Irondekst - instructions for use, dose, side effects, contraindications

The active component of the preparation Irondecxt - iron-sucrose complex - consists of the nucleus of multinucleated iron (III) hydroxide, 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 predominantly by the reticuloendothelial system of the liver, spleen and bone marrow. In the next step, iron is used to synthesize hemoglobin, myoglobin and other iron-containing enzymes, or is stored primarily in the liver in the form of ferritin.

Pharmacokinetics:

Distribution

Ferrokinetics of iron-sucrose complex labeled 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. It is believed that the capture of the radioactive label by the spleen, rich in macrophages, is typical for the capture of iron by the reticuloendothelial system.

After intravenous administration of a single dose Ayrondekst containing 100 mg iron in healthy volunteers maximum total serum iron concentration achieved within 10 minutes after injection, with an average concentration of 538 μmol / 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. After 4 weeks of administration, the iron utilization by erythrocytes is from 59 to 97%.

Excretion

The average molecular weight of the iron-sucrose complex is 43 kDa, which is sufficient to prevent excretion through the kidneys.

The excretion of iron by the kidneys in the first 4 hours after the injection of the dose of Irondecxt preparation containing 100 mg of iron was less than 5% of the administered dose. After 24 hours, the total serum iron concentration was reduced to the level before administration. The excretion of saccharose by the kidneys was about 75% of the administered dose.

Indications:

Irondekst is used to treat iron deficiency conditions in the following cases:

- with a 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:

The use of Irondecst is contraindicated in the following cases:

- hypersensitivity to iron-sucrose complex, solution of iron-sucrose complex or to any of the components of this drug;

- anemia not caused by iron deficiency;

- presence of signs of iron overload or inborn violations of its utilization processes;

- 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 serum and / or deficiency of folic acid Irondext is to be administered with caution. Also, caution is required when administering iron preparations to patients with hepatic insufficiency,with acute or chronic infectious diseases and people who 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.

Pregnancy and lactation:

A moderate amount of data on the use of the preparation Irondekst by pregnant women in the II and III trimesters of pregnancy did not reveal any threats to the mother and newborn.

However, Irondecst should be used during the second and third trimester of pregnancy only when the potential benefit to the mother exceeds the potential risk to the fetus. The use of the drug in the first trimester of pregnancy is contraindicated.

The results of animal studies did not reveal any direct or indirect adverse effects on the course of pregnancy, embryo / fetal development, childbirth and postnatal development.

The amount of data on the release of iron with human breast milk after intravenous iron-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 the treatment, the content of iron in breast milk did not increase, and the difference in comparison with the control group (n= 5) was not observed. It is impossible to exclude the fact that iron from Irondekst preparation may be given to a newborn / infant with mother's milk, therefore an assessment of the risk-benefit ratio should be made.

Dosing and Administration:

Application

The preparation Irondeksst is administered only intravenously: by drip infusion, or by slow injection, or directly into the venous portion of the dialysis system.

Before using the ampoule, it should be inspected for sediment or damage. Use only ampoules with a homogeneous, non-precipitating brown solution.

Each ampoule of the preparation Irondext is intended exclusively for single use. Any residues of unused medicinal product or its waste should be disposed of in accordance with local requirements.

The introduction of Irondekst preparation should be carried out under the supervision of medical personnel who have experience in the diagnosis and treatment of anaphylactic reactions, in the conditions of a specialized department.It should be possible to carry out anti-shock therapy, which includes a 0.1% solution of epinephrine (adrenaline), antihistamines and / or corticosteroids. 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 monitor each patient for at least 30 minutes after each Irredekst treatment in a therapeutic dose for the absence of undesirable phenomena.

Intravenous drip infusion

Irondekst is diluted 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:

The dose of irondecest (mg of iron)	The dose of Irondekst preparation (ml of Irondekst preparation)	The maximum dilution volume of a sterile 0.9% (w / v) solution of 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

Irondecst can be administered by slow intravenous injection at a rate of 1 ml of undiluted solution per minute and its dose should not exceed 10 ml (200 mg of iron) per injection.

Injection into the venous site of the dialysis system

Irnodext can be administered during the hemodialysis session directly to the venous site of the dialysis system, subject to the same conditions as for intravenous injection.

Doses

For each patient, one should individually calculate the cumulative dose of Irondecxt, which can not be exceeded.

Calculation of dose

The total cumulative dose of Irondecxt, equivalent to total iron deficiency (mg), is determined based on the hemoglobin (Hb) content and body weight (MT). The dose of Irondextxt should be individually calculated for each patient according to the total iron deficiency calculated according to the following formula of Hansoni, for example:

Total iron deficiency [mg] = body weight [kg] x (target hemoglobin content - actual hemoglobin content) [g / l] x 0.24 * + deposited iron [mg]

With a body weight of less than 35 kg: the target hemoglobin content is 130 g / l, and

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, and

amount of deposited iron = 500 mg

* Coefficient 0.24 = 0.0034 (iron content in hemoglobin = 0.34%) x 0.07 (blood mass ~ 7% of body weight) x 1000 (translation of [g] into [mg])

The total amount of Irondekst preparation, Total iron deficiency [mg]

which should be entered (in ml) = 20 mg iron / ml

The total amount of Irondecxt preparation (ml), which should be entered, depending on body weight, actual hemoglobin content and target hemoglobin content *:

Weight bodies [kg]	The total amount of Irondecxt preparation (20 mg of iron per ml), which should be entered
	hemoglobin 60 g / l		hemoglobin 75 g / l		hemoglobin 90 g / l		hemoglobin 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: Target hemoglobin content = 130 g / l

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

To transfer hemoglobin (mmol) to 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 administrations

If after 1-2 weeks there is no response from hematological parameters, the initial diagnosis should be reviewed.

Calculation of the dose for replenishment of iron stores after blood loss or when autologous blood is taken

The dose of irondextext, needed to compensate for iron deficiency, can be calculated by the following formulas:

If the amount of lost blood is known: the administration of 200 mg of iron (10 ml of Irondecxt) should lead to approximately the same increase in hemoglobin concentration as the transfusion of 1 blood sample (400 ml with hemoglobin concentration = 150 g / l).

The amount of iron that		Number of servings	lost
it is necessary to replenish [mg]	=	blood x 200 mg
or
The required volume of the drug		Number of servings	lost
Irondekst [ml]	=	blood x 10 ml

If the hemoglobin content is lower than desired: the formula assumes that it is not necessary to replenish the iron depot.

The amount of iron that must be replenished [mg] = body weight [kg] x 0.24 x (target hemoglobin - actual hemoglobin content) [g / l]

Example:

With a body weight of 60 kg and a decrease in hemoglobin content of 10 g / L

→ 150 mg of iron must be replenished

→ need 7.5 ml of the preparation Irondeext

The maximum tolerable single and weekly doses are indicated below in the sections "Standard doses" and "Maximum tolerable single and weekly doses".

Standard doses

Patients of adult and advanced age

5 - 10 ml of Irondecxt preparation (100-200 mg of iron) 1-3 times a week.

The time of administration and the method of dilution are indicated in the section "Application".

Children

There is only a moderate amount of data on the use of the drug in children in the study. In case of clinical necessity of use, it is not recommended to exceed the dose of 0.15 ml of Irondecxt preparation (3 mg of iron) per kg of body weight not more than 3 times a week.

The time of administration and the method of dilution are indicated in the section "Application".

Maximum tolerated single and weekly doses

Patients of adult and advanced age

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

- 10 ml of Irondecxt preparation (200 mg of iron), administered for a minimum of 10 minutes.

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

- Patients with a body weight of more than 70 kg: 500 mg of iron (25 ml of the preparation Irondekst), administered for a minimum of 3.5 hours.

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

It is necessary to strictly adhere to the infusion time specified in the "Application" section, even if the patient has not received the maximum tolerable single dose.

Side effects:

The most frequent undesirable drug reaction (NLR) recorded in the clinical trials of Irondekst 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 Irondecst preparation 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 recorded after the application of iron (III) preparations of the hydroxide of the sucrose complex within the framework of clinical trials, as well as in the post-marketing period.

Systematically-organ class	Frequent (≥1 / 100, <1/10)	Infrequent (≥1 / 1000, <1/100)	Rare (≥1 / 10,000, <1/1000)	Frequency unknown¹⁾
Immune system disorders		Hypersensitivity		Anaphylactoid reactions, angioedema
Disturbances from the nervous system	Disorders of taste sensations	Headache, dizziness, paresthesia, hypoesthesia	Fainting, migraine, drowsiness	Reduced consciousness, confusion, loss of consciousness, anxiety, tremor
Heart Disease			Heart palpitations	Bradycardia, tachycardia
Vascular disorders	Reduction of arterial pressure, arterial hypertension	Phlebitis, hyperemia		Thrombophlebitis, vascular collapse
Disturbances from the respiratory system, chest and mediastinal organs		Dyspnea		Bronchospasm
Disorders from the gastrointestinal tract	Nausea	Vomiting, abdominal pain, diarrhea, constipation
Disturbances from the skin and subcutaneous tissues		Skin itching, skin rash		Hives, erythema
Disturbances from musculoskeletal and connective tissue		Muscle cramps, myalgia, arthralgia, pain in the limbs, back pain
Disorders from the kidneys and urinary tract			Chromaturia
General disorders and disorders at the site of administration	Reactions at the injection / infusion site²	Chills, asthenia, fatigue, pain, hyperhidrosis	Feeling of heat, chest pain, pyrexia	Cold sweat, general malaise, pallor
Laboratory and instrumental data		Increased activity of gamma-glutamyl transferase, increased activity of alanine aminotransferase, increased activity of aspartate aminotransferase	Increased lactate dehydrogenase activity in the blood

¹⁾ Spontaneous messages received in the post-registration period

²⁾ Pain, reaction, irritation, extravasation, discoloration, burning sensation, swelling, itching, bruising at the injection site.

Overdose:

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

Interaction:

As with all parenteral iron preparations, Irondext is not recommended to be used concomitantly with oral iron preparations, since oral absorption of iron can decrease, so oral iron therapy should be started no earlier than 5 days after the last injection.

Irondekst can be mixed only with a sterile 0.9% (w / v) solution of sodium chloride. When mixed with other solutions or medicines, there is a risk of precipitation and / or interaction. Compatibility with containers from other materials, besides glass, polyethylene and polyvinyl chloride, has not been studied.

Special instructions: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 the preparation, Irondecst for all patients should be monitored for no undesirable events for at least 30 minutes.

Patients with an asthma history of bronchial asthma, eczema, other atopic allergies or allergic reactions to other parenteral iron preparations should be treated with caution because 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 provocative factor, not Parenteral iron should be used. In order to avoid overloading with iron, it is recommended to carefully monitor the level of iron in the body. Parenteral iron should be used with caution in the presence of acute or chronic infection. Patients with bacteremia are advised to discontinue the use of Irondekst. In patients with chronic infection, an assessment should be made of the relationship between risk and benefit.

Avoid penetration of the drug into the peri-venous space, as this can lead to the appearance of pain, the development of inflammation 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.

Irondext is to be used only when the indication for use is confirmed by the results of the relevant studies (for example,Serum ferritin level, transferrin saturation level, hemoglobin content (Hb), erythrocyte indices - MCV, SIT, ICSU).

Shelf life after the first opening of the container

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

Shelf life after dilution with 0.9% solution of sodium chloride (NaCl)

The chemical and physical stability after dilution at room temperature (15-25 ° C) is 12 hours. However, from a microbiological point of view, the drug should be used immediately after dilution. If the product has not been used immediately after dilution, the person who uses this solution is responsible for the conditions and storage time after dilution, which in any case should not exceed 3 hours at room temperature, unless dilution was performed in 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 other mechanisms is not available. However, some unwanted reactions (such as dizziness,confusion and others (listed in the "Side effect" section)) may 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 they disappear completely. of these symptoms.

Form release / dosage:

Solution for intravenous administration, 20 mg / ml.

Packaging:

5 ml per ampoules of clear glass type I with a break point.

5 ampoules per pallet. 1 pallet together with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004509

Date of registration:25.10.2017

Expiration Date:25.10.2022

The owner of the registration certificate:Pharmaceutical Projects, LLCPharmaceutical Projects, LLC Russia

Manufacturer: & nbsp

GLAND PHARMA, Limited India

Information update date: & nbsp21.11.2017

Illustrated instructions

Instructions

Irondequext (Irondext)