Javlor 25 mg/ml concentrate for solution for infusion

Javlor contains the active substance vinflunine, which belongs to a group of anticancer medicines called vinca alkaloids. These medicines affect cancer cell growth by stopping cell division, leading to cell death (cytotoxicity).

Javlor is used to treat advanced or metastatic cancer of the bladder and urinary tract when a previous therapy with platinum-containing medicines has failed.

Do not use Javlor

• if you are allergic (hypersensitive) to the active substance (vinflunine) or to other vinca alkaloids (vinblastine, vincristine, vindesine, vinorelbine),
• if you have had (within 2 weeks) or currently have a severe infection,
• if you are breast-feeding,
• if your levels of white blood cells and/or platelets are too low

Take special care with Javlor

Tell your doctor:

• if you have liver, kidney or heart problems,
• if you are taking other medicines mentioned in ?Using other medicines? below,
• if you have constipation, or if you are treated with drugs against pain (opioids), or if you have an abdominal cancer, or if you had abdominal surgery,
• if you would like to father a child (see ?Pregnancy and breast-feeding? below).

Your blood cell counts will be checked regularly before and during your treatment, since low counts of blood cells is a very common side effect with Javlor.
Javlor is not intended for use in children.

Using other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription and herbal preparations.

In particular, you should tell your doctor if you are taking medicines containing any of the following active substances:

• ketoconazole and itraconazole, used to treat fungal infection,
• ritonavir, used to treat HIV infection,
• pegylated liposomal doxorubicin, used to treat some kinds of cancer,
• rifampicin, used to treat tuberculosis or meningitidis,
• herbal preparation containing hypericum perforatum (St John?s wort) used to treat minor to moderate depression. You should tell your doctor if you are drinking grapefruit juice.

You may be given laxatives to prevent constipation, which is a very common side effect of Javlor. You should also drink water.

Pregnancy and breast-feeding

Tell your doctor if you are pregnant or think you may be pregnant.
You should not be given Javlor if you are pregnant, unless it is absolutely necessary.

If you are a woman or a man of reproductive potential, you should use an adequate method of contraception during treatment and for 3 months after your last dose of Javlor. If you would like to father a child, seek advice from your doctor. You may want to seek counseling on sperm storage before starting your therapy.

You must not breastfeed during treatment with Javlor

Driving and using machines

Javlor has not been studied for its possible effects on the ability to drive and use machines. If you experience common side effects, such as dizziness or syncope, that affect your ability to concentrate and react, do not drive or use machines.

Dose

The usual dose in adult patients is 320 mg/m² body surface (this is calculated by the doctor based on your weight and your height). The treatment will be repeated every 3 weeks.

Your doctor will adjust the dose of Javlor based on your age and physical conditions and in specific situations::

• if you had a previous irradiation of the pelvis.
• if you experience certain side effects
• if you have moderate or severe kidney or liver problems.

How Javlor is given

Javlor will be given to you by a qualified healthcare professional as an intravenous infusion (drip into your vein) lasting 20 minutes. Javlor is a concentrate that has to be diluted before administration.

Like all medicines, Javlor can cause side effects, although not everybody gets them.

These side effects may occur with certain frequencies, which are defined as follows: very common: affects more than 1 user in 10
common: affects 1 to 10 users in 100
uncommon: affects 1 to 10 users in 1,000
rare: affects 1 to 10 users in 10,000
very rare: affects less than 1 user in 10,000
not known: frequency cannot be estimated from the available data.

Very common side effects

• abdominal pain, nausea, vomiting
• constipation, diarrhoea
• inflammation of the mucosa of the mouth
• fatigue, muscle pain
• weight decrease, loss of appetite
• loss of hair
• pain at the site of injection
• decrease in the number of white blood cells (neutropenia) or red blood cells (anaemia) or platelets
• fever.

Common side effects

• fever with infection, chills, excessive sweating
• allergy, dehydration, headache, cutaneous reaction, itching
• digestive problems, paralytic intestine, pain in the mouth, on the tongue and toothache, modification of the taste
• muscular weakness, pain in jaw, pain in extremity, back pain, pain in joints, muscular pain, bone pain
• dizziness, insomnia, neurologic disorders, loss of consciousness
• difficulties with body movements or sens of touch,
• accelerated heartbeat, raised blood pressure, reduced blood pressure, vein thrombosis
• breathing difficulties, cough, swelling (oedema), chest pain.

Uncommon side effects

• increase of liver enzymes
• generalized infection
• visual disturbances, dry eye
• vertigo, muscle contraction disorders
• heart attack (myocardial infection, myocardial ischaemia)
• acute respiratory distress, pain in the throat, gum disorders
• renal failure
• weight increase.

Cases of electrocardiography alterations have been observed after the administration of Javlor.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor. Your doctor may reduce the dose of Javlor or interrupt the treatment.

Keep out of the reach and sight of children.

Do not use Javlor after the expiry date which is stated on the vial label and the carton after EXP.

It is most unlikely that you will be asked to store this medicine yourself.
Storage conditions are detailed in the section intended for medicinal or heathcare professionals.

Unopened vials:

Store in a refrigerator (2°C-8°C).
Store in the original package in order to protect from light.
Diluted solution
The diluted solution should be use immediately

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Javlor contains

• The active substance is vinflunine. Each ml of concentrate contains 25 mg of vinflunine (as ditartrate).One 2 ml vial contains 50 mg of vinflunine (as ditartrate). One 4 ml vial contains 100 mg of vinflunine (as ditartrate). One 10 ml vial contains 250 mg of vinflunine (as ditartrate).
• The other ingredient is water for injections.

What Javor looks like and contents of the pack

Javlor is a clear, colourless to pale yellow solution. It comes in clear glass vials closed by a rubber stopper containing 2 ml, 4 ml or 10 ml concentrate. Each pack contains 1 or 10 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Pierre Fabre Médicament
45 place Abel Gance
F-92100 Boulogne
France

Manufacturer

Pierre Fabre Médicament Production
Etablissement Aquitaine Pharm International
Avenue du Béarn
F-64320 Idron
France

This leaflet was last approved in {MM/YYYY}.

For any information about this medicine, please contact the Marketing Authorisation Holder.

<------------------------------------------------------------------------------------------------------------------------> The following information is intended for medical or healthcare professionals only: INSTRUCTION FOR USE

General precautions for preparation and administration.
Vinflunine is a cytotoxic anticancer medicinal product and, as with other potentially toxic compounds, caution should be exercised in handling Javlor. Procedure for proper handling and disposal of anticancer medicinal products should be considered. All transfer procedures require strict adherence to aseptic techniques, preferably employing a vertical laminar flow safety hood. The use of gloves, goggles and protective clothing is recommended.

If the solution comes into contact with the skin, the skin should be washed immediately and thoroughly with soap and water. If it comes into contact with mucous membranes, the membranes should be flushed thoroughly with water . Javlor solution for infusion should only be prepared and administered by personnel appropriately trained in the handling of cytotoxic agents. Pregnant staff should not handle Javlor. Javlor is for single use only.

Dilution of the concentrate
The volume of Javlor (concentrate) corresponding to the calculated dose of vinflunine should be mixed in a 100 ml bag of sodium chloride 9 mg/ml (0.9%) solution for infusion. Glucose 50 mg/ml (5%) solution for infusion may also be used. The diluted solution should be protected from light until administration.

Method of Administration
Javlor is for intravenous use ONLY.
After dilution of the Javlor concentrate, the Javlor solution for infusion will be administered as follows:

• A venous access should be established for a 500 ml bag of sodium chloride 9 mg/ml (0.9%) solution for injection or glucose 50 mg/ml (5%) solution for infusion.
• upper part of the forearm or central venous arm
• the veins of the hand dorsum and those close to joints should be avoided
• The intravenous infusion should be started with half of the 500 ml bag of sodium chloride 9 mg/ml (0.9%) solution for infusion or of glucose 50 mg/ml (5%) solution for infusion, i.e. 250 ml, at a free flowing rate to flush the vein.
• The Javlor solution for infusion should be piggy-backed to the side injection port closest to the 500 ml bag to further dilute Javlor during administration.
• The Javlor solution for infusion should be infused over 20 minutes.
• The patency should be assessed frequently and extravasation precautions should be maintained throughout the infusion.
• After Javlor infusion is completed, the remaining 250 ml from the sodium chloride 9 mg/ml (0.9%) solution for infusion or of glucose 50 mg/ml (5%) solution for infusion bag should be run at a flowing rate of 300 ml/h. In order to flush the vein, administration of Javlor solution for infusion should always be followed by at least an equal volume of sodium chloride 9 mg/ml (0.9%) solution for infusion or of glucose 50 mg/ml (5%) solution for infusion.

Disposal
Any unused product or waste material should be disposed of in accordance with local requirements for cytotoxic medicinal products.

Storage conditionsUnopened vials
Store in a refrigerator (2°C-8°C).
Store in the original packaging in order to protect from light
Diluted solution:
Chemical and physical in-use stability has been demonstrated for the diluted medicinal product as follows:

• protected from light in polyethylene or polyvinylchloride infusion bag: for up to 6 days in arefrigerator (2°C-8°C) or for up to 24 hours at 25°C;
• exposed to light in polyethylene or polyvinylchloride infusion set: for up to 1 hour at 25°C.From a microbiological point of view, the product should be used immediately after dilution. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.