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

The multinuclear centers of iron (III) hydroxide are surrounded from the outside by a multitude of non-covalently bound sucrose molecules.As a result, a complex is formed, the molecular mass of which is approximately 43 kD, as a result of which its excretion through the kidneys in an unchanged form is impossible. This complex is stable and does not release iron ions under physiological conditions. The structure of the multinucleated iron-containing nucleus is similar to the structure of the ferritin nucleus, the physiological depot of iron. This complex is designed to create a controlled source of recycled iron for transferrin and ferritin, responsible for the transport and deposition of iron in the body.

After intravenous administration, iron from this complex is mainly taken up by the liver, spleen and bone marrow, and then used for the synthesis of hemoglobin, myoglobin and other iron-containing enzymes, or stored in the liver in the form of ferritin.

Pharmacokinetics:

After a single intravenous injection of Iron [III], a hydroxide sucrose complex containing 100 mg of iron, the maximum concentration of iron, on average 538 μmol, is reached 10 minutes after the injection. The volume of distribution of the central chamber corresponds almost completely to the volume of the serum (about 3 liters).

The half-life is about 6 hours.The volume of distribution in the equilibrium state is approximately 8 liters, which indicates a low distribution of iron in the body fluids, due to the low stability of iron saccharate in comparison with transferrin, there is a competitive exchange of iron in favor of transferrin and as a result, about 24 mg of iron .

The excretion of iron by the kidneys for the first 4 hours after injection is less than 5% of the total clearance. After 24 hours, the serum iron level returns to its original (before administration) value, and about 75% sucrose leaves the vascular bed.

Indications:

Iron [III] hydroxide, the sucrose complex is used to treat iron deficiency states in the following cases:

if it is necessary to quickly fill iron;
in patients who do not tolerate oral iron preparations or do not comply with the treatment regimen;
in the presence of active inflammatory bowel disease, when oral iron preparations are ineffective.

Contraindications:

The use of the drug 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 preparation Iron [III] hydroxide sucrose complex or its components;
I trimester of pregnancy.

Carefully:

Patients with bronchial asthma, eczema, polyvalent allergies, allergic reactions to other parenteral iron preparations and to persons who have low serum iron-binding capacity and / or folic acid deficiency 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 individuals who have increased serum ferritin levels because parenterally administered iron can have adverse effects in the presence of a bacterial or viral infection.

Pregnancy and lactation:

Limited experience in the use of the preparation Iron [III] hydroxide sucrose complex in pregnant patients showed no undesirable effects of iron sugarate on the course of pregnancy and fetus / newborn health.To date, there have not been well-controlled studies in pregnant women. The results of reproduction studies in animals showed no direct or indirect adverse effects on embryo / fetal development, childbirth, or postnatal development. However, an assessment of the risk / benefit ratio is required.

The intake of unmetabolized iron saccharate in breast milk is unlikely. Thus, Iron [III] hydroxide sucrose complex is not dangerous for infants who are breastfed.

Dosing and Administration:

Introduction: Iron [III] hydroxide sucrose complex is administered only intravenously - slow bolus or infusion, and in the venous portion of the dialysis system and is not intended for intramuscular administration. Impossible simultaneous introduction of the full therapeutic dose of the drug.

Before the introduction of the first therapeutic dose, it is necessary to prescribe a test dose. If during the observation period there were intolerance phenomena, the drug should be discontinued immediately. Before opening, the ampoule should be inspected for possible sediment and damage. You can use only a brown solution without sediment.

Drip introduction: preparation Iron [III] hydroxide, the sucrose complex is preferable to be administered during the drip infusion in order to reduce the risk of a pronounced decrease in blood pressure (BP) and the risk of getting the solution into the circumveneous area. Immediately prior to infusion, the preparation of Iron [III] hydroxide sucrose complex should be diluted with 0.9% sodium chloride solution in a ratio of 1:20 [eg, I ml (20 mg of iron) in 20 ml of 0.9% sodium chloride solution]. The resulting solution is introduced at the following rate: 100 mg of iron - not less than 15 minutes; 200 mg of iron - for 30 minutes; 300 mg of iron - for 1.5 hours; 400 mg of iron - for 2.5 hours; 500 mg of iron for 3.5 hours. The maximum tolerated single dose of 7 mg of iron / kg of body weight should be administered for a minimum of 3.5 hours, regardless of the total dose of the drug.

Before the first droplet administration of the therapeutic dose of the preparation of Iron [III] hydroxide sucrose complex, a test dose should be administered: 20 mg of iron for adults and children weighing more than 14 kg and half of the daily dose (1.5 mg of iron / kg) for children weighing less than 14 kg, for 15 minutes. In the absence of adverse events, the rest of the solution should be administered at the recommended rate.

Inkjet introduction: the preparation of Iron [III] hydroxide, the sucrose complex can also be administered as an undiluted solution intravenously slowly, at a rate of 1 ml of iron preparation [III] hydroxide sucrose complex (20 mg of iron) per minute (5 ml of iron [III] hydroxide a sucrose complex (100 mg of iron) is introduced for at least 5 minutes). The maximum volume of the drug should not exceed 10 ml of the preparation Iron [III] hydroxide sucrose complex (200 mg of iron) per injection.

Before the first jet administration of the therapeutic dose of the preparation of Iron [III] hydroxide sucrose complex, a test dose should be prescribed: 1 ml of the preparation Iron [III] hydroxide saccharose complex (20 mg iron) for adults and children weighing more than 14 kg, and half the daily dose (1.5 mg iron / kg) for children weighing less than 14 kg for 1-2 minutes. In the absence of adverse events during the next 15 minutes of observation, the remainder of the solution should be administered at the recommended rate. After the injection, the patient is recommended to fix his hand for a while in the extended position.

Introduction to the dialysis system: Iron [III] hydroxide, the sucrose complex can be injected directly into the venous portion of the dialysis system, strictly observing the rules described for intravenous injection.

Dose calculation: The dose is calculated individually according to the total iron deficiency in the body but the formula:

Total iron deficiency (mg) = body weight (kg) x (normal level Hb - Hb patient) (g / l) x 0.24 * + deposited iron (mg).

For patients with a body weight of less than 35 kg: a normal level of Hb = 130 g / l, the amount of deposited iron = 15 mg / kg of body weight.

For patients with a body weight of more than 35 kg: normal level Hb = 150 g / l, the amount of deposited iron = 500 mg.

*Coefficient 0.24 = 0.0034 x 0.07 x 1000 (The content of iron in Hb = 0.34%; Blood volume = 7% of body weight; coefficient 1000 = translating "g" into "mg").

Total volume of the preparation Iron [III] hydroxide sucrose complex, which must be administered (in ml) = total iron deficiency (mg)/20 mg / ml.

Body mass (kg)	Cumulative therapeutic dose of iron preparation [III] hydroxide sucrose complex for administration:
	Hb 60 g / l		Hb 75g / 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	1 140	57	980	49
50	1580	79	1400	70	1220	61	1040	52
55	1680	84	1500	75	1300	65	1 100	55
60	1800	90	1580	79	1360	68	1 140	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

In the case where the total therapeutic dose exceeds the maximum allowable single dose, fractional administration of the drug is recommended.

If, 1-2 weeks after the beginning 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 the replacement of iron deficiency after blood loss of sludge 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 iron preparation [III] hydroxide sucrose complex) leads to the same increase in concentration Hb, as well as a transfusion of I unit of blood (= 400 ml with concentration Hb 150 g / l).

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

Necessary volume of the preparation Iron [III] hydroxide sucrose complex (ml) =

number of units of lost blood x 10

With a decrease Hb: 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 (normal level Hb - level Hb patient) (g / l),

For example: body weight 60 kg, deficit Hb = 10 g / l => necessary amount of iron in 150 mg => necessary volume of preparation Iron [III] hydroxide sucrose complex = 7.5 ml

Standard dosage:

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.

Children: There are only limited data on the use of the drug in children under 3 years of age. The recommended dose for children of other age groups 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.

Maximum tolerable single dose:

Adults and elderly patients:

For inkjet insertion: 10 ml of preparation Iron [III] hydroxide sucrose complex (200 mg of iron), the duration of administration is not less than 10 min.

For drip introduction: Depending on the indications, a single dose can reach 500 mg of iron. The maximum permissible single dose is 7 mg of iron per kg of body weight and is administered once a week, but it should not exceed 500 mg gland. The time of administration and the method of dilution, see the section "Methods of administration and dose".

Side effects:

The most frequently detected undesirable drug reactions with iron preparations [III] hydroxide of the sucrose complex were a change in taste sensations, a decrease in blood pressure, pyrexia and chills, reactions at the injection site, and nausea.

Very frequent (> 1/10), frequent (> 1/100 - <1/10), infrequent (> 1 / 1000- <1/100), rare (> 1/10000 - <1/100), very rare (<1/10000), the frequency is unknown (their frequency can not be estimated from the available data).

From the immune system

Rare: anaphylactoid reactions.

From the nervous system

Frequent: a violation of taste. Infrequent: dizziness, headache. Rare: paresthesia, fainting, loss of consciousness, burning sensation. Frequency is unknown: decreased levels of consciousness, confusion.

From the heart

Infrequent: tachycardia, palpitations. Unknown: bradycardia.

From the side of the vessels

Infrequent: a decrease in blood pressure. cardiovascular collapse. Rare: increased blood pressure.

From the respiratory, thoracic and mediastinal

Infrequent: bronchospasm, shortness of breath.

From the gastrointestinal tract

Infrequent: nausea, vomiting, abdominal pain, diarrhea.

From the skin and subcutaneous tissues

Infrequent: itching, hives, rashes, erythema

From the side of the musculoskeletal system and connective tissue

Infrequent: muscle spasms, pain in the muscles.

Rare: edema of the joints, joint pain.

General disorders and reactions at the injection site

Infrequent: pyrexia, chills, hot flashes, pain in labor, reactions at the injection site (eg, superficial phlebitis and swelling).Rare: angioedema, peripheral edema, fatigue, asthenia, general malaise, fever, swelling. Very rare: hyperhidrosis, back pain. Unknown: chromaturia.

Overdose:

Overdose can cause acute overload with iron, which manifests itself as symptoms of hemosiderosis. In case of overdose, it is recommended to use symptomatic agents and, if necessary, iron binding substances (chelates), for example, deferoxamine intravenously.

Interaction:

Iron [III] hydroxide, the sucrose complex should not be administered concomitantly with the medicinal forms of iron for oral administration, since it helps to reduce the absorption of iron from the gastrointestinal tract. Treatment with oral iron preparations can begin no earlier than 5 days after the last injection.

Preparation Iron [III] hydroxide sucrose complex can be mixed in a single syringe only with a sterile 0.9% sodium chloride solution. Incompatible with other solutions for intravenous administration and therapeutic agents because of the risk of precipitation and / or other pharmaceutical interactions.Compatibility with containers of other materials (polyethylene and polyvinyl chloride), with the exception of glass, has not been studied.

Special instructions:

Iron [III] hydroxide sucrose complex should be administered only to those patients in whom the diagnosis of anemia confirmed corresponding laboratory data (e.g., results of determination of serum ferritin and hemoglobin and hematocrit, number of erythrocytes and their parameters - mean cell volume, the average content of hemoglobin in the erythrocyte or medium: the concentration of hemoglobin in the erythrocyte).

Intravenous iron preparations can cause allergic or anaphylactoid reactions, which can be potentially life threatening.

It should be strictly observed the rate of administration of the drug Iron [III] hydroxide sucrose complex (with rapid administration of the drug, blood pressure may decrease). A higher incidence of undesirable side effects (in particular, lowering blood pressure), which may also be severe, is associated with an increase in the dose. Thus, the time of administration of the drug, given in the section "Methods of administration and dose", should be strictly observed, even if the patient does not receive the drug in the maximum tolerable single dose.

Studies carried out in patients with hypersensitivity reactions to iron dextran showed no complications during the treatment with preparations of iron [III] hydroxide of the sucrose complex.

It is necessary to avoid penetration of the drug into the circumveneous area, because ingestion of iron [III] hydroxide, the sucrose complex beyond the vessel leads to tissue necrosis and brown coloration of the skin. In case of this complication, to accelerate the excretion of iron and prevent its further penetration into surrounding tissues, it is recommended to apply the heparin-containing preparations to the injection site (gel or ointment is applied lightly without rubbing).

Shelf life after the first opening of the container: From a microbiological point of view, the drug should be used immediately.

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

It is unlikely that the preparation Iron [III] hydroxide sucrose complex can have an undesirable effect on the ability to drive a car and work with mechanisms. However, with the development of symptoms such as dizziness, confusion or fainting,patients should not drive vehicles or mechanisms until these symptoms disappear.

Form release / dosage:

Solution for intravenous administration of 20 mg / ml.

Packaging:

5 ml in a dark glass ampoule with a break ring or with a notch and a dot.

5 ampoules per plastic pallet.

1 plastic pallet together with instructions for use are placed in a pack of cardboard.

Storage conditions:

In a protected spotlight at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002843

Date of registration:26.01.2015

Expiration Date:26.01.2020

The owner of the registration certificate:INDUKERN-RUS, OOO INDUKERN-RUS, OOO Russia

Manufacturer: & nbsp

NANJING PHARMACEUTICAL FACTORY Co. Ltd. China

Information update date: & nbsp17.05.2017

Illustrated instructions

Instructions

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