PATIENT INFORMATION LEAFLET

MESNA ALTAN 100 mg/ml injectable and infusion solution EFG

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

MESNA ALTAN 100 mg/ml injectable solution and for perfusion is a detoxifying agent for antineoplastic treatment, it is indicated for the prevention of urothelial toxicity including hemorrhagic cystitis (inflammation of the urinary bladder with blood in urine), microhematuria and macrohematuria in patients treated with oxazaphosphorines (ifosfamide, cyclophosphamide, trophosphamide), in doses considered urototoxic.

Urothelial irritant corrector in therapies with cytostatics (drugs used in cancer treatment).

No useMESNA ALTAN 100 mg/ml

If you are allergic to Mesna or any of the other components of this medication (listed in section 6).

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use MESNA ALTAN 100 mg/ml.,Mesna 100 mg/ml does not prevent hemorrhagic cystitis in all patients, so appropriate controls should be performed.You should maintain a sufficient urine production, as required for treatment with oxazaphosphorines.

Children and adolescents

The safety and efficacy of Mesna 100 mg/ml in pediatric patients (<16 years old) have not been established.

Use of MESNA Altan 100 mg/ml with other medications

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medication.

The systemic effects of oxazaphosphorines are not affected by MESNA ALTAN 100 mg/ml.In clinical trials, it has been demonstrated that mesna overdoses do not decrease the acute toxicity, subacute toxicity, leukocytic activity, and immunosuppressive efficacy of oxazaphosphorines.Studies in animals with ifosfamide and cyclophosphamide in a variety of tumors have also shown that mesna does not interfere with their antineoplastic activity.Mesna does not affect the antineoplastic efficacy of other cytostatics (e.g., adriamycin, BCNU, (carmustine), methotrexate, vincristine), nor the therapeutic effect of other drugs such as digitalis glycosides.

Use of Mesna 100 mg/ml with food

Food does not affect the absorption and urinary excretion of mesna.

Pregnancy, lactation and fertility

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

Mesna 100 mg/ml is not recommended during pregnancy or lactation.The doctor should carefully consider the potential risks and benefits for each patient individually, before prescribing Mesna 100 mg/ml.Pregnancy, lactation, and fertility are contraindications for treatment with cytostatics; consequently, MESNA ALTAN 100 mg/ml solution for injection and infusion is likely to be used in these circumstances.It may be the case that an individual patient on oxazaphosphorine therapy during pregnancy needs to be administered MESNA ALTAN 100 mg/ml solution for injection and infusion.Mothers should not breastfeed while being treated with these medications.

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

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

Driving and operating machinery

No studies have been conducted on the effects on the ability to drive and operate machinery.Some of the side effects of mesna treatment may affect your ability to drive and operate machinery.Your doctor will decide if it is safe for you to do so.

Mesna 100 mg/ml contains sodium

This medication contains 0.610 mmol (14.03 mg) of sodium per ml of solution, which should be taken into account in the treatment of patients with low-sodium diets.

MESNA ALTAN 100 mg/ml injectable solution and for infusion will be administered by your doctor or nurse. Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Sufficient amounts of MESNA ALTAN 100 mg/ml injectable solution and for infusion should be administered to adequately protect the patient from the urotropic effects of oxazaphosphorine. Your doctor will decide on the amount and frequency of administration necessary according to the dose of oxazaphosphorine received.

The duration of treatment should be equal to the duration of treatment with oxazaphosphorine, plus the time necessary for the urinary concentration of oxazaphosphorine metabolites to decrease to non-toxic levels, which usually occurs within 8-12 hours after the end of treatment with oxazaphosphorine, but may vary depending on the oxazaphosphorine schedule. Urine production should be maintained at a rate of 100 ml/h (as required for oxazaphosphorine treatment) and should be monitored for hematuria and proteinuria throughout the treatment period.

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

If the dose of oxazaphosphorine is modified, the mesna dose should also be modified to maintain the relationship between both drugs..

When ifosfamide or cyclophosphamide is administered as a bolus IV: Mesna 100 mg/ml injectable solution and for infusion will be administered simultaneously via intravenous injection during 15-30 minutes at 20% body weight/body weight (b/w) of oxazaphosphorine. Repeat the same dose of Mesna 100 mg/ml injectable solution and for infusion after 4 and 8 hours. The total dose of mesna is 60% b/w of the dose of oxazaphosphorine.

Repeat this dosing regimen every time cytotoxic agents are used.

Example of dosing

MESNA ALTAN 100 mg/ml can be mixed in the same infusion bag with ifosfamide.

Use in children and adolescents

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

Use in elderly patients

Clinical trials have included patients aged 65 years and no specific adverse reactions have been reported for this age group.

If you use more Mesna Altan 100mg/ml injectable solution and for infusion than you should:

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological 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/colic, diarrhea, headache, fatigue, joint and limb pain, skin rash, redness, hypotension, bradycardia, tachycardia, paresthesia, fever, and bronchospasm.

If you forgot to use Mesna Altan 100mg/ml injectable solution and for infusion:

Do not use a double dose to compensate for the missed doses.

If you interrupt treatment with Mesna Altan 100mg/ml injectable solution and for infusion:

Do not interrupt treatment with Mesna without consulting your doctor first.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

There have been reports of hypersensitivity reactions more frequently in immunocompromised patients than in cancer patients. Similarly, cases of venous irritation at the injection site have been reported. During treatment, it is difficult to clearly evaluate adverse reactions to Mesna Altan 100 mg/ml injectable and perfusion solution and those related to other medications administered at the same time.

Clinical studies in patients over 65 years of age have not shown specific adverse reactions related to age.

Since patients receive powerful cytotoxic agents at the same time, the side effect profile of mesna is difficult to define. The following side effects may occur during treatment with MESNA 100 mg/ml: The frequency of possible side effects listed below is defined as follows: Very common (may affect more than 1 in 10 patients) Common (may affect between 1 and 10 in 100 patients) Uncommon (may affect between 1 and 10 in 1,000 patients) Rare (may affect between 1 and 10 in 10,000 patients) Very rare (may affect fewer than 1 in 10,000 patients)Unknown frequency(adverse reactions reported in post-marketing experience).

Reporting of adverse reactions

If you experience any type of adverse reaction,consult your doctor, pharmacist or nurse, even if it is a possible adverse reaction that does not appear in this leaflet.You can also report them directly through theSpanish System for the Pharmacovigilance of Medicines for Human Usewww.notificaRAM.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

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

No special storage conditions are required.

Keep the container in the outer packaging.

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

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

Use only if the solution is transparent, free of visible particles, and the container is not damaged.

The solution must be administered at the time of opening.

MESNA ALTAN 100 mg/ml Composition

The active ingredient ismesna, each ampule of 2 ml contains 200 mg of mesna and each ampule of 4 ml contains 400 mg of mesna.

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

MESNA ALTAN 100 mg/ml injection or infusion solution is chemically compatible with 0.9% sodium chloride solution or 5.0% dextrose/sodium chloride solution for 24 hours at room temperature.

MESNA ALTAN 100 mg/ml injection or infusion solution and ifosfamide are chemically compatible with:

• 0.9% sodium chloride solution and dextrose/sodium chloride solution for one week at room temperature,
• water for injection for one week in refrigeration,
• 5% dextrose solution for 24 hours at room temperature.

MESNA ALTAN 100 mg/ml injection or infusion solution and cyclophosphamide are chemically compatible with:

• 10% dextrose solution for 2 hours at room temperature.

From a microbiological point of view, the product must be used immediately.

If not used immediately, the times and conditions of conservation during use are the responsibility of the user and should normally not exceed 24 hours (less when combined with cyclophosphamide in dextrose, see above) between 2 and 8°C and that the dilution has taken place in controlled and validated aseptic conditions.

MESNA ALTAN 100 mg/ml injection and infusion solutioncan also be stored in water. Once opened, mix to drink and the mixture should be kept in the refrigerator for no more than 24 hours.

Hospital use medications.

Product appearance and packaging contents

Transparent glass type I ampules. Each ampule contains 2 ml or 4 ml of solution.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

Altan Pharmaceuticals, S.A.

C/Cólquide, Nº 6 portal 2 planta 1. Oficina F. Edificio Prisma.

28230 Las Rozas Madrid.

Responsible manufacturerAltan Pharmaceuticals, S.A.

Avda. Constitución 198 – 199, Polígono Industrial Monte Boyal

45950 Casarrubios del Monte (Toledo)

Last review date of this leaflet: April 2015

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