Ferinject

Dispersion for injection/infusion. Dark brown, non-transparent, aqueous solution.
One mL of dispersion contains ferric carboxymaltose corresponding to 50 mg iron (Ph. Eur, USP).
Each 2 mL vial contains ferric carboxymaltose corresponding to 100 mg iron.
Each 10 mL vial contains ferric carboxymaltose corresponding to 500 mg iron.
Excipients with known effect: One mL of dispersion contains up to 5.5 mg (0.24 mmol) sodium, see Precautions.
Excipients/Inactive Ingredients: Sodium hydroxide (for pH adjustment), Hydrochloric acid (for pH adjustment), Water for injections.

Anti-anemia.
Pharmacotherapeutic group: Iron trivalent, parenteral preparation. ATC code: B03AC.
Pharmacology: Pharmacodynamics: Ferric carboxymaltose (Ferinject) dispersion for injection/infusion is a colloidal solution of the iron complex ferric carboxymaltose.
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).
Red cell utilisation of ⁵⁹Fe from radio-labelled Ferric carboxymaltose (Ferinject) 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 (Ferinject) treatment results in an increase in reticulocyte count, serum ferritin levels and TSAT levels to within normal ranges.
Clinical efficacy and safety: The efficacy and safety of Ferric carboxymaltose (Ferinject) has been studied in different therapeutic areas necessitating intravenous iron to correct iron deficiency. The main studies are described in more detail as follows.
Cardiology: Chronic heart failure: Study CONFIRM-HF was a double-blind, randomised, 2-arm study comparing Ferric carboxymaltose (Ferinject) (n=150) vs. placebo (n=151) in subjects with chronic heart failure (CHF) and ID for a treatment period of 52 weeks. At Day 1 and Week 6 (correction phase), subjects received either Ferric carboxymaltose (Ferinject) according to a simplified dosing grid using baseline Hb and body weight at screening (see Dosage & Administration), placebo or no dose. At Weeks 12, 24, and 36 (maintenance phase) subjects received Ferric carboxymaltose (Ferinject) (500 mg iron) or placebo if serum ferritin was <100 ng/mL or 100-300 ng/mL with TSAT <20%. The treatment benefit of Ferric carboxymaltose (Ferinject) vs. placebo was demonstrated with the primary efficacy endpoint, the change in the 6-minute walk test (6MWT) from baseline to Week 24 (33±11 metres, p=0.002). This effect was sustained throughout the study to Week 52 (36±11 metres p<0.001).
Study EFFECT-HF was an open-label (with blinded endpoint evaluation), randomised, 2-arm study comparing Ferinject (n=86) vs. standard of care (n=86) in subjects with chronic heart failure and ID for a treatment period of 24 weeks. At Day 1 and Week 6 (correction phase), subjects received either Ferinject according to a simplified dosing grid using baseline Hb and body weight at screening (see Dosage & Administration) or standard of care. At Week 12, (maintenance phase) subjects received Ferinject (500 mg iron) or standard of care if serum ferritin <100 ng/ml or 100 to 300 ng/ml and TSAT <20%. The treatment benefit of Ferinject vs. standard of care was demonstrated with the primary efficacy endpoint, the change in weight-adjusted peak VO₂ from baseline to Week 24 (LS Mean 1.04 ±0.44, p=0.02).
Nephrology: Haemodialysis-dependent chronic kidney disease: Study VIT-IV-CL-015 was an open-label, randomised parallel group study comparing Ferric carboxymaltose (Ferinject) (n=97) to iron sucrose (n=86) in subjects with ID anaemia undergoing haemodialysis. Subjects received Ferric carboxymaltose (Ferinject) or iron sucrose 2-3 times per week in single doses of 200 mg iron directly into the dialyser until the individually calculated cumulative iron dose was reached (mean cumulative dose of iron as Ferric carboxymaltose (Ferinject): 1,700 mg). The primary efficacy endpoint was the percentage of subjects reaching an increase in Hb of ≥1.0 g/dL at 4 weeks after baseline. At 4 weeks after baseline, 44.1% responded to treatment with Ferric carboxymaltose (Ferinject) (i.e. Hb increase of ≥1.0 g/dL) compared to 35.3% for iron sucrose (p=0.2254).
Non-dialysis-dependent chronic kidney disease: Study 1VIT04004 was an open-label, randomised active-control study, evaluating the safety and efficacy of Ferric carboxymaltose (Ferinject) (n=147) vs. oral iron (n=103). Subjects in the Ferric carboxymaltose (Ferinject) group received 1,000 mg of iron at baseline and 500 mg of iron at days 14 and 28, if TSAT was <30% and serum ferritin was <500 ng/mL at the respective visit. Subjects in the oral iron arm received 65 mg iron TID as ferrous sulphate from baseline to day 56. Subjects were followed-up until day 56. The primary efficacy endpoint was the percentage of subjects achieving an increase in Hb of ≥1.0 g/dL anytime between baseline and end of study or time of intervention. This was achieved by 60.54% of subjects receiving Ferric carboxymaltose (Ferinject) vs. 34.7% of subjects in the oral iron group (p<0.001). Mean haemoglobin change to day 56/end of study was 1.0 g/dL in the Ferric carboxymaltose (Ferinject) group and 0.7 g/dL in the oral iron group (p=0.034, 95% CI: 0.0, 0.7).
Gastroenterology: Inflammatory bowel disease: Study VIT-IV-CL-008 was a randomised, open-label study which compared the efficacy of Ferric carboxymaltose (Ferinject) vs. oral ferrous sulphate in reducing ID anaemia in subjects with inflammatory bowel disease (IBD). Subjects received either Ferric carboxymaltose (Ferinject) (n=111) in single doses of up to 1,000 mg iron once per week until the individually calculated iron dose (per Ganzoni formula) was reached (mean cumulative iron dose: 1,490 mg), or 100 mg iron BID as ferrous sulphate (n=49) for 12 weeks. Subjects receiving Ferric carboxymaltose (Ferinject) showed a mean increase in Hb from baseline to Week 12 of 3.83 g/dL, which was non-inferior to 12 weeks of twice daily therapy with ferrous sulphate (3.75 g/dL, p=0.8016).
Study FER-IBD-07-COR was a randomised, open-label study comparing the efficacy of Ferric carboxymaltose (Ferinject) vs. iron sucrose in subjects with remitting or mild IBD. Subjects receiving Ferric carboxymaltose (Ferinject) were dosed according to a simplified dosing grid using baseline Hb and body weight (see Dosage & Administration) in single doses up to 1,000 mg iron, whereas subjects receiving iron sucrose were dosed according to individually calculated iron doses using the Ganzoni formula in doses of 200 mg iron until the cumulative iron dose was reached. Subjects were followed-up for 12 weeks. 65.8% of subjects receiving Ferric carboxymaltose (Ferinject) (n=240; mean cumulative iron dose: 1,414 mg) vs. 53.6% receiving iron sucrose (n=235; mean cumulative dose 1,207 mg; p=0.004) had responded at Week 12 (defined as Hb increase ≥2 g/dL). 83.8% of Ferric carboxymaltose (Ferinject)-treated subjects vs. 75.9% of iron sucrose-treated subjects achieved a Hb increase ≥2 g/dL or had Hb within normal limits at Week 12 (p=0.019).
Women's health: Postpartum: Study VIT-IV-CL-009 was a randomised open-label non-inferiority study comparing the efficacy of Ferric carboxymaltose (Ferinject) (n=227) vs. ferrous sulphate (n=117) in women suffering from post-partum anaemia. Subjects received either Ferric carboxymaltose (Ferinject) in single doses of up to 1,000 mg iron until their individually calculated cumulative iron dose (per Ganzoni formula) was reached, or 100 mg of iron as oral ferrous sulphate BID for 12 weeks. Subjects were followed-up for 12 weeks. The mean change in Hb from baseline to Week 12 was 3.37 g/dL in the Ferric carboxymaltose (Ferinject) group (n=179; mean cumulative iron dose: 1,347 mg) vs. 3.29 g/dL in the ferrous sulphate group (n=89), showing non-inferiority between the treatments.
Pregnancy: Intravenous iron medicines should not be used during pregnancy unless clearly necessary. Treatment with Ferric carboxymaltose (Ferinject) should be confined to the second and third trimester if the benefit is judged to outweigh the potential risk for both the mother and the foetus, see Use in Pregnancy & Lactation.
Limited safety data in pregnant women are available from study FER-ASAP-2009-01, a randomised, open-label study comparing Ferric carboxymaltose (Ferinject) (n=121) vs. oral ferrous sulphate (n=115) in pregnant women in the second and third trimester with ID anaemia for a treatment period of 12 weeks. Subjects received Ferric carboxymaltose (Ferinject) in cumulative doses of 1,000 mg or 1,500 mg of iron (mean cumulative dose: 1,029 mg iron) based on Hb and body weight at screening, or 100 mg of oral iron BID for 12 weeks. The incidence of treatment-related adverse events was similar between Ferric carboxymaltose (Ferinject) treated women and those treated with oral iron (11.4% Ferric carboxymaltose (Ferinject) group; 15.3% oral iron group). The most commonly reported treatment-related adverse events were nausea, upper abdominal pain and headache. Newborn Apgar scores as well as newborn iron parameters were similar between treatment groups.
Paediatric population: Adolescents aged 14 years or older were included in 4 studies performed in adults. In addition, paediatric studies were performed in children and adolescents aged 1 to 17 years with iron deficiency anaemia. The most common aetiologies for iron deficiency anaemia were gastrointestinal diseases (e.g. inflammatory bowel disease, Helicobacter pylori gastritis, coeliacic disease) and heavy uterine bleeding.
In a prospective pharmacokinetic/pharmacodynamic phase 2 study (1VIT13036), 35 children at a median age of 9.8 years (range: 1.5-17.5 years) were treated in 2 consecutive dose cohorts with single doses of Ferinject 7.5 mg iron/kg body weight (n = 16) or Ferinject 15 mg iron/kg body weight (n = 19), at a maximum dose of 750 mg iron. Hb, ferritin and TSAT increased dose-dependently. On day 35 after injection, the mean (SD) increase in Hb was 1.9 (1.38) g/dL with Ferinject 7.5 mg iron/kg and 2.8 (1.15) g/dL with Ferinject 15 mg iron/kg. See Adverse Reactions.
In a prospective, open-label, parallel-group phase 3 study (1VIT17044), efficacy and safety of Ferinject were compared with oral iron therapy. 40 children at a median age of 14.5 years (range:1 to 17 years) were treated with 2 doses of Ferinject 15 mg iron/kg body weight at a 7-day interval (maximum single dose 750 mg) and 39 children at a median age of 14.0 years (range: 1 to 17 years) with oral ferrous sulphate for 28 days. A similar increase in Hb was observed after both treatment with Ferinject and treatment with oral iron sulphate. The increase in Hb from baseline to day 35 (LS Mean [95%CI]) was 2.22 [1.69, 2.75] g/dL after Ferinject and 1.92 [1.43, 2.41] g/dL after oral iron sulphate. In total, 87.5% of patients in the intravenous iron group achieved a Hb increase >1 g/dL at EOS. The increase in ferritin and TSAT, used as a measure for the replenishment of iron stores, was higher after Ferinject therapy compared to oral iron sulphate therapy, with an increase in ferritin from baseline to day 35 (LS Mean [95%CI]) of 132.1 [105.44, 158.76] ng/mL after Ferinject and 11.0 [-15.62, 37.65] ng/mL after oral iron sulphate. The corresponding increase in TSAT was 24.3 [19.19, 29.41]% and 8.7 [3.70, 13.63]%, respectively. See Adverse Reactions.
Ferritin monitoring after replacement therapy: There is limited data from study VIT-IV-CL-008 which demonstrates that ferritin levels decrease rapidly 2-4 weeks following replacement and more slowly thereafter. The mean ferritin levels did not drop to levels where retreatment might be considered during the 12 weeks of study follow up. Thus, the available data does not clearly indicate an optimal time for ferritin retesting although assessing ferritin levels earlier than 4 weeks after replacement therapy appears premature. Thus, it is recommended that further re-assessment of ferritin should be made by the clinician based on the individual patient's condition.
Pharmacokinetics: Distribution: Positron emission tomography demonstrated that ⁵⁹Fe and ⁵²Fe from Ferric carboxymaltose (Ferinject) 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 (Ferinject) of 100 to 1,000 mg of iron in ID 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 the central compartment corresponds well to the volume of the plasma (approximately 3 litres).
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.
Paediatric population: The pharmacokinetic properties of Ferinject at a dose of 15 mg iron/kg were similar to those for adult patients with iron deficiency. Serum iron increased proportionally to the dose after a single dose of 7.5 mg iron/kg or 15 mg iron/kg. After a single dose of Ferinject of 15 mg iron/kg body weight (maximum 750 mg), average maximum total serum iron values of 310 μg/mL were measured after 1.12 hours. The terminal half-life was 9.8 hours, and the distribution volume estimated by the population pharmacokinetic analysis was 0.42 to 3.14 l. Based on model-based simulations, the paediatrics subjects tended to have lower systemic exposure (lower AUC0-72h) compared to the adults (median per age group: 3,340 μg×h/mL (1 to 2 years), 4,110 μg×h/mL (3 to 12 years), 4,740 μg×h/mL (13 to 17 years), 8,864 μg×h/mL (adults)).
Toxicology: Preclinical safety data: 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 (Ferinject) does cross the placental barrier and is excreted in milk in limited, controlled amounts. In reproductive toxicology studies using iron replete rabbits Ferric carboxymaltose (Ferinject) 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 (Ferinject). No evidence of allergic or immunotoxic potential has been observed. A controlled in-vivo test demonstrated no cross-reactivity of Ferric carboxymaltose (Ferinject) with anti-dextran antibodies. No local irritation or intolerance was observed after intravenous administration.

Ferric carboxymaltose (Ferinject) is indicated for the treatment of iron deficiency when oral iron preparations are ineffective; oral iron preparations cannot be used (see Pharmacology: Pharmacodynamics under Actions); there is a clinical need to deliver iron rapidly.
The diagnosis of iron deficiency must be based on laboratory tests.

Monitor carefully patients for signs and symptoms of hypersensitivity reactions during and following each administration of ferric carboxymaltose (Ferinject).
Ferric carboxymaltose (Ferinject) 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 (Ferinject) administration (see Precautions).
Posology: The posology of ferric carboxymaltose (Ferinject) follows a stepwise approach: [1] determination of the individual iron need, [2] calculation and administration of the iron dose(s), and [3] post-iron repletion assessments. These steps are outlined as follows: Step 1: Determination of the iron need: The individual iron need for repletion using ferric carboxymaltose (Ferric carboxymaltose (Ferinject)) is determined based on the patient's body weight and hemoglobin (Hb) level. Refer to Table 1 for determination of the total iron need. 2 doses may be required to replenish the total iron need, see Step 2 for the maximum individual iron doses. (See Table 1.)

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Step 2: Calculation and administration of the maximum individual iron dose(s): Based on the total iron need determined as previously mentioned the appropriate dose(s) of Ferric carboxymaltose (Ferinject) should be administered taking into consideration the following: Adults and adolescents aged 14 years or older: A single Ferric carboxymaltose (Ferinject) 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 (Ferinject)).
The maximum recommended cumulative dose of Ferric carboxymaltose (Ferinject) is 1,000 mg of iron (20 mL Ferric carboxymaltose (Ferinject) per week. If the total iron need is higher, then the administration of an additional dose should be a minimum of 7 days apart from the first dose.
Children and adolescents aged 1 to 13 years: A single Ferric carboxymaltose (Ferinject) administration should not exceed: 15 mg iron/kg body weight; 750 mg of iron (15 mL Ferric carboxymaltose (Ferinject)).
The maximum recommended cumulative dose of Ferric carboxymaltose (Ferinject) is 750 mg of iron (15 mL Ferric carboxymaltose (Ferinject)) per week. If the total iron need is higher, then the administration of an additional dose should be a minimum of 7 days apart from the first dose.
Step 3: 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 final Ferinject administration to allow adequate time for erythropoiesis and iron utilisation. In the event the patient requires further iron repletion, the iron need should be recalculated (see Step 1).
Children below 1 year of age: The efficacy and safety of Ferric carboxymaltose (Ferinject) has not been investigated in children below 1 year of age. Ferric carboxymaltose (Ferinject) is therefore not recommended for use in children in this age group.
Patients with haemodialysis-dependent chronic kidney disease: In adults and adolescents aged 14 years and older, a single maximum daily dose of 200 mg iron should not be exceeded in haemodialysis-dependent chronic kidney disease patients (see Precautions).
Children below 1 year of age: The efficacy and safety of Ferric carboxymaltose (Ferinject) has not been investigated in children below 1 year of age. Ferric carboxymaltose (Ferinject) is therefore not recommended for use in children in this age group.
Method of administration: Ferric carboxymaltose (Ferinject) 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 (Ferinject) must not be administered by the subcutaneous or intramuscular route.
Intravenous injection: Ferric carboxymaltose (Ferinject) may be administered by intravenous injection using undiluted dispersion. In adults and adolescents aged 14 years and older, the maximum single dose is 15 mg iron/kg body weight but should not exceed 1,000 mg of iron. In children aged 1 to 13 years, the maximum single dose is 15 mg iron/kg body weight but should not exceed 750 mg of iron. The administration rates are as shown in Table 2: See Table 2.

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Intravenous infusion: Ferric carboxymaltose (Ferinject) may be administered by intravenous infusion, in which case it must be diluted. In adults and adolescents aged 14 years and older, the maximum single dose is 20 mg iron/kg body weight, but should not exceed 1,000 mg of iron. In children aged 1 to 13 years, the maximum single dose is 15 mg iron/kg body weight but should not exceed 750 mg of iron.
For infusion, Ferric carboxymaltose (Ferinject) must only be diluted in sterile 0.9% m/V sodium chloride solution as shown in Table 3. Note: for stability reasons, Ferric carboxymaltose (Ferinject) should not be diluted to concentrations less than 2 mg iron/mL (not including the volume of the ferric carboxymaltose dispersion). For further instructions on dilution of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage. (See Table 3.)

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Administration of Ferric carboxymaltose (Ferinject) 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 haemosiderosis. Monitoring of iron parameters such as serum ferritin and transferrin saturation (TSAT) 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.

The use of Ferric carboxymaltose (Ferinject) is contraindicated in cases of: hypersensitivity to the active substance, to Ferric carboxymaltose (Ferinject) or any of its excipients listed in Description; 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.

Hypersensitivity reactions: Parenterally administered iron preparations can cause hypersensitivity reactions including serious and potentially fatal anaphylactic reactions. Hypersensitivity reactions have also been reported after previously uneventful doses of parenteral iron complexes. There have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute allergic coronary arteriospasm that can result in myocardial infarction, see Adverse Reactions).
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 inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis).
Ferric carboxymaltose (Ferinject) should only be administered when staff trained to evaluate and manage anaphylactic reactions are 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 (Ferinject) administration. 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 reactions should be available, including an injectable 1:1000 adrenaline solution. Additional treatment with antihistamines and/or corticosteroids should be given as appropriate.
Hypophosphataemia/Hypophosphataemic osteomalacia: Parenterally iron preparations can lead to hypophosphataemia which is transient and without clinical symptoms. Hypophosphataemia requiring treatment has mainly been reported in individual cases, in patients with known risk factors and after sustained higher dosing.
Cases of symptomatic hypophosphataemia leading to hypophosphataemic osteomalacia, and fractures requiring clinical intervention, including surgery, were reported after market introduction. In case of arthralgia or bone pain, patients should be advised to seek medical advice.
Patients receiving multiple higher doses as part of long-term treatment, and who have underlying risk factors (e.g. vitamin D deficiency, calcium and phosphate malabsorption, secondary hyperparathyroidism, hereditary haemorrhagic telangiectasia, inflammatory bowel disease and osteoporosis) should be monitored for hypophosphataemic osteomalacia, including serum phosphate control. In case of persistent hypophosphataemia, treatment with Ferinject should be re-evaluated.
Hepatic or renal impairment: In patients with liver dysfunction, parenteral iron should only be administered after careful benefit/risk 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 dose of more than 200 mg iron are available.
Infection: Parenteral iron must be used with caution in case of acute or chronic infection, asthma, eczema or atopic allergies. It is recommended that the treatment with Ferric carboxymaltose (Ferinject) is stopped in patients with ongoing bacteraemia. Therefore, in patients with chronic infection a benefit/risk evaluation has to be performed, taking into account the suppression of erythropoiesis.
Extravasation: Caution should be exercised to avoid paravenous leakage when administering Ferric carboxymaltose (Ferinject). Paravenous leakage of Ferric carboxymaltose (Ferinject) at the administration site may lead to irritation of the skin and potentially long lasting brown discolouration at the site of administration. In case of paravenous leakage, the administration of Ferric carboxymaltose (Ferinject) must be stopped immediately.
Excipients: Ferric carboxymaltose (Ferinject) contains up to 5.5 mg (0.24 mmol) sodium per mL of undiluted solution, equivalent to 0.3% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Effects on ability to drive and use machines: Ferric carboxymaltose (Ferinject) is unlikely to impair the ability to drive and use machines.

Pregnancy: There are limited data from the use of Ferric carboxymaltose (Ferinject) in pregnant women (see Pharmacology: Pharmacodynamics under Actions). A careful benefit/risk evaluation is required before use during pregnancy and Ferric carboxymaltose (Ferinject) should not be used during pregnancy unless clearly necessary.
Iron deficiency occurring in the first trimester of pregnancy can in many cases be treated with oral iron. Treatment with Ferric carboxymaltose (Ferinject) should be confined to the second and third trimester if the benefit is judged to outweigh the potential risk for both the mother and the foetus.
Foetal bradycardia may occur following administration of parenteral irons. It is usually transient and a consequence of a hypersensitivity reaction in the mother. The unborn baby should be carefully monitored during intravenous administration of parenteral irons to pregnant women.
Animal data suggest that iron released from Ferric carboxymaltose (Ferinject) can cross the placental barrier and that its use during pregnancy may influence skeletal development in the fetus (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Breast-feeding: Clinical studies showed that transfer of iron from Ferric carboxymaltose (Ferinject) to human milk was negligible (≤1%). Based on limited data on breast-feeding women it is unlikely that Ferric carboxymaltose (Ferinject) represents a risk to the breast-fed child.
Fertility: There are no data on the effect of Ferric carboxymaltose (Ferinject) on human fertility. Fertility was unaffected following Ferric carboxymaltose (Ferinject) treatment in animal studies (see Pharmacology: Toxicology: Preclinical safety data under Actions).

Table 4 presents the adverse drug reactions (ADRs) reported during clinical studies in which >9,000 subjects (including >100 children and adolescents 1 to 17 years) received Ferric carboxymaltose (Ferinject), as well as those reported from the post-marketing experience (see table footnotes for details).
The most commonly reported ADR is nausea (occurring in 2.9% of the subjects), followed by injection/infusion site reactions, hypophosphataemia, headache, flushing, dizziness and hypertension. Injection/infusion site reactions comprise several ADRs which individually are either uncommon or rare.
For subjects in clinical trials that showed a decrease in serum phosphorous, the minimum values were obtained after approximately 2 weeks, and in most cases returned to baseline values by 12 weeks following Ferric carboxymaltose (Ferinject) treatment. The most serious ADR is anaphylactic reactions (rare); fatalities have been reported. See Precautions for further details. (See Table 4.)

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Pediatric population: The safety profile of children and adolescents aged 1 to 17 years is comparable with that of adults. 110 paediatric patients received Ferric carboxymaltose (Ferinject) in 7 clinical studies. No serious ADRs were reported. The reported non-serious ADRs were hypophosphataemia (n=5), urticaria (n=5), injection/infusion site reactions (n=4), abdominal pain (n=2), flushing (n=2), headache (n=2), pyrexia (n=2), liver enzymes increased (n=2), and rash (n=2). Constipation, gastritis, hypertension, pruritus and thirst were reported only once.
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.

The absorption of oral iron is reduced when administered concomitantly with parenteral iron preparations. Therefore, if required, oral iron therapy should not be started for at least 5 days after the last administration of Ferric carboxymaltose (Ferinject).

Special precautions for disposal and other handling: Inspect vials visually for sediment and damage before use. Use only those containing sediment-free, homogeneous dispersion.
Each vial of Ferric carboxymaltose (Ferinject) is intended for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.
Ferric carboxymaltose (Ferinject) must only be mixed with sterile 0.9% m/V sodium chloride solution. No other intravenous dilution solutions and therapeutic agents should be used, as there is the potential for precipitation and/or interaction. For dilution instructions, see Dosage & Administration.
Incompatibilities: This medicinal product must not be mixed with other medicinal products except those mentioned previously.
The compatibility with containers other than polyethylene and glass is not known.

Store in the original package in order to protect from light. Do not store above 30°C. Do not freeze.
For storage conditions after dilution or first opening of the medical product, see Shelf life as follows.
Shelf life: Shelf life of the product as packaged for sale: 3 years.
Shelf life after first opening of the container: From a microbiological point of view, preparations for parenteral administration should be used immediately.
Shelf life after dilution with sterile 0.9% m/V sodium chloride solution: From a microbiological point of view, preparations for parenteral administration should be used immediately after dilution with sterile 0.9% m/V sodium chloride solution.

Vitamins & Minerals (Pre & Post Natal) / Antianemics

B03AC - Iron, parenteral preparations ; Used in the treatment of anemia

Rx