Desferal

Desferal - a preparation that forms chelate bonds with iron.

[1], [2], [3]

Indications of the desferal

It is used when the body is overloaded with iron in a chronic form - as a monotherapeutic agent:

• sidereous transfusion, marked with a hemolytic form of anemia of autoimmune origin, sideroblastic form of anemia and other chronic anemia, as well as with severe thalassemia;
• hemochromatosis of a primary nature in people with concomitant pathologies that interfere with phlebotomy (such disorders as cardiac pathologies, severe anemia, and hypoproteinemia in addition);
• iron overload due to cutaneous porphyria at a late stage in people with intolerance to phlebotomy.

It is also used to eliminate iron intoxication in acute form.

Helps to avoid overloading of aluminum, which is chronic, in people with terminal type kidney failure (on the supporting dialysis), against which there is an aluminum-dependent bone disease, aluminum-dependent anemia or encephalopathy of dialysis origin.

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

[4], [5]

Release form

The release is made in the form of injection lyophilizate, in flakonchikah volume of 0.5 g. Inside the box - 10 such bottles.

[6], [7], [8], [9], [10], [11]

Pharmacodynamics

Desferrioxamine is mainly combined with Fe ions, and in addition, 3-valence Al ions: the constants of these complexes are respectively 10 31, and also 10 25. The affinity of the DFO element for such 2-valence ions as Cu2 + with Fe2 +, and besides Zn2 + and Ca2 +, it is much lower (the parameter of the constant of such complexation is 10 14 and less). The chelation process is carried out in molar proportions 1k1 - 1 g of active substance is able in theory to synthesize 85 mg of 3-valent Fe or 41 mg of Al3 +.

The chelating effect of the DFO component allows it to capture the free iron in the cells or plasma, resulting in the formation of the ferrioxamine compound (PL). Excretion of iron in the form of PL together with urine mainly demonstrates the volume of iron withdrawn from the plasma, and excretion with feces mainly shows the number of chelated Fe inside the liver.

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

Element DFO is able to chelate and mobilize aluminum, which contributes to the subsequent formation of aluminoxamine compound (AlO).

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

[12], [13], [14]

Pharmacokinetics

Suction.

DFO is absorbed fairly quickly after a bolus-type injection or slow p / c injection. From the gastrointestinal tract the substance is not absorbed badly because of the presence of intact mucosa. The level of absolute bioavailability of the 1st g of the drug, taken orally, is less than 2%.

When DFO is added to the dialysis fluid, it can be absorbed by the peritoneal dialysis procedure.

Distribution processes.

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

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

The processes of metabolism.

Inside the urine of people in whom the element Fe is overloaded, 4 metabolites of the DFO element are detected and recorded. It has been revealed that this substance undergoes such biotransformation processes: oxidation with transamination, which results in the formation of an acidic metabolic product, and in addition N-hydroxylation and decarboxylation, in which neutral decay products are formed.

Excretion.

After administration to the patient of Desferal, the components of DFO and PL have a two-stage excretion. The explicit distribution half-cycle of the DFO substance is 60 minutes, while the PL is 2.4 hours. The apparent final half-cycle of excretion in both elements is 6 hours. With a 6-hour injection, 22% of the dose is detected inside the urine in the form of DFO, and 1% in the form of FL.

[15], [16], [17], [18]

Dosing and administration

The average size of the initial portion per day is 1 g (1-2 injections); and maintenance - 500 mg / day. The drug is often injected in / m way. Use a 10% solution. To get it, you should dissolve 0.5 g of the substance (1 ampoule) in a sterile injectable liquid (5 ml).

Intravenously, the drug is administered only through a dropper in a ratio of at most 15 mg / kg / h. For a day is allowed to enter no more than 80 mg / kg.

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

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

To remove absorbed iron, you should inject the drug in / m method - 1-2 grams, with intervals of 3-12 hours. In case of serious intravenous infringements, 1 g of substance is administered through a dropper.

[23], [24], [25]

Use of the desferal during pregnancy

Tests on rabbits have shown that the DFO can have a teratogenic effect. At the moment, all women who used Desferal during pregnancy, gave birth to children who did not have congenital anomalies. But at the same time to use the medication during this period, especially in the first trimester, should only be in extreme cases, first matching the benefits and risks of its use.

There is no information as to whether the active ingredient of the drug passes into the mother's milk, so during the therapy, nursing patients are required to refuse breastfeeding.

Contraindications

It is forbidden to use the drug in the presence of intolerance with respect to the active element (except for situations where successful implementation of desensitization allows for therapy).

[19]

Side effects of the desferal

Individual signs perceived as negative reactions to the use of drugs can in fact turn out to be symptoms of concomitant pathology (overload by aluminum or iron).

• lesions of an infectious or invasive nature: mucormycosis is occasionally observed. Gastroenteritis, provoked by the activity of yersinia, develops sporadically;
• violations of the function of the lymph and circulatory system: there is a single disorder of blood levels (this includes thrombocytopenia);
• immune disorders: anaphylactic symptoms develop singly, Quincke edema or anaphylaxis;
• problems with the work of the National Assembly: often headaches occur. Separately, neurological disorders are noted, progression or inhibition of encephalopathy caused by increased indices of aluminum with hemodialysis, and in addition dizziness, paresthesia and polyneuropathy;
• disturbances of visual function: occasionally there is a loss of vision, degenerative processes in the retina, scotoma, cataract and neuritis in the optic nerve. In addition, visual fuzziness, turbidity in the cornea, vision loss, hemorrhagia, chromatopsy and visual field disorder occur;
• problems with the work of auditory organs: sometimes there is an ear ringing or deafness of neurosensory character;
• lesions affecting the vascular system: often, in case of non-compliance with the regime of use, a decrease in blood pressure values is noted;
• disorders in the sternum, mediastinum and respiratory organs: sometimes there is asthma. Single development of ARDS and infiltrate in the lungs;
• digestive disorders: often there is nausea. Sometimes abdominal pain or vomiting may occur. Diarrhea develops singly;
• lesions affecting the subcutaneous layer and skin surface: often hives begin. Single lesions appear generalized;
• disorders affecting the urinary system and kidneys: problems with renal activity;
• systemic disorders and lesions at the site of administration: often there are symptoms such as swelling, pain, itching, redness, infiltration and scab. A febrile condition may also develop; there is burning, swelling or vesicles at the injection site.

[20], [21], [22]

Overdose

Manifestations of intoxication.

In case of accidental administration of too large portions of drugs, accidental intravenous injection of a bolus character or rapid infusion, some disorders may develop. Among them, tachycardia, depression of pressure, GI function disorders, state of arousal, aphasia, nausea, headache and bradycardia, and in addition acute, but transient loss of vision, and renal failure in the acute stage.

Therapy.

The medication does not have an antidote. It is required to cancel the introduction of drugs, and then to carry out the corresponding symptomatic procedures.

Desferal undergoes dialysis.

[26], [27],

Interactions with other drugs

When the drug is combined with prochlorperazine (phenothiazine derivative), a transient consciousness disorder can develop.

In persons with severe iron deficiency in chronic form, combined use of the drug and large portions of ascorbic acid (per day of 0.5 g) led to problems with the work of the heart, which disappeared after the termination of the reception of the latter.

The data of the contrast test using gallium ⁶⁷  can be distorted - due to the rapid excretion through the kidneys caused by gallium desulfate. It is recommended to cancel the use of the medication 48 hours before performing the scintigraphy.

Has an incompatibility with the injectable solution of heparin.

Do not use 0.9% sodium chloride solution to dilute the dry lyophilizate, although after reconstitution with the injection liquid, this solvent can be used for subsequent dilution.

Storage conditions

Desferal in the form of a dry lyophilizate is kept in a place that is closed from the access of young children, at temperatures that are not more than 25 ° C. Each ampoule is intended exclusively for single use. The reconstituted medical solution is used immediately after manufacturing (maximum - in the period of 3 hours). When carrying out the aseptic recovery procedure, the storage time of the solution is increased to 24 hours.

[28], [29], [30]

Shelf life

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

[31], [32], [33], [34], [35]

Application for children

Children younger than 3 years of age, the chelation procedure must be carried out under special supervision. The average daily dose should not be above 40 mg / kg, because the use of large doses leads to growth retardation and bone tissue disorders (eg, metaphyseal osteodysplasia).

[36], [37], [38], [39]

Analogues

Analogues of the medication are preparations of Eksidzhad, as well as Deferoxamine with Defoxamine.

[40], [41], [42], [43], [44], [45], [46], [47]

Reviews

Desferal gets good feedback about his medicinal effect. It is noted that he perfectly copes with the function of excretion of iron from the body, and at the same time has at times a lower level of toxicity than some of its analogues - therefore, the frequency of development of adverse symptoms in this medicine is much lower.