JAVLOR 25 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Javlor 25 mg/ml concentrate for solution for infusion

vinflunina

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.

• If you experience 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 vinflunina, 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 (vinflunina) or to other vinca alkaloids (vinblastine, vincristine, vindesine, vinorelbine),

• if you have had an infection (in the last 2 weeks) or currently have a severe infection,

• if your white blood cell and/or platelet counts are too low,

• if you are breast-feeding.

Warnings and precautions

Tell your doctor:

• if you have liver, kidney, or heart problems,

• if you have any neurological symptoms that could be a sign of "posterior reversible encephalopathy syndrome": brain inflammation with generally temporary effects such as headache, changes in mental status leading to confusion and coma, seizures, changes in vision, high blood pressure, nausea, and vomiting, it may be necessary to stop using this medicine,

• If you have symptoms of hyponatremia (low sodium levels in the blood) or "inappropriate antidiuretic hormone secretion syndrome", such as headache, fatigue, seizures, or coma. Regular monitoring of serum sodium levels is recommended during treatment with Javlor.

• if you are taking any of the medicines mentioned below in "Other medicines and Javlor",

• if you have constipation, or if you are being treated with painkillers (opioids), or if you have had abdominal cancer, or if you have had previous abdominal surgery. Constipation is a very common side effect of Javlor. To prevent constipation, you may be given laxatives,

• if you plan to conceive a child (see important recommendations for men and women in "Pregnancy, breast-feeding, and fertility" below).

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

Intrathecal administration of Javlor can be fatal. Javlor should not be administered intrathecally (in the spine).

Children and adolescents

Javlor should not be used in children and adolescents.

Other medicines and Javlor

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, pegylated liposomal doxorubicin, paclitaxel, and docetaxel 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.

Or if you are taking medicines that are known to affect the electrocardiogram (ECG), especially medicines that are known to cause "QT interval prolongation".

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 are planning to have a baby, ask your doctor for advice before taking this medicine.

If you are a woman or a man of childbearing age, you should use an effective method of contraception during treatment and for 4 months after the last dose of Javlor if you are a man, or 7 months if you are a woman.

Pregnancy

You should not receive Javlor if you are pregnant, unless it is absolutely necessary.

If you become pregnant during treatment, you should be informed of the risk to the fetus and be closely monitored.

Breast-feeding

You should not breast-feed during treatment with Javlor.

Fertility

If you wish to have children, ask your doctor for advice. You may want to seek advice on sperm banking before starting treatment due to the possibility of irreversible infertility due to treatment with vinflunina.

Driving and using machines

Javlor may cause side effects such as fatigue, dizziness, visual disturbances, and fainting.

Do not drive or use machines without consulting your doctor.

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 according to your weight and height). The treatment will be repeated every 3 weeks.

No dose adjustment is necessary in patients under 75 years of age. Your doctor will adjust your dose if you are 75 years or older.

Your doctor will also adjust the initial dose of Javlor based on your 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 SHOULD ONLY BE administered intravenously.

Javlor will be administered by intravenous infusion (drip into a vein) over 20 minutes, by a healthcare professional (with experience in the use of cancer treatment in specialized health units).

Javlor is a concentrate that must be diluted before administration.

If you are given too much Javlor

This medicine will be administered to you by your doctor or nurse. If you are given too much (an overdose), your doctor will monitor you for side effects.

If you miss a dose of Javlor

It is very important that you do not miss any dose of this medicine. If you miss an appointment, call your doctor immediatelyto reschedule your appointment.

If you stop treatment with Javlor

Your doctor will decide when you should stop your treatment. If you want to stop treatment prematurely, you should consult your doctor about other available treatment options.

If you have any further questions on the use of this product, ask your doctor.

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 could be signs of an infection,

• chest pain that could be a sign of a heart attack,

• constipation that does not respond to treatment with laxatives,

• neurological symptoms that could be a sign of "posterior reversible encephalopathy syndrome": brain inflammation with generally temporary effects such as headache, changes in mental status leading to confusion and coma, seizures, changes in vision, high blood pressure, nausea, and vomiting (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 (stomatitis)
• fatigue (asthenia), muscle pain (myalgia)
• loss of sensation in touch due to nerve damage (peripheral sensory neuropathy)
• weight loss, decreased appetite
• hair loss (alopecia)
• reactions at the injection site (pain, redness, swelling)
• fever

• low levels of white blood cells, red blood cells, and/or platelets in the blood (seen in a blood test)

• low sodium levels in the blood (hyponatremia) seen in a blood test

Common (may affect up to 1 in 10 people)

• infections (neutropenic infection, febrile neutropenia, viral, bacterial, fungal infections) with symptoms such as high fever and deterioration of general health
• chills, excessive sweating (hyperhidrosis), pain
• allergy (hypersensitivity), dehydration, headache, skin rash, itching (pruritus), hives
• loss of bowel movement (ileus) digestive problems (dyspepsia), difficulty swallowing (dysphagia), oral disorders (mouth pain, tongue pain, toothache), taste disturbance
• muscle weakness, jaw pain, pain in arms and legs, back pain, joint pain, muscle pain, bone pain, ear pain
• dizziness, insomnia, transient loss of consciousness (fainting)
• difficulty moving due to nerve damage (neuropathy) and nerve pain (neuralgia)
• rapid heartbeat (tachycardia), increased blood pressure, decreased blood pressure
• difficulty breathing (dyspnea), cough, chest pain
• swelling of arms, hands, feet, ankles, legs, or other parts of your body (edema)

• inflammation of the veins (phlebitis) and formation of blood clots in the blood vessels (venous thrombosis)

Uncommon (may affect up to 1 in 100 people)

• blood infection with low white blood cell counts (neutropenic septicemia)
• vision changes
• dry skin, skin redness (erythema)

• nerve damage that causes muscle contraction disorders (peripheral motor neuropathy)
• inflammation of the tube that leads to the stomach (esophagitis), pain when swallowing (odynophagia) throat pain (pharyngolaryngeal pain), gum disorders
• weight gain
• urinary problems, which could be a sign of kidney failure (renal failure)
• ringing or buzzing in the ears (tinnitus)

• • increased liver enzymes (transaminases) seen in a blood test,
• "Inappropriate antidiuretic hormone secretion syndrome", which is a disease that causes low sodium levels in the blood
• tumor pain

• dizziness (vertigo)
• heart attack (myocardial infarction), reduced blood supply (myocardial ischemia)

• difficulty breathing, which can be a symptom of a condition known as acute respiratory distress syndrome and can be severe and life-threatening
• extravasation (when a medicine that is normally injected into a vein escapes or is accidentally injected into the tissue surrounding the vein, where it can cause serious damage)

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 through the national reporting system listed in Appendix 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 or CAD.

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

Storage conditions are detailed in the section for healthcare professionals.

Unopened 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. These measures will help protect the environment.

6. Container contents and additional information

Javlor composition

• The active ingredient is vinflunina. Each ml of concentrate contains 25 mg of vinflunina (as ditartrate).

A 2 ml vial contains 50 mg of vinflunina (as ditartrate).

A 4 ml vial contains 100 mg of vinflunina (as ditartrate).

A 10 ml vial contains 250 mg of vinflunina (as ditartrate).

• The other component is water for injectables.

Appearance of the product and container contents

Javlor is a clear, colorless or slightly yellowish solution. It is presented in transparent glass vials closed with a rubber stopper covered with a flip-off aluminum seal with a yellow cap for the 2 ml vial, pink cap for the 4 ml vial or orange cap for the 10 ml vial of concentrate. Each container contains 1 or 10 vials.

Only some 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

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.

<---------------------------------------------------------------------------------------------------------------->

This information is intended only for healthcare professionals:

INSTRUCTIONS FOR USE

General precautions for preparation and administration

Vinflunina 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 taken into account. All transfer procedures require strict adherence to aseptic techniques, preferably using a vertical laminar flow safety cabinet. 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 glasses, 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 thoroughly washed with plenty of water.

Dilution of the concentrate

The volume of Javlor (concentrate) corresponding to the calculated dose of vinflunina 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 500 ml bag 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 should be infused through an intravenous infusion device in a "Y" shape at the closest possible port to the 500 ml bag to further dilute the medicinal product during administration.
• The Javlor infusion solution should be infused over 20 minutes.
• The absence of obstruction will be frequently checked 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 should be infused 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 regarding 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.