Iron [III] hydroxide sucrose complex - instructions for use, dose, side effects, contraindications

Active component of the preparation Iron (III) The hydroxide sucrose complex consists of the nucleus of multinucleated iron hydroxide (III), surrounded by a large number of non-covalently bound sucrose molecules. The average molecular weight of this complex is approximately 43 kDa. The structure of a multinucleated iron-containing nucleus is similar to that of the core of the ferritin protein, the physiological iron depot. This complex is designed to create a controlled source of iron for the proteins responsible for the transport and deposition of iron in the body (respectively, transferrin and ferritin).

After intravenous injection, the multinuclear iron-containing core of this complex is captured mainly by the reticuloendothelial system of the liver, spleen, and bone marrow. At the next stage, iron is used to synthesize hemoglobin, Myoglobin and other iron-containing enzymes, or stored in the liver mainly in the form of ferritin.

Pharmacokinetics:

Distribution

Kinetics of Iron (III) hydroxide of a sucrose complex labeled with ⁵²Fe and ⁵⁹Fe, was evaluated in patients with anemia and chronic renal failure. During the first 6-8 hours Fe was captured by the liver, spleen and bone marrow.

After intravenous administration of a single dose of iron (III) hydroxide sucrose complex containing 100 mg iron in healthy volunteers,the maximum total iron concentrations were achieved in the serum 10 minutes after the injection, the average concentration was 538 mmol / l. The volume distribution of the central chamber fully corresponded to the volume of the plasma (about 3 liters).

Biotransformation

After injection, sucrose is mostly disintegrated, and the multinuclear iron-containing nucleus is mainly captured by the reticuloendothelial system of the liver, spleen, and bone marrow. At 4 weeks after the administration, iron utilization by erythrocytes is from 59% to 97%.

Excretion

The average molecular weight of Iron (III) hydroxide of the sucrose complex is approximately 43 kDa, which is large enough to prevent excretion through the kidneys. The excretion of iron by the kidneys within the first 4 hours after the injection is less than 5% of the total clearance. After 24 hours, the serum level of iron returns to its original (before administration) value. Isolation of sucrose by the kidneys was about 75% of the administered dose.

Indications:

Iron (III) hydroxide is a sucrose complex used to treat iron deficiency conditions in the following cases:

- with the clinical need for rapid replacement of iron stores;

- in patients who do not tolerate oral iron preparations or do not follow the treatment regimen;

- in the presence of active inflammatory bowel disease, when oral iron preparations are ineffective.

Contraindications:

Use of the preparation Iron (III) hydroxide sucrose complex is contraindicated in the event that:

- Anemia is not associated with iron deficiency;

- There are signs of iron overload (hemosiderosis, hemochromatosis) or disruption of the process of its utilization;

- there is an increased sensitivity to the iron-sucrose complex, a solution of the iron-sucrose complex, or to any of the components of the drug;

- I trimester of pregnancy.

Carefully:

Patients with bronchial asthma, eczema, polyvalent allergies, allergic reactions to other parenteral iron preparations, and individuals who have low iron-binding capacity of blood serum and / or deficiency of folic acid, Iron (III) hydroxide sucrose complex should be administered with caution. Also, caution is required when administering iron preparations to patients with hepatic insufficiency, with acute or chronic infectious diseases and persons,which have increased serum ferritin levels due to the fact that parenterally administered iron can have adverse effects in the presence of a bacterial or viral infection. Iron (III) hydroxide sucrose complex should be used with caution in patients with diabetes mellitus and in children under the age of 18 (due to inadequate safety and efficacy data).

Pregnancy and lactation:

Pregnancy

Limited experience in the use of the preparation Iron (III) hydroxide sucrose complex in pregnant women in the II and III trimesters showed no undesirable effects of iron sugarate on the course of pregnancy and fetal / newborn health. To date, there have not been well-controlled studies in pregnant women.

The use of the drug in the first trimester of pregnancy is contraindicated.

The results of reproduction studies in animals showed no direct or indirect adverse effects on embryo / fetal development, childbirth, or postnatal development. Nevertheless, an assessment of the risk / benefit ratio is required.

Breastfeeding period

The amount of data on excretion of iron with human breast milk after intravenous administration of Iron (III) the hydroxide of the sucrose complex is limited. In a small clinical study, healthy, breast-feeding mothers with iron deficiency received 100 mg of iron in the form of an iron-sucrose complex. Four days after treatment, the content of iron in breast milk did not increase, and there was no difference in comparison with the control group. It can not be ruled out that iron from Iron (III) the hydroxide of the sucrose complex can enter the newborn / infant with the mother's milk, therefore an assessment of the risk-benefit ratio should be made.

Dosing and Administration:

Application

Gland (III) The hydroxide sucrose complex is administered only intravenously: by drip infusion, or by slow injection, or directly into the venous portion of the dialysis system. The drug is not intended for intramuscular injection.

Before applying the ampoule of the preparation Iron (III) The hydroxide sucrose complex should be inspected for sediment or damage. Apply only ampoules with a homogeneous, non-precipitating brown solution.Each ampoule of iron preparation (III) The hydroxide of the sucrose complex is intended exclusively for single use. Any residues of unapplied medicinal product or its waste should be disposed of in accordance with local requirements.

Introduction of the preparation Iron (III) hydroxide sucrose complex should be carried out under the supervision of medical personnel who have experience in the diagnosis and treatment of anaphylactic reactions in a specialized department. It should be possible to carry out anti-shock therapy, including a 0.1% solution of epinephrine (adrenaline), antihistamines and / or corticosteroid drugs. The test dose is not a reliable prognostic factor for the development of subsequent hypersensitivity reactions, and therefore its preliminary administration is not recommended.

During the administration of the drug and immediately after the administration, patients should be under the supervision of a physician. When the first signs of anaphylactic reactions appear, the drug should be discontinued immediately.

It is necessary to observe each patient for at least 30 minutes after each injection of Iron (III)hydroxide sucrose complex in a therapeutic dose for the absence of undesirable phenomena.

Intravenous drip infusion

Iron (III) hydroxide, the sucrose complex is diluted only with a sterile 0.9% (w / v) solution of sodium chloride (NaCl). The diluted solution should be clear, brown in color. Dilution should be performed immediately before infusion, and the resulting solution should be administered as follows:

Dose of the preparation Iron (III) hydroxide sucrose complex (mg iron)	Dose of the preparation Iron (III) hydroxide sucrose complex (ml preparation Iron (III) hydroxide sucrose complex)	The maximum dilution volume of a sterile 0.9% (w / v) solution NaCl	Minimal infusion time
100 mg	5 ml	100 ml	15 minutes
200 mg	10 ml	200 ml	30 minutes
300 mg	15 ml	300 ml	1,5 hour
400 mg	20 ml	400 ml	2,5 hours
500 mg	25 ml	500 ml	3,5 hours

Dilution of the drug to lower concentrations of iron is unacceptable for reasons related to the stability of the solution.

Intravenous injection

Iron (III) hydroxide sucrose complex may be administered by slow intravenous injection at a rate of 1 ml undiluted solution per minute.The dose should not exceed 10 ml (200 mg of iron) per injection.

Injection into the venous site of the dialysis system

Iron (III) hydroxide, the sucrose complex can be administered during the hemodialysis session directly to the venous portion of the dialysis membrane, under the same conditions as for intravenous injection.

Doses

For each patient, the cumulative dose of Iron (III) must be individually calculated, the hydroxide is a sucrose complex that can not be exceeded.

Calculation of dose

The total cumulative dose of Iron (III) hydroxide, a sucrose complex equivalent to total iron deficiency (mg), is determined based on the hemoglobin (Hb) and body weight (MT). The dose of the preparation Iron (III) hydroxide sucrose complex should be calculated individually for each patient in accordance with the general iron deficiency according to the following formula Ganzoni:

Total iron deficiency (mg) = body weight (kg) x (the target hemoglobin content is the actual hemoglobin content) (g / l) x 0.24 * + deposited iron (mg).

At body weight less than 35 kg: the target hemoglobin content = 130 g / l,

amount of deposited iron = 15 mg / kg body weight

With a body weight of 35 kg or more: the target hemoglobin content = 150 g / l,

amount of deposited iron = 500 mg.

* Coefficient 0.24 = 0.0034 (iron content in hemoglobin = 0.34%) x 0.07 (blood mass about 7% of body weight) x 1000 (transfer of g in mg).

Total amount of iron preparation (III) hydroxide saccharose complex to be administered (in ml) = total iron deficiency (mg) / 20 mg iron / ml

Total amount of the preparation Iron (III) hydroxide is a sucrose complex, which must be introduced, depending on the body weight, the actual hemoglobin content and the target hemoglobin content:

Weight Cumulative therapeutic dose Iron (III) body hydroxide [kg] sucrose complex (20 mg iron per ml), which should be introduced

	Hb 60 g / l		Hb 75 g / l		Hb 90 g / l		Hb 105 g / l
	mg Fe	ml	mg Fe	ml	mg Fe	ml	mg Fe	ml
5	160	8	140	7	120	6	100	5
10	320	16	280	14	240	12	220	11
15	480	24	420	21	380	19	320	16
20	640	32	560	28	500	25	420	21
25	800	40	700	35	620	31	520	26
30	960	48	840	42	740	37	640	32
35	1260	63	1140	57	1000	50	880	44
40	1360	68	1220	61	1080	54	940	47
45	1480	74	1320	66	1140	57	980	49
50	1580	79	1400	70	1220	61	1040	52
55	1680	84	1500	75	1300	65	1100	55
60	1800	90	1580	79	1360	68	1140	57
65	1900	95	1680	84	1440	72	1200	60
70	2020	101	1760	88	1500	75	1260	63
75	2120	106	1860	93	1580	79	1320	66
80	2220	111	1940	97	1660	83	1360	68
85	2340	117	2040	102	1720	86	1420	71
90	2440	122	2120	106	1800	90	1480	74

* At a body weight of less than 35 kg: the target hemoglobin content is 130 g / l At a body weight of 35 kg or more: the target hemoglobin content is 150 g / l

To transfer hemoglobin (mmol) into hemoglobin (g / l), multiply the first value by 16. If the total required dose exceeds the maximum permissible single dose, it should be divided into several injections.

If, 1-2 weeks after the start of treatment with the preparation of Iron (III), the hydroxide of the sucrose complex does not improve the hematological parameters,it is necessary to revise the initial diagnosis.

Calculation of the dose for replenishment of iron stores after blood loss or delivery of autologous blood.

Dose of Iron (III) The hydroxide sucrose complex necessary to compensate for iron deficiency is calculated by the following formula:

- If the amount of blood lost is known:

intravenous administration of 200 mg of iron (= 10 ml of the preparation Iron (III) hydroxide saccharose complex) leads to the same increase in hemoglobin concentration as transfusion of 1 blood sample (400 ml with 150 g / l hemoglobin concentration).

The amount of iron that must be replenished (mg) = the number of portions of lost blood x 200 mg

Required volume of the preparation Iron (III) hydroxide sucrose complex (ml) = number of portions of lost blood x 10 ml

- If the hemoglobin content is lower than desired:

Use the previous formula, provided that the iron depot is not required to replenish.

The amount of iron that must be replenished (mg) = body weight (kg) x 0,24 x (the target hemoglobin content is the actual hemoglobin content) (g / l).

For example: body weight 60 kg, deficiency of Hb = 10 g / l => necessary amount of iron = 150 mg => necessary volume of the preparation Iron (III) hydroxide sucrose complex = 7.5 ml.

Standard doses

Adults and elderly patients: 5-10 ml Iron (III) hydroxide sucrose complex (100-200 mg iron) 1-3 times a week, depending on hemoglobin level. The time of administration and the method of dilution, see section "Application".

Children: There are only limited data on the use of the drug in children in the study. The recommended dose for children is not more than 0.15 ml of the preparation Iron (III) hydroxide saccharose complex (3 mg of iron) per kg of body weight 1-3 times a week, depending on the level of hemoglobin. The time of administration of the preparation and the method of dilution, section "Application".

Maximum tolerated single and weekly doses

Adults and elderly patients.

The maximum tolerable dose per day, injected as an injection, is not more than 3 times a week:

- 10 ml of the preparation Iron (III) hydroxide sucrose complex (200 mg of iron), the duration of administration is not less than 10 minutes.

The maximum tolerated dose per day, administered as an infusion is not more often than 1 time per week:

- Patients weighing more than 70 kg: 500 mg of iron (25 ml of Iron (III) hydroxide, a sucrose complex) administered for a minimum of 3.5 hours.

- Patients weighing 70 kg or less: 7 mg of iron per 1 kg of body weight, administered for a minimum of 3.5 hours.

Side effects:

The most frequent undesirable drug reaction (NLR) recorded in the clinical studies of the Iron drug (III) hydroxide sucrose complex was a change in taste sensations, which was observed at a frequency of 4.5 events per 100 subjects. The most important serious undesirable drug reactions associated with the use of the Iron drug (III) hydroxide sucrose complex were hypersensitivity reactions that were observed in clinical trials with a frequency of 0.25 events per 100 subjects.

The table below shows the undesirable drug reactions registered with the preparation Iron (III) hydroxide sucrose complex in clinical trials, as well as in the post-marketing period.

System-Organ Class	Frequent (>1/100, <1/10)	Infrequent (> 1/1000, <1/100)	Rare (>1/10000, <1/1000)	Frequency unknown¹⁾
Infections and invasions			Pneumonia
Violations of the blood and lymphatic system		Polycythemia²⁾
Immune system disorders		Hypersensitivity		Anaphylactoid reaction, angioedema
Metabolic and nutritional disorders			Overload iron
Disturbances from the nervous system	Violation flavoring sensations	Headache, dizziness, sensation burning, paresthesia, hypoesthesia	Fainting, migraine, drowsiness	Reduced consciousness, confusion, loss of consciousness, anxiety, tremor
Heart Disease			Feeling palpitation	Bradycardia, tachycardia
Vascular disorders	Reduction of arterial pressure, arterial hypertension	Thrombophlebitis, phlebitis	Hyperemia	Vascular collapse, superficial vein thrombosis
Violations from hand respiratory system, thoracic cells and the mediastinum		Dyspnea		Bronchospasm
Violations from hand gastrointestinal tract	Nausea	Vomiting, abdominal pain, constipation	Dry mouth
Disturbances from the skin and subcutaneous tissues		Skin itching, skin rash		Hives, erythema, violation of pigmentation
Disturbances from musculoskeletal and connective tissue		Muscle cramps, myalgia, arthralgia, pain in the limbs, back pain	Feeling discomfort in the extremities, muscle spasms	Muscular hypotension
Disorders from the kidneys and urinary tract		Chromaturia
General disorders and disorders at the site of administration	Pain at the injection site	Chills, reactions at the injection site, irritation at the injection site, extravasation at the injection site, discoloration of the skin at the injection site, burning sensation at the injection site, edema at the injection site, asthenia, fatigue, pain	Feeling of heat, chest pain, pyrexia, itching at the injection site, bruising at the injection site	Hyperhidrosis, cold sweat, general malaise, pallor
Laboratory and instrumental data		Increased activity of gamma-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, pathological changes in the results "Hepatic samples "	Increase serum ferritin concentration²⁾, increase in creatinine concentration in the blood, increase lactate dehydrogenase activity in the blood

¹⁾ Spontaneous messages received in the post-registration period

²⁾ Perhaps as a consequence of an iron overdose or iron overload.

Overdose:

Overdose can cause an overload with iron, which is manifested by symptoms of hemosiderosis. Overdose should be treated with a chelating agent for binding iron or in accordance with standards of medical practice.

Interaction:

Iron (III) hydroxide, the sucrose complex is not recommended to be administered simultaneously with oral forms of iron, as the absorption of iron from the gastrointestinal tract decreases. Treatment with oral iron preparations can begin no earlier than 5 days after the last injection.

Iron (III) the hydroxide sucrose complex can be mixed in a single syringe only with a sterile 0.9% (w / v) solution of sodium chloride. No other solutions for intravenous administration and therapeutic agents are added, since there is a risk of precipitation and / or other pharmaceutical interactions. Compatibility with containers from other materials, besides glass, polyethylene and polyvinyl chloride, has not been studied.

Special instructions:

In 1 ml of the drug contains from 260 mg to 340 mg of sucrose. These data should be taken into account in patients with diabetes mellitus. Drip administration of the drug, depending on the indications, the maximum tolerated dose can reach 500 mg of iron, which corresponds to the introduction of 8.5 g of sucrose. When recalculating a given amount of carbohydrates into grain units (XE) (1 XE = 12 g carbohydrates), it corresponds to 0.7 XE.

It is necessary to strictly adhere to the speed of administration of the drug (with rapid administration of the drug, blood pressure can decrease). A higher incidence of undesirable adverse reactions (in particular, lowering blood pressure), including severe ones, is associated with an increase in the dose. Thus, the time of administration of the drug, given in the section "Method application and dose "should be strictly observed, even if the patient does not receive drug in the maximum tolerated single dose. During the period of drug administration, it is necessary to monitor parameters of hemodynamics.

Parenterally administered iron preparations can cause allergic or anaphylactoid reactions that can potentially be lethal, so there should be antiallergic drugs, as well as equipment for cardiopulmonary resuscitation and appropriate procedures. After previous uncomplicated injections of parenteral iron complexes, hypersensitivity reactions were also observed. After each injection of Iron (III), the hydroxide of the sucrose complex should be monitored for all patients for no undesirable effects for at least 30 minutes.

Patients with a history of bronchial asthma, eczema, other atopic allergies or allergic reactions to other parenteral iron preparations, Iron (III) preparation, hydroxide sucrose complex should be used with caution, since such patients in particular may have a risk of developing an allergic reaction.

In patients with impaired liver function, parenteral iron should be used only after a thorough assessment of the risk-benefit ratio. Patients with impaired liver function, when iron overload is a provoking factor, parenteral iron should not be used. In order to avoid overloading with iron, it is recommended to carefully monitor the level of iron in the body.

Iron stimulates the growth of most microorganisms, and therefore parenteral iron preparations should be used with caution in acute and chronic infections. Patients with bacteremia are advised to discontinue use of the drug. In patients with chronic infection, the benefit / risk ratio should be assessed before using the drug.

Avoid penetration of the drug into the paralellar space, as this can lead to the appearance of pain, the development of inflammation, necrosis of the tissues and the dyeing of the skin in brown. In cases of unintentional penetration of the drug into the circumferential space, treatment should be carried out in accordance with the standards of medical practice.

Iron (III) hydroxide sucrose complex should be used only in cases when the indication for use is confirmed by the results of the relevant studies (for example, serum ferritin level, transferrin saturation level, hemoglobin content, erythrocyte indices - MCV, SIT, ICSU).

Shelf life after first opening of ampoule

From a microbiological point of view, the drug should be applied immediately.

Shelf life after dilution with 0.9% sodium chloride solution

The chemical and physical stability after dilution at room temperature (15-25 ° C) is 12 hours. From the microbiological point of view, the drug should be applied immediately after dilution. If the drug has not been applied immediately after dilution, the user is responsible for the storage conditions and time,which in any case should not exceed 3 hours at room temperature, unless the dilution was carried out under controlled and proper aseptic conditions.

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

Data on the impact on the ability to drive vehicles or work with mechanisms are not available. However, some unwanted reactions (dizziness, confusion, and other (see section "Side effect")) can have a negative impact on the ability to drive vehicles or work with other mechanisms. Patients who report these adverse reactions are advised not to drive vehicles or work with other mechanisms until these symptoms disappear completely.

Form release / dosage:

Solution for intravenous administration, 20 mg / ml.

Packaging:

By 2 ml or 5 ml of the drug in ampoules of colorless or light-protective glass I hydrolytic class.

5 ampoules in a contoured cell pack of a polyvinyl chloride film. One contour pack with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004118

Date of registration:03.02.2017

Expiration Date:03.02.2022

The owner of the registration certificate:FARMSTANDART-UFAVITA, JSC FARMSTANDART-UFAVITA, JSC Russia

Manufacturer: & nbsp

FARMSTANDART-UFAVITA, JSC Russia

Information update date: & nbsp09.03.2017

Illustrated instructions

Instructions

Iron [III] hydroxide sucrose complex (Ferric (III) hydroxide sacharose complex)