Cosmofer

Leaflet accompanying the packaging: patient information

CosmoFer 50 mg Fe(III)/ml, solution for injection and infusion

Ferri hydroxide dextran

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or nurse.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or nurse. See section 4.

Table of contents of the leaflet

• 1. What is CosmoFer and what is it used for
• 2. Important information before taking CosmoFer
• 3. How to use CosmoFer
• 4. Possible side effects
• 5. How to store CosmoFer
• 6. Contents of the packaging and other information

1. What is CosmoFer and what is it used for

CosmoFer contains iron in the form of a complex with dextran (a long-chain sugar molecule) that is an analogue of the physiological form of iron, ferritin, in the body. The use of this medicine allows for the administration of iron in large doses by injection. CosmoFer is indicated for the treatment of iron deficiency in the following cases: When oral preparations cannot be used, e.g., due to intolerance, or when oral iron therapy is ineffective. When there is a clinical need for rapid iron delivery to iron storage sites in the body.

2. Important information before taking CosmoFer

When not to take CosmoFer

In case of hypersensitivity (allergy) to the product or any of the other ingredients of this medicine (listed in section 6); In case of severe allergic reactions (hypersensitivity) to other injectable iron preparations; If the patient has anemia due to other causes than iron deficiency, such as hemolytic anemia; If the patient has an excess of iron or disorders of iron utilization; If the patient has liver cirrhosis or hepatitis (which are severe liver diseases); If the patient has an acute or chronic infection; If the patient has acute renal failure.

Warnings and precautions

Before starting treatment with CosmoFer, the patient should discuss it with their doctor or nurse: If the patient has a history of drug allergy; If the patient has systemic lupus erythematosus; If the patient has rheumatoid arthritis; If the patient has asthma, eczema, or other atopic allergies.

Children

CosmoFer is recommended only for adults. This medicine should not be used in children under 14 years of age.

CosmoFer and other medicines

The patient should inform their doctor, pharmacist, or nurse about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. This includes over-the-counter and herbal medicines, as CosmoFer may affect the way some medicines work. Also, some other medicines may affect the way CosmoFer works. In particular, the patient should inform their doctor or nurse if they are taking any of the following medicines: Vitamins and minerals; Oral iron preparations. Oral iron therapy should not be started earlier than 5 days after the last injection of CosmoFer.

Pregnancy and breastfeeding

CosmoFer has not been studied in pregnant women. This medicine should not be used during pregnancy. It is essential to inform the doctor about confirmed or suspected pregnancy or planning to have a child. If the patient becomes pregnant during treatment, they should consult their doctor, who will decide whether to continue using the medicine. If the patient is breastfeeding, they should consult their doctor before taking CosmoFer.

Driving and using machines

The patient should ask their doctor if they can drive or operate machines after taking CosmoFer.

Blood tests during CosmoFer therapy

CosmoFer may affect the results of blood tests for bilirubin and calcium. The patient should inform their doctor if they have had any blood tests while taking CosmoFer.

3. How to use CosmoFer

CosmoFer is administered by a doctor or nurse through intravenous injection; CosmoFer can only be administered in places where immediate and appropriate medical help is available in case of an allergic reaction. After each administration of the medicine, the patient should be monitored by a doctor or nurse for at least 30 minutes to detect any side effects.

Overdose of CosmoFer

CosmoFer will be administered by qualified personnel. It is unlikely that the patient will receive too high a dose. The dosage will be supervised, so the patient will not accumulate too much iron. If there is a suspicion that a higher dose of the medicine has been administered by mistake, the medical staff should be informed immediately.

4. Possible side effects

Like all medicines, CosmoFer can cause side effects, although not everybody gets them. The following side effects may occur in connection with the use of this medicine:

Allergic reactions

The patient should immediately inform their doctor if they experience any of the following symptoms, which may indicate a severe allergic reaction: shortness of breath, hives, rash (redness of the skin), itching, nausea, and chills, as well as chest pain, which can be a sign of a sometimes severe allergic reaction called Kounis syndrome. Severe, acute allergic reactions can occur within the first few minutes after administration of CosmoFer (occur less frequently than 1 in 10,000 people). Symptoms that may occur include: sudden difficulty breathing; cardiovascular collapse (disorders of heart function and circulation); death.

• sudden difficulty breathing
• cardiovascular collapse (disorders of heart function and circulation)
• death

Delayed reactions are also known, for which the onset of symptoms ranges from a few hours to four days after administration of CosmoFer. They are characterized by symptoms such as: joint or muscle pain; sometimes high body temperature (fever). If such reactions occur, the patient should contact their doctor.

• joint or muscle pain
• sometimes high body temperature (fever)

Other side effects:

Uncommon(occur less frequently than 1 in 100 people):

• abdominal pain, nausea, vomiting
• blurred vision
• shortness of breath
• flushing
• itching, rash
• feeling of heat
• cramps
• numbness
• pseudo-anaphylactic reactions (symptoms: shortness of breath, hives, rash, itching, nausea, and chills)

Rare(occur less frequently than 1 in 1,000 people):

• loss of consciousness
• seizures (seizure attacks)
• dizziness
• restlessness
• altered mental state
• tremors
• fatigue
• pain and brown pigmentation at the injection site
• low blood pressure
• angioedema (a type of severe allergic reaction, symptoms may include swelling)
• muscle pain
• irregular heartbeat (arrhythmia)
• rapid heartbeat (tachycardia)
• chest pain
• diarrhea
• excessive sweating

Very rare(occur less frequently than 1 in 10,000 people):

• decreased red blood cell count (visible in some blood tests)
• headache
• tingling sensation
• increased blood pressure
• transient deafness
• palpitations
• severe pseudo-anaphylactic reaction (sudden breathing difficulties and/or cardiovascular collapse)
• in pregnancy, the fetal heart rate may be decreased

Frequency not known

• flu-like symptoms may occur within a few hours to a few days after injection; typical symptoms are: high body temperature and muscle and joint pain

Other side effects have also been observed. There may be an exacerbation of joint pain in rheumatoid arthritis.

Possible side effects after intravenous administration

After intravenous administration, local reactions may occur, such as pain and swelling (inflammation) at the injection site or nearby. Local vein inflammation has also been reported.

Possible side effects after intramuscular administration

After intramuscular administration, local reactions may occur at the injection site, such as: skin discoloration, bleeding, formation of sterile abscesses, tissue necrosis, or atrophy, and pain.

Reporting side effects

If the patient experiences any side effects, including those not listed in the leaflet, they should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49 21 301, fax: 22 49 21 309, website: https//smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store CosmoFer

There are no special precautions for storage. Do not freeze. The ampoule should be inspected before use to ensure that the solution does not contain sediment and that the ampoule is not damaged. Only ampoules with a homogeneous solution that does not contain sediment should be used. The medicine should be stored out of sight and reach of children. Do not use this medicine after the expiry date stated on the ampoule and carton. "EXP" is an abbreviation for the expiry date. The expiry date refers to the last day of the specified month.

6. Contents of the packaging and other information

What CosmoFer contains

The active substance of CosmoFer is a complex of iron(III) hydroxide with dextran. A 2 ml ampoule contains 100 mg of iron(III), and a 10 ml ampoule contains 500 mg of iron(III). The other ingredients are: water for injections, sodium hydroxide (10%), and hydrochloric acid (10%).

What CosmoFer looks like and contents of the pack

CosmoFer is packaged in dark glass ampoules. The pack sizes are: 5 x 2 ml, 10 x 2 ml, 2 x 10 ml. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Pharmacosmos A/S, Roervangsvej 30, DK-4300 Holbaek, Denmark. For more detailed information, please contact the local representative of the marketing authorization holder: Ewopharma AG Sp. z o.o., 01-192 Warsaw, ul. Leszno 14, Tel. 22 620-11-71

Date of last revision of the leaflet: ---------------------------------------------------------------------------------------------------------------------------------------

Information intended for healthcare professionals only:

Patient monitoring is required to detect subjective and objective signs of hypersensitivity reactions during each administration of CosmoFer and after administration. If a hypersensitivity reaction occurs, the administration of the medicine should be discontinued. CosmoFer should only be administered under the direct supervision of a healthcare professional trained in the evaluation and treatment of anaphylactic reactions, in a location fully equipped with resuscitation equipment. The patient should be monitored for side effects for at least 30 minutes after each administration of CosmoFer. Administration method: CosmoFer solution for injection can be administered as an intravenous drip infusion or intravenous injection, with intravenous drip infusion being the preferred method of administration, as it reduces the risk of hypotension episodes. However, CosmoFer can also be administered undiluted as intramuscular injections. Adults and elderly patientsThe total cumulative dose of CosmoFer is determined based on hemoglobin levels and body weight. The dose and dosing regimen of CosmoFer must be individualized for each patient based on the calculation of the total iron deficiency. Children (under 14 years of age)CosmoFer should not be used in children. There are no data on the efficacy and safety of this medicine in this population. Dosage: The standard dosing program includes 100-200 mg of iron, which corresponds to 2-4 ml, two or three times a week, depending on the hemoglobin level. However, if clinical circumstances require very rapid iron delivery to iron storage sites in the body, CosmoFer can be administered as a total dose in the form of an infusion in an amount of up to 20 mg/kg body weight. CosmoFer should not be administered simultaneously with oral iron preparations, as the absorption of oral iron will be impaired. Intravenous drip infusion: CosmoFer should be diluted only in 0.9% sodium chloride solution (physiological saline) or 5% glucose solution. CosmoFer at a dose of 100-200 mg of iron (2-4 ml) can be diluted in 100 ml. Each time, the first 25 mg of iron should be infused over 15 minutes. If no adverse reactions occur during this time, the remaining amount of the solution can be administered at a rate not exceeding 100 ml in 30 minutes. Intravenous injections: CosmoFer can be administered at a dose of 100-200 mg of iron (2-4 ml) by slow intravenous injection (0.2 ml/min), preferably diluted in 10-20 ml of 0.9% sodium chloride solution or 5% glucose solution. Each time, before starting the slow injection, 25 mg of iron should be injected over 1-2 minutes. If no adverse reaction occurs within 15 minutes, the remaining amount of the medicine can be administered. Infusion of the total dose: Immediately before administration of the total required amount of CosmoFer, as specified in the dosing table or calculations, the required volume is added aseptically, usually 500 ml of sterile sodium chloride solution or 5% glucose solution. The total amount of CosmoFer up to 20 mg/kg body weight is administered intravenously over 4-6 hours. The first 25 mg of iron should be administered over 15 minutes. During this period, the patient should be closely monitored. If no adverse reactions occur during this time, the remaining portion of the prepared solution can be administered. The rate of administration can be gradually increased to 45-60 drops per minute. The patient should be monitored during and after the infusion for at least 30 minutes. Administration of the total dose is associated with an increased frequency of adverse reactions, particularly with regard to delayed hypersensitivity reactions. The administration of CosmoFer by the method of total dose infusion should be limited to hospital practice. Injections into the dialyzer: CosmoFer can be administered during hemodialysis directly into the venous part of the apparatus, according to the procedure described in the section on intravenous administration. Intramuscular injections: The required amount of CosmoFer, either from the dosing table or calculated, is administered in the form of a series of undiluted injections of up to 100 mg of iron (2.0 ml) each, individually calculated based on the patient's body weight. If the patient is moderately active, injections can be performed daily, alternating between buttocks. In inactive or bedridden patients, the frequency of injections should be reduced to once or twice a week. To minimize the risk of subcutaneous staining, CosmoFer should be injected using the deep intramuscular injection method. It should be injected only into the muscle mass of the upper outer quadrant of the buttock, and never into the arm or other exposed areas of the body. For normally developed adults, a 20-21 "gauge" needle with a length of at least 50 mm should be used. For obese patients, the needle should be 80-100 mm long, while for adults of small stature, a shorter and smaller needle (23 "gauge" x 32 mm) should be used. The patient should lie on their side with the injection site facing up or stand with their weight shifted to the leg on the opposite side of the injection site. To avoid injecting or introducing the injected medicine into the subcutaneous tissue, the "Z-track" method (causing the skin to move horizontally before injection) is recommended. CosmoFer is injected slowly and smoothly. It is essential to wait a few seconds before withdrawing the needle to allow the muscle mass to absorb the injected volume. To minimize the leakage of the injected medicine through the needle channel, the patient should be advised not to rub the injection site.

Dose calculation

a) Iron supplementation in patients with iron deficiency anemia The factors that make up the appropriate formula are given below. The required dose must be individualized based on the total iron deficiency calculated from the following formula - hemoglobin is given in grams per liter (g/l) or millimoles per liter (mmol/l). Total dose (mg Fe) - Hb in g/l: (body weight (kg) x (target Hb level - actual Hb level) (g/l) x 0.24) + mg of iron stores in the body. The factor of 0.24 is based on the following assumptions: a) blood volume 70 ml/kg body weight ≈ 7% of body weight; b) iron content in hemoglobin 0.34%. The factor of 0.24 = 0.0034 x 0.07 x 1000 (conversion from g to mg). Total dose (mg Fe) - Hb in mmol/l: Body weight, in kg, x (target Hb level, in mmol/l - actual Hb level, in mmol/l) x 3.84 + mg of iron for iron stores in the body. The factor of 3.84 is based on the following assumptions: a) blood volume 70 ml/kg body weight ≈ 7% of body weight; b) iron content in hemoglobin 0.34%; c) the conversion factor for hemoglobin from g/l to mmol/l is 0.06205. The factor of 3.84 = 0.0034 x 0.07 x 1000 / 0.06205. b) Iron supplementation due to blood loss: Iron therapy in patients with blood loss should aim to replenish the amount of iron equivalent to the amount of iron lost with the blood. The formula described with the table does not apply to the case of ordinary iron supplementation. Quantitative assessment of periodic blood loss in the patient and hematocrit level during bleeding provides a convenient method for calculating the required dose of iron. The dose of CosmoFer required to compensate for the iron deficiency is calculated from the following formulas:

• If the volume of lost blood is known: intravenous administration of 200 mg of CosmoFer (4 ml of CosmoFer) results in an increase in hemoglobin, which corresponds to one unit of blood (= 400 ml with a hemoglobin content of 150 g/l or 9.3 mmol/l - equivalent to 0.34% 0.4 x 150 or 204 mg of iron). The amount of iron (in mg) to be replenished = number of lost blood units x 200. The required number of milliliters of CosmoFer = number of lost blood units x 4.
• In case of decreased Hb level: use the previously given formula, taking into account that there is no need to replenish stored iron in the body.

The amount of iron (in mg) to be replenished = body weight (kg) x 0.24 x (target Hb level, in g/l - actual Hb level, in g/l), or The amount of iron (in mg) to be replenished = body weight (kg) x 3.84 x (target Hb level, in mmol/l - actual Hb level, in mmol/l). Example: for a body weight of 60 kg, Hb deficit = 10 g/l or 0.62 mmol/l; The amount of iron to be replenished = 60 x 0.24 x 10 = 60 x 3.84 x 0.62 = 143 mg (~ 3 ml of CosmoFer).