JAVLOR 25 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Javlor 25 mg/ml concentrate for solution for infusion

vinflunine

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Javlor and what is it used for
2. What you need to know before you use Javlor
3. How to use Javlor
4. Possible side effects
5. Storage of Javlor
6. Contents of the pack and other information

1. What is Javlor and what is it used for

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

Javlor is used to treat bladder and urinary tract cancer in advanced or metastatic stages, when previous treatment with medicines that included platinum derivatives has failed.

2. What you need to know before you use Javlor

Do not use JAVLOR

• if you are allergic to the active substance (vinflunine) or to other vinca alkaloids (vinblastine, vincristine, vindesine, vinorelbine),
• if you have had an infection (in the last 2 weeks) or are currently suffering from a severe infection,
• if you are breast-feeding,
• if your white blood cell and/or platelet counts are too low.

Warnings and precautions

Tell your doctor:

• if you have liver, kidney, or heart problems,
• if you have any neurological symptoms such as headache, changes in mental status that can lead to confusion and coma, seizures, blurred vision, and high blood pressure, which may be a sign of a neurological disorder such as "posterior reversible encephalopathy syndrome" (see section 2 "warnings and precautions"),
• if you are taking any of the medicines mentioned below in "Use with other medicines",
• if you have constipation, or if you are being treated with painkillers (opioids), or if you have had abdominal cancer, or have undergone abdominal surgery,
• if you plan to conceive a child (see "Pregnancy, breast-feeding, and fertility" below).

Your doctor will regularly check your blood cell counts before and during treatment, as a decrease in blood cell counts is a common side effect of treatment with Javlor.

Constipation is a very common side effect of Javlor. To prevent constipation, you may be given laxatives.

Use in children and adolescents

Javlor should not be used in children and adolescents.

Use of Javlor with other medicines

Tell your doctor if you are using, have recently used, or might use any other medicines.

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

• ketoconazole and itraconazole, used for fungal infections,
• opioids, used to treat pain.
• ritonavir, used to treat HIV infection,
• doxorubicin and pegylated liposomal doxorubicin, used to treat certain types of cancer,
• rifampicin, used to treat tuberculosis or meningitis,
• herbal preparations containing Hypericum perforatum(St. John's Wort) used to treat mild or moderate depression.

Javlor with food and drinks

Tell your doctor if you consume grapefruit juice, as it may increase the effect of Javlor. You should also drink water and eat high-fiber foods.

Pregnancy, breast-feeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or plan to become pregnant, consult your doctor before starting treatment.

If you are a woman or man of childbearing age, you should use an adequate contraceptive method during treatment and for 3 months after your last dose of Javlor.

You should not receive Javlor if you are pregnant, unless it is absolutely necessary. You should not breast-feed during treatment with Javlor.

If you want to have children, consult your doctor. You may want to ask for advice on sperm banks before starting treatment.

Driving and using machines

Javlor may cause side effects such as fatigue and dizziness.

Do not drive or use machines if you experience side effects that may affect your ability to concentrate and react.

3. How to use Javlor

Dose

The recommended dose in adult patients is 320 mg/m2 of body surface area (your doctor will calculate this based on your weight and height). Treatment will be repeated every 3 weeks.

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

• if you have previously undergone pelvic irradiation,
• if you have moderate or severe kidney problems,
• if you have liver problems.

During treatment, your doctor may reduce the dose of Javlor, delay it, or interrupt treatment if you experience certain side effects.

How Javlor is administered

Javlor will be administered to you by intravenous infusion (drip into a vein) over 20 minutes, by a healthcare professional with experience. Javlor should not be administered intrathecally (into the spine).

Javlor is a concentrate that must be diluted before administration.

4. Possible side effects

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

Tell your doctor immediatelyif you experience any of the following serious side effects while being treated with Javlor:

• fever and/or chills that may be signs of an infection,
• chest pain that may be a sign of a heart attack,
• constipation that does not respond to treatment with laxatives,
• headache, changes in mental status that can lead to confusion and coma, seizures, blurred vision, and high blood pressure, which may be a sign of a neurological disorder such as "posterior reversible encephalopathy syndrome" (see section 2 "warnings and precautions").

Other side effects may include:

Very common (may affect more than 1 in 10 people)

• abdominal pain, nausea, vomiting,
• constipation, diarrhea,
• inflammation of the mouth mucosa,
• fatigue, muscle pain,
• loss of sensitivity to touch,
• weight loss, decreased appetite,
• hair loss,
• reactions at the injection site (pain, redness, swelling),
• fever,
• low white blood cell, red blood cell, and/or platelet counts (seen in a blood test),
• low sodium levels in the blood (hyponatremia).

Common (may affect up to 1 in 10 people)

• chills, excessive sweating,
• allergy, dehydration, headache, skin rash, itching,
• digestive problems, mouth pain, tongue pain, tooth pain, taste disturbance,
• muscle weakness, jaw pain, pain in the arms and legs, back pain, joint pain, muscle pain, bone pain, ear pain,
• dizziness, insomnia, transient loss of consciousness,
• difficulty performing body movements,
• rapid heartbeat, increased blood pressure, decreased blood pressure,
• difficulty breathing, cough, chest pain,
• swelling of the arms, hands, feet, ankles, legs, or other parts of the body,
• inflammation of the veins (phlebitis).

Uncommon (may affect up to 1 in 100 people)

• vision changes,
• dry skin, skin redness,
• muscle contraction disorders,
• throat pain, gum disorders,
• weight gain,
• urinary problems,
• ringing or buzzing in the ears (tinnitus),
• increased liver enzymes (seen in a blood test),
• "Syndrome of Inadequate Secretion of Antidiuretic Hormone", which is a disease that causes low sodium levels in the blood,
• tumor pain.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Javlor

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label of the vial and on the carton after the abbreviation EXP.

It is unlikely that you will be asked to store this medicine.

Storage conditions are detailed in the section for healthcare professionals.

Closed vial

Store in a refrigerator (2°C to 8°C).

Store in the original packaging to protect from light.

Diluted solution

The diluted solution should be used immediately.

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

6. Contents of the pack and other information

Composition of Javlor

• The active substance is vinflunine. Each ml of concentrate contains 25 mg of vinflunine (as tartrate).

A 2 ml vial contains 50 mg of vinflunine (as tartrate).

A 4 ml vial contains 100 mg of vinflunine (as tartrate).

A 10 ml vial contains 250 mg of vinflunine (as tartrate).

• The other ingredient is water for injections.

Appearance and packaging

Javlor is a clear, colorless or slightly yellowish solution. It is presented in transparent glass vials containing 2 ml, 4 ml, or 10 ml of concentrate, closed with a rubber stopper. Each pack contains 1 or 10 vials.

Not all pack sizes may be marketed.

Marketing authorization holder

PIERRE FABRE MEDICAMENT

Les Cauquillous

81500 Lavaur

France

Manufacturer

FAREVA PAU

FAREVA PAU 1

Avenue du Béarn

F-64320 Idron

France

For any information about this medicinal product, please contact the Marketing Authorization Holder.

Date of last revision of this leaflet: MM/AAAA.

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

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This information is intended only for healthcare professionals:

INSTRUCTIONS FOR USE

General precautions for preparation and administration

Vinflunine is a cytotoxic antineoplastic medicinal product and, as with other potentially toxic compounds, Javlor should be handled with caution. The procedures for the correct handling and disposal of antineoplastic medicinal products should be followed. All transfer procedures require strict adherence to aseptic techniques, using a vertical laminar flow safety cabinet whenever possible. Javlor solution for infusion can only be prepared and administered by personnel with the appropriate training and experience in the handling of cytotoxic agents. Female hospital staff who are pregnant should not handle Javlor. The use of gloves, protective goggles, and protective clothing is recommended.

In case of skin contact, the affected area should be washed immediately with plenty of water and soap. In case of contact with mucous membranes, they should be rinsed thoroughly with plenty of water.

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%) infusion solution. Glucose 50 mg/ml (5%) infusion solution may also be used. The diluted solution should be protected from light until administration.

Method of administration

For intravenous use only.

Javlor is for single use.

After dissolution of the Javlor concentrate, the infusion solution will be administered as follows:

• A venous access will be established for a 500 ml bag of sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%) infusion solution, preferably in a large vein in the upper arm or using a central venous line.
• The intravenous infusion will be started with half a bag of 500 ml of sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%) infusion solution, i.e., 250 ml, at an appropriate flow rate to irrigate the vein.
• The Javlor infusion solution will be administered through a "Y" infusion device at the closest possible point to the 500 ml bag to further dilute the medicinal product during administration.
• The Javlor infusion solution will be administered over 20 minutes.
• The absence of obstruction will be checked frequently and extravasation precautions will be maintained throughout the infusion.
• Once the infusion is complete, the remaining 250 ml of the bag with sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%) infusion solution will be administered at a flow rate of 300 ml/h. To irrigate the vein, the administration of Javlor should always be followed by the administration of at least an equal volume of sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%) infusion solution.

Disposal

Disposal of the unused medicinal product and all materials that have come into contact with it will be carried out in accordance with local regulations on the disposal of cytotoxic medicinal products.

Storage conditions:

Closed vials:

Store in a refrigerator (2°C to 8°C).

Store in the original packaging to protect from light.

Diluted solution:

Chemical and physical stability in use has been demonstrated for the diluted solution:

• protected from light, in polyethylene or polyvinyl chloride infusion bags for up to 6 days in a refrigerator (2°C - 8°C) or up to 24 hours at 25°C.
• exposed to light, in polyethylene or polyvinyl chloride infusion equipment at 25°C for a period of up to 1 hour.

From a microbiological point of view, the product should be used immediately after dilution. If not used immediately, the storage times and conditions of the solution before administration are the responsibility of the user and should not normally exceed 24 hours at 2°C - 8°C, unless the dilution has been carried out under controlled and validated aseptic conditions.