Venofer, 20 mg/ml 5 ml 5 pcs

The iron preparation. The multinuclear centers of iron (III) hydroxide are surrounded on the outside by many non-covalently bound sucrose molecules. As a result, a complex is formed with a molecular weight of approximately 43 kD; as a consequence, it cannot be excreted unchanged by the kidneys.

This complex is stable and does not release iron ions under physiological conditions. The iron in this complex is bound to structures similar to natural ferritin.

Pharmacokinetics

Distribution

. After a single intravenous injection of Venofer containing 100 mg of iron, Cmax of iron, averaging 538 μmol, is reached 10 min after injection.

The Vd of the central chamber corresponds almost entirely to the serum volume – about 3 liters.

The Vd in equilibrium is approximately 8 liters (indicating a low distribution of iron in the body fluids).

Due to the low stability of iron sugars compared to transferrin, there is a competitive exchange of iron in favor of transferrin. As a result, about 31 mg of iron (III) is transferred in 24 h.

Elevation

The T1/2 is about 6 h. In the first 4 h, the kidneys excrete less than 5% of iron from total clearance. After 24 h, serum iron levels return to the original (pre-injection) value, and approximately 75% of sucrose leaves the vascular stream.

Indications

Anemia

The treatment of iron deficiency in the following cases:

• need to quickly replenish iron deficiency;
• in patients who cannot 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.

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Composition

Active ingredient:

iron (III) hydroxide sucrose complex 540 mg (equivalent to iron content 20 mg);

excipients:

sodium hydroxide;

water for injection – up to 1 ml

How to take, the dosage

Venofer is administered only intravenously – slowly by trickle or drip and into the venous area of the dialysis system – and is not intended for intramuscular administration. A full therapeutic dose of the drug should not be administered at one time.

A test dose should be administered before the first therapeutic dose is administered. If intolerance occurs during the observation period, the drug administration should be stopped immediately. Before opening the ampoule it should be inspected for possible sediment and damage. Only brown solution without residue may be used.

Drip administration: Venofer is preferably administered by drip infusion in order to reduce the risk of markedly decreased BP and the danger of solution entering the pericolonasal space. Immediately before infusion, Venofer should be diluted with 0.9% sodium chloride solution in a ratio of 1:20, for example – 1 ml (20 mg of iron) in 20 ml of 0.9% sodium chloride solution. The resulting solution is administered at the following rate: 100 mg of iron within at least 15 minutes; 200 mg of iron within 30 minutes; 300 mg of iron within 1.5 hours; 400 mg of iron within 2.5 hours; 500 mg of iron within 3.5 hours. The maximum tolerated single dose of 7 mg of iron/kg should be administered for at least 3.5 hours, regardless of the total dose of the drug.

Before the first instillation of a therapeutic dose of Venofer, a test dose should be given: 20 mg of iron in adults and children over 14 kg and half the daily dose (1.5 mg of iron/kg) in children less than 14 kg for 15 minutes. In the absence of adverse events, the remainder of the solution should be administered at the recommended rate.

Stroke administration: Venofer can also be administered as an undiluted solution intravenously slowly, at a rate (rate) of 1 ml of Venofer (20 mg of iron) per min, i.e. 5 ml of Venofer (100 mg of iron) in at least 5 minutes. The maximum volume should not exceed 10 ml of the preparation Venofer (200 mg of iron) in 1 injection.

Before the first jet injection of the therapeutic dose of Venofer, a test dose should be administered: 1 ml of Venofer (20 mg of iron) to adults and children over 14 kg and half the daily dose (1.5 mg of iron/kg) to children under 14 kg for 1-2 minutes. In the absence of adverse events during the next 15 min of observation, the remainder of the solution should be injected at the recommended rate. After the injection, the patient is recommended to fix the arm in an extended position for a while.

Injection into a dialysis system: Venofer can be injected directly into the venous area of the dialysis system, strictly following the rules described for intravenous injections.

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

Total iron deficiency, mg = body weight, kg × (normal Hb level – patient’s Hb level), g/L × 0.24* + deposited iron, mg.

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

For patients weighing more than 35 kg: normal Hb=150 g/l, amount of iron deposited = 500 mg.

*Factor 0.24 = 0.0034×0.07×1000 (Hb iron content=0.34%; blood volume = 7% of body weight; factor 1000 = conversion from “g” to “mg”).

The total volume of Venofer to be administered (in ml) = total iron deficiency (mg)/20 mg/mL (see table).

Table

Total amount of Venofer drug to treat

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

If there is no improvement in hematologic parameters 1-2 weeks after starting treatment with Venofer, the initial diagnosis should be reconsidered.

Calculating the dose to replenish iron levels after blood loss or autologous blood donation

The dose of Venofer is calculated using the following formula:

If the amount of blood lost is known: an intravenous injection of 200 mg of iron (10 ml of Venofer) results in the same increase in Hb concentration as a transfusion of 1 unit of blood (400 ml with Hb concentration=150 g/L).

The amount of iron to be replenished (mg) = number of units of blood lost × 200

or

The amount of Venofer product needed (ml) = number of units of blood lost × 10.

If Hb levels decrease: Use the previous formula provided that the iron depot does not need to be replenished.

The amount of iron to be replenished (mg) = body weight, kg × 0.24 × (normal Hb level – patient Hb level), g/l.

For example: body weight 60 kg, Hb deficiency = 10 g/l ” amount of iron needed ” 150 mg ” amount of Venofer needed = 7.5 ml.

Standard dosage

Adults and elderly patients: 5-10 ml of Venofer (100-200 mg of 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 in other age groups is not more than 0.15 ml (3 mg of iron) per kg of body weight 1-3 times a week, depending on the hemoglobin level.

Maximum tolerated single dose

Adults and elderly patients:

– for jet administration: 10 ml of Venofer (200 mg of iron), duration of administration at least 10 minutes.

– for drip administration: depending on indications, single dose may be up to 500 mg of iron. The maximum permissible single dose is 7 mg/kg and is administered once a week, but it should not exceed 500 mg of iron.

Interaction

Venofer should not be administered concomitantly with oral iron dosage forms because it reduces iron absorption from the gastrointestinal tract.

The treatment with oral iron preparations can be started not earlier than 5 days after the last injection.

Venofer can only be mixed in the same syringe with sterile saline solution.

No other IV solutions or therapeutic drugs may be added, since there is a risk of precipitation and/or other pharmaceutical interactions.

Compatibility with containers made of materials other than glass, PE and PVC has not been studied.

Special Instructions

Venofer should only be administered to patients whose diagnosis of anemia has been confirmed by appropriate laboratory data (e.g. serum ferritin or hemoglobin and hematocrit levels, erythrocyte count and its parameters – mean erythrocyte volume, mean erythrocyte hemoglobin content).

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

The speed of administration of Venofer should be strictly observed (BP may decrease if the drug is administered rapidly). A higher incidence of adverse events (especially BP decrease), which may also be severe, is associated with a higher dose. Therefore, the dosing times listed in the administration instructions must be strictly adhered to, even if the patient is not receiving the drug in the maximum tolerated single dose.

Studies in patients with hypersensitivity reactions to iron dextran have shown no complications with treatment with Venofer.

To avoid penetration of the drug into the peroventricular space, venofer outside the vessel leads to tissue necrosis and brown staining of the skin. If this complication develops, to accelerate the elimination of iron and prevent its further penetration into the surrounding tissues, it is recommended to apply heparin-containing preparations to the injection site (the gel or ointment is applied with light movements, without rubbing).

The shelf life after the first opening of the container: microbiologically, the drug should be used immediately.

Stable shelf life after dilution with saline: Chemical and physical stability lasts for 12 hours after dilution at room temperature. From the microbiological point of view, the solution should be used immediately. If the product is not used immediately after dilution, the user is responsible for the conditions and storage time, which in any case should not exceed 3 hours at room temperature, as long as the dilution has been performed under controlled and assured aseptic conditions.

The effect on driving and operating ability. It is unlikely that Venofer may have adverse effects on driving and operating machinery.

Contraindications

• hypersensitivity
• anemia not associated with iron deficiency
• signs of iron overload (hemosiderosis, hemochromatosis) or disorders of its utilization
• I trimester of pregnancy.

With caution: bronchial asthma, eczema, polyvalent allergies, allergic reactions to other parenteral iron preparations, low serum iron-binding capacity and/or folic acid deficiency; liver failure, acute or chronic infectious diseases (due to the fact that parenterally administered iron may have adverse effects if there is a bacterial or viral infection) and individuals with elevated serum ferritin values.

Side effects

The following adverse events are currently known to be temporarily and possibly causally related to the administration of Venofer^®. All symptoms have been observed very rarely (incidence less than 0.01% and greater than or equal to 0.001%).

Nervous system disorders: dizziness, headache, loss of consciousness, paresthesias.

System adverse reactions: palpitations, tachycardia, decreased BP, collaptoid states, fever, flushes to the face, peripheral edema.

Respiratory system disorders: bronchospasm, dyspnea.

Gastrointestinal disorders: diffuse abdominal pain, epigastric pain, diarrhea, perversion of taste, nausea, vomiting.

Skin disorders: erythema, itching, rash, impaired pigmentation, increased sweating.

Musculoskeletal disorders: arthralgia, back pain, joint swelling, myalgia, pain in the extremities.

Immune system disorders: allergic, anaphylactoid reactions, including facial edema, laryngeal edema.

General disorders and reactions at the injection site: asthenia, chest pain, feeling of heaviness in the chest, weakness, pain and swelling at the injection site (especially with extravasal ingestion of the drug), feeling of malaise, paleness, fever, chills.

Overdose

Overdose can cause acute iron overload, which manifests as symptoms of hemosiderosis.

Treatment:Symptomatic agents and, if necessary, iron binding agents (chelates) such as intravenous deferoxamine are recommended.

Pregnancy use

Limited experience with the use of Venofer in pregnant patients has shown no adverse effects of iron glucose on pregnancy and fetal/newborn health.

There have been no well-controlled studies in pregnant women to date.

The results of reproductive studies in animals have shown no direct or indirect harmful effects on embryo/fetal development, birth or postnatal development.

However, further research on the risk/benefit ratio is needed.

The ingestion of unmetabolized iron sugar into breast milk is unlikely. Therefore, Venofer does not pose a risk to breastfed infants.