Treatment of iron deficiency without anaemia and iron deficiency anaemia (IDA). 

Prophylactic therapy of iron deficiency. 

Prophylactic therapy of iron deficiency during pregnancy. 

Posology

 

Treatment of iron deficiency anaemia in children over 12 years and adults:

100 mg to 300 mg iron (1 to 3 tablets) daily for 3 to 5 months until a normalisation of the haemoglobin (Hb) value is achieved. Afterwards, the therapy should be continued for several weeks with a dosage such as described for iron deficiency without anaemia to replenish the iron stores.

 

Treatment of iron deficiency anaemia in pregnancy:

200 mg to 300 mg iron (2 to 3 tablets) daily until a normalisation of the Hb value is achieved. Afterwards, the therapy should be continued at least until the end of the pregnancy with a dosage such as described for iron deficiency without anaemia to replenish iron stores and to supplement the increased iron need during pregnancy.

 

Treatment and prevention of iron deficiency without anaemia in children over 12 years and adults:

100 mg (1 tablet) daily for 1 to 2 months. If a smaller dose is required for prevention, Ferose^® syrup can be used.

 

Paediatric population

Ferose^® chewable tablets are not recommended for children 12 years and younger. Ferose^® syrup and drops have a more suitable form and concentration for administration of the recommended dosages of this age group.

 

Method of administration

The daily dose can be divided into separate doses or can be taken at once. Ferose^® should be taken during or immediately after a meal.

Ferose^® chewable tablets can be chewed or swallowed whole.

The dosage and duration of treatment depend on the degree of the iron deficit.

In the case of iron deficiency with anaemia, treatment until the haemoglobin value has normalised lasts an average of 3–5 months.

Treatment is then continued with treatment at the respective dose for iron deficiency without anaemia to fill up the iron stores. Treatment of iron deficiency without anaemia lasts around 1–2 months. 

 

Known hypersensitivity to iron (III)-hydroxide polymaltose complex (IPC) or to any of the excipients listed in section 6.1. Iron overload, such as haemochromatosis, haemosiderosis. Disturbances in iron utilisation, such as anaemia from lead poisoning, sidero-achrestic anaemia,thalassaemia. Anaemia not caused by iron deficiency, such as haemolytic anaemia or megaloblastic anaemia due to vitamin B12 deficiency.

Infections or tumour may cause anaemia. Since iron can be utilised only after correcting the primary disease, a benefit/risk evaluation is advisable.

If therapeutic success (increase in haemoglobin by about 2-3 g/dL after 3 weeks) is not achieved, treatment should be reconsidered. 

Caution is recommended in patients who receive repeated blood transfusions, as there is a supply of iron with erythrocytes, which can lead to iron overload. 

During the treatment with Ferose^® there may be dark discolouration of the faeces, but this is of no clinical relevance.

The intake of Ferose^® is not expected to have an impact on the daily insulin management of diabetes patients. [Please enter the respective information according to the local label]

Ferose^® contains aspartame (E951) - a source of phenylalanine. May be harmful for people with phenylketonuria. (Not included in all formulations; consult local labelling).

Interactions IPC (with and without folic acid) with tetracycline or aluminium hydroxide were investigated in 3 human studies (crossover design, 22 patients per study). No significant reduction in the absorption of tetracycline was observed. The plasma tetracycline concentration did not fall below the level necessary for efficacy. Iron absorption from IPC was not reduced by aluminium hydroxide or tetracycline. Iron (III) hydroxide polymaltose complex can therefore be administered at the same time as tetracycline or other phenolic compounds, as well as aluminium hydroxide.

 

Studies in rats with tetracycline, aluminium hydroxide, acetylsalicylate, sulphasalazine, calcium carbonate, calcium acetate and calcium phosphate in combination with vitamin D3, bromazepam, magnesium aspartate, D-penicillamine, methyldopa, paracetamol and auranofin have not shown any interactions with IPC.

 

Similarly, no interactions with food constituents such as phytic acid, oxalic acid, tannin, sodium alginate, choline and choline salts, vitamin A, vitamin D3 and vitamin E, soya oil and soya flour were observed in in vitro studies with IPC. These results suggest that IPC can be taken during or immediately after food intake.

 

The haemoccult test (selective for Hb) for the detection of occult blood is not impaired, and therefore there is no need to interrupt the therapy.

 

Concomitant administration of parenteral and oral iron is not recommended since the absorption of oral iron would be inhibited.

Pregnancy

No data from clinical studies are available on the use of Ferose^® in pregnant women during the first trimester. To date, there have been no reports of serious adverse reactions after ingestion of Ferose^® in therapeutic doses for the treatment of anaemia in pregnancy. Animal data showed no evidence of risk to foetus and mother (see Section 5.3).

 

Studies in pregnant women after the first trimester have not shown any undesirable effect of Ferose^® on mothers and/or neonates. Therefore, a negative influence on the foetus is unlikely with the administration of Ferose^®.

 

Lactation

Human breast milk naturally contains iron, which is bound to lactoferrin. The amount of iron passing from IPC to the mother’s milk is unknown. It is unlikely that the administration of Ferose^® in women who are breast-feeding causes undesirable effects to the infant.

 

As a precautionary measure, women of childbearing age, and women during pregnancy and lactation should only use Ferose® after consulting a medical doctor. A benefit/risk evaluation is advisable.

No data available. However, it is unlikely that Ferose has any effect on the ability to drive and use machines. 

The safety and tolerability of Ferose were assessed in a meta-analysis of 24 publications or clinical trial reports with a total number of 1473 exposed patients. The most significant adverse drug reactions reported by these trials occurred in 4 system organ classes (see below). 

Stool discolouration is a well known adverse drug reaction of oral iron preparations but it is not considered clinically relevant and is often not reported. Other commonly observed undesirable effects were gastrointestinal disorders (nausea, constipation, diarrhoea and abdominal pain). 

 

Table 1. Adverse Drug Reactions Detected in Clinical Trials

System Organ Class	Very common (≥1/10)	Common (≥1/100, <1/10)	Uncommon (≥1/1,000, <1/100)	Rare (<1/1‚000)
Gastrointestinal Disorders	Discoloured faeces*	Diarrhoea,  nausea,  abdominal pain (including: dyspepsia, epigastric discomfort, abdominal distension), constipation	Vomiting (including: vomiting, regurgitation), teeth discolouration, gastritis.
Skin and Subcutaneous Tissue Disorders			Pruritus, rash (including: rash, macular rash, bullous rash)**, urticaria**, erythema**.
Nervous System Disorders			Headache
Musculoskeletal and   connective tissue disorders				Muscle spasms (including: involuntary muscle contraction, tremor), myalgia.

* Stool discolourations were reported in the meta-analysis at a lower frequency but they are generally a well known adverse drug effect of an oral iron therapy. For this reason, stool discolouration was classified under very common undesirable effects. 

** Events came from spontaneous reports after market introduction, with an estimated incidence of <1/491 patients (upper limit of 95% confidence interval). 

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:  

To report any side effect(s): For Saudi Arabia :  The National Pharmacovigilance and Drug Safety Centre (NPC) o SFDA call center : 19999 o E-mail: npc.drug@sfda.gov.sa o Website: https://ade.sfda.gov.sa  For UAE :  Pharmacovigilance & Medical Device section  P.O. Box : 1853  Tel : 80011111 Email: pv@mohap.gov.ae  Drug Department          Ministry of Health & Prevention , Dubai , UAE  For Oman  Department of Pharmacovigilance & Drug Infromation  Direcotorate General of Pharmaceutical Affairs & Drug Control  Ministry of Health , Sultanate of Oman  Phone Nos : 22357687/ 22357686 Fax : 22358489 Email : dg-padc@moh.gov.om Website : www.moh.gov.om

 

 

 

 

 

 

 

 

 

 

 

 

In case of overdose, iron overload or intoxications are unlikely with Ferose® due to the low toxicity of IPC (i.e., in mice or rats: lethal dose, 50% (LD50) >2,000 mg Fe/kg body weight) and controlled uptake of iron. No cases of accidental poisoning with fatal outcome have been reported 

 

Mechanism of action 

In IPC, the polynuclear iron(III)-hydroxide core is superficially surrounded by a number of non-covalently bound polymaltose molecules resulting in an overall average molecular weight of approximately 50 kDa. The polynuclear core of IPC has a structure similar to that of the physiological iron storage protein ferritin. Iron(III)-hydroxide polymaltose is a stable complex and does not release large amounts of iron under physiological conditions. Because of its size, the extent of diffusion of the iron(III)-hydroxide polymaltose complex through the membrane of the mucosa is about 40 times less than that of the hexaquo-iron(II) complex. Iron from IPC is taken up in the gut via an active mechanism. 

Pharmacodynamic effects 

The absorbed iron is bound to transferrin and is used for haemoglobin synthesis in the bone marrow or is stored, mainly in the liver, where it is bound to ferritin. 

For pharmacodynamic drug interaction properties, see Section 4.5.  

 

Clinical Efficacy 

The efficacy of Ferose compared to a placebo or similar preparations with different iron formulations in terms of normalising haemoglobin values and replenishing iron stores has been demonstrated in numerous clinical studies in infants, children, adolescents and adults. Both solid and liquid galenic forms of IPC were used in these studies. The primary goal of an oral iron replacement is to maintain the body’s own iron stores within normal limit values (to prevent an iron deficiency, e.g. in case of increased requirements), replenish iron stores or correct existing iron deficiency anaemia. 

 

Clinical studies in adults 

A total of 11 controlled clinical studies have been carried out with IPC mono-preparations in comparison with a placebo and/or oral iron(II) preparations. 

A total of more than 900 patients were involved, and approximately 500 of these patients received IPC mono-preparations. The patient population studied demonstrated no relevant differences in haematological and iron parameters (haemoglobin (Hb), mean red blood cell haemoglobin (MCV), serum ferritin) at the start of treatment. The oral iron replacement with IPC at a dose of 100–200 mg iron/day for several weeks up to a maximum of 6 months demonstrated a clinically relevant increase in iron and haematological parameters at the end of treatment compared to those at the start of treatment. The improvement in haematological parameters (Hb, MCV, serum ferritin) after a 12week treatment with IPC was comparable to treatment with iron(II) sulphate. 

The efficacy of IPC compared to iron(II) sulphate was investigated on the basis of a meta-analysis of 6 prospective, randomised clinical studies in adult patients with iron deficiency anaemia. The total number of patients included in the study was 557; 319 patients received IPC and 238 patients iron(II) sulphate. The pooled mean haemoglobin values at the start of treatment were 10.35 ±0.92 g/dL (IPC) and 10.20 ±0.93 g/dL (iron(II) sulphate). After an average treatment period of 8 to 13 weeks with equivalent posology, mean haemoglobin values were determined 12.13 ±1.19 g/dL (IPC) and 11.94 ±1.84 g/dL (iron(II) sulphate), p=0.93increases in haemoglobin were greater after a longer treatment duration for both iron formulations. 

 

Clinical studies in children and adolescents 

The use of Ferose in children and adolescents (18 years old or younger) was investigated in a number of clinical studies involving over 1000 patients. The efficacy of Ferose in terms of improving iron values compared to the placebo or comparable preparations with different iron formulations was thereby confirmed. 

 

 

Absorption 

Studies with radio-labelled IPC show a good correlation between iron absorption and build-up of iron in haemoglobin. The relative absorption of iron correlates with the degree of iron deficiency (i.e. the greater the iron deficiency, the higher the iron absorption). In contrast to iron(II) salts, it was determined that food had no negative effect on the bioavailability of iron from Ferose: significantly increased bioavailability of iron with concomitant ingestion of food was demonstrated in a clinical study, while three other studies showed a positive trend but no clinically significant effects. 

Elimination 

Iron that is not absorbed is excreted via the faeces. 

 

Pharmacokinetics in special populations 

No data available. 

Nonclinical data established with IPC reveal no special hazard for humans based on conventional studies of single-dose and repeated dose toxicity, genotoxicity, or reproductive and developmental toxicity. 

Other information 

The LD50 for IPC, as determined in animal studies with mice or rats was greater than an orally administered dose of 2,000 mg of iron per kilogram body weight. The available preclinical data on toxicity after a single dose and repeated administration have yielded no further information that has not already been mentioned in other sections. 

Aspartame NF. 

Chocolate Essence Powder. 

Polyethylene glycol MW 6000. 

Purified Talc. 

Ethanol 96 percent. 

Emdex. 

Not applicable.

36Months/3Years.

Store below 30°C and keep in the original package (i.e., outer carton) in order to protect from light.

30/pack. 

100/pack. 

White Opaque PVC/PE/PVDC blister strips with aluminum foil lid.  

 

No special requirements.