Javlor 25 mg/ml concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Javlor 25 mg/ml concentrate for solution for infusion

vinflunine

Read the entire 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, ask your doctor.
• If you experience any side effects, talk to your doctor, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Javlor is and what it is 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 inhibiting cell division, leading to cell death (cytotoxicity).

Javlor is used to treat advanced or metastatic bladder and urinary tract cancer when prior treatment with platinum-containing medicines has failed.

2. What you need to know before using 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 (within the last 2 weeks) or currently suffer from a serious infection,
• if your levels of white blood cells and/or platelets are too low,
• if you are breastfeeding.

Warnings and precautions

Inform your doctor:

• if you have liver, kidney, or heart problems,
• if you experience any neurological symptoms that could be signs of "reversible posterior encephalopathy syndrome": brain swelling with generally temporary effects such as headache, changes in mental status that may lead to confusion and coma, seizures, vision changes, high blood pressure, nausea, and vomiting; it may be necessary to discontinue this medication,
• if you have symptoms of hyponatremia (low sodium levels in blood) or "syndrome of inappropriate antidiuretic hormone secretion," such as headache, fatigue, seizures, or coma. Regular monitoring of serum sodium levels during treatment with Javlor is recommended,
• if you are taking any of the medicines listed below under "Other medicines and Javlor",
• if you have constipation, or if you are being treated with pain medications (opioids), or if you have abdominal cancer, or have had previous abdominal surgery. Constipation is a very common adverse effect of Javlor. Laxatives may be administered to prevent constipation,
• if you intend to father or conceive a child (see important recommendations for men and women under "Pregnancy, breastfeeding, and fertility" below).

Your doctor will regularly monitor your blood cell counts before and during treatment, as decreased blood cell counts are a common adverse effect of treatment with Javlor.

Intrathecal administration of Javlor can be fatal. Javlor must not be administered intrathecally (into the spinal canal).

Children and adolescents

Javlor must not be used in children and adolescents.

Other medicines and Javlor

Inform your doctor if you are currently using, have recently used, or might need to use any other medicines.

Specifically, inform your doctor if you are taking any medicine containing 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 for the treatment of tuberculosis or meningitis,
• herbal preparations containing Hypericum perforatum (St. John's Wort), used for the treatment of mild to moderate depression.

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

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 a woman or a man of reproductive age, you must use an adequate and effective method of contraception during treatment and for 4 months if you are a man, or 7 months if you are a woman, after your last dose of Javlor.

Pregnancy

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

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

Breastfeeding

You must not breastfeed during treatment with Javlor.

Fertility

If you wish to have children, consult your doctor. You may wish to seek advice about sperm banking before starting treatment due to the possibility of irreversible infertility caused by treatment with vinflunine.

Driving and using machines

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

Do not drive or operate machinery without consulting your doctor.

3. How to use Javlor

Dosage

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

There is no need to adjust the dose based on age in patients under 75 years of age. Your doctor will adjust your dose if you are 75 years of age 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 administration, or interrupt treatment if you experience certain adverse effects.

How Javlor is administered

Javlor MUST ONLY be administered intravenously.

Javlor will be given as an intravenous infusion (intravenous drip) over 20 minutes by a healthcare professional experienced in cancer treatment within specialized healthcare units.

Javlor is a concentrate that must be diluted before administration.

If you are given more Javlor than you should receive

This medicine will be administered by your doctor or nurse. In the event that you are given too much (an overdose), your doctor will examine you for adverse effects.

If you miss a dose of Javlor

It is very important not to miss any doses of this medicine. If you miss an appointment, contact your doctor immediately to reschedule.

If you interrupt treatment with Javlor

Your doctor will decide when you should interrupt treatment. If you wish to discontinue treatment prematurely, you must discuss with your doctor the other available treatment options.

If you have any further questions about the use of this medicine, ask your doctor.

4. Possible adverse effects

Like all medicines, Javlor can cause adverse effects, although not everyone experiences them.

Tell your doctor immediately if you experience any of the following serious adverse effects while being treated with Javlor:

• fever and/or chills, which could be signs of an infection,
• chest pain, which could be a sign of a heart attack,
• constipation that does not respond to treatment with laxatives,
• neurological symptoms that could indicate "reversible posterior encephalopathy syndrome": brain inflammation with usually temporary effects such as headache, changes in mental status that may lead to confusion and coma, seizures, vision changes, high blood pressure, nausea and vomiting (see section 2, "Warnings and precautions").

Other adverse effects may include:

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

• abdominal pain, nausea, vomiting
• constipation, diarrhea
• inflammation of the mouth lining (stomatitis)
• fatigue (asthenia), muscle pain (myalgia)
• loss of touch sensation due to nerve damage (peripheral sensory neuropathy)
• weight loss, decreased appetite
• hair loss (alopecia)
• injection site reactions (pain, redness, swelling)
• fever
• low levels of white blood cells, red blood cells, and/or platelets in the blood (observed in blood tests)
• low sodium levels in the blood (hyponatremia), seen in blood tests

Common (may affect up to 1 in 10 people)

• infections (neutropenic infection, febrile neutropenia, infections (viral, bacterial, fungal)) with symptoms such as high fever and deterioration in general health
• chills, excessive sweating (hyperhidrosis), pain
• allergy (hypersensitivity), dehydration, headache, skin rash, itching (pruritus), hives
• loss of movement in intestinal muscles (ileus), digestive problems (dyspepsia), difficulty swallowing (dysphagia), oral disorders (mouth pain, tongue pain, dental pain), taste disturbances
• 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 performing body movements 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 body parts (edema)
• inflammation of veins (phlebitis) and formation of blood clots in blood vessels (venous thrombosis)

Uncommon (may affect up to 1 in 100 people)

• blood infection with low white blood cell count (neutropenic sepsis)
• vision disturbances
• dry skin, skin redness (erythema)
• nerve damage causing muscle contraction disorders (peripheral motor neuropathy)
• inflammation of the tube leading to the stomach (esophagitis), pain when swallowing (odynophagia), sore throat (pharyngolaryngeal pain), gingival disorders
• weight gain
• urinary problems, which could be a sign of the kidneys being unable to function properly (renal failure)
• ringing or buzzing in the ears (tinnitus)
• increased liver enzymes (transaminases), observed in blood tests
• "Syndrome of Inappropriate Antidiuretic Hormone Secretion" (SIADH), a condition causing low sodium levels in the blood
• tumour pain
• sensation of spinning (vertigo)
• heart attack (myocardial infarction), reduced blood supply (myocardial ischemia)
• difficulty breathing, which may be a symptom of a condition known as acute respiratory distress syndrome and may be severe and life-threatening
• extravasation (when a medicine normally injected into a vein leaks or is accidentally injected into the surrounding tissue, potentially causing serious damage)

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a side effect not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Javlor Storage

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

Do not use this medicine after the expiry date stated on the vial label and outer packaging following the abbreviation EXP or CAD.

You are very unlikely to be asked to store this medicine yourself.

Storage conditions are specified in the section intended for doctors or healthcare professionals.

Unopened vial

Store in a refrigerator (2°C to 8°C).

Keep 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 unused medicines and their packaging. This will help protect the environment.

6. Pack contents and other information

Composition of Javlor

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

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

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

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

• The other component is water for injections.

Appearance of the product and contents of the pack

Javlor is a clear, colourless or slightly yellowish solution. It is supplied in clear glass vials closed with a rubber stopper and sealed with an aluminium flip-off cap with a yellow cover for the 2 ml vial, a pink cover for the 4 ml vial, or an orange cover for the 10 ml concentrate vial. Each pack contains 1 or 10 vials.

Only certain pack sizes may be marketed.

Marketing Authorisation 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 Authorisation Holder.

Date of the most recent revision of this leaflet: MM/YYYY.

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 for healthcare professionals only:

INSTRUCTIONS FOR USE

General precautions for preparation and administration

Vinflunine is a cytotoxic antineoplastic medicinal product and, as with other potentially toxic compounds, Javlor must be handled with care. Procedures for the proper handling and disposal of antineoplastic medicinal products should be observed. All transfer procedures require strict adherence to aseptic techniques, preferably using a vertical laminar flow safety cabinet. Javlor infusion solution must only be prepared and administered by personnel trained and experienced in the handling of cytotoxic agents. 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 copious amounts of water and soap. In case of contact with mucous membranes, these should be thoroughly rinsed with abundant 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 must be protected from light until administration.

Method of administration

FOR INTRAVENOUS USE ONLY.

Javlor is for single use only.

After reconstitution of the Javlor concentrate, the infusion solution should be administered as follows:

• A venous access should be established for a 500 ml bag of sodium chloride 9 mg/ml (0.9%) infusion solution or glucose 50 mg/ml (5%) infusion solution, preferably into a large vein in the upper forearm or via a central venous line.
• Intravenous infusion should begin with half of a 500 ml bag of sodium chloride 9 mg/ml (0.9%) infusion solution or glucose 50 mg/ml (5%) infusion solution, i.e., 250 ml, at a flow rate adequate to flush the vein.
• The Javlor infusion solution should be administered via a Y-site intravenous infusion device into the port closest to the 500 ml bag to further dilute the medicinal product during administration.
• The Javlor infusion solution should be infused over 20 minutes.
• Frequent checks for obstruction must be performed, and precautions against extravasation must be maintained throughout the infusion.
• After completion of the infusion, the remaining 250 ml of the bag containing sodium chloride 9 mg/ml (0.9%) infusion solution or glucose 50 mg/ml (5%) infusion solution should be infused at a flow rate of 300 ml/h. To flush the vein, administration of Javlor must always be followed by administration of at least an equal volume of sodium chloride 9 mg/ml (0.9%) infusion solution or glucose 50 mg/ml (5%) infusion solution.

Disposal

Disposal of unused medicinal product and of all materials that have come into contact with it must 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).

Keep in the original packaging to protect from light.

Diluted solution:

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

• 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 sets, for up to 1 hour at 25°C.

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