Desferrioxamine Mesilate 2 g powder for solution for injection or infusion – patient leaflet, side effects, dosage

1. What Desferrioxamine Mesilate is and what it is used for

Desferrioxamine Mesilate is an injection used to remove excess iron or aluminium from your blood.

Desferrioxamine mesilate, the active ingredient in this medicine, is a substance called a ‘chelating’ agent. This means that it binds to the iron and aluminium ions in the blood to form a complex which is then excreted from the body. You may have too much iron or aluminium in your blood as a result of iron poisoning or as a side effect of blood transfusion or kidney dialysis. Certain illnesses can also have the same effect.

Desferrioxamine Mesilate can also be used to test whether you have certain anaemias or diseases affecting the amount of iron in your blood.

2. What you need to know before you use Desferrioxamine Mesilate

Do not use Desferrioxamine Mesilate:

• If you are allergic to desferrioxamine or any of the other

  ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, or nurse before using Desferrioxamine Mesilate:

• If you are pregnant or planning to become pregnant. If

  you become pregnant while you are being treated with Desferrioxamine Mesilate you must tell your doctor straight away.

• If you are breast feeding.
• If you have any kidney problems or you are on dialysis.
• If you have a heart condition.
• If you have the blood condition thalassaemia.

• If Desferrioxamine Mesilate is going to be given to a child

  under the age of 3 years. If it is, the doctor may want to monitor the child’s growth regularly to make sure it is not being affected by the Desferrioxamine Mesilate.

• If your doctor has told you that you have

  hyperparathyroidism (a condition resulting in excess calcium in the blood and problems with the bones).

• If your doctor has told you that aluminium has affected

  your nerves. If so, you may be given a dose of clonazepam before you are given Desferrioxamine Mesilate.

Other warnings and precautions

• Medical check-ups while you are using

  Desferrioxamine Mesilate

If you use Desferrioxamine Mesilate for a long time or you have kidney problems and are on dialysis, your doctor may want to give you regular eye tests and hearing tests. This is because Desferrioxamine Mesilate can affect your vision and your hearing. These tests are usually done every 3 months.

• Children

In children under the age of 3 years high doses of Desferrioxamine Mesilate may affect growth. Regular checks on body weight and height are, therefore, recommended in children using Desferrioxamine Mesilate. These checks are usually done every 3 months.

• X-rays or scans

The results may be affected by treatment with Desferrioxamine Mesilate. Make sure that the doctor or nurse knows that you are being treated with Desferrioxamine Mesilate if an X-ray or scan is suggested.

Other medicines and Desferrioxamine Mesilate

Some medicines can interfere with your treatment. Tell your doctor if you are taking any of the following:

• prochlorperazine, a medicine used to control vertigo or nausea and vomiting, anxiety or schizophrenia.
• erythropoietin (used to treat anaemia, particularly in people who are on dialysis).
• Vitamin C.

Tell your doctor if you are taking, have recently taken or might take any other medicines.

This means medicines you have bought yourself as well as medicines on prescription from your doctor.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Driving and using machines

This medicine can make you feel dizzy or drowsy. It can also affect your vision or hearing. You must not drive, operate machinery or do anything else, which requires concentration, until you know how your medicine affects you.

3. How to use Desferrioxamine Mesilate

The doctor will have decided what dose of Desferrioxamine Mesilate you need and when you should receive it. The dose will be on the pharmacist’s label. Check the label carefully. Check with your doctor or nurse if you are not sure. A doctor or nurse may prepare your injection for you, or you may be taught how to do this yourself. The Desferrioxamine Mesilate powder should be dissolved in the ‘water for injection’ that your pharmacist has given you.

Treatment with the solution should start within 3 hours of the vial being reconstituted. If the solution has been prepared under sterile conditions (for instance in a hospital), it may be stored at room temperature (25 ^oC or below) for up to 24 hours before being used. Any unused Desferrioxamine Mesilate injection should be thrown away.

Ways in which Desferrioxamine Mesilate can be given

Desferrioxamine Mesilate can be given in different ways, for example:

• By injection into a muscle. This is called being given intramuscularly.
• By injection into a vein. This is called being given intravenously. It should be given slowly over a period of time rather than all in one go. This is called a slow infusion.
• By injection under your skin. This is called being given subcutaneously. It may be given over a period of time using a special pump. This is called an infusion.
• By injection into the peritoneum (the membrane that lines the abdominal cavity and forms the outer coating of the abdominal organs). This is called intraperitoneal administration.

The dose that you need will depend on why you have to use Desferrioxamine Mesilate. Your doctor will work out exactly how much Desferrioxamine Mesilate you need. This is especially important if you have low serum ferritin levels or acute iron intoxication.

The recommended doses and ways of taking Desferrioxamine Mesilate are as follows:

• Iron Poisoning Treatment

To treat iron poisoning Desferrioxamine Mesilate is usually given intravenously (injected into the vein). The recommended dose is 15 mg/kg body weight every hour. This may be reduced after 4 to 6 hours. The maximum recommended dose is 80 mg/kg body weight every 24 hours.

Desferrioxamine Mesilate may also be given intramuscularly (injected into the muscle). The recommended dose if Desferrioxamine Mesilate is given like this is 2 g for an adult or 1 g for a child. This is usually given in a single injection.

• Iron Overload Treatment

Your doctor will work out exactly how much Desferrioxamine Mesilate you will need. This will depend on how much extra iron you have in your body. Desferrioxamine Mesilate is usually given subcutaneously (a slow injection under the skin). It can sometimes be given intramuscularly (injected into the muscle) though. The recommended dose is usually between 20 and 60 mg/kg body weight. It is usually given between 5 and 7 times a week, depending on how much extra iron you have got in your body. In children under 3 years of age the average daily dose is not usually more than

40 mg/kg.

• Aluminium Overload Treatment

Desferrioxamine Mesilate is usually given by slow intravenous injection.

The exact dose of Desferrioxamine Mesilate that you need will depend on how much extra aluminium you have in your body. Your doctor will do tests to work this out.

If you are on dialysis, the recommended dose of Desferrioxamine Mesilate is 5 mg/kg body weight. This is normally given once a week. When you are given Desferrioxamine Mesilate will depend on how much extra aluminium you have in your body. It will either be given during the last 60 minutes of your dialysis or 5 hours before your dialysis starts.

If you are on peritoneal dialysis (CAPD or CCPD), the Arial 9pt - 160x840 mm

The following information is intended for healthcare professionals only:

Special precautions for storage and disposal and other handling

Vial: Store below 25^oC.

Reconstituted solution: Single use only.

The product should be used immediately after reconstitution (commencement of treatment within 3 hours). When prepared under validated aseptic conditions the reconstituted solution may be stored for a maximum of 24 hours at room temperature (25 ^oC or below) before administration. If not used immediately, in-use storage times and conditions prior to administration are the responsibility of the user. Unused solution should be discarded.

The reconstituted solution should be clear. Do not use if particles are present. Desferrioxamine Mesilate should preferably be employed in the form of a 10% aqueous solution, by dissolving the contents of one 500 mg vial in 5 mL of Water for injections or 2 g vial in 20 mL of Water for injections.

Therapeutic indications

Treatment for chronic iron overload, e.g.

• transfusional haemosiderosis in patients receiving regular

  transfusions e.g. thalassaemia major

• primary and secondary haemochromatosis in patients

  in whom concomitant disorders (e.g. severe anaemia, hypoproteinaemia, renal or cardiac failure) preclude phlebotomy.

Treatment for acute iron poisoning.

For the diagnosis of iron storage disease and certain anaemias.

Aluminium overload - In patients on maintenance dialysis for end stage renal failure where preventative measures (e.g. reverse osmosis) have failed and with proven aluminium-related bone disease and/or anaemia, dialysis encephalopathy; and for diagnosis of aluminium overload.

Posology and method of administration

Method of administration

Desferrioxamine Mesilate may be administered parenterally (intramuscularly, intravenously, or subcutaneously).

For parenteral administration:

The medicinal product should preferably be employed in the form of a 10% solution, e.g. 500 mg: by dissolving the contents of one 500 mg vial in 5 mL of water for injection or 2 g: by dissolving the contents of one 2 g vial in 20 mL of water for injection. When administered subcutaneously the needle should not be inserted too close to the dermis. The 10% Desferrioxamine Mesilate solution can be diluted with routinely employed infusion solutions (Sodium Chloride 0.9% Infusion, Dextrose 5% Infusion, combination of Sodium Chloride 0.9% and Dextrose 5% Infusion solutions, Ringer’s Lactate), although these should not be used as solvent for the dry substance. Dissolved Desferrioxamine Mesilate can also be added to dialysis fluid and given intraperitoneally to patients on continuous ambulatory peritoneal dialysis (CAPD) or continuous cyclic peritoneal dialysis (CCPD). Only clear pale yellow Desferrioxamine Mesilate solutions should be used. Opaque, cloudy or discoloured solutions should be discarded. Heparin is pharmaceutically incompatible with Desferrioxamine Mesilate solutions.

Posology

1. 1) Treatment of acute iron poisoning

Adults and children:

Desferrioxamine Mesilate may be administered parenterally. Desferrioxamine Mesilate is an adjunct to standard measures generally used in treating acute iron poisoning. It is important to initiate treatment as soon as possible.

Parenteral Desferrioxamine Mesilate treatment should be considered in any of the following situations:

• all symptomatic patients exhibiting more than transient

  minor symptoms (e.g. more than one episode of emesis or passage of one soft stool).

• patients with evidence of lethargy, significant abdominal

  pain, hypovolaemia, or acidosis.

• patients with positive abdominal radiograph results

  demonstrating multiple radio-opacities (the great majority of these patients will go on to develop symptomatic iron poisoning).

• any symptomatic patient with a serum iron level greater

  than 300 to 350 micro g/dL regardless of the total iron binding capacity (TIBC). It has also been suggested that a conservative approach without Desferrioxamine Mesilate therapy or challenge should be considered when serum iron levels are in the 300 to 500 micro g/dL range in asymptomatic patients, as well as in those with self-limited, non-bloody emesis or diarrhoea without other symptoms.

The dosage and route of administration should be adapted to the severity of the poisoning.

Dose and method of administration

The continuous intravenous administration of Desferrioxamine Mesilate is the preferred route and the recommended rate for infusion is 15 mg/kg per hour and should be reduced as soon as the situation permits, usually after 4 to 6 hours so that the total intravenous dose does not exceed a recommended 80 mg/kg in any 24 hour period.

However, if the option to infuse intravenously is not available and if the intramuscular route is used the normal dosage is 2 g for an adult and 1 g for a child, administered as a single intramuscular dose.

The decision to discontinue Desferrioxamine Mesilate therapy must be a clinical decision; however, the following suggested criteria are believed to represent appropriate requirements for the cessation of Desferrioxamine Mesilate. Chelation therapy should be continued until all of the following criteria are satisfied:

• The patient must be free of signs and symptoms of

  systemic iron poisoning (e.g. no acidosis, no worsening hepatoxicity).

• Ideally, a corrected serum iron level should be normal or

  low (when iron level falls below 100 micro g/dL). Given that laboratories cannot measure serum

  iron concentrations accurately in the presence of Desferrioxamine Mesilate, it is acceptable to discontinue Desferrioxamine Mesilate when all other criteria are met if

  the measured serum iron concentration is not elevated.

  • Repeat abdominal radiograph test should be obtained in patients who initially demonstrated multiple radio-opacities to ensure they have disappeared before Desferrioxamine Mesilate is discontinued because they serve as a marker for continued iron absorption.
  • If the patient initially developed vin-rose coloured urine with Desferrioxamine Mesilate therapy, it seems reasonable that urine colour should return to normal before halting Desferrioxamine Mesilate (absence of vin-rose urine is not sufficient by itself to indicate discontinuation of Desferrioxamine Mesilate).

The effectiveness of treatment is dependent on an adequate urine output in order that the iron complex (ferrioxamine) is excreted from the body. Therefore if oliguria or anuria develop, peritoneal dialysis or haemodialysis may become necessary to remove ferrioxamine.

It should be noted that the serum iron level may rise sharply when the iron is released from the tissues.

Theoretically 100 mg Desferrioxamine Mesilate can chelate 8.5 mg of ferric iron.

1. 2) Chronic Iron Overload

The main aim of therapy in well-controlled patients is to maintain an iron balance and prevent haemosiderosis, whilst in overloaded patients a negative iron balance is desirable in order to deplete the increased iron stores and to prevent the toxic effects of iron.

Adults and children

Desferrioxamine Mesilate therapy should be commenced after the first 10-20 blood transfusions, or when there is evidence from clinical monitoring that chronic iron overload is present (e.g. serum ferritin >1000 ng/mL). The dose and mode of administration should be individually adapted according to the degree of iron overload.

Growth retardation may result from iron overload or excessive Desferrioxamine Mesilate doses. If chelation is started before 3 years of age growth must be monitored carefully and the mean daily dose should not exceed 40 mg/kg (see section 4.4 Special warnings and precautions for use of the SmPC).

Dose

The lowest effective dose should be used. The average daily dose will probably lie between 20 and 60 mg/kg/day. Patients with serum ferritin levels of < 2000 ng/mL should require about 25 mg/kg/day and those with levels between 2000 and 3000 ng/mL about 35 mg/kg/day. Higher doses should only be employed if the benefit for the patient outweighs the risk of unwanted effects.

Patients with higher serum ferritin may require up to 55 mg/kg/day. It is inadvisable to regularly exceed an average daily dose of 50 mg/kg/day except when very intensive chelation is needed in patients who have completed growth. If ferritin values fall below 1000 ng/mL, the risk of Desferrioxamine Mesilate toxicity increases; it is important to monitor these patients particularly carefully and perhaps to consider lowering the total weekly dose.

To assess the chelation therapy, 24 hour urinary iron excretion should initially be monitored daily. Starting with a dose of 500 mg daily the dose should be raised until a plateau of iron excretion is reached. Once the appropriate dose has been established, urinary iron excretion rates can be assessed at intervals of a few weeks.

Alternatively the mean daily dose may be adjusted based on ferritin level in order to keep the therapeutic index below 0.025 (i.e. the mean daily dose (mg/kg) of Desferrioxamine Mesilate divided by the serum ferritin level (micro g/L) should be below 0.025). The therapeutic index is a valuable tool in protecting the patient from excess chelation, but it is not a substitute for careful clinical monitoring.

Method of administration

Slow subcutaneous infusion using a portable, light-weight, infusion pump over a period of 8-12 hours is effective and particularly convenient for ambulant patients. It may be possible to achieve a further increase in iron excretion by infusing the same daily dose over a 24 hour period. Desferrioxamine Mesilate should normally be used with the pump 5-7 times a week. Desferrioxamine Mesilate is not formulated to support subcutaneous bolus injection. Since the subcutaneous infusions are more effective, intramuscular injections are given only when subcutaneous infusions are not feasible.

Elderly

Clinical studies of desferrioxamine did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently compared to younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other medicinal product therapy’ (see sections 4.4 Special warnings and precautions for use and 4.8 Undesirable effects of the SmPC).

Hepatic impairment

No studies have been performed in patients with hepatic impairment.

Intravenous infusion during blood transfusion

The availability of an intravenous line during blood transfusions makes it possible to administer an intravenous infusion, e.g. in patients who comply poorly with and/or do not tolerate subcutaneous infusions.

The Desferrioxamine Mesilate solution should not be put directly into the blood bag but may be added to the blood line by means of a “Y” adaptor located near to venous site of injection. The patient’s pump should be used to administer Desferrioxamine Mesilate as usual. Because of the limited amount of medicinal product that can be administered by IV infusion during blood transfusion, the clinical benefit of this mode of administration is limited. Patients and nurses should be warned against accelerating the infusion, as an intravenous bolus of Desferrioxamine Mesilate may lead to flushing, hypotension and acute collapse (see section 4.4 Special warnings and precautions for use of the SmPC). Continuous intravenous infusion is recommended for patients incapable of continuing subcutaneous infusions and in those who have cardiac problems secondary to iron overload. 24 hour urinary iron excretion should be measured regularly recommended dose of Desferrioxamine Mesilate is again 5 mg/kg body weight. This is normally given once a week. Usually the Desferrioxamine Mesilate is mixed with the fluid in your dialysis bag. However, it can also be given by any of the other ways listed above.

• Testing to see if you have got too much iron in your body

Desferrioxamine Mesilate is usually given intramuscularly (injected into a muscle). The recommended dose is 500 mg. After you have had your Desferrioxamine Mesilate, your doctor or nurse will probably want you to collect urine samples for about 6 hours. They will then do tests on your urine to see how much iron is in it.

• Testing to see if you have got too much aluminium in your body if you are on dialysis

Your doctor or nurse will probably take a blood sample from you before you are given Desferrioxamine Mesilate. This will be taken just before your dialysis. Tests will be done on the blood to see how much aluminium is in it.

The recommended dose of Desferrioxamine Mesilate is 5 mg/kg body weight. It is usually given by slow intravenous infusion (slow injection into a vein) during the last hour of dialysis.

Another blood test will probably be taken before your next session of haemodialysis to check how much aluminium is in your blood.

Use in older patients

Desferrioxamine Mesilate is used in older patients at the same doses as for other adults.

If you use more Desferrioxamine Mesilate than you should

If you think you have either been given or have used too much Desferrioxamine Mesilate tell your doctor or nurse straight away. If you think you have either been given it or have used it too often, also tell your doctor or nurse straight away.

If you forget to use Desferrioxamine Mesilate

If you miss one of your appointments, please let your doctor or nurse know immediately.

4. Possible side effects

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

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Your urine may turn a reddish-brown colour. This is because there is more iron in your urine. This is usually nothing to worry about, but if you are worried you should talk to your doctor or nurse.

Some side effects can be serious

Stop using Desferrioxamine Mesilate and tell your doctor straight away:

• If you feel faint (you might have low blood pressure),

  have a rash or experience itching, tightness of chest with wheezing or coughing and difficulty in breathing (Bronchospasm) or facial and throat swelling. These might be the result of an allergic reaction which is very rare (likely to affect fewer than 1 in 10,000 patients).

• If you notice severe decrease of urine output (sign of

  kidney problem) or experience convulsion (reported mainly in patients on dialysis). Those side effects were reported with unknown frequency.

Important information if you get an infection while you are taking Desferrioxamine Mesilate

If you start to feel feverish with a sore throat or stomach pains or general discomfort or develop shortness of breath while you are taking Desferrioxamine Mesilate, you must seek medical advice immediately.

This is because people who have iron or aluminium overload are more vulnerable to certain types of infection. If you get an infection your doctor may want you to do some tests and give you some medicines to treat the infection. You may also have to stop using Desferrioxamine Mesilate until any infections clear up.

It is very common (may affect more than 1 in 10 people) to develop pain, swelling, redness, a rash, itch or scabbing at the Desferrioxamine Mesilate injection site. Less frequently blisters and a burning sensation might be experienced. Aching muscles or joints in the arms or legs is also very common.

The side effects listed below have also been reported. Common: may affect up to 1 in 10 people:

• Headache, nausea (feeling sick) or fever.
• Itchy rash.

• Changes in their bones, slowing down of growth

  (especially in children under 3).

Uncommon: may affect up to 1 in 100 people:

• Vomiting, stomach pains.
• Asthma.
• Problems with their ears such as tinnitus and deafness.

Rare: may affect up to 1 in 1,000 people:

• Problems with their eyes such as blurred vision, impaired

  or loss of vision, not being able to see colours as well (colour blindness), not being able to see at night (night

  blindness), blind spots, changes in the retina, cataracts (cloudy lenses), cloudiness on the front of the eye (or cornea).

  • Low blood pressure (light headedness, dizziness, faintness). This can happen if Desferrioxamine Mesilate is not given correctly.
  • Increased risk of getting certain infections.

Very rare: may affect up to 1 in 10,000 people:

• Skin rash covering most of the body.
• A serious condition which causes severe breathing problems called Acute Respiratory Distress Syndrome.
• Diarrhoea.
• Changes in the blood which can make you look pale or cause tiredness, headaches, nosebleeds, dizziness or being short of breath when exercising. You might also get more frequent viral infections (fever, chills, sore throat or mouth ulcers), or find that you bleed or bruise more easily than normal.
• Stomach and gut infections.
• Other effects such as dizziness, loss of feeling in their hands, feet, arms or legs, numbness or tingling (pins and needles).
• In patients on dialysis: personality changes, headache, confusion, paralysis of part or all of the body, stiff neck, abnormal speech and eye movements.

Not known: frequency cannot be estimated from the available data.

• Muscle spasms.
• Abnormal liver or kidney function test results.

If any of the symptoms become troublesome or if you notice anything else not mentioned here, please go and see your doctor or check with your pharmacist.

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme, www.mhra.gov.uk/yellowcard.

By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Desferrioxamine Mesilate

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 and on the label of the glass container (vial) after (EXP). If your doctor tells you to stop using Desferrioxamine Mesilate, ask your pharmacist how to throw away medicines you no longer use. Do not throw away any medicines via wastewater or household waste. These measures will help protect the environment.

Vial: Store below 25° C.

Each vial is for single use only.

After dilution: Do not refrigerate or freeze.

From a microbiological point of view, the 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. Do not use the solution if it is not clear, not free of particles or there has been a colour change.

6. Contents of the pack and other information

What Desferrioxamine Mesilate contains

• The active substance is desferrioxamine mesilate.

What Desferrioxamine Mesilate looks like and contents of the pack

Desferrioxamine Mesilate is a white or off-white powder for solution for injection or infusion. This means that a liquid must be added to make a solution, before it can be given to you as an injection. In some cases, more liquid may be added to make a weaker solution which can be given to you as an infusion (drip).

Normally, your doctor or nurse will prepare your medicine before it is given to you.

Each pack contains 10 vials (glass containers) of Desferrioxamine Mesilate 500 mg or 1, 5, 10 and 50 vials of Desferrioxamine Mesilate 2 g. Not all pack sizes may be available.

Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder:

Noridem Enterprises Ltd., Evagorou & Makariou, Mitsi Building 3, Office 115, 1065 Nicosia, Cyprus. Manufacturer: DEMO S.A., PHARMACEUTICAL INDUSTRY, 21^st km National Road Athens-Lamia, 14568 Krioneri, Attiki, Greece, Τ: +30 210 8161802, F: +30 210 8161587.

This leaflet was last revised in 02/2026.

where intensive chelation (IV) is required, and the dose adjusted accordingly. Implanted intravenous systems can be used when intensive chelation is carried out.

Care should be taken when flushing the line to avoid sudden infusion of residual Desferrioxamine Mesilate which may be present in the dead space of the line, as this may lead to flushing; hypotension and circulatory collapse (see section 4.4 Special warnings and precautions for use of the SmPC).

1. 3) Diagnosis of iron storage disease and certain anaemias

The Desferrioxamine Mesilate test for iron overload is based on the principle that normal subjects do not excrete more than a fraction of a milligram of iron in their urine daily and that a standard intramuscular injection of 500 mg of Desferrioxamine Mesilate will not increase this above 1 mg of iron (18 micro mol). In iron storage diseases, however, the increase may be well over 1.5 mg (27 micro mol). It should be borne in mind that the test only yields reliable results when renal function is normal.

Desferrioxamine Mesilate is administered as 500 mg intramuscular injection. Urine is then collected for a period of 6 hours and its iron content determined.

Excretion of 1-1.5 mg (18-27 micro mol) of iron during this 6-hour period is suggestive of iron overload; values greater than 1.5 mg (27 micro mol) can be regarded as pathological.

1. 4) Treatment for aluminium overload in patients with end stage renal failure

Patients should receive Desferrioxamine Mesilate if:

• they have symptoms or evidence of organ impairment due

  to aluminium overload

• they are asymptomatic but their serum aluminium levels

  are consistently above 60 ng/mL and associated with a positive Desferrioxamine Mesilate test (see below), particularly if a bone biopsy provides evidence of aluminium related bone disease.

The iron and aluminium complexes of Desferrioxamine Mesilate are dialysable. In patients with renal failure their elimination will be increased by dialysis.

Adults and children

Patients on maintenance haemodialysis or haemofiltration: 5 mg/kg once a week. Patients with post-desferrioxamine test serum aluminium levels up to 300 ng/mL: Desferrioxamine Mesilate should be given as a slow IV infusion during the last 60 minutes of a dialysis session (to reduce loss of free active substance in the dialysate). Patients with a post-desferrioxamine test serum aluminium value above 300 ng/mL: Desferrioxamine Mesilate should be administered by slow IV infusion 5 hours prior to the dialysis session.

Four weeks after the completion of a three month course of Desferrioxamine Mesilate treatment a Desferrioxamine Mesilate infusion test should be performed, followed by a second test 1 month later. Serum aluminium increases of less than 50 ng/mL above baseline measured in 2 successive infusion tests indicate that further Desferrioxamine Mesilate treatment is not necessary.

Patients on CAPD or CCPD

5 mg/kg once a week prior to the final exchange of the day. It is recommended that the intraperitoneal route be used in these patients. However, Desferrioxamine Mesilate can also be given i.m., by slow infusion IV or s.c.

1. 5) Diagnosis of aluminium overload in patients with end stage renal failure

A Desferrioxamine Mesilate infusion test is recommended in patients with serum aluminium levels > 60ng/mL associated with serum ferritin levels >100 ng/mL.

Just before starting the haemodialysis session, a blood sample is taken to determine the baseline level serum aluminium level. During the last 60 minutes of the haemodialysis session a 5 mg/kg dose is given as a slow intravenous infusion. At the start of the next haemodialysis session (i.e. 44 hours after the aforementioned Desferrioxamine Mesilate infusion) the second blood sample is taken to determine the serum aluminium level once more.

An increase in serum aluminium above baseline of more than 150 ng/mL is suggestive of aluminium overload. It should be noted that a negative test does not completely exclude the possibility of aluminium overload.

Theoretically 100 mg desferrioxamine can bind 4.1 mg Al³⁺.

Use in the elderly

No special dosage regime is necessary but concurrent renal insufficiency should be taken into account.

Contraindications

Hypersensitivity to the active substance unless the patients can be desensitised.

Special warnings and precautions and Interactions

Renal impairment

Desferrioxamine Mesilate should be used with caution in patients with renal impairment since the metal complexes are excreted via the kidneys. In these patients, dialysis will increase the elimination of chelated iron and aluminium. Isolated cases of acute renal failure have been reported (see also section 4.8 Undesirable effects of the SmPC). Monitoring patients for changes in renal function (e.g. increased serum creatinine) should be considered.

Neurological impairment

Used alone desferrioxamine may exacerbate neurological impairment in patients with aluminium-related encephalopathy. This deterioration (manifest as seizures) is probably related to an acute increase in brain aluminium secondary to elevated circulating levels. Pretreatment with clonazepam has been shown to afford protection against such impairment. Also, treatment of aluminium overload may result in decreased serum calcium and aggravation of hyperparathyroidism.

Rapid intravenous infusion

Treatment with Desferrioxamine Mesilate by the intravenous route should only be administered in the form of slow infusions. Rapid intravenous infusion may lead to hypotension and shock (e.g. flushing, tachycardia, circulatory collapse and urticaria).

Instructions for use and handling

Desferrioxamine Mesilate should not be administered s.c. in concentrations and/or doses higher than those recommended

as local irritation at the site of administration may occur more frequently.

Infections

Patients suffering from iron overload are particularly susceptible to infection. There have been reports of desferrioxamine promoting some infections such as Yersinia enterocolitica and Y. pseudotuberculosis. If patients develop fever with pharyngitis, diffuse abdominal pain or enteritis/enterocolitis, Desferrioxamine Mesilate therapy should be stopped and appropriate treatment with antibiotics should be instituted. Desferrioxamine Mesilate therapy may be resumed once the infection has cleared.

In patients, receiving desferrioxamine for aluminium and/or iron overload there have been rare reports of mucormycosis (a severe fungal infection), some with fatal outcome. If any characteristic signs or symptoms occur desferrioxamine treatment should be discontinued, mycological tests carried out and appropriate treatment immediately instituted. Mucormycosis has been reported to occur in dialysis patients not receiving desferrioxamine, thus no causal link with the use of the medicinal product has been established.

Visual and hearing impairment

Disturbances of vision and hearing have been reported during prolonged desferrioxamine therapy. In particular, this has occurred in patients on higher than recommended therapy or in patients with low serum ferritin levels. Patients with renal failure who are receiving maintenance dialysis and have low ferritin levels may be particularly prone to adverse reactions, visual symptoms have been reported after single doses of desferrioxamine. Therefore, ophthalmological and audiological tests should be carried out both prior to the institution of therapy with Desferrioxamine Mesilate and at 3-monthly intervals during treatment particularly if ferritin levels are low. By keeping the ratio of the mean daily dose (mg/kg of Desferrioxamine Mesilate) divided by the serum ferritin (micro g/L) below 0.025 the risk of audiometric abnormalities may be reduced in thalassaemia patients. A detailed ophthalmological assessment is recommended (visual field measurements, fundoscopy, and colour vision testing using pseudoisochromatic plates and the Farnsworth D-15 colour test, slit lamp investigation, visual evoked potential studies).

If disturbances of vision or hearing do occur, treatment with Desferrioxamine Mesilate should be stopped. Such disturbances are usually reversible. If Desferrioxamine Mesilate therapy is re-instituted later at a lower dosage, close monitoring of ophthalmological/auditory function should be carried out with due regard to the risk-benefit ratio.

Paediatric population: growth retardation

The use of inappropriately high doses of desferrioxamine in patients with low ferritin levels or young children (<3 years at commencement of treatment) has also been associated with growth retardation; dose reduction has been found to restore the growth rate to pretreatment levels in some cases. Three monthly checks on body weight and height are recommended in children. Growth retardation if associated with excessive doses of desferrioxamine must be distinguished from growth retardation from iron overload.

Growth retardation from desferrioxamine use is rare if the dose is kept below 40 mg/kg; if growth retardation has been associated with doses above this value, then reduction of the dose may result in return in growth velocity, however, predicted adult height is not attained.

Acute respiratory distress syndrome

Acute respiratory distress syndrome has been described following treatment with excessively high IV doses of desferrioxamine in patients with acute iron intoxication and also in thalassaemic patients (see section 4.8 Undesirable effects of the SmPC). The recommended daily doses should therefore not be exceeded.

It should be noted that desferrioxamine will affect aluminium levels and may necessitate some dosage adjustment of erythropoietin if co-prescribed.

Interaction with other medicinal products and other forms of interaction

Oral administration of vitamin C (up to a maximum of 200 mg daily, given in divided doses) may serve to enhance excretion of the iron complex in response to desferrioxamine; larger doses of vitamin C fail to produce an additional effect. Monitoring of cardiac function is indicated during such combined therapy. Vitamin C should be given only if the patient is receiving desferrioxamine regularly and should not be administered within the first month of desferrioxamine therapy. In patients with severe chronic iron-storage disease undergoing combined treatment with desferrioxamine and high doses of vitamin C (more than 500 mg daily) impairment of cardiac function has been encountered; this proved reversible when the vitamin C was withdrawn. Vitamin C supplements should not, therefore, be given to patients with cardiac failure. Desferrioxamine Mesilate should not be used in combination with prochlorperazine (a phenothiazine derivative) since prolonged unconsciousness may result.

Gallium⁶⁷ imaging results may be distorted because of the rapid urinary excretion of desferrioxamine bound radiolabel. Discontinuation of desferrioxamine 48 hours prior to scintigraphy is advised.