Consumer medicine information

UROMITEXAN Injection

Mesna

BRAND INFORMATION

Brand name

Uromitexan Injection

Active ingredient

Mesna

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using UROMITEXAN Injection.

What is in this leaflet

This leaflet answers some common questions about UROMITEXAN Injection.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given UROMITEXAN Injection against the benefits they expect it will have for you.

If you have any concerns about having this medicine, ask your doctor or pharmacist.

Keep this leaflet in a safe place.

You may need to read it again.

What UROMITEXAN Injection is used for

UROMITEXAN Injection is a protective agent which is used to prevent damage to your bladder and urinary system, that may be caused by some drugs used to treat cancer or auto-immune diseases. These drugs can cause a condition of the bladder, with pain in the bladder or back and blood in the urine. UROMITEXAN Injection can help prevent this.

Your doctor may have prescribed UROMITEXAN Injection for another reason. Ask your doctor if you have any questions about why UROMITEXAN Injection has been prescribed for you.

Your doctor may decide to give you some of your doses in the form of UROMITEXAN Tablets instead of UROMITEXAN Injection. Both work just as well.

UROMITEXAN Injection is not addictive.

This medicine is available only with a doctor's prescription.

Before you are given UROMITEXAN Injection

When you must not be given it

Do not have UROMITEXAN Injection if you have an allergy to UROMITEXAN Injection or any related products (thiols), or to any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction to UROMITEXAN Injection may include:

  • shortness of breath, wheezing, difficulty breathing or a tight feeling in your chest
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching, hives or flushed, red skin
  • dizziness or lightheadedness
  • fast heart beat

If you are not sure whether you should start having UROMITEXAN Injection, talk to your doctor or pharmacist.

Before you are given it

Tell your doctor or pharmacist if you have allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes

Tell your doctor if you have or have had any medical conditions, especially the following:

  • bladder problems
  • auto-immune disease

Tell your doctor if you have had radiation therapy to the area of the pelvis.

This could mean you need a higher dose of UROMITEXAN Injection.

Tell your doctor if you are pregnant or intend to become pregnant.

Your doctor will discuss the risks and benefits of having your medicines during pregnancy.

Tell your doctor if you are breast-feeding or plan to breast-feed.

It is not known whether UROMITEXAN passes into breast milk. There is also the possibility that the breast-fed baby may be affected by the anti-cancer medicines you are receiving.

If you have not told your doctor about any of the above, tell them before you start having UROMITEXAN Injection.

Taking other medicines

Tell your doctor or pharmacist if you are having any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

It is possible that some medicines and UROMITEXAN Injection may interfere with each other.

How UROMITEXAN Injection is given

How much is given

Your doctor will decide what dose of UROMITEXAN Injection you will receive. This depends mainly on the dose of the anti-cancer medicines you are receiving, and other factors such as any bladder problems you have had in the past.

Ask your doctor if you want to know more about the dose of UROMITEXAN Injection you receive.

How it is given

UROMITEXAN Injection is usually given as an injection into your veins (intravenously).

It may be given either as an injection approximately every 4 hours, or continuously, as an infusion (drip) mixed with other liquids.

How long it is given

UROMITEXAN Injection is usually given just before, during, and for a few hours after each dose of your anti-cancer medicine.

Overdose

As UROMITEXAN Injection is given to you under the supervision of your doctor, it is very unlikely that you will receive too much. However, if you experience any side effects after being given UROMITEXAN Injection, tell your doctor immediately or go to Accident and Emergency at your nearest hospital.

You may need urgent medical attention.

Symptoms of a UROMITEXAN Injection overdose include the side effects listed below in the 'Side Effects' section, but are usually of a more severe nature.

While you are having UROMITEXAN Injection

Things you must do

Be sure to keep all your doctor's appointments so your progress can be checked.

Your doctor may want to check your urine and do some other tests from time to time to check on your progress and detect any unwanted side effects.

Be sure to follow your doctor's instructions about other medicines you should take, and other things you should do.

The protective effect of UROMITEXAN Injection applies only to the bladder and urinary system. You may still need to take additional medicines to protect other body systems.

Your doctor may also advise you to drink extra fluid while you are receiving UROMITEXAN Injection. This will help to prevent damage to your bladder and urinary system. Ask your doctor or pharmacist if you have any questions.

Tell your doctor or nurse if you experience any pain at the injection site.

Tell any other doctors, dentists, and pharmacists who are treating you that you are having UROMITEXAN Injection.

If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are having UROMITEXAN Injection.

If you become pregnant while having UROMITEXAN Injection, tell your doctor.

If you are having any tests on your urine such as for diabetic acidosis, tell your doctor or pharmacist that you are having UROMITEXAN Injection.

UROMITEXAN Injection can interfere with some urine tests.

Things to be careful of

Be careful driving or operating machinery until you know how UROMITEXAN Injection affects you.

As with many other medicines, UROMITEXAN Injection may cause dizziness, light-headedness, and tiredness in some people. Make sure you know how you react to UROMITEXAN Injection before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or light-headed. If this occurs do not drive. If you drink alcohol, dizziness or light-headedness may be worse.

Side effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are having UROMITEXAN Injection.

UROMITEXAN Injection may have unwanted side effects. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

  • headache
  • tiredness, sleepiness
  • nausea, vomiting
  • diarrhoea, soft stools
  • wind
  • constipation
  • abdominal pain
  • loss of appetite
  • bad taste in the mouth
  • fever
  • chills, shivering
  • flushing
  • cough
  • sore throat
  • dizziness
  • pain in the arms or legs
  • pain in the back or joints
  • pain at the injection site

These are the more common or less serious side effects of UROMITEXAN Injection.

If any of the following happen, tell your doctor or nurse immediately, or go to Accident and Emergency at your nearest hospital:

Sudden life-threatening allergic reaction, with symptoms such as:

  • shortness of breath, wheezing, fast breathing, difficulty breathing or a tight feeling in your chest
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching, hives or flushed, red skin
  • conjunctivitis
  • dizziness or light-headedness
  • fast heart beat
  • muscle pain
  • bleeing or bruising more easily than normal

These allergic reactions occur more often in patients being treated for auto-immune diseases than in patients being treated for cancer.

These are very serious side effects. You may need urgent medical attention or hospitalisation.

Other side effects not listed above may occur in some patients. Tell your doctor, nurse or pharmacist if you notice anything that is making you feel unwell.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

The benefits and side effects of UROMITEXAN Injection may take some time to occur. Therefore even after you have finished your treatment with UROMITEXAN Injection you should tell your doctor immediately if you notice any of the side effects listed in this section.

Storage

UROMITEXAN Injection will be stored in the pharmacy or on the ward. It is kept in a cool dry place, where the temperature stays below 30 deg C.

Product description

What it looks like

UROMITEXAN Injection is a clear, colourless liquid in a clear glass ampoule. Each ampoule is used only once and any left over material is discarded.

Ingredients

Active ingredient:

  • mesna

Other ingredients

  • disodium edetate
  • sodium hydroxide
  • water for injection

UROMITEXAN Injection does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

Baxter Healthcare Pty Limited
(ABN 43 000 392 781)
1 Baxter Drive
Old Toongabbie NSW 2146

UROMITEXAN Injection is available in the following sizes:

400mg/4mL AUST R 46627
1g/10mL AUST R 46629

Date of Preparation of this leaflet:
5 April 2006

UROMITEXAN is a trademark of Baxter Healthcare S.A.

BRAND INFORMATION

Brand name

Uromitexan Injection

Active ingredient

Mesna

Schedule

S4

 

1 Name of Medicine

Mesna.

6.7 Physicochemical Properties

Molecular formula: C2H5NaO3S2. Molecular weight: 164.18.

Chemical structure.


CAS number.

19767-45-4.

2 Qualitative and Quantitative Composition

Active ingredient: mesna 100 mg/mL.
The active ingredient, mesna, is a synthetic sulphydryl compound designated as sodium 2mercapto-ethane sulphonate.
Uromitexan contains 100 mg/mL mesna, 0.2 - 0.3 mg/mL edetate disodium and sodium hydroxide for pH adjustment. The solution has a pH range of 6.5 - 8.5.
Excipients: Disodium edetate, sodium hydroxide and water for injections.

3 Pharmaceutical Form

Uromitexan is a sterile preservative-free aqueous solution of clear and colourless appearance in clear glass ampoules for intravenous administration.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Uromitexan was developed as a prophylactic agent used to prevent and reduce the urothelial toxicity (haemorrhagic cystitis) induced by oxazaphosphorine alkylating agents such as ifosfamide or cyclophosphamide.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Metabolism.

Analogous to the physiological cysteine-cystine system, following intravenous administration, mesna is rapidly and easily converted by auto-oxidation to its only metabolite, disodium 2,2'-dithio-bisethane sulphonate (mesna disulphide, dimesna) forming a disulphide link. Following i.v. injection, only a small portion of the administered dose is detected in the blood as a reduced thiol compound (mesna). Mesna disulphide remains in the intravascular space and is rapidly delivered to the kidney. In the renal tubular epithelium a considerable proportion of mesna disulphide is again reduced to a free thiol compound, presumably mediated by glutathione reductase. Acrolein or other urotoxic oxazaphosphorine metabolites are detoxified by chemical reaction with the free thiol compound, i.e. mesna.

Excretion.

The first and most important step towards detoxification is the reaction of mesna with the double bond of acrolein, resulting in the formation of a stable thioether which can be detected in the urine by chromatography. In the second step, mesna reduces the speed of degradation of the 4-hydroxy metabolite in the urine. A relatively stable, nonurotoxic condensation product from 4-hydroxycyclophosphamide or 4-hydroxyifosfamide and mesna is formed. As a result of this chemical interaction, mesna inhibits the degradation of 4-hydroxycyclophosphamide or 4-hydroxyifosfamide and hence the formation of acrolein. The presence of this intermediate chemical species can be detected by chromatographic urinalysis.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No long-term animal studies have been performed to evaluate the carcinogenic potential of mesna.

4 Clinical Particulars

4.1 Therapeutic Indications

For the reduction and prevention of urinary tract toxicity (haemorrhagic cystitis) of oxazaphosphorines (see Section 4.8 Adverse Effects (Undesirable Effects) of the cyclophosphamide and ifosfamide Product Information).

4.3 Contraindications

Uromitexan is contraindicated in individuals with a known hypersensitivity to mesna or any of the excipients (see Section 6.1 List of Excipients) and other thiols.

4.4 Special Warnings and Precautions for Use

The protective effect of mesna applies only to the urothelial toxic effects of oxazaphosphorines (viz. ifosfamide or cyclophosphamide) not to their renal and other toxic effects. Additional prophylactic or accompanying measures recommended during treatment with oxazaphosphorines are thus not affected and should not be discontinued.
Severe allergic symptoms, such as systemic anaphylactic reactions, have occurred with mesna, especially in patients suffering from autoimmune diseases.
Due to the possibility of anaphylactoid reactions, it should be ensured that adequate emergency medication is available.
Patients with autoimmune diseases who were treated with cyclophosphamide and Uromitexan appeared to have a higher incidence of hypersensitivity reactions: skin and mucosal reactions of varying extent and severity (rash, itching, redness, severe bullous and ulcerative skin, vesiculation, Lyell syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema exudative multiforme), localised or generalised urticarial or other forms of exanthema, pruritus, burning, local tissue swelling (urticarial oedema), angioedema and/or flushing. Some reactions appeared to be consistent with a diagnosis of fixed drug eruption. Skin reactions were accompanied by one or more other symptoms (see Section 4.8 Adverse Effects (Undesirable Effects)) such as:
fever;
conjunctivitis;
cardiovascular symptoms (hypotension, in some cases reported as fluid refractory, associated with circulatory reactions and increased pulse rate above 100/min (tachycardia) hypertension, ST segment elevation, ECG signs consistent with perimyocarditis);
signs consistent with acute renal failure;
pulmonary symptoms (hypoxia, respiratory distress, bronchospasm, cough, bloody sputum and increased respiration rate (tachypnoea) due to severe acute hypersensitivity reactions;
prolonged prothrombin time and partial prothrombin time, laboratory signs of disseminated intravascular coagulopathy;
haematological abnormalities (leukopaenia, eosinophilia, lymphopaenia, thrombocytopaenia, pancytopaenia;
pain in the extremities, arthralgia, myalgia, malaise;
transient rise in certain liver function tests (e.g. transaminases);
nausea, vomiting, stomatitis.
Photodistribution of a rash has also been reported. Some reactions have presented as anaphylaxis. Fever accompanied by e.g. hypotension but no skin manifestations has also been reported.
Severe as well as minor reactions were reported with the use of mesna in regimens to treat both severe systemic autoimmune disorders and malignancy. In most cases, reactions occurred during or after a first treatment occasion or after several weeks of mesna exposure. In other cases, the initial reaction was observed only after several months of exposure. In many cases, symptoms appeared on the day of exposure, with a tendency to shorter intervals following subsequent exposures.
In some patients, the occurrence and/or severity of reaction appeared to vary with the dose administered. Recurrence of reactions, in some cases with increasing severity, has been reported with re-exposure. However, in some cases, a reaction did not recur with re-exposure.
Some patients with a history of a reaction have shown positive delayed type skin test results. However, a negative delayed reaction does not exclude hypersensitivity to mesna. Positive immediate type skin test reactions have occurred in patients regardless of previous mesna exposure or history of hypersensitivity reactions, and may be related to the concentration of the mesna solution used for testing.
Protection of the urinary tract with mesna should therefore only be undertaken in such patients with autoimmune diseases following careful risk benefit analysis and under medical supervision. Prescribers should:
be aware of the potential for such reactions and that reactions may worsen with re-exposure and may in some cases be life threatening;
be aware that hypersensitivity reactions to mesna were interpreted to resemble the clinical picture of sepsis and, in patients with autoimmune disorders, resemble an exacerbation of the underlying disease.

Thiol compounds.

Mesna is a thiol compound, i.e. a sulfhydryl group containing organic compound. Thiol compounds show some similarities in their adverse reaction profile, including a potential to elicit severe skin reactions. Examples of drugs that are thiol compounds include amifostine, penicillamine, and captopril.
It is not clear whether patients who experienced an adverse reaction to such a drug are at increased risk for any reactions, or similar reactions, to another thiol compound. However, when considering subsequent use of another thiol compound in such patients, the possibility of an increased risk should be taken into account.
Uromitexan does not prevent haemorrhagic cystitis in all patients. As a result, a morning specimen of urine should be examined for the presence of haematuria (microscopic evidence of red blood cells) and proteinuria, each day prior to oxazaphosphorine therapy. If haematuria develops when Uromitexan is given with oxazaphosphorines according to the recommended dosage schedule, depending on the severity of the haematuria, dosage reduction or discontinuation of oxazaphosphorine therapy may be indicated.
Urinary output should be maintained at 100 mL/hr (as required for oxazaphosphorine treatment). The urine should be monitored for haematuria and proteinuria throughout the treatment period.

Use in the elderly.

In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. The ratio of oxazaphosphorines to mesna should remain unchanged.

Paediatric use.

Safety and effectiveness of Mesna in paediatric patients (< 16 years of age) have not been established in formal clinical studies but its use in paediatric patients is referenced in the medical literature.

Effects on laboratory tests.

A false positive test in nitroprusside sodium-based urine tests (including dipstick tests) for urinary ketones may arise in patients treated with Uromitexan. In this test, a red-violet (rather than purple) colour develops which is less stable, e.g. with the addition of glacial acetic acid, will return to violet.
Mesna treatment may cause false positive reactions in Tillman's reagent-based urine screening tests for ascorbic acid.
Mesna may also cause false positive or false negative reactions in the dipstick test for erythrocytes in urine. To exactly determine erythrocytes in the urine, urinary microscopy is recommended.
In pharmacokinetics studies in healthy volunteers, serum creatine phosphokinase (CPK) values were lower in samples taken 24 hours after mesna dosing than in pre-dosing samples. While available data are insufficient to determine the cause of this phenomenon, it might be considered to represent a significant interference with thiol (e.g. N-acetylcysteine) dependent enzymatic CPK tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

In vitro and in vivo animal tumour models have shown that mesna does not have any effect on the antitumour efficacy of concomitantly administered cytotoxic agents.
Also see Section 6.2 Incompatibilities.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Animal studies of potential toxicity in a fertility and general reproductive screen have not been carried out. It is not known whether Uromitexan can affect reproductive capacity.
(Category B1)
Teratology studies with oral doses of mesna to rabbits at up to 1000 mg/kg/day and to rats at up to 2000 mg/kg/day have revealed no harm to the foetus. Animal studies of potential toxicity in a peri-/post-natal screen has not been carried out. It is not known whether Uromitexan can cause foetal harm when administered to a pregnant woman. Uromitexan should be given to a pregnant woman only if the benefits clearly outweigh any possible risks.
It is not known whether mesna or dimesna are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breast-fed infants, a decision should be made whether to discontinue breast-feeding or discontinue the drug, taking into account the importance of the drug to the mother.

4.8 Adverse Effects (Undesirable Effects)

As Uromitexan is used in combination with oxazaphosphorine alkylating agents and other chemotherapeutic agents with documented toxicities, it is difficult to distinguish the adverse reactions which may be due to Uromitexan from those caused by the concomitantly administered cytotoxic agents.
As a result, the adverse reaction profile of Uromitexan was determined in three phase I studies (16 subjects) utilising intravenous and oral administration and 2 controlled studies in which ifosfamide and Uromitexan were compared to ifosfamide and standard prophylaxis.
In phase I studies in which i.v. bolus doses of 0.8-1.6 g/m2 Uromitexan were administered as a single or three repeated doses to a total of 10 subjects, a bad taste in the mouth (100%) and soft stools (70%) were reported. At intravenous and oral bolus doses of 2.4 g/m2, headache (50%), fatigue (33%), nausea (33%), diarrhoea (83%), limb pain (50%), hypotension (17%) and allergy (17%) were reported in the 6 subjects who participated in this study.
Frequently reported side effects from clinical studies and/or spontaneous reporting are nausea, vomiting, flatulence, diarrhoea, constipation, colic (e.g. abdominal pain), anorexia, influenza-like reactions, fever, rigors, flushing, cough, pharyngitis, lightheadedness/ dizziness, lethargy/ somnolence, headache, back pain, arthralgia.
Venous irritation may occur in rare instances. This reaction may be attributed to the physical properties of mesna (i.e. pH 6 and hypertonic solution). No venous complications were observed when the solution was given diluted with Sterile Water for Injection BP (1 part mesna solution to 3 parts water).
Isolated cases of partially organ related hypersensitivity reactions have been reported, e.g. in some cases associated with decreased platelet counts (thrombocytopenia), skin and mucosal reactions of varying extent and severity (rash, itching, redness, vesiculation, Lyell syndrome, Stevens-Johnson syndrome), local tissue swelling (urticarial oedema), conjunctivitis. Very rare cases of hypotension associated with circulatory reactions and increased pulse rate above 100/min (tachycardia), as well as increased respiration rate (tachypnoea) due to severe acute hypersensitivity reactions (anaphylactoid reactions), hypertension, ST segment elevation, myalgia and also a transient rise in certain liver function tests (e.g. transaminases) have been reported.
The most severe adverse reactions associated with use of mesna are: toxic epidermal necrolysis, Stevens-Johnson syndrome, anaphylaxis, and drug rash with eosinophilia and systemic symptoms (DRESS). The occurrence of hypersensitivity reactions (hyperergic reactions) following Uromitexan has been reported more frequently in patients with autoimmune disorders than in tumour patients (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use). See Table 1.

Time to onset.

In these studies, some subjects experienced their events on first exposure to mesna and others after the second or third exposure. In general, the complete spectrum of symptoms experienced by a subject developed over a period of several hours.

Experience with re-exposure.

Some subjects experienced no further reactions after their initial event while others experienced an exacerbation of events upon repeated dosing.

Infusion site reactions.

In some subjects experiencing local cutaneous infusion site reactions, subsequent exposure to mesna resulted in a cutaneous event in other areas.

Cutaneous/ mucosal reactions.

Cutaneous and mucosal reactions were reported to occur after both intravenous and oral mesna. These reactions included rashes, pruritus, flushing, mucosal irritation, pleuritic pain, and conjunctivitis. Approximately one-quarter of subjects with any event experienced cutaneous/ mucosal reactions in conjunction with other adverse symptoms, which included, dyspnoea, fever, headache, gastrointestinal symptoms, drowsiness, malaise, myalgia, and influenza-like symptoms.

Gastrointestinal reactions.

Gastrointestinal reactions reported in healthy subjects included nausea, vomiting, diarrhoea, abdominal pain/ colic, epigastric pain/ burning, constipation, and flatulence and were reported to occur after intravenous and oral mesna administration.

In vivo effect on lymphocyte counts.

In pharmacokinetics studies in healthy volunteers, administration of single doses of mesna was commonly associated with a rapid (within 24 hours) and in some cases marked decrease in lymphocyte count, which was generally reversible within 1 week of administration. Data from studies with repeated dosing over several days are insufficient to characterize the time course of lymphocyte count changes under such conditions.

In vivo effect on serum phosphorus levels.

In pharmacokinetics studies in healthy volunteers, administration of mesna on single or multiple days was in some cases associated with moderate transient increases in serum phosphorus concentration. These phenomena should be considered when interpreting laboratory results.

Postmarketing adverse reactions.

The following adverse reactions have been identified from postmarketing reports of patients receiving mesna in combination with oxazaphosphorine cytostatics and other medications.
Many of the adverse reactions listed occurred as part of a syndrome suggestive of hypersensitivity reactions (see Section 4.4 Special Warnings and Precautions for Use).

Blood and lymphatic system disorders.

Pancytopaenia, leukopaenia, lymphopaenia, thrombocytopaenia, eosinophilia.

Immune system disorders.

Anaphylaxis, hypersensitivity.

Nervous system disorders.

Convulsion.

Eye disorders.

Periorbital oedema.

Cardiac disorders.

Electrocardiogram abnormal (consistent with perimyocarditis), tachycardia.

Vascular disorders.

Hypotension (in some cases fluid refractory), hypertension.

Respiratory, thoracic, mediastinal disorders.

Respiratory distress, hypoxia, oxygen saturation decreased, tachypnoea, haemoptysis.

Gastrointestinal disorders.

Stomatitis, bad taste.

Hepatobiliary disorders.

Hepatitis, gamma-glutamyl transferase increased, blood alkaline phosphatase increased.

Skin and subcutaneous tissue disorders.

Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, drug rash with eosinophilia and systemic symptoms, ulcerations and/or bullae/ blistering (mucocutaneous, mucosal, oral, vulvovaginal, anorectal), angioedema, fixed drug eruption, rash (vesicular, exfoliative, maculopapular, morbilliform), photodistributed rash, urticaria, burning sensation, erythema.

Renal and urinary disorders.

Acute renal failure.

General disorders and administration site conditions.

Face oedema, oedema peripheral, asthenia, infusion site reactions (thrombophlebitis, irritation).

Investigations.

Laboratory signs of disseminated intravascular coagulation, prothrombin time prolonged, activated partial thromboplastin time prolonged.

Injury, poisoning and procedural complications.

Occupational sensitization to other mesna formulations used for inhalation (manifested as eczema, papulovesicular rash, erythema, pruritus).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Sufficient mesna must be given to protect the patient adequately from the urothelial toxic effects of the oxazaphosphorine. When calculating the dose of mesna, the quantity should be rounded up to the nearest whole ampoule.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration. Any solutions which are discoloured or contain visible particulate matter should not be used.
Mesna injection should be administered intravenously only, over 15-30 minutes, usually at 20% of the respective oxazaphosphorine dose, at each of the times 0 (= administration of the cytostatic agent), 4 hours and 8 hours. The total dose of mesna is 60% of the oxazaphosphorine dose and is repeated on each occasion that the cytotoxic agents are used.

Preparation.

For intravenous administration. The drug can be diluted by adding the contents of a Uromitexan ampoule to any of the following fluids obtaining final concentrations of 1.5 to 3 mg mesna/mL fluid:
glucose injection 5%;
sodium chloride injection 0.9%;
sodium chloride and glucose injection (with concentrations ranging from 0 - 0.9% sodium chloride and 0 - 5% glucose);
lactated Ringer's injection.
Solutions of mesna when diluted in the solutions nominated above may be prepared and, if necessary, stored for short periods under refrigeration. However, the diluted solutions do not contain an antimicrobial preservative, and in order to reduce microbial hazards, it is recommended that dilution should be effected as soon as practicable prior to use, and infusion commenced as soon as practicable thereafter.
Infusion should be started within 6 to 8 hours of preparation of the admixture and completed within 24 hours, with any residue discarded.
Diluted solutions should be inspected visually before use. Any solutions which are discoloured, hazy or contain visible particulate matter should not be used.

4.7 Effects on Ability to Drive and Use Machines

Patients undergoing treatment with mesna may experience undesirable effects (including, e.g. syncope, lightheadedness, lethargy/ drowsiness, dizziness, and blurred vision) which could affect the ability to drive or use machines. The decision to drive or operate machinery should be made on an individual basis.

4.9 Overdose

No specific antidote for mesna is known. Overdosage should be managed with supportive measures to sustain the patient through any period of toxicity. Mesna has been administered at doses from 70 to 100 mg/kg without any toxic effect on haematopoiesis, hepatic or renal function or the CNS.
Overdose may lead to the reactions observed in a tolerability study in healthy volunteers at single doses of 60-70 mg/kg: nausea, vomiting, abdominal pain, colic, diarrhoea, headache, fatigue, paresthesia, fever, limb and joint pains, lack of energy like exhaustion and weakness, depression, irritability, rash, bronchospasm, flushing, hypotension, bradycardia and tachycardia.
A markedly increased rate of nausea, vomiting and diarrhoea has also been found in oxazaphosphorine treated patients receiving mesna ≥ 80 mg/kg/day intravenously compared with patients receiving lower doses or hydration treatment only.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

In vitro mesna is incompatible with cisplatin, carboplatin and nitrogen mustard. The combination of an oxazaphosphorine cytostatic agent with mesna and cisplatin in the same infusion solution is not stable and is not to be used.
Holoxan (ifosfamide, 3 mg/mL) may be admixed with diluted mesna solutions 1.5 to 3.0 mg/mL (0.15 to 0.3%). Admixtures of Holoxan 3.0 mg/mL and Uromitexan 1.5 to 3.0 mg/mL stored in PVC plastic bags and refrigerated have been shown to be chemically and physically stable for 24 hours when diluted in the following sterile solutions:
Sodium Chloride Injection 0.9%;
Compound Sodium Lactate Injection;
Glucose Injection 5%;
Glucose 2.5% + Sodium Chloride 0.45% Injection.
However, because of the risk of microbial contamination it is recommended that admixtures be administered within 6 to 8 hours of preparation.
Mixing mesna and epirubicin leads to inactivation of epirubicin and should be avoided.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

The ampoules should be stored below 30°C (unopened vials).

6.5 Nature and Contents of Container

Uromitexan (mesna) Solution for Injection 100 mg/mL.

Package size.

400 mg Single Dose Ampoule. Box of 15 glass ampoules of 4 mL (colour-ring coding blue/green).
1 g Single Dose Ampoule. Box of 15 glass ampoules of 10 mL (colour-ring coding blue/green).

6.6 Special Precautions for Disposal

Any unused product or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes