapy
  • you are pregnant or plan to become pregnant
  • you are breastfeeding

Check with your doctor if you:

  • have or have had a severe infection in the last 2 weeks. Your doctor may decide to delay your treatment until theinfection has gone.
  • have allergies to
    - any other medicines
    - any other substances, such as foods, preservatives or dyes
  • if you have, or have had, any of the following medical conditions:
    - heart problems (including chest pain and heart attack)
    - liver problems
    - a low white blood cell and/or platelet count which you may notice as signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers
    - stomach problems (including surgery on your stomach)
    - lung problems, including asthma
    - the rare hereditary problem of fructose intolerance (due to the presence of sorbitol).
  • take any medicines for any other condition or treatments for cancer, including radiation therapy.
    VELABINE capsules must not be taken if you are currently receiving radiation therapy to your liver.
  • if you plan to have a vaccination. Having a live attenuated vaccine (eg: measles, mumps, rubella vaccine) is not recommended while taking VELABINE capsules as they may increase the risk of life-threatening vaccine disease.
  • if your ability to carry out activities of daily living is strongly reduced.

VELABINE capsules are a potent cytotoxic drug that results in a decrease in blood cells. Your blood count will be carefullymonitored before and during your treatment.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Do not take VELABINE capsules if you are pregnant or intend to become pregnant.

Like most medicines used to treat cancer, VELABINE capsules are not recommended for use in pregnancy. VELABINE capsules may affect your developing baby if you take it during pregnancy.

If you are a fertile man or woman, you should use an effective method of contraception during your treatment with VELABINE capsules and for three months after your last dose of VELABINE capsules.

Men being treated with VELABINE capsules are advised not to father a child during and up to a minimum of 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 VELABINE capsules.

If there is a need to consider VELABINE capsules during your pregnancy, your doctor will discuss with you the benefits and risks of using it.

Do not breastfeed while being treated with VELABINE capsules.

VELABINE capsules may pass into breast milk and therefore there is a possibility that the breast-fed baby may be affected.

Talk to your doctor if you are breastfeeding or intend to breastfeed. You must stop breast-feeding before starting treatment with VELABINE capsules.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with VELABINE capsules and affect how it works. These include:

  • mitomycin and lapatinib, medicines used to treat cancer;
  • warfarin, phenindione and other medicines used to prevent blood clots;
  • other medicines used to treat cancer such as cisplatin;
  • ketoconazole and itraconazole, medicines used to treat fungal infections;
  • ritonavir, a medicine used to treat HIV and AIDS;
  • rifampicin, a medicine used to treat tuberculosis or meningitis;
  • phenytoin, a medicine used to treat epilepsy or fits.
  • ciclosporin and tacrolimus, drugs which reduce the body's ability to fight illness/ disease (known as immunosuppressants).

These medicines may be affected by VELABINE capsules or may affect how well it works. You may need to take different amounts of your medicine, or you may need to take different medicines. Your doctor or pharmacist will advise you.

Your doctor and pharmacist may have more information on medicines to be careful with or to avoid while having VELABINE capsules.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect VELABINE capsules.

4. How do I take VELABINE capsules?

How much to take

  • Your doctor will decide what dose you will receive. This depends on your body surface area, your condition and factors such as your liver function and whether you are receiving any other chemotherapy medicines. Your doctor may adjust your dose during treatment. Your dose may be more than 1 capsule.
  • VELABINE capsules may be given alone or in combination with other drugs.
  • Several courses of VELABINE therapy may be required depending on your response to treatment.
  • VELABINE capsules reduce the number of white blood cells in the body. Your doctor will check these levels regularly. Further doses of VELABINE may be delayed until your blood cell numbers return to acceptable levels.

When to take VELABINE

  • VELABINE is given as a capsule. Swallow your VELABINE capsules whole with a full glass of water, without chewing or sucking the capsule. The liquid inside VELABINE capsules is an irritant and may cause damage if it comes in contact with your skin, mucosa or eyes.
  • Damaged capsules should not be swallowed.
  • If contact with the contents of the capsule does occur, wash the affected area thoroughly with water or a normal saline solution.
  • VELABINE capsules should be taken with food.
  • If vomiting occurs within a few hours of taking VELABINE capsules, the dose should not be repeated. Your doctor may prescribe a medication to help with vomiting if it is a problem.
  • To open the child resistant packaging:
  • Cut the blister along the black dotted line;
  • Peel off the soft plastic foil;
  • Push the capsule through the aluminium foil.

How long it is given

VELABINE capsules are usually given every week, but it may be given less often if you are also having other medicines to treat cancer. Your doctor will decide how many doses you will need.

If you forget to take VELABINE capsules

Tell your doctor as soon as possible if you realise that you have missed your dose of VELABINE capsules.

If you have problems remembering when your next dose is due, use a diary or calendar or ask a friend to remind you.

If you take too much VELABINE

If you think that you have used too much VELABINE, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while taking VELABINE capsules?

Things you should do

  • Keep all appointments with your doctor. Your doctor may want to do some blood and other tests from time to time to check on your progress and monitor any unwanted side effects.
  • If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are having treatment with VELABINE capsules.
  • If you become pregnant while taking VELABINE capsules, tell your doctor immediately. VELABINE capsules can lower the number of white blood cells and platelets in your blood. This means that you have an increased chance of getting an infection or bleeding.
  • Take the following precautions to reduce your risk of infection or bleeding:
    - Check with your doctor immediately if you think you may be getting an infection, or if you get a fever, chills, cough, hoarse throat, lower back or side pain or find it painful or difficult to urinate.
    - Avoid people who have infections.
    - Be careful when using a toothbrush, toothpick or dental floss. Your doctor, dentist, nurse or pharmacist may recommend other ways to clean your teeth and gums. Check with your doctor before having any dental work.
    - Be careful not to cut yourself when you are using sharp objects such as a razor or nail cutters.
    - Avoid contact sports or other situations where you may bruise or get injured.

Call your doctor straight away if you:

  • are feeling unwell after taking VELABINE capsules.

Remind any doctor, dentist or pharmacist you visit that you are having treatment with VELABINE capsules.

Things you should not do

  • You should not breast-feed while you are being treated with VELABINE capsules. Breastfeeding must be discontinued before starting treatment with VELABINE capsules.
  • Men being treated with VELABINE capsules are advised not to father a child during and up to a minimum of 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 VELABINE capsules.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how VELABINE capsules affect you.

If you experience symptoms that affect your ability to concentrate and react, do not drive a car or operate machinery. Dizziness and fatigue are common side effects of VELABINE capsules. Make sure you know how VELABINE capsules affect you before you drive a car, operate machinery or do anything else that could be dangerous if you are feeling tired or dizzy.

Drinking alcohol

Tell your doctor if you drink alcohol.

Drinking alcohol may make the tiredness and dizziness worse.

Looking after your medicine

If you are storing VELABINE capsules at home, store VELABINE capsules in the refrigerator (2 to 8°C) in the original packaging. Do not freeze it.

Do not store VELABINE capsules or any other medicine in the bathroom or near a sink. Do not leave it on a windowsill or in the car.

Heat and dampness will destroy the medicine.

Follow the instructions in the carton on how to take care of your medicine properly

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If your doctor stops your treatment with VELABINE capsules, or it has passed its expiry date, return any leftover capsules to your pharmacist. Do not dispose of VELABINE capsules via wastewater or household waste. This will help to protect the environment.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Pain Related
  • aching muscles, muscle tenderness or weakness, not caused by exercise
  • pain, including pain at the tumour site
  • jaw pain
  • painful swollen joints
Problems with skin and hair
  • skin reactions
  • unusual hair loss or thinning
Head and neurology related
  • unusual tiredness, weakness, sleepiness, drowsiness or lack of energy
  • trouble sleeping
  • dizziness
  • headache
Gastrointestinal upset
  • Nausea
  • vomiting
  • diarrhoea
  • constipation
  • upset stomach
  • loss of appetite
  • indigestion
  • weight loss
  • weight gain
Respiratory related
  • coughing
  • change in or loss of taste
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Breathing problems
  • difficulty breathing, short of breath
Infection related
  • frequent infections or signs of infection such as fever, severe chills, sore throat, mouth ulcers (symptoms of a lack of white blood cells)
  • sore mouth
  • mouth ulcers and cold sores
  • viral, bacterial or fungal infections
  • blood infections (sepsis) symptoms such as high fever and deterioration in general health
Head and neurology related
  • tiredness, headaches, dizziness and looking pale (symptoms of a decreased number of red blood cells)
  • Lack of muscle control may be associated with abnormal gait, speech changes and abnormalities in eyes movement
Bleeding related
  • bleeding or bruising more easily than normal or nosebleeds (symptoms of a low blood platelet count)
Eye problems
  • changes in your vision
Gastrointestinal problems
  • stomach pain
Throat related
  • difficulty swallowing
Urinary related
  • pain or burning feeling when passing urine or other urinary problems.
Heart related
  • chest pain
  • palpitations, fast or irregular heart beat
  • high blood pressure
  • low blood pressure
Allergy related
  • rash, itching or hives on the skin
  • swelling of the feet and ankles, face, lips, tongue or other parts of the body
Liver related
  • liver disorders (abnormal liver test).
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What VELABINE capsules contain

Active ingredient
(main ingredient)		vinorelbine tartrate
Other ingredients
(inactive ingredients)

ethanol
medium-chain triglycerides
purified water
polysorbate 80
macrogol 400

The capsule shell contains:
gelatin
sorbitol
titanium dioxide,
iron oxide yellow (20 mg and 80 mg capsules only)
iron oxide red (30 mg capsules only)

Do not take this medicine if you are allergic to any of these ingredients.

What VELABINE capsules look like

20 mg soft capsule: oval-shaped light brown soft capsule (AUST R 381471)

30 mg soft capsule: oblong-shaped pink soft capsule (AUST R 381470)

80 mg soft capsule: oblong-shaped pale yellow soft capsule (AUST R 381472)

Who distributes VELABINE capsules

Luminarie Pty Ltd
Level 5 Nexus Building
4 Columbia Court Baulkham Hills NSW 2153
www.luminarie.com.au

This leaflet was prepared in September 2022.

Published by MIMS June 2023

BRAND INFORMATION

Brand name

Velabine

Active ingredient

Vinorelbine

Schedule

S4

 

1 Name of Medicine

Vinorelbine.

2 Qualitative and Quantitative Composition

Capsules contain 20 mg, 30 mg and 80 mg vinorelbine (as tartrate).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Soft capsule.

20 mg soft capsule.

Oval-shaped light brown soft capsule.

30 mg soft capsule.

Oblong-shaped pink soft capsule.

80 mg soft capsule.

Oblong-shaped pale yellow soft capsule.

4 Clinical Particulars

4.1 Therapeutic Indications

Non-small cell lung cancer.

Velabine is indicated for the first line treatment of advanced non-small cell lung cancer, as a single agent or in combination.

Breast cancer.

Velabine is indicated for the treatment of advanced breast cancer after failure of standard therapy as a single agent or in combination.

4.2 Dose and Method of Administration

Adults.

Single agent. The recommended regimen is:

First three administrations.

60 mg/m2, administered once weekly.

Subsequent administrations.

Beyond the third administration, increasing the dose of vinorelbine soft capsules to 80 mg/m2 once weekly is recommended, except in those patients for whom the neutrophil count has dropped once below 500/mm3 or more than once between 500 and 1000/mm3 during the first 3 administrations at 60 mg/m2.
Dose modifications according to haematological status. If the neutrophil count is below 1500/mm3 and/or the platelet count is below 100,000/mm3, then treatment should be delayed until recovery. See Table 1.
For any administration planned at the 80 mg/m2/week dose, if the neutrophil count falls below 500/mm3 or more than once between 500 and 1000/mm3, the dose must be delayed until recovery and reduced from 80 to 60 mg/m2 per week during the 3 subsequent administrations. See Table 2.
It is possible to re-escalate the dose from 60 to 80 mg/m2/week if the neutrophil count does not drop below 500/mm3, or more than once between 500 and 1000/mm3 during the three administrations given at the 60 mg/m2 dose.
Dose modification for hepatic impairment. Vinorelbine is contraindicated in patients with severe hepatic impairment. In patients with moderate hepatic impairment (serum bilirubin between 1.5 and 3 x ULN, independent of ALT and AST concentrations), vinorelbine capsules monotherapy should be administered at a dose of 50 mg/m2/week. In patients with mild hepatic impairment (serum bilirubin < 1.5 x ULN and ALT and/or AST between 1.5 and 2.5 x ULN), vinorelbine capsules may be administered at the standard dose of 60 mg/m2/week. Haematological toxicity should be closely monitored. Hepatic impairment has not been studied in combination chemotherapy.
Combination chemotherapy.

General.

The use of oral vinorelbine in combination regimens has not been extensively studied. However, based on pharmacokinetic studies, the oral dose of 80 mg/m2 was demonstrated to correspond to 30 mg/m2 of the IV* form and 60 mg/m2 orally to 25 mg/m2 IV.
In combination regimens, intravenous vinorelbine dosing may be replaced with oral vinorelbine therapy. The recommended dose is 60 mg/m2. The safety of higher doses of oral vinorelbine (e.g. 80 mg/m2) in combination regimens has not been established, except for use with capecitabine in advanced breast cancer (see below).
* Vinorelbine injection for intravenous administration is available in other brands.

Combination with capecitabine in advanced breast cancer.

In combination with capecitabine for the treatment of advanced breast cancer, the administration of vinorelbine capsules is recommended on days 1 and 8 for three week cycles at 60 mg/m2 for the first cycle, then increased to 80 mg/m2 for subsequent cycles, except in patients for whom the neutrophil count has dropped below 500/mm3 or more than once between 500 and 1000/mm3 during the first administration at 60 mg/m2. Capecitabine should be administered at a dose of 1000 mg/m2, twice daily on Days 1-14 of the three week cycle.
Table 3 gives the dose required for appropriate ranges of body surface area (BSA).
Even for patients with a body surface area (BSA) ≥ 2 m2, the dose should never exceed 120 mg per week at 60 mg/m2 and 160 mg per week at 80 mg/m2.
Procedures for proper handling and disposal of anticancer drugs should be used. Several guidelines on this subject have been published.

Method of administration.

Velabine soft capsules must be given strictly by the oral route. They should be swallowed whole with water and should not be chewed or sucked. It is recommended that the capsule be taken with food.

4.3 Contraindications

Known hypersensitivity to vinorelbine or to other vinca alkaloids or to any of the excipients listed in Section 6.1 List of Excipients.
Disease significantly affecting absorption.
Previous significant surgical resection of stomach or small bowel.
Neutrophil counts < 1500 cells/mm3, or current or recent severe infection due to neutropenia (within 2 weeks).
Platelet count < 100,000 cells/mm3.
Pregnancy.
Lactation (see Section 4.6 Fertility, Pregnancy and Lactation).
Patients requiring long-term oxygen therapy.
Severe hepatic insufficiency.
In combination with yellow fever vaccine (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Administration.

Vinorelbine soft capsules should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents with facilities for monitoring cytotoxic drugs.
If the patient chews or sucks the capsule by mistake, rinse mouth with water or preferably a normal saline solution. In the event of the capsule being cut or damaged, the liquid content is an irritant, and so may cause damage if in contact with skin, mucosa or eyes. Damaged capsules should not be swallowed and should be returned to the pharmacy or to the physician in order to be properly destroyed. If any contact occurs, immediate thorough washing with water or preferably with normal saline solution should be undertaken.
If vomiting occurs within a few hours of drug intake, administration of the dose should not be repeated. Prophylactic treatment such as 5HT3 antagonists (e.g. ondansetron, granisetron) may reduce the incidence. Vinorelbine capsules are associated with a higher incidence of nausea/vomiting than the IV formulation. A primary prophylaxis with antiemetics is recommended. It is recommended that the capsule be taken with food.
Constipation is a very common gastrointestinal disorder. The prescription of laxatives may be appropriate for patients with a prior history of constipation and/or are receiving concomitant treatment with opiates.

Myelosuppression.

Neutropenia is dose-limiting. Complete blood counts with differentials should be performed and results reviewed prior to administering each dose of vinorelbine capsules. Patients treated with vinorelbine capsules should be frequently monitored for myelosuppression both during and after therapy. Vinorelbine capsules should not be administered to patients with neutrophil counts < 1500 cells/mm3 and/or platelet counts below 100,000 cells/mm3. Patients developing severe neutropenia should be monitored carefully for evidence of infection and/or fever. If patients present signs or symptoms suggestive of infection, a prompt investigation should be carried out (see Section 4.2 Dose and Method of Administration, Dose modifications according to haematological status).
Vinorelbine capsules should be used with extreme caution in patients whose bone marrow reserve may have been compromised by prior irradiation or chemotherapy, or whose marrow function is recovering from the effects of previous chemotherapy (see Section 4.2 Dose and Method of Administration).
During clinical trials, where treatment was initiated at a weekly dose of 80 mg/m2 (corresponding to an IV dose of 30 mg/m2 in terms of systemic exposure), febrile neutropenia, in some cases fatal, was encountered in about 15% of patients. Therefore, it is recommended that the starting dose should be 60 mg/m2 and increased to 80 mg/m2 only if the dose is tolerated (see Section 4.2 Dose and Method of Administration).

General.

Most drug-related adverse events of vinorelbine capsules are reversible. If severe adverse events occur, vinorelbine capsules should be reduced in dosage or discontinued and appropriate corrective measures taken. Reinstitution of therapy with vinorelbine capsules should be carried out with caution and alertness as to possible recurrence of toxicity.
Special care should be taken when prescribing for patients: with a history of ischaemic heart disease; with poor performance status.
Patients presenting with ischaemic cardiac disease should be carefully monitored (see Section 4.8 Adverse Effects (Undesirable Effects)).
This product is specifically contraindicated with yellow fever vaccine. Its concomitant use with other live attenuated vaccines is not recommended.
Acute shortness of breath and severe bronchospasm have been reported infrequently along with rare cases of interstitial pneumopathy following the administration of vinorelbine and other vinca alkaloids, most commonly when the vinca alkaloid was used in combination with mitomycin. These adverse events may require treatment with supplemental oxygen, bronchodilators and/or corticosteroids, particularly when there is a pre-existing pulmonary dysfunction.
Due to the presence of sorbitol, patients with the rare hereditary problem of fructose intolerance should not take this medicine.
Vinorelbine capsules contain small amounts of ethanol (alcohol), less than 100 mg per dose. The small amount of alcohol in this medicine will not have any noticeable effects.
Vinorelbine capsules should not be given concomitantly with radiotherapy if the treatment field includes the liver.

Use in hepatic impairment.

Vinorelbine is contraindicated in patients with severe hepatic impairment. In patients with moderate hepatic impairment (serum bilirubin between 1.5 and 3 x ULN, independent of ALT and AST concentrations), dose reduction is recommended (see Section 4.2 Dose and Method of Administration). In patients with mild hepatic impairment (serum bilirubin < 1.5 x ULN and ALT and/or AST between 1.5 and 2.5 x ULN), no dose reduction is required. Haematological toxicity should be closely monitored.

Use in renal impairment.

Because of the low level of renal excretion, no dose modification is necessary in patients with renal impairment.

Use in the elderly.

Clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Paediatric use.

Safety and effectiveness have not been established. Use in children and adolescents aged < 18 years is therefore not recommended.

Effects on laboratory tests.

Since dose-limiting clinical toxicity is the result of depression of the white blood cell count, it is imperative that complete blood counts with differentials be obtained and reviewed on the day of treatment prior to each dose of vinorelbine capsules. If the neutrophil count is below 1500/mm3 and/or the platelet count is below 100,000/mm3, then treatment should be delayed until recovery.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interactions common to all cytotoxics.

Due to the increase of thrombotic risk in the case of tumoral diseases, the use of anticoagulative treatment is frequent. As the intra-individual variability of the coagulability during diseases is high and there is the risk of interaction between oral anticoagulants and anticancer therapy, if the patient is treated with oral anticoagulants, increasing the frequency of INR (International Normalised Ratio) monitoring is recommended.
Concomitant use contraindicated.

Yellow fever vaccine.

Risk of fatal generalised vaccine disease.
Concomitant use not recommended.

Live attenuated vaccines.

Risk of generalised vaccine disease, possibly fatal. This risk is increased in patients already immunodepressed by their underlying disease. The use of an inactivated vaccine where one exists is recommended (e.g. poliomyelitis).

Phenytoin.

Risk of exacerbation of convulsions resulting from the decrease in phenytoin absorption by the cytotoxic drug or loss of efficacy of the cytotoxic drug due to increased hepatic metabolism by phenytoin.
Concomitant use with caution.

Ciclosporin, tacrolimus.

Excessive immunodepression with risk of lymphoproliferation.

Interactions specific to vinca alkaloids.

Concomitant use not recommended.

Itraconazole.

Increased neurotoxicity of vinca alkaloids due to the decrease in their hepatic metabolism.
Concomitant use with caution.

Mitomycin.

Acute pulmonary reactions have been reported with vinorelbine and other vinca alkaloids used in conjunction with mitomycin: risk of bronchospasm and dyspnoea are increased; in a rare case, an interstitial pneumonitis was observed. Vinorelbine capsules should be administered with caution in combination with mitomycin.
As vinca alkaloids are known as substrates for P-glycoprotein, and in the absence of a specific study, caution should be exercised when combining vinorelbine with strong modulators of this membrane transporter.

Interactions specific to vinorelbine.

The combination of vinorelbine capsules and other drugs with known bone marrow toxicity is likely to exacerbate the myelosuppressive adverse effects.
In the absence of specific studies evaluating drug-drug interaction with warfarin, the patient should be cautiously monitored when vinorelbine is given in combination with warfarin.
Although the pharmacokinetics of vinorelbine are not influenced by the concurrent administration of cisplatin, the incidence of toxicities, specifically granulocytopenia, with the combination of vinorelbine capsules and cisplatin is significantly higher than with single-agent vinorelbine capsules.
In studies with rats, the anticoagulant effect of phenindione was potentiated when given in combination with a high dose of vinorelbine (30 mg/m2/day for 4 consecutive days or 15 mg/m2/day for 5 consecutive days) but combination treatment with sodium valproate did not cause any increase in anticonvulsant activity.
Vinorelbine is metabolised by cytochrome CYP3A4. Although interaction studies have not been performed, it is expected that inhibitors of CYP3A4 such as ketoconazole, itraconazole, ritonavir etc. would result in elevated blood concentrations of vinorelbine. Inducers of CYP3A4 such as rifampicin and phenytoin may reduce concentrations of vinorelbine. Since the magnitude of the inducing or inhibiting effects is unknown, such drug combinations should be avoided.
An increased incidence of grade 3/4 neutropenia has been suggested when intravenous vinorelbine and lapatinib were associated in one clinical phase I study. In this study, the recommended dose of the 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 1000 mg. This type of combination should be administered with caution.

Food.

Simultaneous intake of a low fat standard meal does not modify exposure to vinorelbine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Adverse effects on the male reproductive system were observed in repeat-dose toxicity studies in animals, including decreased spermatogenesis in rats dosed twice weekly at 2.1 - 7.2 mg/m2 for 13 weeks, reduced prostate/seminal vesicle secretion in rats dosed twice weekly at 3 mg/m2 for 26 weeks, reduced testicular weight in mice dosed at 19 mg/m2/day for three 5-day cycles and reduced epididymal weight in dogs dosed at 5 mg/m2 for 26 weeks. Vinorelbine tartrate did not affect fertility when administered to male and female rats prior to and during mating; however, the doses used in these studies (9 mg/m2 once weekly or up to 4.2 mg/m2 at 3-day intervals) were lower than the human dose.
Men being treated with vinorelbine capsules are advised not to father a child during and up to a minimum of 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 oral vinorelbine.
(Category D)
Vinorelbine capsules may cause foetal harm if administered to a pregnant woman. When given every three days during organogenesis, vinorelbine tartrate has been shown to be teratogenic in rats and rabbits at doses of 3 and 7.7 mg/m2 respectively. A single 9 mg/m2 dose of vinorelbine tartrate caused embryonic deaths in mice. Doses causing adverse foetal effects in animals were lower than the human dose. There are no studies in pregnant women. If vinorelbine capsules are used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the foetus. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with vinorelbine capsules. Effective contraception must be used during treatment and up to 3 months after the treatment.
 It is not known whether vinorelbine is excreted in milk of animals or humans. A study in rats showed that growth of the offspring was suppressed when vinorelbine tartrate was administered to lactating dams at 6 mg/m2 every three days. Because many drugs are excreted in human milk and because of the potential serious adverse reactions in nursing infants from vinorelbine capsules, breast-feeding must be discontinued in women before starting treatment with vinorelbine capsules.

4.7 Effects on Ability to Drive and Use Machines

The effect of vinorelbine on the ability to drive and use machines has not been studied. However, patients should be advised not to drive or operate machinery if they experience any adverse reactions with a potential impact on their ability to perform these activities (e.g. dizziness and fatigue are common).

4.8 Adverse Effects (Undesirable Effects)

The overall reported incidence of adverse 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 80 mg/m2/week).
Adverse reactions reported are listed below by MedDRA body system organ class and the frequency convention.
Frequency of adverse reactions is defined as: very common (≥ 1/10); common (≥ 1/100 and < 1/10); uncommon (≥ 1/1000 and < 1/100); rare (≥ 1/10,000 and < 1/1000) and very rare (< 1/10,000). Additional adverse reactions pooled from post-marketing experience and clinical trials have been added according to the MedDRA classification with the frequency 'Not known'.
The reactions were described using the Common Terminology Criteria for Adverse Events (CTCAE) classification which provides a terminology for adverse events (Aes) and a grading scale the severity of AEs (grade 1=G1; grade 2=G2; grade 3=G3; grade 4=G4; grade 1-4=G1-4; grade 1-2=G1-2; grade 34=G3-4).

Adverse effects reported with oral vinorelbine.

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. Gastrointestinal adverse events occur more commonly with oral vinorelbine than with intravenous administration. Fatigue and fever were also very commonly reported.
Post-marketing experience. Vinorelbine capsules are used as a single agent or in combination with other chemotherapeutic agents or targeted therapy agents such as cisplatin or capecitabine. The most common system organ classes involved from post-marketing experience are: 'blood and lymphatic system disorders', 'gastrointestinal disorders', 'infections and infestations' and 'general disorders and administration site conditions'. This information is consistent with pre-marketing experience. See Table 4.

Adverse effects with vinorelbine IV.

In addition, some adverse effects have been observed with vinorelbine IV from pre- and postmarketing experience which were not reported with vinorelbine oral. It cannot be ruled out that these effects may also be experienced with the use of vinorelbine oral as with other vinca alkaloids. See Table 5.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

There is no known antidote for overdoses of oral vinorelbine. No case of overdosage has been reported with oral vinorelbine, however the primary anticipated complications of overdosage would consist of bone marrow suppression and peripheral neurotoxicity. If overdosage occurs, general supportive measures together with appropriate blood transfusions, growth factors, and antibiotics should be instituted as deemed necessary by the physician. A close monitoring of hepatic function is recommended.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Vinorelbine injection for intravenous administration is unavailable in this brand, however this dosage form is available in other brands. Clinical trial and pharmacokinetic information obtained using a vinorelbine intravenous formulation are also included in the following sections for prescriber information.

Mechanism of action.

Vinorelbine is an antineoplastic drug. It is a semi-synthetic member of the vinca alkaloid family that interferes with microtubule assembly. The vinca alkaloids are structurally similar compounds comprised of two multiringed units, vindoline and catharanthine. Unlike other vinca alkaloids, the catharanthine unit is the site of structural modification for vinorelbine. The antitumor activity of vinorelbine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. In intact tectal plates from mouse embryos, vinorelbine, vincristine and vinblastine inhibited mitotic microtubule formation at the same concentration (2 micromolar), including a blockade of cells at metaphase. Vincristine produced depolymerisation of axonal tubules at 5 micromolar, but vinblastine and vinorelbine did not have this effect until concentrations of 30 micromolar and 40 micromolar respectively. These data suggest relative selectivity of vinorelbine for mitotic microtubules.

Clinical trials.

Vinorelbine IV.

Non-small cell lung cancer.

The activity of vinorelbine was investigated in a series of phase II trials. The overall response rate to vinorelbine single agent in NSCLC patients ranged from 8% to 33% in previously untreated patients. In the two major phase II trials with more than 60 evaluable patients, the overall response rate was over 30% in chemotherapy-naive patients. The high activity of vinorelbine as single agent in nonsmall cell lung cancer which was observed in non-controlled phase II studies has also been confirmed in three randomised phase III trials. In one prospective randomised study with 216 stage IV patients, vinorelbine was compared to 5-fluorouracil with leucovorin (considered equivalent to best supportive care for the purposes of the study).
The median survival time of patients who received vinorelbine was 30 weeks compared to 22 weeks for those on the 5-fluorouracil/leucovorin arm (log-rank p=0.03). The response rates were 12% for the vinorelbine arm and 3% for the fluorouracil/leucovorin arm.
The activity of vinorelbine in combination with cisplatin has been investigated in two randomised phase III trials in a total of 782 patients. In a two arm trial, vinorelbine was compared to vinorelbine with cisplatin. The overall response rate to vinorelbine as single agent was 16% while that of the combination vinorelbine/cisplatin was 43%. The median survival time for patients receiving vinorelbine as single agent was similar to that observed with vinorelbine and cisplatin.
In a large European clinical trial, 612 patients with Stage III or IV non-small cell lung cancer, no prior chemotherapy and WHO performance status of 0, 1 or 2 were randomised to treatment with single agent vinorelbine (30 mg/m2/week), vinorelbine (30 mg/m2/week), cisplatin (120 mg/m2 days 1 and 29 then every 6 weeks), and vindesine (3 mg/m2/week for 7 weeks, then every second week) plus cisplatin (120 mg/m2 days 1 and 29 then every 6 weeks). Vinorelbine plus cisplatin produced longer survival times than vindesine plus cisplatin (median survival 40 weeks vs 32 weeks, p=0.03). The median survival time for patients receiving single-agent vinorelbine was similar to that observed with vindesine plus cisplatin (31 weeks vs 32 weeks). The 1-year survival rates were 36% for vinorelbine plus cisplatin, 27% for vindesine plus cisplatin and 30% for single-agent vinorelbine. The overall objective response rate (all partial responses) was significantly higher in patients treated with vinorelbine plus cisplatin (28%) than in those treated with vindesine plus cisplatin (19%, p=0.03) and in those treated with single-agent vinorelbine (14%, p < 0.001). The response rates reported for vindesine plus cisplatin and single-agent vinorelbine were not significantly different. Significantly, less nausea, vomiting, alopecia and neurotoxicity were observed in patients receiving single-agent vinorelbine compared to those receiving the combination of vindesine and cisplatin.

Advanced breast cancer - second line.

Twenty phase II studies of IV vinorelbine monotherapy have been performed as second line or subsequent treatment of advanced breast cancer patients. The response rate and duration of response to chemotherapy declines as patients progress through first, second and third line chemotherapy. Thirteen of these phase II studies were in mixed anthracycline-pretreated and anthracycline-naive populations, entering 494 patients and reporting overall response rates of 14 - 45% (patients weighted average = 29.2%) and median survival times of 58 - 69 weeks.
The remaining seven phase II studies were in anthracycline-pretreated patients, entering a total of 339 patients, reporting response rates of 16 - 64% (patient weighted average = 30.9%) and median survival was 24 - 82 weeks.
In a randomised phase III study conducted to investigate efficacy in anthracycline-refractory advanced breast cancer, 115 patients received IV vinorelbine as a single agent versus sixty four patients who received intravenous melphalan. The median dose, number of doses and duration of treatment for vinorelbine were 27.5 mg/m2, 9 doses and 12 weeks respectively and for melphalan, 25 mg/m2, 2 doses and 8 weeks respectively. Of those receiving vinorelbine, thirteen of 84 (15.5%) patients with measurable disease achieved an objective response compared with four of 46 (8.7%) receiving melphalan. Overall survival was 35 weeks for patients receiving vinorelbine compared with 31 weeks for those receiving melphalan (log-rank p=0.023). Neither treatment had an adverse effect on quality of life.
IV vinorelbine has also been studied in combination with other agents in the second-line treatment of advanced breast cancer. Results from trials are summarised in Table 6.
Vinorelbine oral. Oral vinorelbine has been developed as a line extension of the IV dosage form. Hence, the primary objective of the clinical program was to demonstrate bioequivalence between the oral and intravenous formulations on the basis of pharmacokinetic studies. An oral dose of 80 mg/m2 was demonstrated to correspond to 30 mg/m2 of the IV formulation and 60 mg/m2 orally to 25 mg/m2 given by the IV route. Subsequent phase II studies were conducted to examine the efficacy and tolerance of oral vinorelbine.

Non-small cell lung cancer.

One randomised phase II study (97 CA 205) with the recommended oral dose regimen was conducted, comparing oral and IV vinorelbine in patients with advanced or metastatic NSCLC who had not previously been treated with cytotoxic chemotherapy. The results are summarised in Table 7.
In a multicentre, phase II study of 56 patients in combination with cisplatin 100 mg/m2 (day 1 q 4 weeks), the weekly administration of vinorelbine (IV vinorelbine 25 mg/m2 day 1, oral vinorelbine 60 mg/m2 days 8, 15 and 22) produced a response rate of 30% for all registered patients and 33% for evaluable patients in the first line treatment of unresectable, localised or metastatic NSCLC. Median progression-free survival and survival were 5.5 and 8.9 months, respectively.

Advanced breast cancer. As a single agent.

Two non-comparative multi-centre phase II studies (96 CA 201 and 97 CA 206) of oral vinorelbine given weekly at a dose of 60 mg/m2 for the first 3 weeks and then increased to 80 mg/m2 as a single agent, were conducted in the first line treatment of advanced breast cancer. A total of 184 patients were enrolled.
The majority of patients had metastatic disease at study entry, visceral lesions and had received prior hormonotherapy. The proportion of patients having received prior neo/adjuvant chemotherapy was 49.2% (96 CA 201) and 26.5% (97 CA 206). No patient had received prior chemotherapy for advanced/metastatic disease.
The efficacy results are summarised in Table 8.
A response rate of 30% was reported in Study 97 CA 206 and 21% in Study 96 CA 201. The lower response rate observed in the latter study could be explained by the very poor prognosis features in the patients having received no prior adjuvant chemotherapy: 57% of patients had stage IIIB - IV disease, 67% had a disease-free interval less than 2 years and 62% had at least 3 organs involved. In this subset of patients, the response rate was only 14%.
Median durations of progression-free survival and overall survival were consistent in the 2 studies: 4.6 and 4.2 months; and 19.3 and 23.9 months respectively.
A randomised phase II trial (CA221) assessed in parallel the efficacy and safety of oral vinorelbine at 60 mg/m2 on days 1 and 8 every 3 weeks for the first cycle then increased to 80 mg/m2 on days 1 and 8 every 3 weeks for subsequent cycles; and IV vinorelbine at 25 mg/m2 on days 1 and 8 every 3 weeks for the first cycle then increased to 30 mg/m2 on days 1 and 8 every 3 weeks for subsequent cycles. The study was closed 2.5 years after its initiation due to low accrual (85 patients enrolled out of 230 planned). Premature closure of the study did not allow for the accurate assessment of the efficacy of oral vinorelbine. The following results were observed: response rate of 7% and disease control rate of 47.4% in the oral arm; response rate of 22% and disease control rate of 51.9% in the IV arm. Median overall survival was similar in the 2 study arms: 9.4 months and 10.2 months respectively.

In combination.

A randomised phase II study (CA 222) of the combination of oral vinorelbine with capecitabine versus a sequential regimen of oral vinorelbine and capecitabine versus the combination of docetaxel and capecitabine was carried out in 139 metastatic breast cancer patients previously treated with anthracyclines.
In combination with capecitabine, oral vinorelbine was given on days 1 and 8 of three-week cycles at 60 mg/m2 for the first cycle and then at 80 mg/m2. In the sequential regimen, patients received oral vinorelbine 60 then 80 mg/m2/week for a total of 3 three-week cycles and then 3 cycles of capecitabine. In the control arm, the standard regimen of docetaxel 75 mg/m2 on day 1 and capecitabine every 3 weeks was used. In the 3 study arms, the dose of capecitabine was 2000 mg/m2/day administered from days 1 to 14 every 3 weeks.
Efficacy results in the 3 study arms are summarised in Table 9.
The two combination arms, oral vinorelbine plus capecitabine and docetaxel plus capecitabine, produced similar disease control rates (70.5% vs 70.8% in the ITT population), similar response rates (31.8% vs 35.4%), similar progression-free survival (7.2 months vs 8.9 months) and similar time-to-treatment failure (5.6 months vs 4.3 months). In comparison, the sequential regimen of oral vinorelbine followed by capecitabine was inferior to the combination regimens for all the efficacy parameters considered.
Oral vinorelbine in combination with other cytotoxics was assessed in three phase I/II studies: with epirubicin (Study CA 205); docetaxel (CA 101); and paclitaxel (CA 102).
The efficacy results of these studies are summarised in Table 10.
The two regimens alternating oral and IV vinorelbine in combination with epirubicin or docetaxel gave similar response rates of approximately 50%. Median durations of overall survival tended to be longer for the taxane combinations than for the combination with epirubicin.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration, vinorelbine is promptly absorbed and the Tmax is reached within 1.5 to 3 hours with a blood concentration peak (Cmax) of approximately 130 nanogram/mL after dosing at 80 mg/m2. The absolute bioavailability is about 40% and simultaneous intake of a low fat standard meal does not modify the area under the concentration-time curve (AUC). The effect of a high fat meal on absorption has not been studied.
Vinorelbine oral 60 and 80 mg/m2 leads to a comparable AUC to that obtained from 25 and 30 mg/m2 of the IV formulation respectively. Interindividual variability of the AUC is similar after administration by both the IV and oral routes. There is a proportional increase between the AUC and dose.

Distribution.

The mean pharmacokinetic parameters were evaluated in blood. After intravenous administration, the terminal half-life averaged 38 hours. Blood clearance was high, approached liver blood flow and averaged 0.72 L/hr/kg (range: 0.32 - 1.26 L/hr/kg), while steady state volume of distribution was large, averaged 21.2 L/kg (range: 7.5 - 39.7 L/kg), and indicated extensive tissue distribution.
Vinorelbine binds extensively to blood cells and especially platelets (70 - 80%), but less extensively (about 15%) to plasma proteins. There is a significant uptake of vinorelbine in lungs, as assessed by pulmonary surgical biopsies showing up to a 300 fold greater concentration than in serum. Vinorelbine has not been detected in the central nervous system.

Metabolism.

Vinorelbine is mostly metabolised by the CYP 3A4 isoform of the cytochrome P450. All the metabolites have been identified and none are active except 4-O-deacetylvinorelbine which is the main metabolite in blood. No sulfo- or glucurono- conjugates are observed.

Excretion.

Renal elimination is low (< 20% of the dose) and consists mostly of the parent compound. Biliary excretion is the predominant elimination route of both metabolites and unchanged vinorelbine, which is the main recovered compound.

Renal impairment.

The effect of renal dysfunction on vinorelbine disposition has not been assessed, however, dose reduction, in the presence of renal insufficiency is not indicated with vinorelbine due to its low renal elimination.

Hepatic impairment.

Vinorelbine is cleared from the circulation primarily by the liver, and therefore elevated blood concentrations may be expected in patients with hepatic impairment. In a phase I pharmacokinetic study, 6 subjects with severe hepatic impairment were treated with 20 mg/m2 intravenously. Blood concentrations were elevated compared to historical data from patients with normal hepatic function. Oral vinorelbine is contraindicated in patients with severe hepatic impairment. In studies in patients with mild and moderate hepatic impairment, the pharmacokinetics of orally administered vinorelbine were not modified after administration of: 60 mg/m2 in patients with mild hepatic impairment (bilirubin < 1.5 x ULN and ALT and/or AST between 1.5 and 2.5 x ULN) and 50 mg/m2 in patients with moderate hepatic impairment (bilirubin between 1.5 and 3 x ULN, independent of ALT and AST levels). Haematological toxicity should be closely monitored.

Pharmacokinetics/pharmacodynamic relationships.

A strong relationship was demonstrated between AUC and leucocyte or PMN decreases.

5.3 Preclinical Safety Data

Genotoxicity.

Vinorelbine tartrate has been shown to affect chromosome number and possibly structure in vivo (polyploidy in bone marrow cells from Chinese hamsters and a positive micronucleus test in mice).
It was not mutagenic or cytotoxic in a reverse histidine mutation (Ames) test but showed mutagenic potential in a mouse forward mutation (TK locus) test.

Carcinogenicity.

Carcinogenicity studies in mice and rats showed no tumorigenic activity at dose levels up to 2.4 mg/m2 given by IV injection every two weeks for 18 months or two years respectively. However, the positive findings in genetic toxicity assays suggest that the drug may have carcinogenic potential at the higher dose level used in humans.

6 Pharmaceutical Particulars

6.1 List of Excipients

Velabine soft capsules also contain the following excipients: ethanol, medium chain triglycerides, purified water, polysorbate 80 and macrogol 400. The soft capsule shell contains: gelatin, sorbitol, titanium dioxide, iron oxide yellow (20 mg and 80 mg capsules only), and iron oxide red (30 mg capsules only).

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2 to 8°C (Refrigerate. Do not freeze) in the original container.

6.5 Nature and Contents of Container

PVC/PVDC/Al blister packs.
Pack size: 1 capsule.
The blister packs are child-resistant and comply with European Standard EN 14375:2003 Child-resistant Non-reclosable Packaging for Pharmaceutical Products - Requirements and Testing.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Vinorelbine tartrate is a semi-synthetic vinca alkaloid with antitumor activity. The chemical name is 3',4'-didehydro-4'-deoxy-C'-norvincaleukoblastine [R-(R*,R*) - 2,3 dihydroxybutanedioate (1:2) (salt)]. Vinorelbine tartrate is a white to yellow or light brown amorphous powder with the molecular formula C45H54N4O8.2C4H6O6 and a molecular weight of 1079.12. The aqueous solubility is > 1000 mg/mL in distilled water.

Chemical structure.


CAS number.

125317-39-7.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes