Desferal - instructions for use, dose, side effects, contraindications

Active substanceDeferoxamineDeferoxamine

Similar drugsTo uncover

Desferal®

lyophilizatesolution for injections

Novartis Pharma AG Switzerland

Dosage form: & nbsplyophilizate for solution for injection

Composition:1 bottle contains: active substance - deferoxamine mesylate 500.00 mg.

Description:

The powder is white or almost white.

Description of reconstituted solution: colorless or slightly yellowish solution.

Pharmacotherapeutic group:Complexing agent

ATX: & nbsp

V.03.A.C.01 Deferoxamine

Pharmacodynamics:

Desferal® is a complexing (chelating) compound. The active substance of the drug - deferoxamine (desferrioxamine = DFO) forms complexes predominantly with ferric and aluminum ions. The complexation constants are respectively 10³^l and 10²⁵. Affinity DFO to such divalent ions as iron, copper, zinc, calcium are much lower (complexation constants 10¹⁴ and below). Chelation occurs at a molar ratio of 1: 1, so that 1 g DFO theoretically can bind 85 mg of ferric ion or 41 mg of trivalent aluminum ion.

Chelating properties DFO allow it to bind free iron, which is in the blood plasma or in cells, forming a complex of ferrioxamine (FO). Excretion of ferrioxamine by the kidneys reflects mainly the removal of iron from the blood plasma, while excretion of iron by the intestine reflects intrahepatic binding of iron.Iron can be chelated from ferritin and hemosidirin, but at clinically significant concentrations DFO it happens slowly. but DFO does not remove iron from transferrin, hemoglobin or other hemin-containing compounds. DFO is also able to mobilize and bind aluminum, forming an aluminoxamine complex (A10). Since both complexes, FO and A1O, completely removed from the body, DFO stimulates the release of iron and aluminum by the kidneys and intestines and as a result reduces the pathological deposition of these metals in the organs.

Pharmacokinetics:

Suction.

Deferoxamine is rapidly absorbed after intramuscular (IM) bolus or subcutaneous (SC) drip administration. Suction DFO From the gastrointestinal tract in the presence of intact mucosa occurs to an insignificant extent. After ingestion 1 g DFO the absolute bioavailability of the drug is less than 2%. With peritoneal dialysis, absorption DFO From the peritoneal cavity to the systemic blood flow occurs when the drug is injected with the dialysis fluid.

Distribution.

In healthy volunteers, the maximum concentration DFO in blood plasma (C_m_Oh) was determined 30 minutes after the / m administration of the drug at a dose of 10 mg / kg and averaged 15.5 μmol / L (8.7 μg / ml). 1 hour after IM injection DFO the concentration of the drug in the blood plasma was reduced to 3.7 μmol / l (2.3 μg / ml). After an intravenous (iv) 2-hour infusion, 2 g DFO (about 29 mg / kg), an equilibrium concentration of the substance, equal to an average of 30.5 μmol / L, was achieved in healthy plasma volunteers. Distribution DFO occurs very quickly: the average half-life is 0.4 hours. Binding DFO with serum proteins in vitro is less than 10%.

Metabolism.

Out of the urine of patients with excess iron, 4 metabolites were isolated and identified in the body DFO. It was found that biotransformation DFO includes the following reactions: transamination and oxidation to form an acid metabolite; (3-oxidation to form an acid metabolite; decarboxylation and N-hydroxylation with the formation of neutral metabolites.

Excretion.

Excretion DFO and FO from the body of healthy volunteers after i / m administration of the drug occurs in 2 phases. In the first fast phase (the "distribution phase"), the apparent half-distribution period is 1 hour for DFO and 2.4 hours for FO. In the second slow phase ("elimination phase"), the apparent half-life for both compounds is 6 hours. Within 6 hours after injection by the kidneys, 22% of the dose in the form DFO and 1% - in the form FO.

Peculiarities of pharmacokinetics in selected patient groups

In patients with hemochromatosis, the maximum plasma concentrations were determined 1 h after IM administration DFO in a dose of 10 mg / kg and averaged 7.0 μmol / L (3.9 μg / ml) for DFO and 15.7 μmol / L (9.6 μg / ml) for FO. Mean half-life values for DFO and FO were 5.6 and 4.6 hours, respectively. Six hours after the injection, a 17% dose was excreted in the urine in the form of DFO and 12% in the form FO.

With prolonged IV infusion DFO patients with thalassemia in a dose of 50 mg / kg for 24 hours, the equilibrium concentration DFO in blood plasma was 7.4 μmol / l (4.1 μg / ml). Reduction in concentration DFO in blood plasma was biphasic with an average half-life of 0.28 hours and an apparent half-life of 3 hours. The total clearance was 0.5 l / h / kg, and the volume of distribution in the equilibrium state was 1.35 l / kg. Value AUC metabolite DFO, which plays a major role in iron binding, is 54% of the value AUC DFO. The apparent half-life (half-elimination) of this metabolite is 1.3 hours.

In patients who underwent hemodialysis for renal failure and who received DFO in a dose of 40 mg / kg IV for 1 hour, the concentration DFO in the blood plasma at the end of the infusion period was 152 μmol / L (85.2 μg / ml) if the infusion was performed between two hemodialysis sessions. If intravenous administration DFO was performed during the hemodialysis session, the concentration of the drug in the blood plasma was 13-27% lower. Concentrations FO in all cases were approximately 7.0 μmol / L (4.3 μg / ml), and AL concentrations were 2-3 μmol / L (1.2-1.8 μg / ml). After discontinuation of the infusion DFO the concentration of the drug in the blood plasma rapidly decreased with a half-life of 20 minutes. The smaller part of the dose had a longer half-life, equal to 14 hours. The concentration of AI in the blood plasma continued to increase within 48 hours after the end of the infusion DFO and reached about 7 μmol / L (4 μg / ml). After the hemodialysis session, the concentration of AO in the blood plasma decreased to 2.2 μmol / l (1.3 μg / ml).

Indications:

- Treatment of chronic iron overload, including:

posttransfusion hemosiderosis with large thalassemia, sideroblastic anemia, autoimmune hemolytic anemia and other chronic anemias;
idiopathic (primary) hemochromatosis in cases where phlebotomy is not possible due to such concomitant diseases as severe anemia, heart disease, hypoproteinemia;
increased deposition of iron in late skin porphyria if phlebotomy is not possible.

- Treatment of acute iron poisoning.

- Treatment of chronic aluminum overload in patients with terminal stage of renal failure (undergoing hemodialysis) under the following conditions:

diseases of the osseous system caused by aluminum;
dialysis encephalopathy;
anemia associated with elevated aluminum content.

- Diagnosis of overload by iron or aluminum.

Contraindications:

- Hypersensitivity to the active substance, unless successful desensitization allows treatment;

- Anuria;

- Pregnancy (1st trimester);

- Lactation period.

Carefully:

Caution is required when using Desferal® in patients with severe renal failure.

If you have any of the listed diseases, always consult a doctor before using the drug.

Pregnancy and lactation:

In experimental studies, the possibility of teratogenic action of deferoxamine has been demonstrated.To date, there have been no birth defects in children born to women treated with Desferal ® during pregnancy. However, the use of the drug during pregnancy, especially in the first trimester, is possible only in case of absolute necessity.

It is not known whether the deferoxamine into breast milk; in each case, the expected benefit for the mother with potential risk for the child should be compared.

Dosing and Administration:

Treatment of chronic iron overload

The main goal of maintenance therapy with complexing compounds is to establish an equilibrium between the intake and excretion of iron and prevention of hemosiderosis, while at the beginning of therapy individuals with iron overload it is desirable to achieve a negative iron balance to gradually reduce the increased iron reserves and prevent toxic effects. In children and adults, it is recommended to begin treatment with Desferal ® after the first 10-20 blood transfusions or when the ferritin level in the serum is 1000 ng / ml. Excess iron or excessive doses of Desferal may cause a slowdown in growth.When conducting therapy with Desferal ® in children under the age of 3 years, it is necessary to carefully monitor their growth; the daily dose of the drug should not exceed 40 mg / kg.

The dose and method of administration of Desferal® should be selected individually and corrected during treatment, depending on the degree of severity of iron overload. The minimum effective dose of the drug should be used. To evaluate the response to therapy with complexing compounds, the daily renal excretion of the kidneys should be measured daily and the response to increasing doses of Desferal® should be determined. After the optimal dose of Desferal® is determined, the amount of iron excretion by the kidneys should be measured at intervals of several weeks. The average daily dose of Desferal can also be determined by taking into account the serum ferritin content and the "therapeutic index", which is the ratio of the average daily dose of Desferal® (in mg / kg) to serum ferritin concentration (in μg / l). The value of this "therapeutic index" should be less than 0.025. The average daily dose is usually in the range of 20 to 60 mg / kg.

Patients who have serum ferritin levels below 2000 ng / ml require a dose of about 25 mg / kg / day; with a ferritin content of 2000 to 3000 ng / ml, a dose of about 35 mg / kg / day is needed. Patients with a higher serum ferritin content may require a dose of up to 55 mg / kg / day. It is not recommended to regularly exceed the average daily dose of 50 mg / kg, unless very intensive chelation therapy is required and the patient has already stopped the growth process. If the ferritin content falls below 1000 ng / ml, the risk of the toxic effect of Desferal ® is increased. It is necessary to carefully observe these patients and keep in mind the possibility of reducing the total weekly dose. The doses given above are the average daily doses of the drug when administered daily. However, since most patients receive Desferal® less than 7 times a week, the daily dose administered usually exceeds the average daily dose. For example, if the required average daily dose is 40 mg / kg (280 mg / kg per week), but the patient is infused only 5 nights a week, the administered dose should be 56 mg / kg (280 mg / kg: 5).

It was shown that regular therapy with Desferal® increases the average life expectancy in patients with thalassemia.

Slow subcutaneous administration using a portable light infusion pump for 8-12 hours is considered quite effective and especially convenient for outpatients. Such administration can continue for 24 hours. This method of administration of Desferal® should be applied 5-7 times a week. Desferal® is not intended for nosocomial bolus injections.

Application in elderly patients

Patients with advanced age should be prescribed a minimum effective dose of the drug.

Intravenous administration during blood transfusion. The availability of / in the route of administration during blood transfusion makes it possible to use it without additional inconvenience to the patient. This is especially useful in cases of poor portability of SC injections. Do not add Desperal® solution directly to a container of blood. It can be introduced into the infusion system by means of Y- shaped connecting adapter located close to the site of the intravenous injection.The patient's infusion pump should be used to administer the Desferal® preparation as usual. This method of administration is rarely used, since a limited amount of Desferal® can be administered intravenously during blood transfusion. It is necessary to warn the patient and the nurse about the fact that the infusion process can not be accelerated, as this can lead to vascular collapse.

Continuous intravenous administration. Implanted systems for intravenous administration can be used in those cases when intensive therapy with complexing compounds is carried out. This method of use is indicated for patients who can not continue SC administration, as well as patients suffering from cardiac diseases due to iron overload. Doses of Desferal ® depend on the severity of iron overload. With intensive IV therapy complexing compounds should regularly determine the daily excretion of iron by the kidneys, and depending on the results of such a determination, you can reduce the dose of the drug. Care must be taken when flushing the system,to avoid the rapid entry into the blood of residual amounts of Desferal ®, which may be present in the "dead" space of the system, due to the possibility of developing a collapse.

Intramuscular injection. Since s / c administration is more effective, I / m injections should be used only in those cases when s / c administration is impossible. The individual maintenance dose should be selected taking into account the values of excretion of iron by the kidneys, while the dose value does not depend on the route of administration.

Simultaneous application of vitamin C. Excess iron is usually accompanied by a deficiency of vitamin C, probably due to its oxidation by iron. After the first month of regular treatment with Desferal®, vitamin C can be prescribed as a supplementary agent in the treatment with complexing compounds in doses up to 200 mg / day in several doses. Vitamin C increases the availability of iron to form chelate complexes. Children under 10 years of vitamin C are usually administered at 50 mg;

to older children - 100 mg each. A further increase in the dose of vitamin C does not cause an additional increase in the release of the iron-containing complex by the kidneys.

Treatment of acute iron poisoning

Desferal® is used in conjunction with other standard measures. Therapy with Desferal® is indicated for the following patients:

- All patients who have not only mild transient symptoms (eg, more than one episode of vomiting or loose stools)

- Patients with signs of lethargy, significant abdominal pain, hypovolemia or acidosis

- Patients who, with X-ray examination of the abdominal cavity, display multiple shadows (most of these patients subsequently show symptoms of iron poisoning)

- Any patient with clinical manifestations and serum iron concentration exceeding 300-350 μg / dl, regardless of the total iron binding ability of blood serum. There is also a conservative approach without the use of Desferal ® in cases where serum iron concentration is in the range of 300 to 500 μg / dl in patients who have no clinical symptoms, as well as in patients with isolated vomiting without blood or isolated diarrhea without other symptoms.

Preferably, continuous iv administration of Desferal® at a rate of 15 mg / kg / hr.The rate of administration should be reduced as soon as the patient's condition (usually in 4-6 hours) allows, so that the total amount of the drug administered IV in any 24 hours does not exceed 80 mg / kg.

Therapy with Desferal® should be continued until all of the following conditions are met:

- The patient should have no signs or symptoms of systemic iron poisoning (such as acidosis and increased hepatotoxicity)

- Ideally, the adjusted serum iron concentration should be normal or low (iron concentration below 100 μg / dL). If it is not possible to accurately measure the concentration of iron in the blood in the presence of Desferal®, it may be possible to discontinue therapy with Desferal® under all other conditions and provided that the serum iron concentration is not increased

- It is necessary to repeat the X-ray study of the abdominal cavity organs in patients with initially identified multiple shadows to confirm their disappearance, as they are a marker of continued iron absorption

- If a wine-rosy staining of urine was observed in the patient at the beginning of therapy with Desferal®,then the color of urine should come back to normal before discontinuing therapy with Desferal® (the absence of vinous-pink staining is not in itself a criterion for stopping therapy with Desferal®)

The effectiveness of treatment depends on adequate diuresis, which should ensure removal of the iron-containing ferrioxamine complex from the body. With the development of oliguria or anuria, there may be a need for peritoneal dialysis, hemodialysis or hemofiltration.

Treatment of chronic aluminum overload in patients with terminal stage of renal failure

Complexes of iron and aluminum with the preparation Desferal® are excreted during dialysis. In patients with renal failure, excretion of these complexes increases with the use of hemodialysis. Treatment with Desferal ® should be carried out in cases where there are symptoms of aluminum overload or signs of impaired function of the organs. The question of prescribing Desferal® should also be considered when there are no symptoms, but the concentration of aluminum in the serum constantly exceeds 60 ng / ml and there is a positive desferate test,if bone biopsy shows signs of their damage caused by aluminum. Desferal® should be administered once a week at a dose of 5 mg / kg. Patients with an aluminum concentration of up to 300 ng / ml, measured after DFO-test, Desferal® is administered slowly over the last 60 minutes of the hemodialysis session. For patients with an aluminum concentration in the serum of more than 300 ng / ml, the drug is also administered iv slowly 5 hours before the hemodialysis session. After the first three-month course of treatment with Desferal® and the subsequent 4-week washout period, a test with Desferal® should be performed. If, according to the results of two desferal tests conducted at intervals of 1 month, it appears that the concentration of aluminum in the blood serum exceeds the baseline by no more than 50 ng / ml, further treatment with Desferal® is not recommended.

Patients on continuous ambulatory peritoneal dialysis (CAPD) or continuous cyclic peritoneal dialysis (CCPD), Desferal® can be administered in / m, slowly in / in or in / or, or intraperitoneally. In this case it is recommended intraperitoneal administration.Enter Desferal® once a week at a rate of 5 mg / kg before the last dialysis session on that day.

The desferal test

This test is based on the fact that in normal Desferal® does not increase the release of iron and aluminum above a certain level.

1. Desferal test for detecting iron overload in patients with normal renal function. In / m 500 mg of Desferal ® are administered. The urine is then collected for 6 hours and the iron content is determined therein. The isolation of 1-1.5 mg (18-27 μmol) of iron during this period suggests iron overload; values above 1.5 mg (27 μmol) can be considered pathological. The sample gives reliable results only with normal kidney function.

2. Desferal test for detecting aluminum overload in patients with terminal stage of renal failure. Conducting a sample with an infusion of Desferal® is recommended for patients who have a serum concentration of more than 60 ng / ml in the serum and a serum ferritin concentration higher than 100 ng / ml. Immediately before the hemodialysis session, blood should be taken for analysis to determine the initial concentration of aluminum. During the last 60 minutes of a hemodialysis session, Desferal® is slowly administered IV to 5 mg / kg. At the beginning of the next session of hemodialysis (i.e.,44 hours after the above-mentioned infusion of Desferal®), a blood sample should be taken to re-determine the aluminum content of serum.

The desferral test is considered positive if the concentration of aluminum in the blood serum increases by more than 150 ng / ml compared to the baseline level. However, a negative test does not completely exclude the presence of excess aluminum.

Instructions for use

For subcutaneous administration, use a solution of the drug concentration of not more than 95 mg / ml in water for injection. For i / m administration, higher concentrations of the solution may be required. 5 ml of water for injection is injected with a syringe into a vial containing 500 mg of Desferal® powder and shaken well. Use only a clear and colorless or slightly yellowish solution. A 10% solution of Desferal® can then be diluted with commonly used infusion solutions (0.9% sodium chloride solution, 5% glucose solution, Ringer's solution, Ringer's lactate solution), peritoneal dialysis solutions (Dianeal 137 Glucose 2.27%, Dianeal PD4 Glucose 2.27%, CAPD/DPCA 2 Glucose 1.5%).

To carry out the desferral test and to treat chronic aluminum overload, the dose of Desferal equal to 5 ml of the solution in the vial is adequate (5 mg / kg) for a patient with a body weight of 100 kg.Given the patient's body weight, the corresponding volume of the Desferal® solution is removed from the vial and added to 150 ml of a 0.9% solution of sodium chloride.

The dissolved preparation of Desferal® can also be added to the dialysis fluid and administered intraperitoneally during CAPD (continuous peritoneal dialysis) and CCPD (continuous cyclic peritoneal dialysis).

The introduction of the preparation Desferal® for chronic iron overload by means of a portable infusion pump is carried out as follows:

1. Draw water for injection into the syringe.

2. Wipe the rubber stopper of the vial with Desferal® with alcohol and insert the contents of the syringe into the vial.

3. Shake the bottle well to dissolve the preparation.

4. Pour the dissolved drug into the syringe.

5. Attach the extension tube to the syringe and connect it to the "butterfly" needle. Fill the empty space of the tube with a solution of the syringe.

6. Place the syringe in the infusion pump.

7. For infusion, the needle-"butterfly" can be inserted under the skin of the abdomen, arms, upper leg, thigh. It is very important to thoroughly clean the skin with alcohol before you insert the needle. The needle should be inserted deep, to the "wings", into the hand-folded skin fold. The tip of the inserted needle should move freely during lateral movements.If this does not happen, the tip of the needle may be too close to the skin. In this case, try to insert the needle again in another place after cleaning the skin with alcohol.

8. Then fix the needle with a plaster.

9. Patients usually wear an infusion pump on the body or shoulder on the strap. Many patients prefer a nocturnal introduction as the most convenient.

The prepared solution of Desferal® should not be stored for more than 24 hours at room temperature (up to 23 ° C).

Side effects:

Below are the undesirable reactions listed by the frequency of development. The frequency of unwanted reactions is estimated as follows: very often (≥ 1/10); often (≥ 1/100 <1/10); infrequently (≥ 1/1000 <1/100); rarely (≥ 1/10000 <1/1000); very rarely (<1/10000); frequency is unknown.

It should be noted that some of the signs and symptoms described as undesirable phenomena may in fact be a manifestation of the underlying disease (iron and / or aluminum overload).

Infectious and parasitic diseases: rarely - mucormycosis; very rarely - iersiniosis gastroenteritis.

Immune system disorders: very rarely - anaphylactic shock, anaphylactic reactions, angioedema.

Disturbances from the nervous system: often - headache; very rarely - neurological disorders, including dizziness; increased manifestations of encephalopathy associated with dialysis in patients with aluminum overload; peripheral neuropathy; paresthesia; frequency is unknown - convulsions. Disturbances on the part of the organ of sight: rare - blurred vision, decreased visual acuity, loss of vision, color perception disorder (chromatopsy), night blindness (hemeralopia), visual field defects, scotoma, retinopathy (pigmentary degeneration of the retina), optic neuritis, cataracts , corneal opacity.

Hearing disorders and labyrinthine disturbances: infrequently - neurosensory deafness, tinnitus.

Vascular disorders: rarely - a marked decrease in blood pressure. Heart Disease: rarely - tachycardia, shock.

Disturbances from the respiratory system, infrequently - asthma; very rarely - acute respiratory distress, lung infiltration.

Disorders from the digestive system: often - nausea; infrequently - vomiting, abdominal pain; very rarely diarrhea.

Disturbances from the skin and subcutaneous tissues: often - hives; very rarely - generalized rash.

Disturbances from musculoskeletal and connective tissue: very often - arthralgia, myalgia; often - growth retardation and bone damage (metaphyseal dysplasia); frequency unknown - muscle spasms.

Disorders from the kidneys and urinary tract: frequency unknown - acute renal failure, renal tubular damage.

General disorders and disorders at the place of administration ', very often - pain, swelling, infiltration, erythema, itching, scab / crust at the injection site; often pyrexia; infrequently - a vesicular rash, local swelling, burning.

Laboratory and instrumental data: very rarely - changes in the pattern of peripheral blood (including thrombocytopenia, leukopenia); the frequency is unknown - an increase in serum creatinine.

The development of convulsions was predominantly noted in patients with aluminum overload, who are on hemodialysis.

There is no correlation between the occurrence of rare cases of increased activity of transaminases in the blood serum and the use of Desferal ®. Excretion of the drug complexes with iron kidneys can lead to a reddish brown color of urine.

Treatment with Desferal ® overload with aluminum can lead to hypocalcemia and exacerbation of hyperparathyroidism.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Symptoms. Accidental administration of the drug in high dose or occasional IV bolus / rapid administration can cause tachycardia, arterial hypotension and gastrointestinal symptoms; acute temporary loss of vision, aphasia, agitation, headache, nausea, bradycardia. Also reported cases of acute renal failure and respiratory distress syndrome (with very high doses of the drug administered intravenously).

Treatment. There is no specific antidote. Discontinue the administration of Desferal® and take appropriate symptomatic measures. Desferal® can be removed by hemodialysis.

Interaction:

Simultaneous treatment with Desferal® and the phenothiazine derivative with prochlorperazine can lead to temporary impairment of consciousness. In patients with iron overload of severe chronic course,who received the preparation Desferal ® in combination with high doses of vitamin C (more than 500 mg / day), cardiac arrhythmias were noted. These disorders were reversible after the withdrawal of vitamin C.

Scintigrams obtained with the use of gallium-67 can be distorted due to the rapid excretion of urine associated with the preparation Desferal® gallium-67. It is advisable to interrupt the administration of Desferal® 48 hours before the scintigraphy.

Pharmaceutical interaction. The solution of Desferal ® is incompatible with the heparin solution for injection. Physiological solution of sodium chloride (0.9%) should not be used as a dry substance solvent, but after dissolving Desferal® in water for injection, saline solution of sodium chloride can be used for further dilution.

Special instructions:

Rapid IV administration of the drug may lead to hypotension and shock (redness of the skin, vascular collapse, tachycardia, urticaria).

The use of Desferal ® in high doses can lead to visual and hearing impairment, especially in people with a low ferritin content in the serum.Sensorine deafness and tinnitus occur sometimes when the dosage regimen is observed and the dose of the drug is decreased with a decrease in ferritin concentration (the ratio of the average daily dose of the preparation of Desferal to the concentration of serum ferritin should be less than 0.025). Visual impairment was noted in such patients after a single injection of the drug. The risk of side effects decreases with the use of low doses of Desferal®. If there are visual or hearing impairments, the drug should be immediately discontinued. Usually, the changes caused by Desferal®, in case of early detection, are reversible after the withdrawal of treatment. The treatment can then be resumed, but in lower doses and under strict control of the functions of hearing and vision. It is recommended that ophthalmic examination and audiometry be performed in patients before starting therapy with Desferal® and every 3 months during therapy, especially with reduced ferritin levels.

Approximately half of the complexes with the metal are excreted by the kidneys in patients with iron overload and normal kidney function.Therefore, care must be taken when using the drug in patients with severe renal failure.

Desferrioxamine complexes of iron and aluminum are excreted by hemodialysis. In patients with renal failure during hemodialysis, an increase in the excretion of these complexes can be achieved. In patients with renal insufficiency, receiving sessions of maintenance hemodialysis and having a reduced serum ferritin content, the risk of side effects is increased. Slowing of growth and disturbances from the bone tissue (for example, metaphyseal dysplasia) occur when the drug is used in doses above 60 mg / kg, especially in those patients who start therapy in the first 3 years of life. The risk of developing these side effects is reduced if the dose is maintained at 40 mg / kg and below. In patients with childhood, receiving the preparation Desferal®, it is recommended to control body weight and growth every 3 months.

Respiratory distress syndrome has been described with intravenous administration of excessively high doses of Desferal® in acute iron poisoning, as well as in thalassemia.Therefore, do not exceed the recommended daily intake of the drug.

There is evidence that in patients with iron overload, Desferal® increases the susceptibility to infections caused, for example, by Yersinia enterocolitica and Yersinia pseudotuberculosis. If, during treatment with Desferal®, there is an increase in body temperature, accompanied by symptoms of acute enteritis / enterocolitis, diffuse abdominal pain or pharyngitis, temporarily stop the treatment with Desferal®, carry out bacteriological analysis and immediately begin the appropriate antibiotic therapy. After curing the infection, you can resume treatment with Desferal®.

In patients receiving the preparation Desferal® due to overloading with aluminum and / or iron, there have been reports of rare cases of development of mucorosis (mucormycosis), in some cases fatal. If any signs of the disease appear, the Desferal® drug should be discarded, mycological examinations should be performed and the appropriate treatment should be started immediately. Mucorosis can occur in patients who do not receive Desferal ®, and this suggests that some other factors, for example, hemodialysis,diabetes mellitus, acid-base balance disorder, malignant blood diseases, use of immunosuppressants or immunity disorders due to other factors, may play a role in the development of this infection. Isolation of iron complexes can cause a reddish brown color of urine. Do not exceed recommended doses of Desferal®. For subcutaneous administration, do not use Despareral® solution in concentrations above 10%, as the risk of local reactions increases. If only I / m is possible, a solution of the drug at higher concentrations may be required to facilitate injection.

The prepared 10% solution should be clear and colorless (or slightly yellowish). Use only clear solutions. Opaque or cloudy solutions should be discarded. The procedure for the administration of Desferal 8 should be treated with particular care.

In case of infusions, the needle should not be inserted too close to the dermis.

There are reports of cardiac abnormalities with simultaneous treatment with Desferal ® and vitamin C in high doses (more than 500 mg / day) of patients with severe chronic iron overload.After the abolition of vitamin C, there was a normalization of cardiac activity.

If simultaneous use of Desferal® and vitamin C is planned, the following precautions should be taken:

- Do not prescribe vitamin C to a patient with heart failure;

- treatment with vitamin C can be started only after the end of the first month of regular treatment with Desferal®;

- Vitamin C can be administered only with regular treatment with Desferal®; its introduction is best to start soon after the infusion of the drug Desferal®;

- Do not exceed the daily dose of vitamin C 200 mg, divided into several doses;

- During this combination therapy, regular monitoring of cardiac activity is desirable.

Before the treatment with Desferal ® and every 3 months during the treatment, a specialized ophthalmological examination and hearing examination is recommended, especially with a low concentration of serum ferritin. The risk of hearing impairment in thalassemia patients may be reduced if the ratio of the average daily dose of Desferal® (in mg / kg) to serum ferritin concentration (in μg / l) is maintained below 0.025.

In pediatric practice, during treatment with Desferal®, body weight and growth should be monitored every 3 months.

In patients with encephalopathy associated with excess aluminum, the use of Desferal® in high doses can lead to exacerbation of neurological symptoms (convulsions), which is probably due to a sharp increase in the concentration of aluminum in the blood. The drug Desferal® can accelerate the onset of dementia associated with hemodialysis. According to reports, preliminary treatment with clonazepam prevents the occurrence of this neurological complication. In addition, the treatment of excess aluminum can lead to a decrease in the level of calcium in the serum and exacerbation of hyperparathyroidism.

Effect on the ability to drive transp. cf. and fur:

Patients who experience dizziness or other central nervous system dysfunction, including visual or visual impairment, should not drive or operate machinery during the period of application of the drug.

Form release / dosage:Lyophilizate for solution for injection 500 mg.

Packaging:For 500 mg of the drug in a bottle of transparent colorless borosilicate glass type I (Hev. F.), sealed with a bromobutyl stopper, coated with an aluminum cap with a plastic flip-off lid of red color (flip-off). 10 vials with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

18 months.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002050

Date of registration:12.04.2013 / 08.08.2016

Expiration Date:12.04.2018

The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland

Manufacturer: & nbsp

NOVARTIS PHARMA, AG Switzerland

WASSERBURGER ARZNEIMITTELWERK, GmbH Germany

Representation: & nbspNOVARTIS PHARMA LLCNOVARTIS PHARMA LLC

Information update date: & nbsp25.03.2017

Illustrated instructions

Instructions

Desferal® (Desferal®)