Fersinol

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FERSINOL (FERSINOL)

Composition:

Active substance: iron (III) hydroxide polymaltose complex;

1 ampoule (2 mL) contains iron (III) hydroxide polymaltose complex equivalent to 100 mg of iron (III);

Excipient: water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: dark, reddish-brown homogeneous liquid, free from mechanical inclusions.

Pharmacotherapeutic group.

Antianaemic agents. Parenteral trivalent iron preparations. ATC code B03AC01.

Pharmacological properties.

Pharmacodynamics.

After intramuscular administration, almost all iron from the polymaltose complex of iron (III) hydroxide, as the active ingredient, enters the reticuloendothelial system of the liver and is also captured by transferrin, apoferritin, spleen, and bone marrow. There, it binds to hemoglobin, myoglobin, and iron-containing enzymes, and is also stored in the body in the form of ferritin. Changes in blood parameters following parenteral iron administration occur no faster than with oral administration of iron salts. Like other iron preparations, the drug does not affect erythropoiesis and is ineffective in anemias unrelated to iron deficiency.

Pharmacokinetics.

After intramuscular administration, the complex enters the bloodstream. Maximum iron concentration is reached approximately 24 hours after injection. In the blood, iron binds to transferrin. From plasma, the macromolecular complex enters the reticuloendothelial system, where it is broken down into iron hydroxide and polymaltose. In tissues, iron is stored as part of ferritin; in the bone marrow, it binds to hemoglobin and is utilized in the process of erythropoiesis.

Only small amounts of iron are excreted from the body. Polymaltose is metabolized via oxidation and excreted.

In small amounts, the unchanged complex may cross the placental barrier; insignificant quantities may pass into breast milk. Iron bound to ferritin or transferrin may cross the placental barrier, and in the form of lactoferrin, is excreted into breast milk in small amounts.

Incorporation of iron into protoporphyrin depends on the degree of iron-deficiency anemia. It is more intensive when hemoglobin levels are low and decreases as hemoglobin levels normalize. The extent of iron utilization cannot exceed the iron-binding capacity of transport proteins.

Clinical Characteristics.

Indications.

Treatment of iron deficiency anemia in the following cases:

• when oral therapy is contraindicated;
• in the presence of impaired intestinal iron absorption;
• in cases of non-compliance with the treatment regimen using oral iron preparations or persistent gastrointestinal intolerance to them.

Contraindications.

• Hypersensitivity to iron hydroxide polymaltose complex;
• anemias unrelated to iron deficiency (e.g., hemolytic anemia, megaloblastic anemia, disorders of erythropoiesis, bone marrow hypoplasia);
• iron overload (hemosiderosis, hemochromatosis);
• Osler–Rendu–Weber syndrome;
• chronic polyarthritis;
• bronchial asthma;
• infectious kidney diseases in the acute phase;
• uncontrolled hyperparathyroidism;
• decompensated liver cirrhosis;
• infectious hepatitis;
• first trimester of pregnancy;
• severe inflammation or infection of the kidneys or liver (due to the ability of elemental iron to accumulate in inflamed tissues).

Interaction with other medicinal products and other forms of interaction.

Like other parenteral iron preparations, this medicinal product should not be used concomitantly with oral iron preparations, as this may lead to reduced absorption of orally administered iron. Therefore, treatment with oral iron preparations should not be initiated earlier than 7 days after the last dose of parenteral iron preparation.

Concomitant use of ACE inhibitors (e.g., enalapril) may enhance systemic effects of parenteral iron preparations, such as erythema, abdominal cramps, nausea, vomiting, and hypotension.

Interaction with laboratory test results.

High intravenous doses of iron preparations (250 mg of iron or more) may cause brown discoloration of plasma in blood samples collected within 4 hours after administration.

Iron preparations may cause falsely elevated plasma bilirubin levels and falsely decreased plasma calcium levels. Determination of plasma iron levels (especially by colorimetric methods) may not be reliable for up to 3 weeks after administration of iron preparations. Plasma iron measurements obtained within 1–2 weeks after high-dose iron administration should be interpreted with caution.

Bone marrow iron stores assessment may remain uninformative for a prolonged period after treatment, as the medicinal product may persist in reticuloendothelial cells.

Bone scintigraphy using Tc-99m diphosphonate performed 1–6 days after intramuscular injection of iron preparation may show dense areas of activity in the femur, repeating the contours of the iliac crest. Bone scintigraphy using Tc-99m-labeled imaging agents in the presence of high plasma ferritin concentrations or after intravenous iron infusions may demonstrate reduced bone uptake, pronounced renal activity, excessive blood pooling, and deposition in soft tissues.

Iron preparations may reduce 67Ga-citrate uptake during tumor and/or abscess imaging, due to competition for the same binding sites.

The presence of iron may lead to false-positive results in the orthotolidine test.

Special precautions for use

The medicinal product should be used only in cases of iron deficiency confirmed by appropriate diagnostic tests (e.g., plasma ferritin, hemoglobin, hematocrit, erythrocyte count, and erythrocyte parameters such as mean corpuscular volume and mean corpuscular hemoglobin concentration).

Unjustified use of parenteral iron preparations in patients whose anemia is not related to iron deficiency (e.g., patients with hemoglobinopathies) may lead to excessive iron accumulation and development of a syndrome resembling hemochromatosis.

Since parenteral administration of iron preparations has led to anaphylactoid reactions with fatal outcomes, the medicinal product should be administered only to patients with a clearly established indication and after confirmation of the patient's condition by laboratory test results. In case of mild allergic reactions, antihistamines should be used.

When parenteral iron preparations are administered, there is a risk of hypersensitivity and anaphylactoid reactions with each dose. Anaphylactoid reactions most commonly occur within the first few minutes after administration and are typically characterized by sudden onset of respiratory distress, tachycardia, and hypotension. A test dose is not required, as the absence of a reaction following a test dose does not guarantee the absence of a reaction with subsequent doses.

The medicinal product should be administered only if medical personnel trained in the assessment and management of anaphylactic reactions are available and if the facility is properly equipped with resuscitation equipment. Each patient should be monitored for adverse reactions for at least 30 minutes after each intravenous administration of iron-containing preparations. If any allergic reactions or signs of intolerance occur during administration, treatment should be immediately discontinued.

Patients with bronchial asthma, low iron-binding capacity, and/or folic acid deficiency belong to a high-risk group for developing allergic or anaphylactic reactions.

The medicinal product should be used with caution in patients with allergies, hepatic or renal insufficiency, or cardiovascular disease.

Patients with rheumatoid arthritis and possibly other inflammatory conditions (e.g., ankylosing spondylitis, systemic lupus erythematosus) may have an increased risk of delayed reactions, including fever and exacerbation or reactivation of joint pain.

In the post-marketing period, symptomatic hypophosphatemia has been reported, leading to osteomalacia and fractures requiring clinical intervention, including surgical treatment. Patients should be advised to consult a physician if they experience increased fatigue accompanied by myalgia or bone pain. In cases of prolonged use of the medicinal product, use at high doses, or presence of risk factors for hypophosphatemia, monitoring of plasma phosphate levels is recommended. In cases of persistent hypophosphatemia, the use of the medicinal product should be re-evaluated.

Use during pregnancy or breastfeeding

Pregnancy

The medicinal product is contraindicated during the first trimester of pregnancy. Data from animal or human studies during pregnancy are lacking. Embryo-fetal toxicity has been observed in animals treated with intravenous iron preparations.

During the second and third trimesters of pregnancy, the medicinal product should be used only if the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding

Data from studies in breastfeeding women are lacking. The possibility of iron passing into breast milk should be considered. When using the medicinal product during breastfeeding, the expected benefit to the mother and the potential risk to the infant should be taken into account.

Ability to affect reaction rate when driving or operating machinery

Appropriate studies have not been conducted.

Method of Administration and Dosage

The medicinal product is intended for deep intramuscular injection. Intravenous administration is contraindicated.

Method of Administration

Before injection, inspect the ampoules and their contents carefully. Only ampoules free from precipitate and physical damage may be used. The medicinal product should be administered immediately after opening the ampoule.

The injection technique is of crucial importance. The solution must not be injected into the shoulder or into damaged areas. Incorrect administration may result in pain and skin discoloration at the injection site.

The medicinal product is recommended to be administered into the ventrogluteal site according to Hochstetter, instead of the conventional injection into the upper outer quadrant of the gluteal muscle.

The needle length should be at least 5–6 cm. The needle lumen should not be excessively wide.

Injection Technique

1. Locate the injection site as follows (Fig. 1): identify point A corresponding to the anterior surface of the iliac crest. For example, if the patient is lying on the right side, the middle finger of the left hand should be placed at point A. The index finger should be moved away from the middle finger so that it lies below the iliac crest line at point B. The triangle formed between the proximal phalanges of the middle and index fingers indicates the injection site (Fig. 2). Disinfection should be performed by the standard method.
2. Before inserting the needle, displace the skin at the injection site approximately 2 cm laterally (Fig. 3), creating an S-shaped needle path. This helps prevent backflow of the injected solution into subcutaneous tissues and subsequent skin discoloration.
3. Insert the needle almost vertically relative to the skin surface, angled more toward the anterior superior iliac spine than toward the femoral joint (Fig. 4).
4. After injection, slowly withdraw the needle and apply finger pressure to the skin area adjacent to the injection site. Maintain pressure for approximately 1 minute.
5. After injection, the patient should move.

Fig. 1 Fig. 2 Fig. 3 Fig. 4

Dosage

Dose Calculation

The dose of the medicinal product should be individually calculated according to the patient's total iron deficit using the following formula:

* Factor 0.24 = 0.0034 × 0.07 × 1000 (iron content in hemoglobin – 0.34% / blood volume – 7% of body weight / factor 1000 – conversion from grams to milligrams).

The above formula can also be used to calculate the total iron deficit.

For body weight less than 35 kg: normal Hb level = 130 g/L, corresponding to iron stores of 15 mg/kg body weight.

For body weight over 35 kg: normal Hb level = 150 g/L, corresponding to iron stores of 500 mg.

Dosing table

Dosing table for determining the required total amount of the medicinal product

The drug should be administered intramuscularly at a dose of 2 ml every other day until the total dose is achieved, or 4 ml administered at longer intervals.

During treatment with the drug, regular monitoring of Hb levels is recommended.

Maximum dosage:

Children with body weight up to 5 kg: 0.5 ml = 25 mg of iron (¼ of an ampoule).

Children with body weight from 5 to 10 kg: 1 ml = 50 mg of iron (½ of an ampoule).

Patients with body weight from 10 to 45 kg: 2 ml = 100 mg of iron (1 ampoule) per day.

Adults with body weight from 45 kg: 4 ml = 200 mg of iron (2 ampoules).

Children.

The drug can be used in children aged 4 months and older.

Overdose.

There have been no reports of overdose.

Overdose may cause acute iron overload, manifesting as symptoms of hemosiderosis. Treatment is symptomatic.

Chronic iron overload may present as haemochromatosis. This may occur when anemia unresponsive to treatment has been incorrectly diagnosed as iron-deficiency anemia.

Periodic monitoring of plasma ferritin levels may help in timely detection of progressive iron accumulation.

If necessary, iron-binding agents (chelators) such as intravenous deferoxamine should be administered.

When the drug is administered in very high doses, the complex cannot be removed from the body by hemodialysis due to the high molecular weight of the active substance.

Side effects.

Side effects occur infrequently. The following adverse reactions may occur after administration of parenteral iron preparations.

Blood and lymphatic system disorders:

generalized lymphadenopathy.

Immune system disorders:

anaphylaxis.

Gastrointestinal disorders:

nausea, vomiting.

Nervous system disorders:

headache, dizziness.

Respiratory, thoracic and mediastinal disorders:

bronchospasm with dyspnea.

Cardiovascular disorders:

loss of consciousness, fainting, tachycardia, hypotension, circulatory collapse.

Skin and subcutaneous tissue disorders:

rash, urticaria, angioneurotic edema.

Musculoskeletal and connective tissue disorders:

joint and muscle pain, arthralgia, feeling of tightness in arms, legs or facial muscles, hypophosphatemic osteomalacia.

General disorders and administration site conditions:

facial flushing, chest and back pain, injection site pain, local inflammation with inguinal lymphadenopathy, lower abdominal quadrant pain.

Adverse reactions may occur with a delay of 1–2 days after treatment.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions occurring after marketing authorization is very important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national pharmacovigilance system.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C, in a place inaccessible to children.

Incompatibilities.

The injection solution should not be mixed with other medicinal products. The medicinal product is compatible only with sterile 0.9 % sodium chloride solution. Any other solutions must not be used.

Packaging.

2 ml in an ampoule, 5 ampoules in a blister pack and cardboard box.

Prescription status.

Prescription only.

Manufacturer.

PharmaVision San. ve Tic. A.S.

Manufacturer's address and location of operations.

Davutpasa Cad. No:145 Zeytinburnu Istanbul, Turkey

Marketing Authorization Holder.

WORLD MEDICINE, LLC, Ukraine