Desferal: instructions for use. Desferal - description of the drug, instructions for use, reviews Chronic aluminum overload in end-stage renal failure

Compound

active substance: deferoxamine;

1 bottle contains 500 mg of desferrioxamine methanesulfonate.

Indications

Chelated iron complex monotherapy for chronic iron overload, for example:

• transfusion hemosiderosis, which is observed in thalassemia major, sideroblastic anemia, autoimmune hemolytic anemia and other chronic anemias;
• idiopathic (primary) hemochromatosis in patients in whom concomitant diseases (for example, severe anemia, heart disease, hypoproteinemia) do not allow phlebotomy;
• Iron overload is associated with cutaneous porphyria tarda in patients who cannot tolerate phlebotomy.

Treatment of acute iron poisoning.

Treatment of chronic aluminum overload in patients with end-stage renal failure (in maintenance dialysis):

• with aluminum-deposited bone disease,
• with dialysis encephalopathy or
• aluminum with long-standing anemia.

Diagnostics.

Diagnosis of iron or aluminum overload.

Directions for use and doses

Treatment of chronic iron overload. The main goal of therapy with complexing compounds in young patients is to establish a balance between the intake and excretion of iron and prevent the occurrence of hemosiderosis, while in elderly patients it is desirable to achieve a negative iron balance in order to gradually reduce the increased iron stores and prevent toxic effects.

Children and adults. It is recommended that treatment with Desferal be started after the first 10-20 blood transfusions or when the serum ferritin level is 1000 ng/ml. Growth retardation may occur due to iron overload or too high a dosage of Desferal. If chelation is initiated in children under 3 years of age, it should be done under close supervision and the average daily dose should not exceed 40 mg/kg.

The dosage and route of administration can be determined individually and changed during treatment depending on the severity of the iron load in the patient’s body. The minimum effective dose should be used. To assess the response to chelation therapy, daily monitoring of renal iron excretion can be carried out at the beginning of treatment and the response to increasing the dose of Desferal can be determined. Once the optimal dose has been established, the rate of iron excretion by the kidneys can be determined every few weeks. Another way to select the average daily dose may be to adjust it by the amount of ferritin with a therapeutic index content of less than 0.025 (i.e., the average daily dose (mg/kg) of Desferal divided by the serum ferritin level (μg/l) should be less 0.025). The average daily dose of Desferal is usually 20-60 mg/kg.

In general, patients with serum ferritin levels less than 2000 ng/ml need about 25 mg/kg/day. Patients with serum ferritin levels between 2000 and 3000 ng/ml need about 35 mg/kg/day. Patients with higher serum ferritin levels may require doses up to 55 mg/kg/day. Continuously exceeding the average daily dose of 50 mg/kg/day is not advisable unless very intensive chelation is required in patients who have already stopped growing. If ferritin levels fall below 1000 ng/ml, the risk of Desferal toxicity increases; Due to the condition of such patients, it is important to carry out particularly careful monitoring and possibly reduce the total weekly dose. The doses given are average daily doses. Since most patients do not need to administer this drug every day during the week, the actual dose in one infusion usually differs from the average daily dose, for example, if an average daily dose of 40 mg / kg / day is needed and infusions are given 5 times a week, in each infusion should contain 56 mg/kg.

Regular chelation treatment with Desferal has been found to increase life expectancy in thalassemia patients.

For outpatients, an effective and convenient device for slow subcutaneous infusion is a portable lightweight infusion pump, which is used for 8-12 hours, and sometimes for 24 hours. Desferal should be administered using a pump 5-7 times a week. Desferal is not used for maintenance subcutaneous painful injections.

Intravenous infusion during blood transfusion. During blood transfusion, the presence of an intravenous catheter allows intravenous infusion without causing additional inconvenience to the patient. This is especially useful for patients who do not tolerate subcutaneous infusions well. Desferal solution should not be added directly to the blood container, but must be injected into the catheter using a Y-type adapter located at the injection site into the vein. An individual pump for administering Desferal should be used in the usual way. Patients and nurses should be warned not to increase the infusion rate, since intravenous bolus administration of Desferal may lead to acute collapse.

Long-term intravenous infusion. When performing intensive chelation, implanted intravenous systems can be used. Long-term intravenous infusions are indicated for patients who cannot tolerate long-term subcutaneous infusions, as well as for those who have heart problems due to iron overload. Dose of Desferal - intensive chelation (c) Daily renal excretion of iron should be regularly determined and the dose adjusted accordingly. Care must be taken when flushing the system to prevent sudden infusion of residual Desferal that may be present in the catheter's dead space, as this may cause acute collapse.

M introduction. Because subcutaneous infusions are effective, intramuscular injections are prescribed only in cases where subcutaneous infusion cannot be performed.

For any route of administration, the choice of individual maintenance dose will depend on the patient's rate of iron excretion.

Simultaneous use with vitamin C. Patients with iron overload often have a deficiency of vitamin C, which may be caused by the oxidation of this vitamin by iron. Such patients, along with chelation therapy, can be prescribed vitamin C at a dose of 200 mg/day in several doses after a month of regular treatment with desferal. Vitamin C increases the availability of iron for chelation. For children under 10 years of age, a dose of 50 mg is sufficient, and for older children - 100 mg. Large doses of vitamin C do not lead to an additional increase in the excretion of complex iron.

Treatment of acute iron poisoning. For the treatment of acute iron poisoning, Desferal is mainly used together with standard methods.

Treatment with Desferal is indicated in the following situations:

• patients with symptoms of poisoning, if these symptoms are severe and not transient (for example, more than one episode of vomiting or loose stools)
• patients with signs of lethargy, severe abdominal pain, hypovolemia or acidosis;
• patients in whom abdominal x-ray results indicate multiple radiopacity (the vast majority of these patients experience symptoms of iron toxicity)
• patients with symptoms of poisoning in which the serum iron level is more than 300-350 mcg/dl, regardless of the overall ability of iron to bind. In addition, for patients without symptoms of poisoning with a serum iron level of 300-500 mcg/dL, as well as for patients with spontaneous relief of non-curvature vomiting or diarrhea and in the absence of other symptoms, it is recommended to carry out conservative treatment without the use of Desferal or loading.

The best route of administration is continuous infusion, the recommended infusion rate is 15 mg/kg per hour, which should be reduced immediately after improvement, most often after 4-6 hours, so that the total intravenous dose does not exceed the recommended dose of 80 mg/kg at any time. What a day.

• the patient must not have signs or symptoms of systemic iron toxicity (eg, no acidosis or increased hepatotoxicity)
• ideally, the corrected serum iron level will be normal or low (when iron levels fall below 100 mcg/dL). Given that laboratory methods do not accurately measure serum iron concentrations in the presence of Desferal, it is recommended that Desferal administration be discontinued when all other criteria are met and serum iron levels are not elevated;
• patients in whom pronounced radiopacity was observed on a previous radiograph require repeat radiography of the abdominal organs to ensure that the radiopacity has disappeared before stopping the administration of Desferal, since it is an indicator of continued iron absorption
• If a patient's urine turns pink during treatment with Desferal, you need to wait until its color is restored again and then stop administering Desferal (the absence of pink urine itself is not enough to cancel Desferal).

The effectiveness of treatment depends on the adequacy of urine output, which ensures the removal of the ferrioxamine iron complex from the body. If oliguria or anuria develops, peritoneal dialysis, hemodialysis or hemofiltration may become necessary.

Treatment of chronic aluminum overload in patients with end-stage renal failure. Iron or aluminum complexes of Desferal are dialyzable. In patients with renal failure, their output increases during dialysis.

Patients with symptoms or organ dysfunction due to aluminum overload should be treated with desferal. The use of this drug should be considered even in asymptomatic patients in whom serum aluminum levels are significantly higher than 60 ng/ml and are accompanied by a positive Desferal infusion test (see below), especially if bone biopsy has demonstrated evidence of aluminum-related bone disease.

Desferal should be administered once a week at a dose of 5 mg/kg. In patients with post-DFO serum aluminum levels of up to 300 ng/mL, Desferal should be administered as a slow infusion during the last 60 minutes of the dialysis session. In patients with post-DFO serum aluminum levels greater than 300 ng/ml, Desferal should be administered as a slow infusion 5 hours before the start of the dialysis session. After completing the first 3-month course of treatment with Desferal, followed by a 4-week break, it is necessary to conduct an infusion test of Desferal. If, during two consecutive Desferal infusion tests with an interval of 1 month, the serum aluminum level exceeds the initial value by less than 50 ng/ml, further treatment with Desferal is not recommended.

For patients on continuous ambulatory peritoneal dialysis (CAPD) or continuous cyclic peritoneal dialysis (CCPD), Desferal should be administered once a week at a dose of 5 mg/kg at the end of the day. For such patients, it is recommended to use the intraperitoneal route of administration. However, Desferal can be administered intramuscularly by slow infusion or subcutaneously.

Desferal test. This test is based on the principle that in healthy people Desferal does not increase the excretion of iron and aluminum above a certain limit.

1. Desferal test for iron overload in patients with normal renal function. Desferal 500 mg should be administered intramuscularly. Then collect urine for 6:00 and determine its iron content. An excretion level of 1-1.5 mg (18-27 µmol) over 6:00 indicates iron overload; a level above 1.5 mg (27 µmol) can be considered pathological. Reliable results with this test can only be obtained with normal kidney function.

2. Desferal infusion test for aluminum overload in patients with end-stage renal failure. A desferal infusion test is recommended for patients with serum aluminum levels greater than 60 ng/ml in the presence of serum ferritin levels greater than 100 ng/ml.

To determine the initial serum aluminum level, a blood sample is taken immediately before the start of a hemodialysis session.

During the last 60 minutes of the hemodialysis session, 5 mg/kg Desferal is administered as a slow infusion.

At the start of the next hemodialysis session (i.e. 44 hours after the above-mentioned Desferal infusion), a second blood sample is taken to re-determine serum aluminum levels.

The desferal test is considered positive if the serum aluminum level upon repeat measurement increases by 150 ng/ml. However, a negative test does not completely exclude the diagnosis of aluminum overload.

Instructions for preparing solutions.

For parenteral administration, it is necessary to use a 10% solution of the drug in water for injection. 5 ml of water for injection is injected with a syringe into a vial containing 500 mg of Desferal powder and shaken well. Only a clear and colorless or yellowish solution can be used. Desferal 10% solution can then be diluted with commonly used infusion solutions (NaCl 0.9%, glucose 5%, Ringer's solutions, Ringer's lactate, peritoneal dialysis solution - Dineal 137 glucose 2.27%, Dineal PD4 glucose 2.27% and CAPD/DPCA 2 glucose 1.5%).

For carrying out the Desferal test and treating chronic excess aluminum, a dose of Desferal equal to 5 ml of solution in a vial is adequate (5 mg/kg) for patients weighing 100 kg. Taking into account the patient’s body weight, the appropriate volume of Desferal solution is drawn from the bottle and added to 150 ml of 0.9% sodium chloride solution. Dissolved Desferal can be added to dialysed fluids and administered intravenously during CARD or CCPD.

Adverse reactions

Adverse reactions are presented by frequency, starting with the most common: very often - ≥ 1/10; often - from ≥ 1/100 to<1/10; нечасто - от ≥ 1/1 000 до <1/100; редко - от ≥ 1/10 000 до <1/1 000; очень редко - <1/10 000, в том числе единичные случаи.

Some signs and symptoms that were thought to be side effects may actually be manifestations of an underlying medical condition (iron and/or aluminum overload).

Infections and infestations: rarely - mucormycosis; very rarely - gastroenteritis caused by Yersinia .

From the blood and lymphatic system: very rarely - abnormal blood counts (including thrombocytopenia).

From the immune system: very rarely - anaphylactic shock, anaphylactic reactions, angioedema.

From the nervous system: often - headache; very rarely - neurological disorders, dizziness, slowing or progression of encephalopathy associated with elevated aluminum levels with hemodialysis, peripheral neuropathy, paresthesia.

From the organs of vision: rarely - loss of vision, scotoma, retinal degeneration, optic neuritis, cataracts, decreased visual acuity, blurred vision, chromatopsia, corneal opacification, night blindness, visual field impairment.

From the side of the hearing organ: uncommon - sensorineural deafness, ringing in the ears.

From the vascular system: often - arterial hypotension if warnings are not followed.

From the respiratory system, chest and mediastinal organs: uncommon - asthma, very rare - acute respiratory distress syndrome, pulmonary infiltrate.

From the digestive tract: often - nausea; infrequently - vomiting, abdominal pain very rarely - diarrhea.

From the skin and subcutaneous tissue: often - urticaria very rarely - generalized rash.

From the musculoskeletal system and connective tissue: often - arthralgia, myalgia; often - growth retardation and dysfunction of bone tissue (for example, metaphyseal dysplasia) when using high doses and in young children.

From the kidneys and urinary system: impaired renal function.

Violation of general condition and associated with the method of administration of the drug: often - reactions at the injection site, including pain, swelling, infiltration, redness of the skin, itching, scab; often - fever, infrequently - reaction at the injection site, including vesicles, swelling, burning.

Sensorineural hearing loss and tinnitus occur infrequently when the recommended dosage is followed and when the dose is reduced when ferritin levels fall (the ratio of the average daily dose of Desferal to serum ferritin levels should be less than 0.025).

Various visual disturbances rarely occur, except when the drug is administered in high doses.

Growth retardation and bone disorders (eg, metaphyseal osteodysplasia) occur frequently at dosages above 60 mg/kg, especially in patients who begin iron chelation in the first three years of life. At dosages of 40 mg/kg and below, the risk is significantly reduced. Pain at the injection site, swelling, infiltration, redness of the skin, itching and scab/crust occur very often, and vesicles, local swelling and burning are rare. Local manifestations may be accompanied by systemic reactions, such as arthralgia/myalgia (very common), headache (common), nausea (common), fever (common), abdominal pain (rare) or asthma (uncommon).

Overdose

Signs and symptoms. Accidental overdose or accidental intravenous bolus or rapid infusion may be associated with hypotension, tachycardia and gastrointestinal disturbances, acute but transient vision loss, aphasia, agitation, headache, nausea, bradycardia, and acute renal failure.

Treatment. There is no special antidote. It is necessary to stop the administration of Desferal and prescribe appropriate symptomatic treatment.

Use during pregnancy or breastfeeding

Pregnancy. Experiments on rabbits have shown that desferrioxamine can have a teratogenic effect. To date, all patients who used Desferal during pregnancy have given birth to children without congenital defects. The drug can be used during pregnancy, especially in the first trimester, only if absolutely necessary and the benefits of treatment must be weighed against the risks for the child.

Lactation. It is unknown whether desferrioxamine is excreted into breast milk, so women receiving Desferal should stop breastfeeding during treatment.

Children

In children under 3 years of age, chelation is carried out under close supervision, and the average daily dose should not exceed 40 mg/kg, since growth retardation and bone disorders (eg, metaphyseal osteodysplasia) occur with high doses.

Features of application

Warning. Rapid infusion may lead to hypotension and shock (eg, flushing, tachycardia, collapse, and urticaria).

Administration of high doses of Desferal, especially to patients with low plasma ferritin levels, can lead to visual and hearing impairment. Patients with renal failure, those on maintenance dialysis and low plasma ferritin levels are especially susceptible to the development of adverse reactions: it was noted that in such cases, visual disturbances occurred even after a single dose of Desferal. The risk of side effects is reduced if you use this drug in a low dose. Adverse reactions caused by Desferal are mostly reversible if detected promptly. Treatment with Desferal can be reinstated later in a reduced dosage, with careful monitoring of vision and hearing function.

Approximately half of the metal complex in patients with normal renal function and iron overload is excreted by the kidneys. Therefore, treatment of patients with severe renal failure should be carried out with caution. Desferrioxamine and iron and aluminum complexes are dialyzable; in patients with renal failure, their excretion from the body during dialysis will increase.

In patients with low serum ferritin levels who were treated with high doses of Desferal, or in children (< 3 years of age at the start of treatment), the use of Desferal was associated with growth retardation. Growth retardation caused by excessive doses of Desferal must be distinguished from growth retardation due to iron overload. Growth retardation associated with Desferal use occurs rarely when doses less than 40 mg/kg are administered; If growth is delayed due to higher doses of this drug, reducing the dosage may restore normal growth rate, but the expected height in adulthood is no longer achieved.

Acute respiratory distress syndrome has been described in patients with acute iron intoxication, as well as in patients with thalassemia, after treatment with exclusively high intravenous doses of Desferal. Therefore, the recommended daily dose should not be exaggerated.

It has been noted that in patients suffering from iron overload, treatment with desferal increases the susceptibility to infections, e.g. Yersinia enterocolitica And Yersinia pseudotuberculosis. If a patient being treated with Desferal develops a fever and acute enteritis/enterocolitis, diffuse abdominal pain or pharyngitis, treatment should be suspended, bacteriological tests performed and appropriate antibiotic therapy initiated immediately. Once the infection has been eradicated, treatment with Desferal can be resumed.

In patients receiving Desferal for the treatment of aluminum and/or iron overload, mucormycosis, a severe fungal infection, has very rarely been reported (sometimes fatal consequences have been reported). If symptoms or suspicious signs of this infection appear, treatment with Desferal should be discontinued, mycological tests should be performed and appropriate therapy should be started immediately. Mucormycosis may occur in patients not receiving Desferal, indicating that other factors, such as dialysis, diabetes mellitus, acid-base imbalance, and malignant blood diseases, may play a role in the development of this infection.

The release of an iron complex can cause urine to appear red-brown in color.

Reservations. Desferal should not be used in doses higher than recommended. This drug, when used by subcutaneous administration, should not be used in concentrations above 10% due to the increased risk of local reactions. If the patient's only route of administration is intramuscular, higher concentrations may need to be used to facilitate injection.

When performing a subcutaneous infusion, the needle should be inserted as close to the dermis as possible.

After simultaneous treatment with desferal and high doses of vitamin C (500 mg per day), cardiac dysfunction was observed in patients with severe chronic iron overload. After discontinuation of vitamin C, cardiac dysfunction ceased. When using Desferal and vitamin C simultaneously, the following measures should be observed.

• Supplemental therapy with vitamin C should not be given to patients with heart failure.
• You can start administering vitamin C only a month after the previous treatment with regular administration of Desferal.
• Vitamin C can only be given when the patient is undergoing regular treatment with Desferal, preferably shortly after the start of the infusion.
• The daily dose of vitamin C 200 mg, which is administered in several doses, should not be exaggerated.
• When carrying out such combination treatment, it is advisable to monitor cardiac function.

Before starting treatment with Desferal and thereafter at certain intervals (every 3 months), it is recommended to have an ophthalmological consultation and audiological examination. In patients with thalassemia, the risk of hearing impairment can be reduced by maintaining the ratio of the average daily dose of Desferal (mg/kg) to serum ferritin concentration (μg/L) below 0.025.

When treating children with Desferal, it is necessary to determine their weight and height every 3 months.

In patients with aluminum encephalopathy, high doses of Desferal may increase neurological dysfunction (the appearance of seizures), which may be caused by a sharp increase in the amount of circulating aluminum. Desferal may accelerate the onset of dialysis dementia. Pretreatment with clonazepam has been shown to prevent the development of this neurological disorder. In addition, treatment of aluminum overload can lead to a decrease in serum calcium levels and increased hyperparathyroidism.

The ability to influence the reaction rate when driving vehicles or other mechanisms

Patients who experience dizziness or other disorders of the central nervous system should avoid driving vehicles or using other machinery.

Pharmacological properties

Pharmacological. Desferrioxamine (DFO) forms complexes predominantly with iron ions and with trivalent aluminum ions: the complexation constants are 10 31 and 10 25, respectively. The affinity of DPO with such divalent ions as Fe 2+, Cu 2+, Zn 2+, Ca 2+ is much lower (complexation constant is 10 14 or less). Chelation occurs in a 1:1 molar ratio, meaning 1 g of DFO can theoretically bind 85 mg of ferric iron or 41 mg of Al 3+.

DFO, due to its chelating properties, is able to capture free iron in plasma or cells, and therefore form ferrioxamine complex (PL). Urinary PL iron excretion primarily reflects the amount of iron that leaves the plasma, whereas fecal iron excretion primarily reflects the amount of chelated iron in the liver. Iron can be chelated from ferritin and hemosiderin, but this process is relatively slow at clinical concentrations of DFO. It should be noted that DFO does not remove iron from transferrin, hemoglobin, or other substances that contain hemin.

DFO can also mobilize and chelate aluminum to form the aluminoxamine (AlO) complex.

Since both complexes - PL and AlO - are completely eliminated from the body, DFO promotes the excretion of iron and aluminum in urine and feces, and therefore reduces the excessive reserves of these elements in the organs.

Pharmacokinetics.

Absorption. DFO is rapidly absorbed after bolus injection or slow subcutaneous administration and is poorly absorbed from the gastrointestinal tract in the presence of intact mucosa. The absolute bioavailability of 1 g of DFO orally administered is less than 2%.

If DFO is added to the dialysis fluid, it can be absorbed during peritoneal dialysis.

Distribution. In healthy subjects, a maximum plasma concentration of 15.5 µmol/L (8.7 µg/ml) was recorded 30 minutes after injection of 10 mg/kg DFO. One hour after injection, the maximum PL concentration was 3.7 μmol/L (2.3 μg/ml). After infusion of 2 g (about 29 mg/kg) of DFO into healthy individuals, the DFO concentration reached a constant level of 30.5 µmol/L after 2:00; Distribution of DFO occurred very quickly with a mean distribution half-life of 0.4 hours. In vitro, less than 10% of DFO is bound to plasma proteins.

Metabolism. Four metabolites of DFO were isolated and identified from the urine of patients with iron overload. It has been shown that during DFO the following biotransformation reactions occur: transamination and oxidation with the formation of an acidic metabolite, beta-oxidation also with the formation of an acidic metabolite, decarboxylation and N-hydroxylation with the formation of neutral metabolites.

Conclusion. In healthy individuals, both DFO and FL have biphasic elimination after injection; The half-period of the explicit distribution for DFO is 1:00, and for FL it is 2.4 hours. The half-life of the apparent final withdrawal for both substances is 6:00. During a 6-hour administration, 22% of the dose appears in the urine as DFO and 1% as FO.

Features of pharmacokinetics in certain diseases. IN patients with hemachromatosis 1:00 after injection of 10 mg/kg DFO, the maximum plasma DFO level is 7.0 μmol/L (3.9 μg/ml) and PL is 15.7 μmol/L (9.6 μg/ml). In these patients, the half-lives of DFO and FL are 5.6 and 4.6 hours, respectively. 6:00 after injection, 17% of the dose is excreted in the urine as DFO and 12% as FO.

IN patients with thalassemia continued infusion of 50 mg/kg/day DFO is accompanied by the creation of a constant plasma DFO concentration of 7.4 µmol/l (4.1 µg/ml). The elimination of DFO from blood plasma is biphasic with an average half-life of 0.28 hours and an apparent final elimination period of 3.0 hours. The total final clearance is 0.5 l/h/kg and the volume of distribution at constant concentration is 1.35 l/kg. The effect of the major metabolite with bound iron on AUC (the plane under the concentration-time curve) is 54% of the effect of DFO. The half-life of the apparent monoexponential release of the metabolite is 1.3 hours.

IN patients undergoing dialysis due to renal failure, An intravenous infusion of 40 mg/kg DFO over 1 hour between dialysis sessions resulted in an end-infusion DFO plasma concentration of 152 μmol/L (85.2 μg/mL). When the infusion was given during dialysis, plasma DFO concentrations were 13-27% lower. The PL concentration in all cases was approximately 7.0 µmol/L (4.3 µg/ml), and the AlO concentration was 2-3 µmol/L (1.2-1.8 µg/ml). After stopping the infusion, plasma DFO concentrations decreased rapidly with a half-life of 20 minutes. Smaller dose fractions were excreted with a long half-life of 14 hours. The concentration of AlO in blood plasma continued to increase for as long as 48 hours after infusion and reached a value of about 7 μmol/L (4 μg/ml). The concentration of AlO in blood plasma after dialysis decreased to 2.2 μmol/L (1.3 μg/ml).

Keep out of the reach of children.

Manufacturer

Novartis Pharma Stein AG (Switzerland) / Novartis Pharma Stein AG (Switzerland)

Name:

Desferal

Pharmachologic effect:

The drug forms a complex compound with iron. When introduced into the body, it promotes the removal of iron from iron-containing proteins (ferritin and hemosiderin), but not from hemoglobin and iron-containing enzymes. It does not significantly affect the release of other metals and trace elements.

Indications for use:

Used for primary and secondary hemochromatosis (impaired metabolism of iron-containing pigments), hemosiderosis (deposition of dark yellow iron-containing pigment in the skin) and for acute iron poisoning.

Method of application:

The average initial dose is 1 g per day (1-2 injections), maintenance dose is 0.5 g per day. It is usually administered intramuscularly. A 10% solution is used, for which the contents of 1 ampoule (0.5 g) are dissolved in 5 ml of sterile water for injection. It is administered intravenously only by drip at a rate of no more than 15 mg/kg per hour, maximum dose 80 mg/kg. For acute iron poisoning, it is prescribed orally and parenterally (bypassing the digestive tract). To bind iron that has not yet been absorbed from the gastrointestinal tract, 5-10 g of the drug is given orally, i.e. the contents of 10-20 ampoules (dissolved in drinking water). To remove absorbed iron, 1-2 g is administered intramuscularly every 3-12 hours. In severe cases, 1 g is administered drip into a vein.

Adverse events:

When using the drug, urticaria and exanthema (skin rash) may appear in some cases. Rapid intravenous administration can lead to collapse (a sharp drop in blood pressure). With long-term use of the drug, it is necessary to examine the condition of the eyes before and during treatment.

Before and during treatment, it is necessary to examine the excretion of iron in the urine.

Contraindications:

Pregnancy.

Release form of the drug:

In ampoules containing 0.5 g (500 mg) of dry drug.

Storage conditions:

In a dark place.

Synonyms:

Deferoxamine, Deferoxamine methanesulfonate, Desferan, Desferex, Desferin, DFOM.

Drugs with similar effects:

Sodium nitrite (Natrii nitris) Amyl nitrite (Amyliinitris) Tetacin-calcium (Tetacinum-calcium) Disodium salt of ethylenediaminetetraacetic acid (Dinatriiaethylendiamintetraacetas) Cuprenil (Cuprenil)

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A drug Desferal- a product that forms chelate compounds with iron.
Desferrioxamine (DFO) forms complexes predominantly with iron ions and with trivalent aluminum ions: the complexation constants are 10 31 and 10 25, respectively. The affinity of DFO with divalent ions such as Fe 2+, Cu 2+, Zn 2+, Ca 2+, significantly lower (complexation constant - 10 14 or less). Chelation occurs in a 1:1 molar ratio, meaning 1 g of DFO can theoretically bind 85 mg of ferric iron or 41 mg of Al 3+.
DFO, due to its chelating properties, is able to capture free iron in plasma or cells, and therefore form ferrioxamine complex (PL). Urinary PL iron excretion primarily reflects the amount of iron that leaves the plasma, whereas fecal iron excretion primarily reflects the amount of chelated iron in the liver. Iron can be chelated from ferritin and hemosiderin, but this process is relatively slow at clinical concentrations of DFO. It should be noted that DFO does not remove iron from transferrin, hemoglobin, or other substances that contain hemin.
DFO can also mobilize and chelate aluminum to form the aluminoxamine (AlO) complex.
Since both complexes - PL and AlO - are completely eliminated from the body, DFO promotes the excretion of iron and aluminum in urine and feces, and therefore reduces the excessive reserves of these elements in the organs.
Pharmacokinetics.
Absorption. DFO is rapidly absorbed after bolus injection or slow subcutaneous administration and is poorly absorbed from the gastrointestinal tract in the presence of intact mucosa. The absolute bioavailability of 1 g of DFO orally administered is less than 2%.
If DFO is added to the dialysis fluid, it can be absorbed during peritoneal dialysis.
Distribution. In healthy subjects, a maximum plasma concentration of 15.5 µmol/L (8.7 µg/ml) was recorded 30 minutes after injection of 10 mg/kg DFO. One hour after injection, the maximum PL concentration was 3.7 μmol/L (2.3 μg/ml). After infusion of 2 g (about 29 mg/kg) of DFO into healthy individuals, the DFO concentration reached a constant level of 30.5 µmol/L after 2:00; Distribution of DFO occurred very quickly with a mean distribution half-life of 0.4 hours. In vitro, less than 10% of DFO is bound to plasma proteins.
Metabolism. Four metabolites of DFO were isolated and identified from the urine of patients with iron overload.

It has been shown that during DFO the following biotransformation reactions occur: transamination and oxidation with the formation of an acidic metabolite, beta-oxidation also with the formation of an acidic metabolite, decarboxylation and N-hydroxylation with the formation of neutral metabolites.
Conclusion. In healthy individuals, both DFO and FL have biphasic elimination after injection; The half-period of the explicit distribution for DFO is 1:00, and for FL it is 2.4 hours. The half-life of the apparent final withdrawal for both substances is 6:00. During a 6-hour administration, 22% of the dose appears in the urine as DFO and 1% as FO.
Features of pharmacokinetics in certain diseases. In patients with hemachromatosis, 1:00 after injection of 10 mg/kg DFO, the maximum plasma level of DFO is 7.0 µmol/L (3.9 µg/ml), and PL is 15.7 µmol/L (9.6 µg/l). ml). In these patients, the half-lives of DFO and FL are 5.6 and 4.6 hours, respectively. 6:00 after injection, 17% of the dose is excreted in the urine as DFO and 12% as FO.
In patients with thalassemia, continued infusion of 50 mg/kg/day DFO is accompanied by the creation of a constant plasma DFO concentration of 7.4 μmol/L (4.1 μg/ml). The elimination of DFO from blood plasma is biphasic with an average half-life of 0.28 hours and an apparent final elimination period of 3.0 hours. The total final clearance is 0.5 l/h/kg and the volume of distribution at constant concentration is 1.35 l/kg. The effect of the major metabolite with bound iron on AUC (the plane under the concentration-time curve) is 54% of the effect of DFO. The half-life of the apparent monoexponential release of the metabolite is 1.3 hours.
In patients undergoing dialysis due to renal failure, intravenous infusion of 40 mg/kg DFO for 1:00 between dialysis sessions was accompanied by the formation of a DFO plasma concentration at the end of the infusion of 152 μmol/L (85.2 μg/ml). When the infusion was given during dialysis, plasma DFO concentrations were 13-27% lower. The PL concentration in all cases was approximately 7.0 µmol/L (4.3 µg/ml), and the AlO concentration was 2-3 µmol/L (1.2-1.8 µg/ml). After stopping the infusion, plasma DFO concentrations decreased rapidly with a half-life of 20 minutes. Smaller dose fractions were excreted with a long half-life of 14 hours. The concentration of AlO in blood plasma continued to increase for as long as 48 hours after infusion and reached a value of about 7 μmol/L (4 μg/ml). The concentration of AlO in blood plasma after dialysis decreased to 2.2 μmol/L (1.3 μg/ml).

Indications for use:
Indications for use of the drug Desferal are:
- Monotherapy with a chelated iron complex for chronic iron overload, for example: transfusion hemosiderosis, which is observed in thalassemia major, sideroblastic anemia, autoimmune hemolytic anemia and other chronic anemias; idiopathic (primary) hemochromatosis in patients in whom concomitant diseases (for example, severe anemia, heart disease, hypoproteinemia) do not allow phlebotomy; Iron overload is associated with cutaneous porphyria tarda in patients who cannot tolerate phlebotomy.
- Treatment of acute iron poisoning.
- Treatment of chronic aluminum overload in patients with end-stage renal failure (in maintenance dialysis): with aluminum-deposited bone disease, with dialysis encephalopathy or aluminum-deposited anemia.
- Diagnosis of iron or aluminum overload.

Mode of application:
Treatment of chronic iron overload.
The main goal of therapy with complexing compounds in young patients is to establish a balance between the intake and excretion of iron and prevent the occurrence of hemosiderosis, while in elderly patients it is desirable to achieve a negative iron balance in order to gradually reduce the increased iron stores and prevent toxic effects.
Children and adults.
It is recommended that treatment with Desferal be started after the first 10-20 blood transfusions or when the serum ferritin level is 1000 ng/ml. Growth retardation may occur due to iron overload or too high dosage Desferala. If chelation is initiated in children under 3 years of age, it should be done under close supervision and the average daily dose should not exceed 40 mg/kg.
The dosage and route of administration can be determined individually and changed during treatment depending on the severity of the iron load in the patient’s body. The minimum effective dose should be used. To assess the response to chelation therapy, daily monitoring of renal iron excretion can be carried out at the beginning of treatment and the response to increasing the dose of Desferal can be determined. Once the optimal dose has been established, the rate of iron excretion by the kidneys can be determined every few weeks. Another way to select the average daily dose may be to adjust it by the amount of ferritin with a therapeutic index content of less than 0.025 (i.e., the average daily dose (mg/kg) of Desferal divided by the serum ferritin level (μg/l) should be less 0.025). The average daily dose of Desferal is usually 20-60 mg/kg.
In general, patients with serum ferritin levels less than 2000 ng/ml need about 25 mg/kg/day. Patients with serum ferritin levels between 2000 and 3000 ng/ml need about 35 mg/kg/day. Patients with higher serum ferritin levels may require doses up to 55 mg/kg/day. Continuously exceeding the average daily dose of 50 mg/kg/day is not advisable unless very intensive chelation is required in patients who have already stopped growing. If ferritin levels fall below 1000 ng/ml, the risk of Desferal toxicity increases; Due to the condition of such patients, it is important to carry out particularly careful monitoring and possibly reduce the total weekly dose. The doses given are average daily doses. Since most patients do not need to administer this drug every day during the week, the actual dose in one infusion usually differs from the average daily dose, for example, if an average daily dose of 40 mg / kg / day is needed and infusions are given 5 times a week, in each infusion should contain 56 mg/kg.
Regular chelation treatment with Desferal has been found to increase life expectancy in thalassemia patients.
For outpatients, an effective and convenient device for slow subcutaneous infusion is a portable lightweight infusion pump, which is used for 8-12 hours, and sometimes for 24 hours.

Desferal should be administered using a pump 5-7 times a week. Desferal is not used for maintenance subcutaneous painful injections.
Intravenous infusion during blood transfusion. During blood transfusion, the presence of an intravenous catheter allows intravenous infusion without causing additional inconvenience to the patient. This is especially useful for patients who do not tolerate subcutaneous infusions well. Desferal solution should not be added directly to the blood container, but must be injected into the catheter using a Y-type adapter located at the injection site into the vein. An individual pump for administering Desferal should be used in the usual way. Patients and nurses should be warned not to increase the infusion rate, since intravenous bolus administration of Desferal may lead to acute collapse.
Long-term intravenous infusion. When performing intensive chelation, implanted intravenous systems can be used. Long-term intravenous infusions are indicated for patients who cannot tolerate long-term subcutaneous infusions, as well as for those who have heart problems due to iron overload. Dose of Desferal - intensive chelation (c) Daily renal excretion of iron should be regularly determined and the dose adjusted accordingly. Care must be taken when flushing the system to prevent sudden infusion of residual Desferal that may be present in the catheter's dead space, as this may cause acute collapse.
M introduction. Because subcutaneous infusions are effective, intramuscular injections are prescribed only in cases where subcutaneous infusion cannot be performed.
For any route of administration, the choice of individual maintenance dose will depend on the patient's rate of iron excretion.
Concomitant use with vitamin C. In the body of patients with iron overload, there is often a deficiency of vitamin C, which can be caused by the oxidation of this vitamin by iron. Such patients, along with chelation therapy, can be prescribed vitamin C at a dose of 200 mg/day in several doses after a month of regular treatment with desferal. Vitamin C increases the availability of iron for chelation. For children under 10 years of age, a dose of 50 mg is sufficient, and for older children - 100 mg. Large doses of vitamin C do not lead to an additional increase in the excretion of complex iron.
Treatment of acute iron poisoning. For the treatment of acute iron poisoning, Desferal is mainly used together with standard methods.
Treatment Desferalom shown in the following situations:
- patients with symptoms of poisoning, if these symptoms are severe and not transient (for example, more than one episode of vomiting or loose stools)
- patients with signs of lethargy, severe abdominal pain, hypovolemia or acidosis;
- patients in whom X-ray results of the abdominal organs indicate multiple radiopacity (the vast majority of such patients experience symptoms of iron poisoning)
- patients with symptoms of poisoning in which the serum iron level is more than 300-350 mcg/dl, regardless of the overall ability of iron to bind.

In addition, for patients without symptoms of poisoning with a serum iron level of 300-500 mcg/dL, as well as for patients with spontaneous relief of non-curvature vomiting or diarrhea and in the absence of other symptoms, it is recommended to carry out conservative treatment without the use of Desferal or loading.
The best route of administration is continuous infusion, the recommended infusion rate is 15 mg/kg per hour, which should be reduced immediately after improvement, most often after 4-6 hours, so that the total intravenous dose does not exceed the recommended dose of 80 mg/kg at any time. What a day.
To cancel Desferal, it is recommended to use the following criteria. Chelation therapy should be continued until all of the following criteria are met: the patient has no signs or symptoms of systemic iron toxicity (eg, no acidosis or increased hepatotoxicity), ideally when the adjusted serum iron level is normal or low (when Iron levels drop below 100 mcg/dL). Given that laboratory methods do not accurately measure serum iron concentrations in the presence of Desferal, it is recommended that Desferal administration be discontinued when all other criteria are met and serum iron levels are not elevated; patients in whom pronounced radiopacity was observed on a previous radiograph require repeated radiography of the abdominal organs to ensure that the radiopacity has disappeared before stopping the administration of Desferal, since it is an indicator of continued iron absorption; if the patient’s urine turns pink during treatment with Desferal, you need to wait so that its color is restored again, and then stop administering Desferal (the absence of pink urine itself is not enough to cancel Desferal).
The effectiveness of treatment depends on the adequacy of urine output, which ensures the removal of the ferrioxamine iron complex from the body. If oliguria or anuria develops, peritoneal dialysis, hemodialysis or hemofiltration may become necessary.
Treatment of chronic aluminum overload in patients with end-stage renal failure. Iron or aluminum complexes of Desferal are dialyzable. In patients with renal failure, their output increases during dialysis.
Patients with symptoms or organ dysfunction due to aluminum overload should be treated with desferal.

The use of this drug should be considered even in asymptomatic patients in whom serum aluminum levels are significantly higher than 60 ng/ml and are accompanied by a positive Desferal infusion test (see below), especially if bone biopsy has demonstrated evidence of aluminum-related bone disease.
Desferal should be administered once a week at a dose of 5 mg/kg. In patients with post-DFO serum aluminum levels of up to 300 ng/mL, Desferal should be administered as a slow infusion during the last 60 minutes of the dialysis session. In patients with post-DFO serum aluminum levels greater than 300 ng/ml, Desferal should be administered as a slow infusion 5 hours before the start of the dialysis session. After completing the first 3-month course of treatment with Desferal, followed by a 4-week break, it is necessary to conduct an infusion test of Desferal. If, during two consecutive Desferal infusion tests with an interval of 1 month, the serum aluminum level exceeds the initial value by less than 50 ng/ml, further treatment with Desferal is not recommended.
For patients on continuous ambulatory peritoneal dialysis (CAPD) or continuous cyclic peritoneal dialysis (CCPD), Desferal should be administered once a week at a dose of 5 mg/kg at the end of the day. For such patients, it is recommended to use the intraperitoneal route of administration. However, Desferal can be administered intramuscularly by slow infusion or subcutaneously.
Desferal test. This test is based on the principle that in healthy people Desferal does not increase the excretion of iron and aluminum above a certain limit.
1. Desferal test for iron overload in patients with normal renal function. Desferal 500 mg should be administered intramuscularly. Then collect urine for 6:00 and determine its iron content. An excretion level of 1-1.5 mg (18-27 µmol) over 6:00 indicates iron overload; a level above 1.5 mg (27 µmol) can be considered pathological. Reliable results with this test can only be obtained with normal kidney function.
2. Desferal infusion test for aluminum overload in patients with end-stage renal failure. A desferal infusion test is recommended for patients with serum aluminum levels greater than 60 ng/ml in the presence of serum ferritin levels greater than 100 ng/ml.
To determine the initial serum aluminum level, a blood sample is taken immediately before the start of a hemodialysis session.
During the last 60 minutes of the hemodialysis session, 5 mg/kg Desferal is administered as a slow infusion.
At the start of the next hemodialysis session (i.e. 44 hours after the above-mentioned Desferal infusion), a second blood sample is taken to re-determine serum aluminum levels.
The desferal test is considered positive if the serum aluminum level upon repeat measurement increases by 150 ng/ml.

However, a negative test does not completely exclude the diagnosis of aluminum overload.
Instructions for preparing solutions.
For parenteral administration, it is necessary to use a 10% solution of the drug in water for injection. 5 ml of water for injection is injected with a syringe into a vial containing 500 mg of Desferal powder and shaken well. Only a clear and colorless or yellowish solution can be used. Desferal 10% solution can then be diluted with commonly used infusion solutions (NaCl 0.9%, glucose 5%, Ringer's solutions, Ringer's lactate, peritoneal dialysis solution - Dineal 137 glucose 2.27%, Dineal PD4 glucose 2.27% and CAPD/DPCA 2 glucose 1.5%).
For carrying out the Desferal test and treating chronic excess aluminum, a dose of Desferal equal to 5 ml of solution in a vial is adequate (5 mg/kg) for patients weighing 100 kg. Taking into account the patient’s body weight, the appropriate volume of Desferal solution is drawn from the bottle and added to 150 ml of 0.9% sodium chloride solution. Dissolved Desferal can be added to dialysed fluids and administered intravenously during CARD or CCPD.

Side effects:
Some signs and symptoms that were thought to be side effects may actually be manifestations of an underlying medical condition (iron and/or aluminum overload).
Infections and infestations: rarely - mucormycosis; very rarely - gastroenteritis caused by Yersinia.
From the blood and lymphatic system: very rarely - abnormal blood counts (including thrombocytopenia).
From the immune system: very rarely - anaphylactic shock, anaphylactic reactions, angioedema.
From the nervous system: often - headache; very rarely - neurological disorders, dizziness, slowing or progression of encephalopathy associated with elevated aluminum levels with hemodialysis, peripheral neuropathy, paresthesia.
From the organs of vision: rarely - loss of vision, scotoma, retinal degeneration, optic neuritis, cataracts, decreased visual acuity, blurred vision, chromatopsia, corneal opacification, night blindness, visual field impairment.
From the organ of hearing: infrequently - sensorineural deafness, ringing in the ears.
From the vascular system: often - arterial hypotension if warnings are not followed.
From the respiratory system, chest and mediastinal organs: infrequently - asthma, very rarely - acute respiratory distress syndrome, pulmonary infiltrate.
From the digestive tract: often - nausea; infrequently - vomiting, abdominal pain very rarely - diarrhea.
From the skin and subcutaneous tissue: often - urticaria, very rarely - generalized rash.
From the musculoskeletal system and connective tissue: often - arthralgia, myalgia; often - growth retardation and dysfunction of bone tissue (for example, metaphyseal dysplasia) when using high doses and in young children.
From the kidneys and urinary system: impaired renal function.
Violation of the general condition and related to the method of administration of the drug: often - reactions at the site of drug administration, including pain, swelling, infiltration, redness of the skin, itching, scab; often - fever, infrequently - reaction at the injection site, including vesicles, swelling, burning.
Sensorineural hearing loss and tinnitus occur infrequently when the recommended dosage is followed and when the dose is reduced when ferritin levels fall (the ratio of the average daily dose of Desferal to serum ferritin levels should be less than 0.025).
Various visual disturbances rarely occur, except when the drug is administered in high doses.
Growth retardation and bone disorders (eg, metaphyseal osteodysplasia) occur frequently at dosages above 60 mg/kg, especially in patients who begin iron chelation in the first three years of life.

At dosages of 40 mg/kg and below, the risk is significantly reduced. Pain at the injection site, swelling, infiltration, redness of the skin, itching and scab/crust occur very often, and vesicles, local swelling and burning are rare. Local manifestations may be accompanied by systemic reactions, such as arthralgia/myalgia (very common), headache (common), nausea (common), fever (common), abdominal pain (rare) or asthma (uncommon).

Contraindications:
Contraindicated for use Desferal with hypersensitivity to the active substance, except in cases where successful desensitization makes treatment possible.

Pregnancy:
To date, all patients who used during pregnancy Desferal, children were born without congenital defects. The drug can be used during pregnancy, especially in the first trimester, only if absolutely necessary and the benefits of treatment must be weighed against the risks for the child.
Lactation. It is unknown whether desferrioxamine is excreted into breast milk, so women receiving Desferal should stop breastfeeding during treatment.
In children under 3 years of age, chelation is carried out under close supervision, and the average daily dose should not exceed 40 mg/kg, since growth retardation and bone disorders (eg, metaphyseal osteodysplasia) occur with high doses.

Interaction with other drugs:
United treatment Desferalom and prochlorperazine, a phenothiazine derivative, can lead to temporary impairment of consciousness.
In patients with severe chronic impairment of iron storage, combined treatment with desferal and high doses of vitamin C (500 mg per day) was accompanied by impaired cardiac function, which was proven to disappear after discontinuation of vitamin C.
The results of gallium 67 contrast studies may be distorted due to rapid renal excretion of desferal-bound gallium. It is advisable to stop using Desferal 48 hours before scintigraphy.

Overdose:
Accidental overdose or accidental intravenous bolus administration of drug Desferal or rapid infusion may be accompanied by hypotension, tachycardia and gastrointestinal disturbances, acute but transient vision loss, aphasia, agitation, headache, nausea, bradycardia, and acute renal failure.
Treatment. There is no special antidote. It is necessary to stop the administration of Desferal and prescribe appropriate symptomatic treatment.
Desferal is dialyzed.

Storage conditions:
Store bottles with dry active substance at temperatures below 25 °C.
One bottle is intended for single use only.
The reconstituted solution must be used immediately after its preparation (administer no later than after 3:00).
If reconstitution of the solution is carried out under aseptic conditions, it can be stored at room temperature for a maximum of 24 hours before administration.
Keep out of the reach of children.

Release form:
Desferal - lyophilisate for the preparation of solution for injection.
Packaging: 500 mg bottles in bottles No. 10.

Compound:
1 bottle Desferal contains 500 mg desferrioxamine methanesulfonate.

Additionally:
Rapid infusion may lead to hypotension and shock (eg, flushing, tachycardia, collapse, and urticaria).
High dose administration Desferala, especially in patients with low plasma ferritin levels, may cause visual and hearing impairment. Patients with renal failure, those on maintenance dialysis and low plasma ferritin levels are especially susceptible to the development of adverse reactions: it was noted that in such cases, visual disturbances occurred even after a single dose of Desferal. The risk of side effects is reduced if you use this drug in a low dose. Adverse reactions caused by Desferal are mostly reversible if detected promptly. Treatment with Desferal can be reinstated later in a reduced dosage, with careful monitoring of vision and hearing function.
Approximately half of the metal complex in patients with normal renal function and iron overload is excreted by the kidneys. Therefore, treatment of patients with severe renal failure should be carried out with caution. Desferrioxamine and iron and aluminum complexes are dialyzable; in patients with renal failure, their excretion from the body during dialysis will increase.
In patients with low serum ferritin levels who were treated with high doses of Desferal, or in children (< 3 years of age at the start of treatment), the use of Desferal was associated with growth retardation. Growth retardation caused by excessive doses of Desferal must be distinguished from growth retardation due to iron overload.

Growth retardation associated with Desferal use occurs rarely when doses less than 40 mg/kg are administered; If growth is delayed due to higher doses of this drug, reducing the dosage may restore normal growth rate, but the expected height in adulthood is no longer achieved.
Acute respiratory distress syndrome has been described in patients with acute iron intoxication, as well as in patients with thalassemia, after treatment with exclusively high intravenous doses of Desferal. Therefore, the recommended daily dose should not be exaggerated.
In patients suffering from iron overload, treatment with desferal has been noted to increase susceptibility to infections, such as Yersinia enterocolitica and Yersinia pseudotuberculosis. If a patient being treated with Desferal develops a fever and acute enteritis/enterocolitis, diffuse abdominal pain or pharyngitis, treatment should be suspended, bacteriological tests performed and appropriate antibiotic therapy initiated immediately. Once the infection has been eradicated, treatment with Desferal can be resumed.
In patients receiving Desferal for the treatment of aluminum and/or iron overload, mucormycosis, a severe fungal infection, has very rarely been reported (sometimes fatal consequences have been reported). If symptoms or suspicious signs of this infection appear, treatment with Desferal should be discontinued, mycological tests should be performed and appropriate therapy should be started immediately. Mucormycosis may occur in patients not receiving Desferal, indicating that other factors, such as dialysis, diabetes mellitus, acid-base imbalance, and malignant blood diseases, may play a role in the development of this infection.
The release of an iron complex can cause urine to appear red-brown in color.
Reservations. Desferal should not be used in doses higher than recommended. This drug, when used by subcutaneous administration, should not be used in concentrations above 10% due to the increased risk of local reactions. If the patient's only route of administration is intramuscular, higher concentrations may need to be used to facilitate injection.
The reconstituted solution at the recommended concentration of 10% is transparent and yellowish in color. Only a clear solution should be used. The cloudy solution must be poured out. The injection should be done very carefully and carefully.
When performing a subcutaneous infusion, the needle should be inserted as close to the dermis as possible.
After simultaneous treatment with desferal and high doses of vitamin C (500 mg per day), cardiac dysfunction was observed in patients with severe chronic iron overload. After discontinuation of vitamin C, cardiac dysfunction ceased. When using Desferal and vitamin C simultaneously, the following measures should be observed.
Supplemental therapy with vitamin C should not be given to patients with heart failure.
You can start administering vitamin C only a month after the previous treatment with regular administration of Desferal.
Vitamin C can only be given when the patient is undergoing regular treatment with Desferal, preferably shortly after the start of the infusion.
The daily dose of vitamin C 200 mg, which is administered in several doses, should not be exaggerated.
When carrying out such combination treatment, it is advisable to monitor cardiac function.
Before starting treatment with Desferal and thereafter at certain intervals (every 3 months), it is recommended to have an ophthalmological consultation and audiological examination. In patients with thalassemia, the risk of hearing impairment can be reduced by maintaining the ratio of the average daily dose of Desferal (mg/kg) to serum ferritin concentration (μg/L) below 0.025.
When treating children with Desferal, it is necessary to determine their weight and height every 3 months.
In patients with aluminum encephalopathy, high doses of Desferal may increase neurological dysfunction (the appearance of seizures), which may be caused by a sharp increase in the amount of circulating aluminum. Desferal may accelerate the onset of dialysis dementia. Pretreatment with clonazepam has been shown to prevent the development of this neurological disorder. In addition, treatment of aluminum overload can lead to a decrease in serum calcium levels and increased hyperparathyroidism.
The ability to influence the reaction rate when driving vehicles or other mechanisms
Patients who experience dizziness or other disorders of the central nervous system should avoid driving vehicles or using other machinery.

Latest update of the description by the manufacturer 31.07.1998

Filterable list

Active substance:

ATX

Pharmacological group

Nosological classification (ICD-10)

Composition and release form

1 bottle of lyophilized powder for injection contains deferoxamine 500 mg; per pack 10 pcs.

pharmachologic effect

Binds iron and aluminum to form chelates.

Indications of the drug Desferal ®

Chronic excess of iron in the body: transfusion hemosiderosis, thalassemia, idiopathic hemochromatosis (if phlebotomy is not possible), porphyria cutanea tarda; acute iron poisoning; chronic excess aluminum in patients with kidney disease on hemodialysis (with the development of diseases of the skeletal system and/or encephalopathy); as a test to determine if there is excess iron or aluminum in the body.

Contraindications

Hypersensitivity.

Use during pregnancy and breastfeeding

During pregnancy (especially in the first trimester) - only for health reasons.

Side effects

Visual and hearing impairment, lens opacities, gastrointestinal disorders, calf muscle cramps, liver or kidney dysfunction, thrombocytopenia, cardiovascular and neurological disorders, allergic skin reactions, local irritation at the injection site.

Directions for use and doses

Parenterally. The dose and regimen of use are determined individually.

Precautionary measures

Before starting and during treatment, ophthalmological and audiological examinations should be carried out (if disorders develop, treatment is canceled). In cases of severe renal failure or anuria (in patients not on dialysis), the IV infusion rate should not exceed 15 mg/kg per hour. Excess iron in the body increases susceptibility to infections caused by Yersinia enterocolitica and Yersinia pseudotuberculosis. If these infections develop during treatment, the drug should be discontinued until they subside.

Storage conditions for the drug Desferal ®

Keep out of the reach of children.

Shelf life of the drug Desferal ®

Do not use after the expiration date stated on the package.

Synonyms of nosological groups

pharmachologic effect

Complexing compound. Forms complexes mainly with trivalent ions of iron and aluminum; binds divalent ions to a lesser extent. Deferoxamine can bind iron, which is in free form or is part of ferritin and hemosiderin, and also binds aluminum found in tissues. The compounds formed in this case are excreted in the urine, which leads to a reduction in pathological deposits of iron and aluminum in tissues.

Pharmacokinetics

Deferoxamine mesylate is poorly absorbed from the gastrointestinal tract. After parenteral administration, deferoxamine forms complex compounds (chelates) with metal ions, which are then excreted in the urine. They are also metabolized, mainly in plasma. The complex compound of deferoxamine with iron is excreted in the urine and bile.

Indications

Transfusion hemosiderosis (especially with thalassemia and other chronic anemias). Acute poisoning with iron preparations (as part of combination therapy). Performing a diagnostic test to determine pathological deposits of iron or aluminum.

Dosage regimen

The exact dose and route of administration are determined individually, and the dose must be reviewed during therapy. For most patients, the daily dose is 20-40 mg/kg body weight. Higher doses should only be used when the expected benefit outweighs the potential risk associated with unwanted side effects.

In case of acute poisoning with iron preparations, it is administered intramuscularly in an initial dose of 1 g. If necessary, repeated administrations are possible, but the daily dose should not exceed 6 g. IV administration in the same doses (slow infusion) is used only in case of a serious condition of the patient (collapse).

Side effect

From the side of the central nervous system: dizziness, convulsions; when used in high doses and/or long-term treatment, a decrease in visual acuity, disturbances in peripheral and twilight vision, color vision disturbances, the development of cataracts, and hearing loss (in the high frequency range) are possible.

From the digestive system: dyspeptic symptoms, diarrhea, liver dysfunction.

From the cardiovascular system: arterial hypotension, collapse.

Others: allergic skin reactions, renal dysfunction, thrombocytopenia.

Contraindications for use

I trimester of pregnancy, increased sensitivity to deferoxamine.

Use during pregnancy and breastfeeding

Contraindicated for use in the first trimester of pregnancy. When using deferoxamine during lactation, breastfeeding should be discontinued.

Use for renal impairment

special instructions

Use with caution in patients with severe renal failure; excretion of the deferoxamine-iron complex in these patients can be increased by hemodialysis.

When used in high doses and/or long-term treatment, regular oculist examinations and audiometry are indicated.

Deferoxamine does not bind iron in hemoglobin, myoglobin, transferrin and iron-containing enzymes (cytochromes, catalase, peroxidases). Deferoxamine is not indicated for the treatment of primary hemochromatosis, since phlebotomy is the method of choice for this pathology.

Deferoxamine may turn urine reddish-brown.