Package leaflet: Information for the patient

Mesna 100 mg/ml solution for injection/infusion

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Read all of this leaflet carefully before you start using this medicine because it contains important information foryou.

•    Keep this leaflet. You may need to read it again

•    If you have any further questions, ask your doctor or pharmacist

•    If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet

What is in this leaflet:

1.    What Mesna is and what it is used for

2.    What you need to know before you use Mesna

3.    Howto use Mesna

4.    Possible side effects

5.    Howto store Mesna

6.    Contents of the pack and other information

1.    What Mesna is and what it is used for

Mesna is a detoxifying agent for anti cancer treatment. It is used to protect the bladder and lower urinary tract against the harmful effects of certain cancer medications known as oxazaphosphorines (e.g., cyclophosphamide, ifosfamide and trofosfamide).

2.    What you need to know before you use Mesna Do not use Mesna

•    if you are allergic (hypersensitive) to mesna, other medicines containing thiols or any of the other ingredients of Mesna (listed in Section 6)

An allergic reaction can include shortness of breath, wheezing, rash, itching or swelling of the face and lips.

Warning and precautions

After using Mesna, allergic reactions are more frequently observed in patients with autoimmune diseases (diseases where your body's immune system attacks itself) than in cancer patients.

Reactions of the skin and mucous membranes (itching, rash, hives, exanthema - widespread rash usually occurring in children, enanthema - rash (small spots) on the mucous membranes), temporary increases in transaminases and also general symptoms such as fever, fatigue, nausea and vomiting were observed. In rare cases, circulatory reactions such as hypotension (too low blood pressure), tachycardia (rapid heartbeat) may occur. The prevention of urotoxicity with mesna should only be undertaken under a doctor's supervision.

Children and adolescents

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

Other medicines and Mesna

The activity of oxazaphosphorines is not affected by Mesna.

Mesna does not affect the efficacy of other cytotoxic drugs (anticancer drugs) and the effect of digitalis (medicines for the treatment of insufficiency of the heart muscle).

Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes medicines you buy withouta prescription.

Pregnancy and breast-feeding

Mesna is only taken with ifosfamide and cyclophosphamide. If you are pregnant and your doctor thinks that you need treatment with these medicines, you will also need to have Mesna.

Discuss pregnancy with your doctor before having this medicine. Do not breast-feed while being treated with these medicines.

Driving and using machines

No studies on the effects on the ability to drive and use machines have been performed.

Known adverse reactions of mesna like nausea, vomiting or circulatory reactions can impair the ability to drive and use machines also at recommended doses.

Mesna contains sodium

Mesna contains 0.610 mmol/ml sodium 1.22 mmol sodium per 2 ampoule and 2.44 mmol per 4ml ampoule).This should be taken into consideration by patients on a controlled sodium diet.

3.    Howto use Mesna

Always use this medicine exactly as your doctor or pharmacist has told you. Check with yourdoctor or pharmacist if you are not sure.

The appropriate dose for your treatment, the frequency of administration and duration of your treatment will be determined by yourdoctor.

If you believe that Mesna is too strong or too weak effect, ask your doctor or pharmacist.

How Mesna is given

•    Mesna a medicine for use in hospitals

•    It will be given to you by a doctor or nurse as an injection into yourvein (intravenously)

•    During the administration, it is important that you get adequate amounts of fluid administered (or take) to protect the bladder and lower urinary tract

Mesna is given by intravenous injection over 15-30 minutes at 20% of the simultaneously administered oxazaphosphorine on a weight for weight basis (w/w). The same dose of mesna is repeated after 4 and 8 hours. The total dose of mesna is 60% (w/w) of the oxazaphosphorine dose.

If you use more Mesna than you should:

I n the event of an overdose or if an overdose is suspected, contact your doctor immediately.

Overdose can cause the following reactions: nausea, vomiting, colic, diarrhea, headache, tiredness, pain in the lymph nodes, pain in the limbs, joint pain, lack of energy such as exhaustion and general weakness, depression (minor or major depression), irritability, rash, hypotension (too low blood pressure), tachycardia (rapid heartbeat).

There is no known specific antidote for Mesna. Your doctor will need to set a treatment solely against the phenomena.

If overdose occurs, your doctor may reduce the flow of the solution for injection and, if necessary, appropriate medication should be administered.

For the risk of anaphylactoid reactions (reactions resembling anaphylaxis, a severe allergic reaction that difficulty swallowing and / or breathing, red or swollen face and / or hands can cause), appropriate medications are available.

4. Possible side effects

Like all medicines, Mesna can cause side effects, although not everybody gets them. Side effects listed below are ordered by the occurrence of the adverse event. The administration should be discontinued and your doctor will put appropriate measures in case of adverse events.

Common side effects (may affect up to 51/100 and <1/10 people) Hypersensitivity reactions, hyperergic reactions, nausea, vomiting, itching, rashes, skin reactions, enanthem, fever.

Uncommon side effects (may affect up to 51/1000 and < 1/100 people)

Urticaria, ocal tissue swelling, local edema, vein irritation at injection site, chills.

Rare side effects (may affect up to 51/10000 and <1/1000 people) Anaphylactoid reactions, allergic reactions, conjunctivitis, hypotension, hypertension, flushing, cardiovascular reactions, increase in the values of various liverfunction tests.

Very rare side effects (may affect up to < 1/10000 people including isolated reporting)

Pharyngitis, anorexia, Irritability, depression, headache, tachycardia, tachypnea, cough, Flatulence, constipation, colic, abdominal pain, Steven-Johnson syndrome, Lyell syndrome, trthralgia, myalgia, joint pain, articular pain, influenza-like symptoms, decrease in platelet count, pulse rate > 100/min, ST elevation, toxic reactions.

Infections and infestations

-    Very rare: pharyngitis (inflammation of the pharynx)

Immune system disorders

-    Common: Hypersensitivity reactions, (undesirable reactions produced by the normal immune system) hyperergic reactions (hypersensitivity to allergen)

-    Rare: Anaphylactoid reactions, (serious allergic reaction, signs may include skin rashes and weals, itchy skin, mouth or skin blisters, sudden drop in blood pressure (feeling dizzy) allergic reactions

Metabolism and nutrition disorders

-    Very rare: anorexia(loss of appetite)

Psychiatric disorders

-    Very rare: irritability, depression.

Nervous system disorders

-    Very rare: headache

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The following information is intended for healthcare professionals only:

Posology and method of administration

Sufficient mesna must be given to adequately protect the patient from the urotoxic effects of the oxazaphosphorine.

The duration of mesna treatment should equal that of the oxazaphosphorine treatment plus the time taken for the urinary concentration of oxazaphosphorine metabolites to fall to non-toxic levels. This usually occurs within 8-12 hours after the end of oxazaphosphorine treatment but may vary depending on the scheduling of oxazaphosphorine. Urinary output should be maintained at 100 ml/hr (as required for oxazaphosphorine treatment) and the urine monitored for haematuria and proteinuria throughout the treatment period.

Where oxazaphosphorine is used as an iv bolus: Mesna is given by intravenous injection/infusion over 15-30 minutes at 20% of the simultaneously administered oxazaphosphorine on a weight for weight basis (w/w). The same dose of mesna is repeated after 4 and 8 hours. The total dose of mesna is 60% (w/w) of the oxazaphosphorine dose. This is repeated on each occasion that the cytotoxic agents are used.

Example dosage schedule:

	0 HRS	4 HRS	8 HRS
Oxazaphosphorine	40 mg/kg	-	-
Mesna 100 mg/ml solution for injection/infusion	8 mg/kg	8 mg/kg	8 mg/kg

If necessary the dose of mesna can be increased to 40% of the oxazaphosphorine dose given four times at three hourly intervals (0, 3, 6 and 9 hours). (Total dose = 160% (w/w) of the oxazaphosphorine dose). This larger dose is recommended in children, in patients whose urothelium may be damaged from previous treatment with oxazaphosphorine or pelvic irradiation, or in patients who are not adequately protected by the standard dose of mesna.

Example dosage schedule:

	0 HRS	3 HRS	6 HRS	9 HRS
oxazaphosphorine	40 mg/kg	-	-
Mesna 100 mg/ml solution for injection/infusion	16 mg/kg	16 mg/kg	16 mg/kg	16 mg/kg

Where oxazaphosphorine is used as a 24-hour infusion'. Mesna can be used as a concurrent infusion. An initial 20% (w/w) of the total oxazaphosphorine dose is given as an i.v. bolus, then an infusion of 100% (w/w) of the oxazaphosphorine over 24 hours, followed by a further 12-hour infusion of up to 50% (w/w) of the oxazaphosphorine dose. Total mesna dose = <170% of the oxazaphosphorine dose.

Example dosage schedule:

	0 hrs	0-24 hrs	24 hrs	28 hrs	32 hrs	36 hrs
oxazaphosphorine	■	5 g/m2 infusion	■	■	■	"
Mesna 100 mg/ml solution for injection/ infusion	1 g/m2 i.v.	5 g/m2 infusion	3 g/m2 infusion —>
				1 g/m2 i.v.	1 g/m2 i.v.	1 g/m2 i.v.

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Eye disorders

-    Rare: conjunctivitis

Cardiac disorders

-    Very rare: tachycardia (rapid heartbeat)

Vasculardisorders

-    Rare: Hypotension, (low blood pressure) hypertension, (high blood pressure) flushing, cardiovascular reactions

Respiratory, thoracic and mediastinal disorders

-    Very rare: tachypnea (rapid breathing), cough

Gastrointestinal disorders

-    Common: nausea, vomit

-    Rare: diarrhea

-    Very rare: constipation, colic (attacks of cramping pain in the gastrointestinal tract), abdominal pain, flatulence

Skin and subcutaneous tissue disorders

-    Common: itching, rashes, skin reactions, enantheme (rash on the mucous membranes)

-    Uncommon: urticarial (hives)

-    Very rare: Steven-Johnson syndrome, (a severe inflammatory eruption of the skin and mucous membranes) Lyell syndrome (top layer of skin detaches from the lower layers of the skin all over the body)

Musculoskeletal and connective tissue disorders

-    Uncommon: ocal tissue swelling

-    Rare: back pain

-    Very rare: arthralgia, (joint pain) myalgia, (muscular pain or tenderness) joint pain, articular pain

General disorders and administration site conditions

-    Common: fever

-    Uncommon: local edema, vein irritation at injection site, chills

-    Rare: fatigue, asthenia, (weakness) mucocutaneous reactions, (to the skin and a mucous membrane)

-    Very rare: influenza-like symptoms

Investigations

-    Rare: increase in the values of various liverfunction tests Very rare: decrease in platelet count, pulse rate>100/min, ST elevation

Injury, poisoning and procedural complications

-    Very rare: toxic reactions

Because mesna is used in combination with anti-cancer drugs, it is difficult to distinguish the adverse reactions which may be due to mesna from those caused by the concomitantly administered cytotoxic drugs.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report any side effects directly (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

5.    How to store Mesna

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 carton or ampoule and on the label after EXR The expiry date refers to the last day of that month.

Do not store above 30°C. Keep the container in the outer carton to protect from light.

Any unused solution must be discarded. After opening, the product must be used immediately.

For microbiological point of view, product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 25°C, unless reconstitution/dilution has taken place in controlled and validated aspectic conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6.    ADDITIONAL IN FORMATION What does Mesna contains

* The active ingredient is mesna

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Where oxazaphosphorine is used as a long-term infusion:

An initial 20% (w/w) of the first 24 hours oxazaphosphorine dose is given as an i.v. bolus as the oxazaphosphorine infusion starts. Then each 24 hour infusion of oxazaphosphorine is given with a concurrent 24 hour infusion (100% w/w) of mesna. A 12 hour infusion of mesna (60% (w/w) of the final 24 hour dose of oxazaphosphorine) should be commenced as the oxazaphosphorine mesna infusion finishes.

Example dosage schedule:

	Day 1		Day 2	Day 3		Day4
	0 hrs	0-24 hrs	0-24 hrs	0-24 hrs	24 hrs	4 hrs	8 hrs	12 hrs
oxazaphosphorine		2 g/m2 infusion	2 g/m2 infusion	2 g/m2 infusion
Mesna 100 mg/ml solution for injection/infusion	0.4g/m2 iv	2 g/m2 infusion	2 g/m2 infusion	2 g/m2 infusion	1.2 g/m2 infusion

dose given fourtimes at three hourly intervals (0,3,6 and 9 hours) (Total dose = 160% (w/w) of the oxazaphosphorine dose). older people:

No specific information is available. Clinical trials have included patients over 65 and no adverse reactions specific to this age group have been reported.

Shelf Life

Unopened: 30 months.

After opening:

The product must be used immediately.

For single use. Any unused solution must be discarded.

Mesna is chemically compatible with Compound Sodium Lactate injection, 0.9 % saline and with 5.0 % dextrose containing diluents for 24 hours.

The final 12-hour infusion of mesna, after long-term or 24 hour infusion of oxazaphosphorine, may be replaced by boluses at 28, 32 and 36 hours, each of 20% (w/w) of the oxazaphosphorine dose, or by oral mesna.

Mesna can be mixed in the same infusion bag as the oxazaphosphorine.

Paediatric population:

Children generally urinate more frequently than adults and therefore it may be necessary to shorten the interval between doses and/or to increase the number of individual doses. The dose of mesna can be increased to 40% of the oxazaphosphorine

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