Feronia FCM 1k Injection

Ferric Carboxymaltose Injection 100 mg / 2 ml, 500 mg / 10 ml & 1 g / 20 ml

Feronia FCM 100

Each ml contains :

Ferric Carboxymaltose

equivalent to elemental Iron 50 mg

Water for Injections IP q.s.

Feronia FCM 500

Each ml contains :

Ferric Carboxymaltose

equivalent to elemental Iron 50 mg

Water for Injections IP q.s.

Feronia FCM 1K

Ferric Carboxymaltose

equivalent to elemental Iron 50 mg

Water for Injections IP q.s.

Injection 100 mg / 2 ml

Injection 500 mg / 10 ml

Injection 1 g / 20 ml

For IV Injection / Infusion

4.1 Therapeutic indication

For treatment of iron deficiency when oral iron preparations are ineffective or cannot be used. The diagnosis must be based on laboratory tests.

4.2 Posology and method of administration

Monitor carefully patients for signs and symptoms of hypersensitivity reactions during and following each administration of Ferric Carboxymaltose. Ferric Carboxymaltose Injection should only be administered when staff trained to evaluate and manage anaphylactic reactions is immediately available, in an environment where full resuscitation facilities can be assured. The patient should be observed for adverse effects for at least 30 minutes following each Ferric Carboxymaltose Injection.

Calculation of the cumulative iron dose

The cumulative dose for repletion of iron using Ferric Carboxymaltose is determined based on the patient's body weight and haemoglobin level and must not be exceeded. The following table should be used to determine the cumulative iron dose :

Note :Acumulative iron dose of 500mg should not be exceeded for patientswith bodyweight<35 kg.

Maximum tolerated single dose

A single Ferric Carboxymaltose administration should not exceed :

• 15 mg iron/kg body weight (for administration by intravenous injection) or 20 mg iron/kg body weight (for administration by intravenous infusion).
• 1,000 mg of iron (20 mL Ferric Carboxymaltose).

Do not administer 1000 mg of iron (20 ml) more than once a week.

Post-iron repletion assessments

Re-assessment should be performed by the clinician based on the individual patient's condition. The Hb level should be re-assessed no earlier than 4 weeks post nal Ferric Carboxymaltose administration to allow adequate time for erythropoiesis and iron utilisation.

Special population

Haemodialysis-dependent chronic kidney disease

A single maximum daily injection dose of 200 mg iron should not be exceeded in haemodialysisdependent chronic kidney disease patients.

Paediatric population

The use of Ferric Carboxymaltose Injection has not been studied in children and therefore is not recommended in children under 14 years.

Method of administration

Ferric Carboxymaltose must only be administered by the intravenous route :

• By injection, or
• By infusion, or
• During a haemodialysis session undiluted directly into the venous limb of the dialyser.

Ferric Carboxymaltose must not be administered by the subcutaneous or intramuscular route.

Intravenous injection

Ferric Carboxymaltose may be administered by intravenous injection using undiluted solution. The maximum single dose is 15 mg iron/kg body weight but should not exceed 1,000 mg iron.

Administration rates for intravenous injection of Ferric Carboxymaltose

Intravenous infusion

Ferric Carboxymaltose Injection may be administered by intravenous infusion, in which case it must be diluted. The maximum single dose is 20 mg iron/kg body weight, but should not exceed 1000 mg iron.

In case of infusion, Ferric Carboxymaltose Injection must be diluted only in sterile 0.9% Sodium Chloride Solution as follows :

Dilution plan of Ferric Carboxymaltose Injection for intravenous drip infusion

Note : For stability reasons, dilutions to concentrations less than 2 mg iron/ml are not permissible. Inspect vials visually for sediment and damage before use. Use only those containing sedimentfree, homogeneous solution.

Each vial of Ferric Carboxymaltose Injection is intended for single use only. Any unused product or waste material should be disposed of in accordance with local requirements. Ferric Carboxymaltose Injection must only be mixed with sterile 0.9% Sodium Chloride Solution. No other intravenous dilution solutions and therapeutic agents should be used, as there is the potential for precipitation and/or interaction.

From a microbiological point of view, preparations for parenteral administration should be used immediately after dilution with sterile 0.9% Sodium Chloride Solution.

4.3 Contraindications

The use is contraindicated in cases of :

• Hypersensitivity to the active substance, to Ferric Carboxymaltose Injection or any of its Excipients.
• Known serious hypersensitivity to other parenteral iron products.
• Anaemia not attributed to iron deficiency, e.g. other microcytic anaemia.
• Evidence of iron overload or disturbances in the utilisation of iron.
• First trimester of pregnancy.

4.4 Warning and precautions

Parenterally administered iron preparations can cause hypersensitivity reactions including anaphylactoid reactions which may be potentially fatal. Therefore, facilities for cardio-pulmonary resuscitation must be available. Hypersensitivity reactions have also been reported after previously uneventful doses of parenteral iron complexes.

The risk is enhanced for patients with known allergies including drug allergies, including patients with a history of severe asthma, eczema or other atopic allergy. There is also an increased risk of hypersensitivity reactions to parenteral iron complexes in patients with immune or inammator y conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis). Ferric Carboxymaltose Injection should only be administered when staff trained to evaluate and manage anaphylactic reactions is immediately available, in an environment where full resuscitation facilities can be assured. Each patient should be observed for adverse effects for at least 30 minutes following each Ferric Carboxymaltose Injection. If hypersensitivity reactions or signs of intolerance occur during administration, the treatment must be stopped immediately. Facilities for cardio respiratory resuscitation and equipment for handling acute anaphylactic / anaphylactoid reactions should be available, including an injectable 1:1000 adrenaline solution. Additional treatment with antihistamines and/or corticosteroids should be given as appropriate.

In patients with liver dysfunction, parenteral iron should only be administered after careful risk/benet assessment. Parenteral iron administration should be avoided in patients with hepatic dysfunction where iron overload is a precipitating factor, in particular Porphyria Cutanea Tarda (PCT). Careful monitoring of iron status is recommended to avoid iron overload. No safety data on haemodialysis-dependent chronic kidney disease patients receiving single doses of more than 200 mg iron are available.

Parenteral iron must be used with caution in cases of acute or chronic infection, asthma, eczema or atopic allergies. It is recommended that the administration of Ferric Carboxymaltose Injection is stopped in patients with ongoing bacteremia. In patients with chronic infection a risk/benet evaluation has to be performed, taking into account the suppression of erythropoiesis. Caution should be exercised to avoid paravenous leakage when administering Ferric Carboxymaltose Injection. Paravenous leakage of Ferric Carboxymaltose Injection at the injection site may lead to brown discolouration and irritation of the skin. In case of paravenous leakage, the administration of Ferric Carboxymaltose Injection must be stopped immediately. As with all parenteral iron preparations the absorption of oral iron is reduced when administered concomitantly.

4.5 Drug interactions

As with all parenteral iron preparations the absorption of oral iron is reduced when administered concomitantly. Therefore, if required, oral iron therapy should not be started for at least 5 days after the last injection of Ferric Carboxymaltose.

4.6 Special populations

Pregnancy

There are no adequate and well-controlled trials of Ferric Carboxymaltose in pregnant women. A careful benet/risk evaluation is required before use during pregnancy and Ferric Carboxymaltose should not be used during pregnancy unless clearly necessary. Treatment with Ferric Carboxymaltose should be conned to the second and third trimester if the benet is judged to outweigh the potential risk for both the mother and the foetus. Animal data suggest that iron released from Ferric Carboxymaltose can cross the placental barrier and that its use during pregnancy may influence skeletal development in the fetus.

Lactation

Clinical studies showed that transfer of iron from Ferric Carboxymaltose to human milk was negligible (≤ 1%). Based on limited data on breast-feeding women it is unlikely that Ferric Carboxymaltose represents a risk to the breast-fed child.

Fertility

There are no data on the effect of Ferric Carboxymaltose on human fertility. Fertility was unaffected following Ferric Carboxymaltose treatment in animal studies.

Pediatric use

The use of Ferric Carboxymaltose Injection has not been studied in children.

4.7 Effects on ability to drive and use machines

Ferric Carboxymaltose Injection is unlikely to impair the ability to drive and use machines.

4.8 Undesirable effects

The most commonly reported ADR is nausea (occurring in 3.2% of the subjects), followed by

injection/infusion site reactions, hypophosphataemia, headache, ushing, dizziness and hypertension. Injection/infusion site reactions comprise several ADRs which individually are either uncommon or rare. The most serious ADR is anaphylactic reactions (rare); fatalities have been reported.

The following denitions of frequencies are used : Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to <1/100) and Rare (≥ 1/10,000 to < 1/1,000).

Immune system disorders

Uncommon : Hypersensitivity

Rare : Anaphylactoid reactions

Metabolism and nutritional disorders

Common : Hypophosphataemia

Nervous system disorders

Common : Headache, dizziness

Uncommon : Paraesthesia, dysgeusia

Frequency not known (estimated as rare) : Loss of consciousness

Psychiatric disorders

Rare : Anxiety

Cardiac disorders

Uncommon : Tachycardia

Frequency not known (estimated as rare) : Kounis syndrome

Vascular disorders

Common : Hypotension, flushing

Uncommon : Hypertension

Rare : Phlebitis, syncope, presyncope

Respiratory, thoracic and mediastinal disorders

Uncommon : Dyspnoea

Rare : Bronchospasm

Gastrointestinal disorders

Common : Nausea

Uncommon : Vomiting, dyspepsia, abdominal pain, constipation, diarrhoea

Rare : Flatulence

Skin and subcutaneous tissue disorders

Uncommon : Pruritus, urticaria, erythema, rash

Rare : Angioedema, pallor, distant skin discolouration

Frequency not known (estimated as rare) : Face oedema

Musculoskeletal and connective tissue disorders

Uncommon : Myalgia, back pain, arthralgia, muscle spasm

Frequency not known (estimated as rare) : Hypophosphataemic osteomalacia

General disorders and administration site conditions

Common : Injection/infusion site reactions - Includes, but is not limited to, the following preferred terms : injection/infusion site -pain, -haematoma, -discolouration, -extravasation, -irritation, - reaction, (all individual ADRs determined to be uncommon) and -paraesthesia (individual ADR determined to be rare).

Uncommon : Pyrexia, fatigue, chest pain, oedema peripheral, chills, malaise Rare : Rigors, malaise, inuenza like illness (onset may vary from a few hours to several days)

Investigations

Uncommon : Alanine aminotransferase increased, Aspartate aminotransferase increased, gamma-glutamyltransferase increased, blood lactate dehydrogenase increased, blood alkaline phosphatase increased

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to : medico@zuventus.com. By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Administration of Ferric Carboxymaltose Injection in quantities exceeding the amount needed to correct iron deficit at the time of administration may lead to accumulation of iron in storage sites eventually leading to hemosiderosis. Monitoring of iron parameters such as serum ferritin and transferrin saturation may assist in recognizing iron accumulation. If iron accumulation has occurred, treat according to standard medical practice, e.g. consider the use of an iron chelator.

5.1 Mechanism of action

Ferric Carboxymaltose is a colloidal iron (III) hydroxide in complex with Carboxymaltose, a carbohydrate polymer that releases iron. The complex is designed to provide, in a controlled way, utilisable iron for the iron transport and storage proteins in the body (transferrin and ferritin, respectively).

5.2 Pharmacodynamic properties

Pharmacotherapeutic group : Iron trivalent, parenteral preparation ATC code : B03AC Using positron emission tomography (PET) it was demonstrated that red cell uptake of 59Fe and 59 52Fe from Ferric Carboxymaltose ranged from 61% to 99%. Red cell utilisation of Fe from radiolabelled Ferric Carboxymaltose ranged from 91% to 99% in subjects with iron deficiency (ID) and 61% to 84% in subjects with renal anaemia at 24 days post-dose. Ferric Carboxymaltose treatment results in an increase in reticulocyte count, serum ferritin levels and TSAT levels to within normal ranges.

5.3 Pharmacokinetic properties

Distribution

Positron emission tomography demonstrated that Fe and Fe from Ferric Carboxymaltose was rapidly eliminated from the blood, transferred to the bone marrow, and deposited in the liver and spleen.

After administration of a single dose of Ferric Carboxymaltose of 100 to 1,000 mg of Iron in iron decient subjects, maximum total serum iron levels of 37 µg/mL up to 333 µg/mL are obtained after 15 minutes to 1.21 hours respectively. The volume of distribution was estimated to be 3 L.

Elimination

The iron injected or infused was rapidly cleared from the plasma, the terminal half-life ranged from 7 to 12 hours, the mean residence time (MRT) from 11 to 18 hours. Renal elimination of iron was negligible.

6.1 Animal toxicology or pharmacology

Preclinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeat dose toxicity and genotoxicity. Preclinical studies indicate that iron released from Ferric Carboxymaltose does cross the placental barrier and is excreted in milk in limited, controlled amounts. In reproductive toxicology studies using iron replete rabbits Ferric Carboxymaltose was associated with minor skeletal abnormalities in the fetus. In a fertility study in rats, there were no effects on fertility for either male or female animals. No long-term studies in animals have been performed to evaluate the carcinogenic potential of Ferric Carboxymaltose. No evidence of allergic or immunotoxic potential has been observed. A controlled in-vivo test demonstrated no cross-reactivity of Ferric Carboxymaltose with anti-dextran antibodies. No local irritation or intolerance was observed after intravenous administration.

Ferric Carboxymaltose, an iron replacement product, is an iron carbohydrate complex with the chemical name of polynuclear iron (III)-hydroxide4(R)-(poly-(1→4)-O-α-Dglucopyranosyl)-oxy2(R),3(R),5(R), 6-tetrahydroxy-hexanoate. It has a relative molecular weight of approximately 150,000 Da corresponding to the following empirical formula :

[FeOx(OH)y(H2O)z]n [{(C6H10O5)m (C6H12O7)}l]k where n ≈ 103, m ≈ 8, l≈ 11 and k ≈ 4 (l represents the mean 

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on the pack.

8.3 Packaging information

Feronia FCM 100 : A vial of 2 ml.

Feronia FCM 500 : A Vial of 10 ml.

Feronia FCM 1K : A vial of 20 ml.

8.4 Storage and handing instructions

Store in a cool & dark place (8°C to 25°C). Do not refrigerate

Keep out of reach of children.

Before using, check for absence of sediments

Advise the patient to read the patient information leaflet and discuss with the patient the etiology of the iron deficiency anemia and the patient’s iron deficiency anemia treatment options. Advise patients of the risks associated with Ferric Carboxymaltose Injection.

Prior history of reactions to parenteral iron products

Question patients regarding any prior history of reactions to parenteral iron products.

Serious hypersensitivity reactions

Advise patients to report any signs and symptoms of hypersensitivity that may develop during and following Ferric Carboxymaltose Injection administration, such as rash, itching, dizziness, lightheadedness, swelling, and breathing problems.

Pregnancy

Advise pregnant women about the risk of hypersensitivity reactions which may have serious consequences for the fetus. Advise patients who may become pregnant to inform their healthcare provider of a known or suspected pregnancy.