Desferal

Desferal is a drug that forms chelate bonds with iron.

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Indications Desferala

It is used in cases of severe iron overload in the body in chronic form – as a monotherapeutic agent:

• transfusion siderosis, observed in the hemolytic form of anemia of autoimmune origin, the sideroblastic form of anemia and other chronic anemias, as well as in severe thalassemia;
• primary hemochromatosis in people with concomitant pathologies that prevent phlebotomy (such disorders as cardiac pathologies, severe anemia, and in addition hypoproteinemia);
• Iron overload due to late-stage cutaneous porphyria in people with phlebotomy intolerance.

It is also used to eliminate acute iron intoxication.

Helps to eliminate chronic aluminum overload in people with end-stage renal failure (on maintenance dialysis), accompanied by aluminum-dependent bone disease, aluminum-dependent anemia, or dialysis-induced encephalopathy.

The medicine is also used to diagnose excess aluminum or iron.

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Release form

The product is produced in the form of an injection lyophilisate, in 0.5 g vials. There are 10 such vials inside the box.

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Pharmacodynamics

Desferrioxamine mainly combines with Fe ions, and also with trivalent Al ions: the constants of these complexes are, respectively, 10 31 and 10 25. The affinity of the DFO element to such divalent ions as Cu2+, with Fe2+, and also Zn2+ and Ca2+, is much lower (the constant of such complex formation is 10 14 or less). The chelation process is carried out in molar proportions of 1 to 1 - 1 g of the active substance is theoretically capable of synthesizing 85 mg of trivalent Fe or 41 mg of Al3+.

The chelating action of the DFO component allows it to capture free iron within cells or plasma, resulting in the formation of a ferrioxamine compound (FC). The excretion of iron in the form of FC with urine mainly shows the amount of iron removed from plasma, and the excretion with feces mainly shows the amount of chelated Fe inside the liver.

Iron chelation can also occur from ferritin with hemosiderin, but this process is quite slow when DFO is administered in therapeutic doses. It should be clarified that DFO does not cause iron removal from hemoglobin with transferrin or from other elements containing hemin.

The element DFO is capable of chelating and mobilizing aluminum, which promotes the subsequent formation of the aluminoxamine compound (AlO).

Because both of these compounds (FL with AlO) are completely excreted from the body, the element DFO helps to remove aluminum and iron with feces and urine, which helps to reduce the volume of these components inside the organs.

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Pharmacokinetics

Suction.

DFO is absorbed fairly quickly after a bolus injection or slow subcutaneous administration. The substance is poorly absorbed from the gastrointestinal tract due to the presence of an intact mucosa. The absolute bioavailability of 1 g of the drug taken orally is less than 2%.

By adding DFO to dialysis fluid, its absorption can occur during the peritoneal dialysis procedure.

Distribution processes.

The peak plasma level is 15.5 μmol/l (or 8.7 μg/ml) – it is observed half an hour after the administration of 10 mg/kg of the drug. After 60 minutes after the administration of the drug, the peak PL level reaches 3.7 μmol/l (or 2.3 μg/ml).

After the introduction of 2 g of the drug infusion (approximately 29 mg/kg), after 120 minutes the DFO indicator acquires a constant value of 30.5 μmol/l. The process of substance distribution is rapid, the average distribution half-life is 0.4 hours. In vitro, it is synthesized with blood plasma protein by less than 10%.

Metabolic processes.

In the urine of people with Fe overload, 4 products of DFO metabolism were identified and registered. It was found that this substance undergoes the following biotransformation processes: oxidation with transamination, resulting in the formation of an acidic metabolic product, and in addition to this, N-hydroxylation and decarboxylation, during which neutral decay products are formed.

Excretion.

After administration of Desferal to a patient, the components DFO and FL have a two-stage excretion. The apparent distribution half-life of the substance DFO is 60 minutes, and that of FL is 2.4 hours. The apparent terminal excretion half-life of both elements is 6 hours. With a 6-hour injection, 22% of the portion is found in the urine in the form of DFO, and 1% in the form of FL.

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Dosing and administration

The average size of the initial daily dose is 1 g (1-2 injections); and the maintenance dose is 500 mg/day. The drug is often administered intramuscularly. A 10% solution should be used. To obtain it, 0.5 g of the substance (1 ampoule) should be dissolved in sterile injection fluid (5 ml).

The drug is administered intravenously only through a drip in a ratio of maximum 15 mg/kg/hour. No more than 80 mg/kg is allowed to be administered per day.

To eliminate acute iron intoxication, it is necessary to take Desferal parenterally or orally.

To synthesize iron that has not yet been absorbed from the gastrointestinal tract, you need to drink 5-10 g of the substance (10-20 ampoules), which must be dissolved in ordinary drinking water.

To remove absorbed iron, the drug should be administered intramuscularly - 1-2 g, at intervals of 3-12 hours. In severe cases, 1 g of the substance is administered intravenously through a drip.

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Use Desferala during pregnancy

Tests on rabbits have shown that DFO may have a teratogenic effect. At the moment, all women who used Desferal during pregnancy gave birth to children who did not have congenital anomalies. However, the use of the drug during this period, especially in the first trimester, should be done only in extreme cases, having previously compared the benefits and risks of its use.

There is no information on whether the active ingredient of the drug passes into breast milk, therefore, nursing patients are required to stop breastfeeding during therapy.

Contraindications

It is prohibited to use the drug in the presence of intolerance to the active ingredient (except for situations where successful desensitization allows therapy).

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Side effects Desferala

Some symptoms perceived as negative reactions to the use of drugs may in fact be symptoms of concomitant pathology (aluminum or iron overload).

• lesions of an infectious or invasive nature: mucormycosis is occasionally observed. Gastroenteritis caused by the activity of yersinia develops occasionally;
• disorders of the lymph and circulatory system: isolated disturbances of blood parameters are noted (this includes thrombocytopenia);
• immune disorders: anaphylactic symptoms, Quincke's edema or anaphylaxis develop occasionally;
• problems with the functioning of the nervous system: headaches often occur. Neurological disorders, progression or inhibition of encephalopathy caused by increased aluminum levels with hemodialysis, as well as dizziness, paresthesia and polyneuropathy are noted sporadically;
• visual impairment: vision loss, degenerative processes in the retina, scotoma, cataracts and neuritis in the optic nerve are occasionally observed. In addition, blurred vision, corneal opacity, weakened vision, hemeralopia, chromatopsia and visual field disorder occur;
• problems with the functioning of the hearing organs: sometimes there is ringing in the ears or deafness of a neurosensory nature;
• lesions affecting the vascular system: often, if the regimen of use is not followed, a decrease in blood pressure values is observed;
• disorders in the sternum, mediastinum and respiratory organs: asthma sometimes occurs. ARDS and pulmonary infiltrate develop occasionally;
• digestive disorders: nausea is often observed. Sometimes abdominal pain or vomiting may occur. Diarrhea develops occasionally;
• lesions affecting the subcutaneous layer and the surface of the skin: urticaria often begins. Generalized rashes appear sporadically;
• disorders affecting the urinary system and kidneys: problems with renal function;
• Systemic disorders and lesions at the injection site: symptoms such as swelling, pain, itching, redness, infiltration and crusting are often observed. Fever may also develop; burning, swelling or vesicles occur at the injection site.

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Overdose

Manifestations of intoxication.

In case of accidental administration of too large a dose of the drug, accidental intravenous bolus injection or rapid infusion, some disorders may develop. Among them are tachycardia, decreased blood pressure, gastrointestinal disorders, agitation, aphasia, nausea, headache and bradycardia, as well as acute but transient loss of vision and acute renal failure.

Therapy.

The drug has no antidote. It is necessary to stop the administration of the drug, and then carry out appropriate symptomatic procedures.

Desferal is dialysable.

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Interactions with other drugs

When the drug is combined with prochlorperazine (a phenothiazine derivative), transient disturbance of consciousness may develop.

In individuals with severe iron formation disorders in chronic form, the combined use of the drug and large doses of ascorbic acid (0.5 g per day) led to problems with the heart, which disappeared after stopping the intake of the latter.

Contrast test data using gallium ⁶⁷ may be subject to distortion due to rapid renal excretion caused by desferal gallium. It is recommended to discontinue use of the medication 48 hours before performing scintigraphy.

Incompatible with heparin injection solution.

It is prohibited to use 0.9% sodium chloride solution for diluting dry lyophilisate, although after reconstitution of the drug with injection liquid, this solvent can be used for subsequent dilution.

Storage conditions

Desferal in the form of dry lyophilisate is kept in a place closed to small children at a temperature of no more than 25°C. Each ampoule is intended for single use only. The reconstituted medicinal solution is used immediately after preparation (maximum – within 3 hours). When performing the reconstitution procedure using the aseptic method, the shelf life of the solution increases to 24 hours.

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Shelf life

Desferal can be used for 4 years from the date of manufacture of the drug.

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Application for children

For children under 3 years of age, the chelation procedure should be performed under special supervision. The average daily dose should not exceed 40 mg/kg, because the use of large doses leads to growth retardation and disorders of bone tissue functioning (for example, to the development of metaphyseal osteodysplasia).

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Analogues

Analogues of the drug are Exjade, as well as Deferoxamine and Defroxamine.

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Reviews

Desferal receives good reviews for its medicinal effect. It is noted that it copes well with the function of iron excretion from the body, and at the same time has a much lower level of toxicity than some of its analogues - therefore, the frequency of side effects of this medication is much lower.