Desferal
Instructions for use:
- 1. Release form and composition
- 2. Indications for use
- 3. Contraindications
- 4. Method of application and dosage
- 5. Side effects
- 6. Special instructions
- 7. Drug interactions
- 8. Analogs
- 9. Terms and conditions of storage
- 10. Terms of dispensing from pharmacies
Desferal is a complexing agent that binds iron and aluminum.
Release form and composition
The dosage form of Desferal is a lyophilisate for the preparation of solution for injection: almost white or white; reconstituted solution - colorless or slightly yellowish (in bottles of 500 mg, in a cardboard box of 10 bottles).
Active ingredient in 1 bottle: deferoxamine mesylate - 500 mg.
Indications for use
- acute iron poisoning (treatment);
- chronic iron overload (treatment): post-transfusion hemosiderosis in case of sideroblastic anemia, thalassemia major, autoimmune hemolytic anemia and other anemias in the chronic course; increased iron deposition with late cutaneous porphyria in cases of impossibility of phlebotomy; idiopathic hemochromatosis in cases where phlebotomy is impossible due to concomitant diseases such as hypoproteinemia, heart disease, severe anemia;
- chronic aluminum overload in patients with end-stage renal disease who are on maintenance hemodialysis (treatment): aluminum-related bone diseases; anemia, which is associated with a high aluminum content; dialysis encephalopathy;
- overload with aluminum / iron (diagnostics).
Contraindications
Absolute:
- anuria;
- I trimester of pregnancy and the period of breastfeeding;
- individual intolerance to the components of the drug, except in cases where successful desensitization allows treatment.
Desferal should be used with caution in patients with severe renal impairment.
Method of administration and dosage
Chronic iron overload
The main goal of maintenance therapy is to balance the intake and excretion of iron and to prevent the development of hemosiderosis.
At the beginning of the use of the drug, it is recommended to achieve a negative balance of iron in order to gradually reduce its increased reserves and prevent the appearance of toxic effects.
Initiate therapy in adults and children after the first 10–20 blood transfusions or when the serum ferritin level reaches 1000 ng / ml. Excessive doses of Desferal or excess iron can lead to growth retardation. When carrying out therapy in children under 3 years of age, their growth must be carefully monitored. The maximum daily dose is 40 mg / kg.
The dose and method of administration of the drug are selected individually, during treatment it can be adjusted (depending on the severity of iron overload).
Desferal should be used at the lowest effective dose. To assess the reaction, it is first necessary to measure daily excretion of iron by the kidneys on a daily basis and to determine the patient's response to increasing doses of the drug. After the optimal dose has been established, 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 taking into account the serum ferritin content and the value of the "therapeutic index", which is the ratio of the average daily dose of the drug (mg / kg) to the serum concentration of ferritin in the blood (μg / L). The value of this indicator should be <0.025. Typically, the daily dose range is 20–60 mg / kg.
Recommended daily doses depending on serum ferritin in the blood:
- <2000 ng / ml: about 25 mg / kg;
- 2000-3000 ng / ml: about 35 mg / kg;
- > 3000 ng / ml: up to 55 mg / kg.
Regular excess of the average daily dose of 50 mg / kg is not recommended. This limitation does not apply to cases where very intensive chelating therapy is required, and patients have already stopped growing.
In cases where the ferritin level falls below 1000 ng / ml, the likelihood of the toxic effect of Desferal increases. When using this dosing regimen, patients need especially careful monitoring. In the future, it is possible to reduce the daily dose.
Since most patients do not receive the drug daily, the dose administered is usually higher than the average daily dose. For example, if a patient is infused 5 nights per week at a prescribed daily dose of 40 mg / kg (280 mg / kg per week), then a single dose will be 280 mg / kg: 5 (56 mg / kg).
It should be borne in mind that with regular therapy, the average life expectancy in patients with thalassemia increases.
Sufficiently effective method of administration of the drug is considered to be slow subcutaneous injection using a portable lightweight infusion pump for 8-12 hours (especially convenient for outpatients). If necessary, it is possible to increase the time of drug administration to 24 hours Desferal should be administered in this way 5-7 times a week.
The drug is not intended for subcutaneous bolus injections.
Elderly patients Desferal is usually prescribed in the minimum effective doses.
The availability of the intravenous route of administration of the drug during blood transfusion allows it to be used without additional inconvenience to the patient. This is especially important in cases where subcutaneous administration is poorly tolerated. Do not add Desferal solution directly to the blood container. It can be inserted into the infusion system through a Y-piece, which must be close to the IV site. This method is rarely used because it limits the amount of the drug. It is impossible to accelerate the infusion process (due to the likelihood of developing vascular collapse).
In cases where intensive therapy with complexing compounds is carried out, it is possible to use implanted systems for intravenous administration. This method is indicated for patients who, for any reason, cannot continue subcutaneous administration, as well as for patients with heart diseases associated with iron overload. The dose of Desferal is determined by the severity of the disorder. With intensive intravenous therapy with complexing compounds, it is necessary to regularly determine the daily excretion of iron by the kidneys (the dose of the drug can be reduced). When flushing the system, care must be taken to avoid the rapid entry into the blood of residual amounts of Desferal (may be present in the “dead” space of the system and lead to the development of collapse).
Intramuscular injections can only be used in cases where subcutaneous administration is not possible. The maintenance dose is determined individually, taking into account the values of the excretion of iron by the kidneys, while its value does not depend on the route of administration.
An excess of iron, as a rule, is accompanied by a lack of vitamin C. After the first month of regular use of Desferal, it is possible to prescribe vitamin C in a daily dose of up to 200 mg in several doses. Vitamin C increases the availability of iron for chelating. For children under 10 years of age, vitamin C is usually prescribed at 50 mg, for older children at 100 mg. An additional increase in the excretion of the iron-containing complex by the kidneys with a further increase in the dose of vitamin C is not observed.
Acute iron poisoning
Desferal should be used in combination with other standard activities.
Therapy is indicated for the following patients:
- patients who show not only mild transient symptoms (for example, more than 1 episode of loose stools or vomiting);
- patients who, during an X-ray examination of the abdominal organs, revealed multiple shadows (in most cases, symptoms of iron poisoning subsequently appear);
- patients with significant abdominal pain, signs of lethargy, acidosis or hypovolemia;
- any patient who has clinical manifestations, and the serum iron concentration in the blood exceeds 0.3-0.35 mg / dl (regardless of the total iron-binding capacity of the blood serum). A conservative approach without the use of Desferal is also possible in cases where the serum iron concentration in the blood is in the range of 0.3-0.5 mg / dL in patients without clinical symptoms, as well as in patients with isolated diarrhea without other symptoms or isolated vomiting without blood.
The preferred route of administration is continuously intravenous at a rate of 15 mg / kg / h. As soon as the patient's condition allows, the rate of administration should be reduced (usually after 4–6 hours). The total amount of Desferal administered in any 24 hours should not exceed 80 mg / kg.
The therapy is continued until all of the following conditions are met:
- absence of signs / symptoms of systemic iron poisoning (acidosis and increased hepatotoxic manifestations);
- corrected serum iron concentration reaches low or normal values. If it is impossible to accurately measure the concentration of iron in the blood in the presence of Desferal, it is possible to discontinue therapy if all other conditions are met, and also provided that the serum concentration of iron in the blood is not increased;
- confirmation of the disappearance of multiple shadows in patients with initially identified shadows (by conducting a repeated X-ray examination of the abdominal organs), since this is a marker of ongoing iron absorption;
- normalization of the color of urine in patients in whom it was previously painted in a wine-pink color.
The effectiveness of therapy depends on adequate diuresis, which should ensure the elimination of the iron-containing complex of ferrioxamine from the body. In cases of anuria / oliguria, it may be necessary to carry out hemofiltration, peritoneal dialysis or hemodialysis.
Chronic aluminum overload in end-stage renal disease
Complexes of aluminum and iron with Desferal are excreted during dialysis. In patients with renal insufficiency, the excretion of these complexes increases with the use of hemodialysis.
Treatment should be given when there are symptoms of aluminum overload or signs of organ dysfunction. Desferal should also be considered in asymptomatic cases, if the serum aluminum concentration in the blood constantly exceeds 60 ng / ml and there is a positive Desferal test, especially if the bone biopsy reveals signs of aluminum-related lesions.
The recommended dosage regimen is 5 mg / kg once a week. At an aluminum concentration of 300 ng / ml, the drug should also be administered slowly intravenously 5 hours before the hemodialysis session.
After the first 3 months of therapy and the subsequent washout period, which lasts 4 weeks, a Desferal test should be performed. If, according to the results of two Desferal tests, carried out with an interval of 30 days, it turns out that the serum aluminum concentration in the blood is not more than 50 ng / ml higher than the initial level, the drug is canceled.
For patients on continuous cyclic peritoneal dialysis (CCPD) or continuous ambulatory peritoneal dialysis (CAPD), Desferal can be administered intramuscularly, subcutaneously, slowly intravenously, or intraperitoneally. In such cases, intraperitoneal administration is recommended.
Desferal should be administered at the rate of 5 mg / kg once a week before the last dialysis session on that day.
Desferal test
The test is based on the property of Desferal not to increase the excretion of aluminum and iron above a certain level.
The scheme of drug use:
- a test to detect iron overload with normal renal function: 500 mg of Desferal is injected intramuscularly, after which urine should be collected for 6 hours to determine its iron content. The release of 1–1.5 mg (18–27 µmol) iron suggests iron overload; higher rates are among pathologies;
- a test to detect aluminum overload in end-stage renal failure (recommended for patients with a serum aluminum concentration> 60 ng / ml, and ferritin> 100 ng / ml): to determine the initial aluminum concentration immediately before the hemodialysis session, blood should be taken for analysis. During the last 60 minutes of the session, 5 mg / kg of Desferal is slowly injected intravenously. At the beginning of the next hemodialysis session (44 hours after the aforementioned drug infusion), a blood sample is taken to re-determine the serum aluminum content in the blood. The result is considered positive in cases where the concentration of aluminum in the blood serum increases by more than 150 ng / ml in comparison with the initial level. However, it should be taken into account that a negative test does not completely exclude the presence of an excess of aluminum.
Instructions for use
For subcutaneous administration, a Desferal solution with a concentration of not higher than 95 mg / ml (solvent - water for injection) should be used. For intramuscular administration, higher concentrations of the solution may be required (5 ml of water for injection must be injected with a syringe into the vial, then shaken well).
Only a clear and slightly yellowish or colorless solution can be used. The 10% solution can be further diluted with commonly used infusion solutions (5% glucose solution, 0.9% sodium chloride solution, Ringer's solution, Ringer's lactate solution), peritoneal dialysis solutions (Dianeal PD4 Glucose 2.27%, Dianeal 137 Glucose 2.27%, CAPD / DPCA 2 Glucose 1.5%).
When conducting the Desferal test and treating chronic aluminum overload, a dose of 5 mg / kg (5 ml solution in a vial) is adequate for patients weighing 100 kg. Taking into account the patient's body weight, the corresponding volume of Desferal solution is removed from the vial and added to 150 ml of 0.9% sodium chloride solution.
The diluted drug can also be added to the dialysis fluid and given intraperitoneally during CAPD and CCPD.
Many patients prefer to use the infusion pump at night.
The prepared solution must be used within 24 hours when stored at room temperature (up to 23 ° C).
Side effects
Some of the symptoms and signs described below as side effects may in fact be a manifestation of the underlying disease (iron / aluminum overload).
Possible violations (> 10% - very often;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rarely; if it is impossible to estimate the frequency of occurrence - with an unknown frequency):
- immune system: very rarely - angioedema, anaphylactic reactions, anaphylactic shock;
- cardiovascular system: rarely - tachycardia, shock, a marked decrease in blood pressure;
- nervous system: often - headache; very rarely - neurological disorders, including dizziness; increased manifestations of encephalopathy, which is associated with dialysis in patients with aluminum overload, paresthesia, peripheral neuropathy; with an unknown frequency - convulsions;
- digestive system: often - nausea; infrequently - abdominal pain, vomiting; very rarely - diarrhea;
- respiratory system: infrequently - asthma; very rarely - lung infiltration, acute respiratory distress;
- organ of vision: rarely - decreased visual acuity, scotoma, blurred (blurred) vision, chromatopsia, loss of vision, visual field defects, hemeralopia, optic neuritis, corneal opacity, cataract, retinopathy;
- hearing organ and labyrinthine disorders: infrequently - tinnitus, sensorineural deafness;
- skin and subcutaneous tissue: often - urticaria; very rarely - generalized rash;
- kidneys and urinary tract: with an unknown frequency - damage to the renal tubules, acute renal failure;
- connective and musculoskeletal tissue: very often - myalgia, arthralgia; often - growth retardation and bone damage (metaphyseal dysplasia); with an unknown frequency - muscle spasms;
- parasitic / infectious diseases: rarely - mucormycosis; very rarely - yersiniosis gastroenteritis;
- instrumental / laboratory data: very rarely - changes in the picture of peripheral blood (including leukopenia, thrombocytopenia); with an unknown frequency - an increase in serum creatinine in the blood;
- general disorders and disorders at the injection site: very often - scab / crust at the injection sites, swelling, pain, infiltration, itching, erythema; often - pyrexia; infrequently - local edema, vesicular rash, burning.
The development of convulsions during therapy is usually observed in hemodialysis patients with aluminum overload.
The excretion of complexes of Desferal with iron by the kidneys can lead to staining of urine in a reddish-brown color.
Treatment of aluminum overload may result in hypocalcemia and exacerbation of hyperparathyroidism.
special instructions
Rapid intravenous administration of Desferal can lead to the development of hypotension and shock (manifested in the form of redness of the skin, vascular collapse, tachycardia, urticaria).
The use of high doses of Desferal can cause hearing and visual impairment, especially in patients with low serum ferritin levels in the blood. Tinnitus and sensorineural deafness sometimes occur if the dosing regimen is observed and the dose of the drug is reduced in cases of a decrease in the concentration of ferritin (the ratio of the average daily dose of the drug to the serum concentration of ferritin in the blood should be <0.025). In such patients, visual impairment was observed after a single administration of the solution. When using low doses, the likelihood of adverse reactions is reduced. In cases of visual or hearing impairment, Desferal should be canceled immediately. In most cases, changes associated with therapy are reversible. In the future, treatment can be resumed,but with the use of lower doses and under close medical supervision of vision and hearing. Before starting therapy and then every 3 months, it is recommended to carry out ophthalmological studies and audiometry, especially with a reduced level of ferritin.
When using Desferal in patients with severe renal failure, caution should be exercised.
Desferrioxamine complexes of aluminum and iron are removed by hemodialysis. With renal failure during hemodialysis, an increase in the excretion of these complexes is possible. Patients with renal insufficiency who receive maintenance hemodialysis sessions and have a reduced serum ferritin level in their blood are more likely to develop adverse reactions. Bone tissue disorders and growth retardation are observed when Desferal is used at doses above 60 mg / kg, especially in those patients who start treatment in the first 3 years of life. At doses of 40 mg / kg and below, this risk is reduced. In children during the period of therapy, it is recommended to monitor the height and weight every 3 months.
Respiratory distress syndrome has been described with intravenous administration of excessively high doses in the treatment of acute iron poisoning as well as thalassemia. In this regard, the recommended daily dose of the drug should not be exceeded.
If during therapy there is an increase in body temperature, which is accompanied by acute enteritis / enterocolitis, pharyngitis or diffuse pain in the abdomen, it is recommended to temporarily interrupt the use of Desferal, conduct a bacteriological analysis, and then immediately begin appropriate antibiotic therapy. After the infection is cured, the drug may be resumed.
There is information about rare cases of mucorosis, in some cases fatal (if signs of illness appear, Desferal should be canceled).
For subcutaneous infusion, the needle should not be inserted too close to the dermis.
There is evidence of cardiac abnormalities during combination therapy with vitamin C (more than 500 mg per day) in patients with severe chronic iron overload (as a rule, after the abolition of vitamin C, the indicators normalize).
Recommendations for the use of vitamin C in combination therapy:
- treatment can be started only after 1 month of using Desferal;
- monitoring of cardiac activity should be carried out regularly;
- the daily dose should not exceed 200 mg, divided into several doses;
- the introduction of vitamin C is best started soon after the start of the Desferal infusion;
- the appointment of patients with heart failure is not recommended.
In case of encephalopathy, which is associated with excess aluminum, the use of high doses of Desferal can lead to an exacerbation of neurological symptoms (convulsions). The drug may help accelerate the onset of hemodialysis-related dementia. Pretreatment with clonazepam has been reported to prevent this neurological complication from occurring. In addition, treatment of excess aluminum can lead to a decrease in serum calcium levels in the blood and an exacerbation of hyperparathyroidism.
Given the safety profile of Desferal, namely the likelihood of developing dizziness or other side effects from the central nervous system, including hearing / visual impairment, the question of the ability to drive vehicles must be decided individually.
Drug interactions
With the combined use of Desferal with certain drugs / substances, the following effects may develop:
- prochlorperazine: temporary impairment of consciousness;
- vitamin C (in a daily dose of 500 mg) in severe chronic iron overload: cardiac dysfunction (reversible);
- heparin solution for injection: incompatibility.
The scintigrams obtained with the use of gallium-67 can be distorted (associated with the rapid excretion of gallium-67 associated with Desferal in the urine). In this regard, it is advisable to interrupt the use of the drug 48 hours before the scintigraphy.
You should not use 0.9% saline sodium chloride solution as a solvent for dry matter (it can be used for further dilution after dissolving the lyophilisate in water for injection).
Analogs
There is no information on analogues.
Terms and conditions of storage
Store at temperatures up to 30 ° C. Keep out of the reach of children.
The shelf life is 1.5 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
