PATIENT INFORMATION LEAFLET

Javlor 25 mg/ml concentrate for solution for infusion

vinflunina

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

• Keep this leaflet, as you may need to read it again.

• If you have any questions, consult your doctor.

• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Javlor contains the active ingredient vinflunine, which belongs to the group of anticancer medications known as vinca alkaloids. These medications affect the growth of cancer cells by stopping cell division, leading to cell death (cytotoxicity).

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

Do not use JAVLOR

• if you are allergic to the active ingredient (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 breastfeeding,

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

Warnings and precautions

Inform your doctor:

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

• if you experience any of the following neurological symptoms: headache, changes in mental state that may lead to confusion and coma, convulsions, blurred vision, and high blood pressure, you may need to stop taking this medication,

• if you are taking any of the medications listed below in “Use of other medications”,

• if you have constipation, or if you are being treated with pain medications (opioids), or if you have had abdominal cancer, or have undergone abdominal surgery,

• if you plan to conceive a child (see “Pregnancy, breastfeeding, and fertility” below).

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

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

Use in children and adolescents

Javlor should not be used in children and adolescents.

Use of Javlor with other medications

Inform your doctor if you are using, have used recently, or may need to use any other medication.

Specifically, inform your doctor if you are taking any medication that contains any of the following active substances:

• ketoconazole and itraconazole, used to treat fungal infections,

• opioids, used to treat pain.

• ritonavir, used to treat HIV infection,

• doxorubicin and doxorubicin pegylated liposomal, used to treat certain types of cancer,

• rifampicin, used to treat tuberculosis or meningitis,

• preparations based on plants containingHypericum perforatum(St. John's Wort) used to treat mild or moderate depression.

Javlor with food and drinks

Inform 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, breastfeeding, and fertility

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

If you are fertile, you should use an appropriate 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 breastfeed during Javlor treatment.

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

Driving and operating machinery

Javlor may cause side effects such as fatigue and dizziness.

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

Dose

The recommended dose in adult patients is 320 mg/m2of body surface area (which will be calculated by the doctor according to their 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 conditions and in specific situations:

• if you have been previously irradiated in the pelvis,
• if you have a moderate or severe kidney problem,

• if you have liver problems.

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

How Javlor is Administered

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

Javlor is a concentrate that must be diluted before administration.

Like all medicines, Javlor may cause side effects, although not everyone will experience them.

Inform your doctor immediatelyif you experience any of the following severe side effectswhile 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 laxative treatment,

• headache, changes in mental state that may lead to confusion and coma, convulsions, 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 mucous membrane of the mouth,
• fatigue, muscle pain,
• numbness to the touch,
• weight loss, decreased appetite,
• hair loss,
• reactions at the injection site (pain, redness, swelling),
• fever,

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

• low levels of sodium in the blood (hyponatremia).

Common (may affect up to 1 in 10 people)

• inflammation of the veins (phlebitis).

Rare (may affect up to 1 in 100 people)

• • increased liver enzymes (observed in a blood test),
• “Inadequate Secretion Syndrome of the Antidiuretic Hormone”, which is a disease that causes low levels of sodium in the blood,
• tumor pain.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a side effect that does not appear in this prospectus. You can also report them directly through the national notification system included in theAnexo V. By reporting side effects, you can contribute to providing more information about the safety of this medication.

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

Do not use this medication after the expiration date that appears on the vial label and on the packaging after the CAD abbreviation.

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

Storage conditions are detailed in the section for healthcare professionals.

Sealed vial

Store in refrigerator (2°C to 8°C).

Store in the original packaging to protect it from light.

Diluted solution

The diluted solution must be used immediately.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. This will help protect the environment.

Composition of Javlor

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

A vial of 2 ml contains 50 mg of vinflunine (as ditartrate). A vial of 4 ml contains 100 mg of vinflunine (as ditartrate). A vial of 10 ml contains 250 mg of vinflunine (as ditartrate).

• The other component is water for injection.

Appearance of the product and contents of the package

Javlor is a transparent, 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 package contains 1 or 10 vials.

Only some package sizes may be commercially available.

Marketing Authorization Holder

Pierre Fabre Médicament

Place Abel Gance, 45

F-92100 Boulogne

France

Responsible for manufacturing

FAREVA PAU 1

Avenue du Béarn

F-64320 Idron

France

Please contact the Marketing Authorization Holder for any information about this medicinal product.

Last review date of this leaflet: MM/AAAA.

Other sources of information

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

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This information is intended solely for healthcare professionals:

INSTRUCTIONS FOR USE

General precautions for preparation and administration

Vinflunine is a cytotoxic anticancer drug, and, like other potentially toxic compounds, Javlor must be handled with caution. The procedures for correct handling and disposal of anticancer drugs must 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 necessary training and experience in the handling of cytotoxic agents. Pregnant hospital staff members 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 vinflunine must be mixed in a 100 ml bag of sodium chloride 9 mg/ml (0.9%) infusion solution. Alternatively, a 5% glucose infusion solution may be used. The diluted solution must be protected from light until administration.

Administration form

FOR USE ONLY BY INTRAVENOUS ROUTE.

Javlor is for single use only.

After dissolving the Javlor concentrate, the infusion solution must be administered as follows:

• An intravenous access must be established for a 500 ml bag of sodium chloride 9 mg/ml (0.9%) or 5% glucose infusion solution, preferably in a large vein in the upper arm or using a central venous catheter.

• The intravenous infusion must be initiated with half of a 500 ml bag of sodium chloride 9 mg/ml (0.9%) or 5% glucose infusion solution, i.e. 250 ml, at a suitable flow rate to irrigate the vein.

• The Javlor infusion solution must be infused through an intravenous infusion device in "Y" at the nearest port to the 500 ml bag to dilute the medication during administration.

• The Javlor infusion solution must be infused over 20 minutes.

• The absence of obstruction must be checked frequently, and precautions against extravasation must be maintained throughout the infusion.

• Once the infusion is complete, the remaining 250 ml of the 500 ml bag with sodium chloride 9 mg/ml (0.9%) or 5% glucose infusion solution must be infused at a flow rate of 300 ml/h. To irrigate the vein, the administration of Javlor must always be followed by the administration of at least an equal volume of sodium chloride 9 mg/ml (0.9%) or 5% glucose infusion solution.

Elimination

The unused medication and all materials that have come into contact with it must be disposed of in accordance with local regulations for the disposal of cytotoxic drugs.

Storage conditions:

Sealed vials:

Store in refrigerator (2°C to 8°C).

Store in the original packaging to protect it from light.

Diluted solution:

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

• Protected from light, in polyethylene or PVC infusion bags for up to 6 days in refrigerator (2°C – 8°C) or up to 24 hours at 25°C.

• Exposed to light, in polyethylene or PVC 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 in use before administration are the responsibility of the user and should not normally exceed 24 hours at 2°C – 8°C, unless the dilution was made in controlled and validated aseptic conditions.

Annex IV

Scientific conclusions and the grounds for the variation to the terms of the

Marketing Authorization

Scientific conclusions

Having regard to the information provided in the Periodic Safety Update Report (PSUR) for Javlor, the scientific conclusions of the PRAC are as follows:

The safety information available during this reporting period is generally consistent with the known safety profile for vinflunine. Although no new safety problems have been identified, the PRAC proposes two changes to the product information.

The PRAC has proposed adding a warning in section 4.4 of the SPC regarding the risk of hyponatremia, including cases due to the Syndrome of Inappropriate Antidiuretic Hormone Secretion, which was identified as a risk in the previous PSUR and included in the SPC as an adverse reaction. Given the high frequency of grade 3 or 4 hyponatremia events (11.7%), which can have a fatal outcome, the adverse impact of hyponatremia on survival in cancer patients, and the possibility of causing severe CNS sequelae (e.g. confusion, convulsions), this proposal was approved.

Finally, the PRAC has proposed minor amendments to the list of adverse reactions in section 4.8 of the SPC to ensure consistency in the way these reactions are coded. The changes do not affect the frequency categories included in the adverse reaction section, except for "peripheral sensory neuropathy", which is elevated from frequent to very frequent, and "tumour pain", which is now classified as uncommon (previously unknown frequency). No new adverse reactions have been added, and no adverse reactions have been deleted, apart from "anorexia", which has been reclassified as "decreased appetite". These changes are considered acceptable.

The CHMP agrees with the scientific conclusions made by the PRAC.

Grounds for the variation to the terms of the Marketing Authorization(s)

Based on the scientific conclusions for Javlor, the CHMP considers that the benefit-risk balance of medicinal products containing the active substance VINFLUNINE DITARTRATE is favorable subject to the proposed changes to the product information.

The CHMP recommends that the terms of the Marketing Authorization be modified.