UROMITEXAN 200 mg injectable solution

Introduction

Leaflet: information for the user

Uromitexan 200 mg injectable solution

mesna

Read the entire leaflet carefully beforestarting to usethis medication,as 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, pharmacist, or nurse.
• If you experience side effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the leaflet:

1. What Uromitexan 200 mg is and what it is used for
2. What you need to know before you are given Uromitexan 200 mg
3. How to use Uromitexan 200 mg
4. Possible side effects
5. Storage of Uromitexan 200 mg
6. Package contents and additional information

1. What Uromitexan 200 mg is and what it is used for

Uromitexan contains the active substance mesna. It is a detoxifying agent for antineoplastic treatment.

Uromitexan is used as a prevention of urothelial toxicity, including hemorrhagic cystitis (inflammation of the urinary bladder with blood in the urine), microhematuria, and macrohematuria in patients treated with oxazaphosphorines (ifosfamide, cyclophosphamide) in doses considered urotoxic.

Corrector of cystitis in therapies with cytostatics (cancer medications). Ifosfamide and cyclophosphamide can cause damage to the bladder lining. This damage can appear as blood in the urine. If there are very small amounts of blood (microhematuria), they may not be visible, so your doctor or nurse will perform a urine test with a "stick" or a microscope to check for blood. If a significant amount of blood appears in the urine (macrohematuria), you will notice it because it will be red, and you may occasionally see blood clots in it.

Uromitexan 200 mg protects the bladder lining from damage caused by ifosfamide and cyclophosphamide.

2. What you need to know before you are given Uromitexan 200 mg

Do not use Uromitexan 200 mg if:

• If you are allergic to the active ingredient or any of the other components of this medication (listed in section 6). An allergic reaction can include difficulty breathing, wheezing, skin rash, itching, or swelling of the face and lips if you have ever had an allergic reaction to a similar medication.
• If you have ever had an allergic reaction to a similar medication.

Uromitexan 200 mg will not be administered to you if any of the above circumstances apply to you. If you are unsure, consult your doctor, nurse, or pharmacist before receiving this medication.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Uromitexan 200 mg if you have any autoimmune disease, such as:

• rheumatoid arthritis
• systemic lupus erythematosus (also called lupus or SLE)
• any other autoimmune disease, where the body's immune system attacks itself

If you have an autoimmune disease, you are at a higher risk of suffering from hypersensitivity reactions, such as skin and mucous membrane reactions of varying extent and severity, local tissue inflammation, conjunctivitis, hypotension (decreased blood pressure) associated with circulatory reactions, and increased heart rate (more than 100 beats per minute), increased respiratory rate, increased blood pressure, muscle pain, and transient increase in certain liver function tests. Therefore, protection of the urinary tract with mesna should only be carried out in these patients after a risk-benefit analysis and under careful medical supervision.

If you are unsure whether any of the above circumstances apply to you, consult your doctor, nurse, or pharmacist.

Uromitexan does not prevent hemorrhagic cystitis in all patients, so appropriate checks should be performed.

A sufficient urine production of 100 ml per hour should be maintained, as required for treatment with oxazaphosphorines (ifosfamide, cyclophosphamide) (see section 3. How to use Uromitexan 200 mg).

Elderly patients (over 65 years old)

The dose for an elderly patient should be chosen taking into account possible hepatic, renal, or cardiac disorders, and concomitant diseases or other therapy with medications.

The ratio of oxazaphosphorine to mesna should remain unchanged (see section 3. How to use Uromitexan 200 mg).

Children and adolescents

The safety and efficacy of Uromitexan in pediatric patients (under 16 years old) have not been established in clinical studies. However, medical literature refers to the use of mesna in pediatric patients.

Using Uromitexan 200 mg with other medications

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

Uromitexan 200 mg is administered with ifosfamide and cyclophosphamide. It does not react with these medications, and it is not known to react with others.

Uromitexan 200 mg also does not affect the antineoplastic efficacy of other cytostatics (cancer medications, such as adriamycin, BCNU (carmustine), methotrexate, vincristine), or the therapeutic effect of other medications, such as digitalis glycosides (like digoxin) used to treat heart failure.

Using Uromitexan 200 mg with food and drinks

Food does not influence the absorption and urinary elimination of Uromitexan 200 mg.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or think you may be pregnant or plan to become pregnant, consult your doctor, pharmacist, or nurse before using this medication.

Uromitexan 200 mg is not recommended during pregnancy or breastfeeding. The doctor should carefully consider the potential risks and benefits for each individual patient before prescribing Uromitexan 200 mg.

Pregnancy, fertility, and breastfeeding are contraindications for treatment with cytostatics (cancer medications), so it is unlikely that Uromitexan 200 mg will be used in these circumstances. In the event that an individual patient may be undergoing therapy with oxazaphosphorines (ifosfamide and cyclophosphamide) during pregnancy, Uromitexan 200 mg should be administered to the patient.

Animal studies have not shown evidence of embryotoxic or teratogenic effects of mesna.

Do not breastfeed while being treated with these medications.

Laboratory tests

Ifosfamide and cyclophosphamide can cause damage to the bladder lining. This damage can appear as blood in the urine. If there are very small amounts of blood, they may not be visible, so your doctor or nurse will regularly analyze your urine with a special "stick" or observe it under a microscope, looking for the presence of blood.

Tell your doctor or nurse if you have any other tests with "dipstick", as this medication may affect the results obtained. These "dipstick" tests can be used in blood or urine and detect certain chemicals present in the blood called "ketones", or red blood cells in the urine.

Treatment with Uromitexan may give false positives in certain laboratory tests.

Driving and using machines

Some of the side effects of treatment with Uromitexan 200 mg may affect your ability to drive and use machines. Your doctor will decide whether it is safe for you to do so.

Uromitexan 200 mg contains sodium

This medication contains less than 1 mmol (23 mg) of sodium per ml. This should be taken into account in the treatment of patients with low-sodium diets.

3. How to use Uromitexan 200 mg

Follow the administration instructions of this medication exactly as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Uromitexan 200 mg is used in the form of an injection, which will be administered by a doctor or nurse.

Sufficient amounts of Uromitexan 200 mg should be administered to adequately protect the patient from the urotoxic effects of ifosfamide or cyclophosphamide. Your doctor will decide the amount and frequency of administration necessary based on the dose of ifosfamide or cyclophosphamide you receive.

While using this medication, you should drink enough liquid every day to maintain a urine production (diuresis) of 100 ml per hour, which will help protect your bladder. You should urinate normally when you need to. Do not try to change your usual pattern.

Your doctor will decide the amount of medication needed and when it is needed. Follow their instructions exactly.

The dose will depend on:

• the dose and timing of your treatment with ifosfamide or cyclophosphamide, and whether you are receiving them in the form of tablets or injection
• if you have urinary tract infections (urinary tract infections)
• if you have ever had signs of bladder damage before using ifosfamide or cyclophosphamide - if you have received radiation therapy near the bladder.

The duration of treatment should be equal to the duration of treatment with ifosfamide or cyclophosphamide, plus the time necessary for the urinary concentration of ifosfamide or cyclophosphamide metabolites to decrease to non-toxic levels, which usually occurs within 8-12 hours after the end of treatment with ifosfamide or cyclophosphamide, but may vary depending on the scheduling of oxazaphosphorine (ifosfamide or cyclophosphamide).

Urine production should be maintained at a rate of 100 ml/h (as required for treatment with ifosfamide or cyclophosphamide) and should be monitored for hematuria (blood in urine) and proteinuria (proteins in urine) throughout the treatment period.

The dosing schedule of mesna should be repeated every day that oxazaphosphorine is received.

If the dose of ifosfamide or cyclophosphamide is modified, the dose of mesna should also be modified to maintain the ratio between the two medications.

Example of dosing:

When oxazaphosphorine is administered as an IV bolus: Uromitexan 200 mg will be administered simultaneously via an intravenous injection over 15-30 minutes at 20% weight/weight (w/w) of the oxazaphosphorine. Repeat the same dose of Uromitexan 200 mg after 4 and 8 hours. The total dose of mesna is 60% w/w (weight/weight) of the oxazaphosphorine dose.

Repeat this dosing regimen every time cytotoxic agents are used.

Use in children and adolescents

Children usually urinate more frequently than adults, and therefore, it may be necessary to shorten the interval between doses and/or increase the number of individual doses.

If you receive more Uromitexan 200 mg than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 915.620.420, indicating the medication and the amount administered.

In case of overdose, you may develop symptoms such as nausea, vomiting, abdominal pain/cramps, diarrhea, headache, fatigue, joint and limb pain, skin rash, redness, hypotension, slow heart rate (bradycardia), fast heart rate (tachycardia), tingling (paresthesia), fever, and wheezing (bronchospasm).

There is no known antidote for mesna overdose.

If it occurs, the injection will be stopped immediately, and you will receive treatment for your symptoms. It is unlikely that you will receive more Uromitexan 200 mg than you should, as it will be administered by a trained and qualified person.

If you miss a dose of Uromitexan 200 mg

It is very important to use Uromitexan 200 mg exactly as your doctor has told you. These times have been carefully calculated to ensure that the bladder is fully protected against damage.

If you think you have missed a dose, inform your doctor or nurse.

You will not be given a double dose to make up for missed doses.

If you stop treatment with Uromitexan 200 mg

Your doctor will decide when to stop treatment with Uromitexan.

Do not stop treatment with Uromitexan without consulting your doctor first.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

The following adverse effects have been reported with Uromitexan 200 mg:

Tell your doctor immediately if you notice any of the following side effects, you may need urgent medical attention:

• The most frequent adverse reactions associated with the use of Uromitexan 200 mg are: headache, reactions at the injection site, abdominal pain/cramps, dizziness, lethargy/drowsiness, fever, rash, diarrhea, nausea, flushing, and flu-like symptoms.

• The most serious adverse reactions associated with the use of Uromitexan 200 mg are: Stevens-Johnson syndrome and toxic epidermal necrolysis (skin diseases), anaphylaxis, and DRESS syndrome (drug allergic reaction characterized by skin rash, fever, and involvement of various organs, such as the kidneys and liver).

• Rarely, it can also cause something similar to an allergic reaction. The signs may include skin rashes and hives, itching of the skin, blisters in the mouth or skin, sudden drop in blood pressure (feeling of dizziness), faster heart rate, and changes in blood test results used to check that your liver is working properly.

Some of these side effects may be caused by ifosfamide or cyclophosphamide instead of Uromitexan 200 mg, since they are always taken together.

Other possible side effects include:

Blood and lymphatic system

• swelling of the lymph nodes (lymphadenopathy)
• decrease in the number of cells in the blood:
• • decrease in all types of blood cells (pancytopenia),
  • or reduction in the number of white blood cells (which fight infections (leukopenia, lymphopenia)),
  • abnormally high levels of eosinophils (a type of white blood cell produced in the bone marrow) either in the blood or in body tissues (eosinophilia); and of platelets (which help blood clotting (thrombocytopenia))

Metabolism and nutrition

• decreased appetite

Psychiatric

• insomnia, nightmares

Immune system

• allergic reactions (hypersensitivity) or severe allergic reactions that occur rapidly (anaphylaxis)

Nervous system

• headache
• dullness
• lethargy/drowsiness
• tingling, numbness, burning, stabbing (paresthesia)
• unusual or pathological sensitivity of the skin, or of a particular sense, to stimulation (hyperesthesia)
• temporary loss of consciousness and postural tone (syncope)
• decrease in the sense of touch or a sensation, or a partial loss of sensitivity to sensory stimuli (hypoesthesia)
• alteration of attention
• seizures (convulsions)

Eyes

• blurred vision, reduced or lost vision
• eye inflammation (conjunctivitis)
• swelling around the eyes (periorbital edema)

Heart and circulation

• flushing
• abnormal heart graph (abnormal electrocardiogram)
• abnormality of the heartbeat (palpitations)
• rapid heart rate (tachycardia)
• high blood pressure (hypertension) or low (hypotension)

Lungs

• difficulty breathing or wheezing (bronchospasm)
• nasal congestion
• cough
• sharp severe pain when inhaling (pleuritic pain)
• dry mouth
• difficulty breathing (dyspnea)
• laryngeal discomfort
• nasal bleeding (epistaxis)
• breathing difficulties
• decrease in oxygen levels in your body (hypoxia, decrease in oxygen saturation)
• rapid breathing (tachypnea)
• coughing up blood or bloody sputum from the lungs or airways (hemoptysis)

Digestive system

• abdominal pain/cramps
• nausea
• vomiting
• diarrhea
• irritation of the mucosa
• burning pain
• constipation
• gum bleeding (gum bleeding)
• inflammation of the mouth mucosa, including ulcers (stomatitis)
• bad taste

Liver

• conditions that cause liver inflammation, which can cause yellowing of the skin or the whites of the eyes (jaundice), weight loss, and general malaise (hepatitis)
• increase in the levels of certain proteins produced by the liver called enzymes. Your doctor will perform blood tests to check for their presence.

Skin and subcutaneous tissue

• rash
• itching
• abnormally high sweating or transpiration, which exceeds that required for body temperature regulation (hyperhidrosis)
• conditions that put life at risk causing rashes, ulcers, sore throat, fever, conjunctivitis, separation of the skin layers (toxic epidermal necrolysis, Stevens-Johnson syndrome)
• itching, red-colored rash that can develop in the mouth sores (erythema multiforme, erythema)
• drug hypersensitivity reaction, characterized by skin rash, fever, lymph node inflammation, and involvement of internal organs (drug rash with eosinophilia and systemic symptoms)
• ulcerations and/or blisters (mucocutaneous, oral mucosa, vulvovaginal, anorectal)
• swelling of the deeper layers of the skin caused by fluid accumulation (angioedema)
• lesions that recur in the same area when the same medicine is given (fixed exanthem)
• rash
• photodistributed rash
• rash on the skin of a notable pale red color, hives, and itching (urticaria)
• burning sensation

Musculoskeletal and connective tissue

• muscle pain (myalgia), or joint pain (arthralgia).
• back pain
• feeling of discomfort in the upper or lower limbs (pain in the limbs)
• jaw pain

Renal and urinary

• pain when urinating (dysuria)
• acute kidney failure

General disorders and administration site conditions

• change in the appearance of the skin and irritation at the injection or infusion site
• chest pain
• fever, chills
• flu-like symptoms, such as headache, fever, chills, joint and muscle pain, weakness, fatigue
• swelling of the tissues, usually in the lower limbs, due to fluid accumulation (peripheral edema)
• facial inflammation (facial edema)
• fatigue
• reactions at the infusion site (thrombophlebitis, irritation)

Reporting of adverse effects:

If you experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Uromitexan 200 mg

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the box after CAD. The expiration date is the last day of the month indicated.

Do not store at a temperature above 30°C.

Keep in the original packaging.

Use only if the solution is transparent, without visible particles, and if the container is not damaged.

The solution must be administered at the moment of opening the injectable ampoule.

Medicines should not be thrown away through the sewers or in the trash. Ask your pharmacist how to dispose of medicines that are no longer needed. This way, you will help protect the environment.

6. Package contents and additional information

Composition ofUromitexan 200 mg

The active ingredient is mesna

One 2 ml ampoule contains 200 mg of mesna.

The other components are: sodium edetate, sodium hydroxide, and water for injectable preparations.

Appearance of the product and package contents

The injectable is a sterile, clear, colorless solution, and is supplied in transparent glass ampoules of 2 ml.

The ampoules are packaged in a plastic tray inside a cardboard box.

Each box contains 15 ampoules with 2 ml of injectable solution.

Marketing authorization holder and manufacturer

Marketing authorization holder

Baxter S.L.

Pouet de Camilo 2, 46394 Ribarroja del Turia (Valencia)

Spain.

Manufacturer:

Prasfarma S.L.

C/ Sant Joan, 11-15

08560 Manlleu (Barcelona)

Spain

Date of the last revision of this prospectus: January 2016

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/