Sodium Feredetate 190mg/5ml Oral Solution – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Sodium Feredetate 190mg/5ml Oral Solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5ml dose contains Sodium Feredetate 190mg (equivalent to 27.5mg of elemental iron/5ml)

Excipients with known effect:

Ponceau 4R lake (E124) 0.08 mg/5ml

Methyl parahydroxybenzoate (E218) 5mg/5ml

Propyl parahydroxybenzoate (E216), 1mg/5ml

Sorbitol liquid (E420) 1500mg/5ml

Ethanol 11mg/5ml

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Oral Solution.

Red coloured liquid.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Sodium Feredetate is indicated for Iron deficiency anaemia,

• Notably in paediatrics.
• In pregnancy when other forms of oral iron may not be well tolerated.
• Anaemias secondary to rheumatoid arthritis.

4.2 Posology and method of administration

Posology:

Paediatric population:

Treatment of iron-deficiency anaemia in all paediatric age groups is 3-6 mg/kg (max 200 mg) of elemental iron daily given in 2-3 divided doses.

Adults: 5ml increasing gradually to 10ml three times daily.

Elderly (over 65 years): As for adults.

Prophylaxis:

Babies of low birth weight who are solely breast-fed:

A daily dose of 5 mg of elemental iron as prophylactic iron supplementation for babies of low birth weight who are solely breast-fed is recommended. Higher doses up to 2 mg/kg of elemental iron per day might be needed to cover the needs of growing exclusively breastfed infants. Supplementation is started 4-6 weeks after birth and continued until mixed feeding is established.

Other children (elemental iron per day):

Age 6 - 24 months: 12.5 mg

Age 2 - 5 years: 20-30 mg

Age 6 - 11 years: 30 – 60 mg

Adolescents: 60 mg

Method of administration

Oral

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

Iron preparations are contraindicated in patients with haemochromatosis and haemosiderosis.

Iron is contraindicated in patients receiving repeated blood transfusions or in patients receiving parenteral iron therapy.

4.4 Special warnings and precautions for use

Care should be taken in patients with haemolytic anaemia, iron-storage or iron-absorption diseases or existing gastrointestinal diseases.

Iron preparations colour the faeces black, which may interfere with tests used for detection of occult blood in the stools.

Prolonged or excessive use in children may lead to toxic accumulation.

Important warnings on Excipients:

• Ponceau 4R (E124): which may cause allergic reactions.
• Sorbitol: This medicine contains 1050 mg per 5 ml of solution which is equivalent to 210 mg per ml of solution. Patients with hereditary fructose intolerance (HFI) should not take/ be given this medicinal product. Sorbitol may also cause gastrointestinal discomfort and mild laxative effects.

• Methyl parahydroxybenzoate (E218)) and Propyl parahydroxybenzoate

  (E216) which may cause allergic reactions (possibly delayed).

• Ponceau 4R (E124) which may cause allergic reactions.

• Ethanol (alcohol): This medicine contains 11 mg of alcohol (ethanol) in each

  5 ml of solution which is equivalent to 2.2 mg per ml. The amount in 5ml of this medicine is equivalent to less than 1 ml beer or 1 ml wine. The small amount of alcohol in this medicine will not have any noticeable effects.

• Sodium: This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’

The label will state:

“Important warning: Contains iron. Keep out of the sight and reach of children, as overdose may be fatal.”

This will appear on the front of the pack within a rectangle in which there is no other information.

4.5 Interaction with other medicinal products and other forms of interaction

Avoid concomitant administration of oral iron with dimercaprol (formation of toxic compounds).

Iron reduces the absorption of penicillamine, mycophenolate, fluoroquinolones, levodopa, carbidopa, thyroxine and bisphosphonates.

Administration of oral iron may reduce the hypotensive effect of methyldopa.

Iron and tetracyclines reduce the absorption of each other.

Iron and zinc reduce the absorption of each other.

Oral chloramphenicol delays plasma iron clearance, incorporation of iron into red blood cells and interferes with erythropoiesis.

Absorption of iron is reduced with entacapone, proton pump inhibitors, bicarbonates, carbonates, calcium, zinc, magnesium and other mineral supplements, trientine, antacids, cholestyramine, tea, eggs and/or milk, but may be increased by ascorbic acid and/or citric acid.

Coffee may be a factor in reducing iron bioavailability.

4.6 Fertility, pregnancy and lactation

Administration of drugs during the first trimester of pregnancy requires careful assessment of potential risks versus benefits to be gained. No adverse events associated with sodium feredetate administration during pregnancy and lactation have been reported.

4.7 Effects on ability to drive and use machines

None known.

4.8 Undesirable effects

Adverse reactions reported as possibly associated to sodium feredetate are presented in the following table by MedDRA System Organ Class (SOC), Preferred Term and frequency. The following frequency categories are used:

Very common (≥1/10)

Common (≥1/100, <1/10)

Uncommon (≥1/1,000, <1/100)

Rare (≥1/10,000, <1/1,000)

Very rare (<1/10,000)

Post-marketing adverse reactions are reported voluntarily from a population with an unknown rate of exposure. Therefore, it is not possible to estimate the true incidence of adverse reactions and the frequency is “Not known”.

Tabulated summary of adverse reactions

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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Symptoms:

Initial symptoms of iron overdosage include nausea, vomiting, diarrhoea, abdominal pain, haematemesis, rectal bleeding, lethargy and circulatory collapse. Hyperglycaemia and metabolic acidosis may occur.

Management:

1. 1. Administer an emetic.
2. 2.

   Emesis should be followed by gastric lavage with desferrioxamine solution (2g/l).

   Desferrioxamine 5g in 50ml to 100ml water should be introduced into the stomach following gastric emptying.

3. 3. Keep the patient under constant surveillance to detect possible aspiration of vomitus. Maintain suction apparatus and standby emergency oxygen in case of need.
4. 4. In adults, a drink of mannitol or sorbitol should be given to induce small bowel emptying. Inducing diarrhoea in children may be dangerous and should not be undertaken in young children.
5. 5. Severe poisoning: in the presence of shock and/or coma with high serum iron levels (adults >142μmol/l, children >90μmol/l), immediate supportive measures should be introduced. Desferrioxamine should be given by slow iv infusion (adults 5mg/kg/h, children 15mg/kg/h). The maximum dose is 80mg/kg/24h. Warning: hypotension may occur if the infusion rate is too rapid.
6. 6.

   Less severe poisoning: im desferrioxamine should be administered (adults

   50mg/kg to a maximum of 4g, children 1g 4 to 6 hourly).

Serum iron levels should be monitored throughout.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Iron preparations, ATC code: B03A

After absorption, elemental iron is available for haemoglobin regeneration and reversal of anaemia associated with iron-deficient states.

5.2 Pharmacokinetic properties

Sodium Feredetate is not an iron salt as it contains iron in an un-ionised form. In this compound the iron is “insulated” or “sequestered” with the sodium salt of ethylenediamine tetra-acetic acid (EDTA) to form a chelate. This accounts for the fact that Sodium Feredetate is not astringent and does not discolour teeth.

Absorption

Studies using radioactive tracers have shown that the iron chelate is split within the gastro-intestinal tract, releasing elemental iron which is absorbed and rendered available for haemoglobin regeneration.

Iron absorption is enhanced in iron-deficiency states.

Distribution

Post-absorption distribution of elemental iron is as follows: 60% to 70% is incorporated into haemoglobin and most of the remainder is present in storage forms, either as ferritin or haemosiderin, in the reticulo-endothelial system and to a lesser extent, hepatocytes. A further 4% is present in myoglobin and haeme-containing enzymes, or bound to transferrin in plasma.

Elimination

Excretion is mainly in the faeces.

EDTA passes through the body unchanged. The compound is poorly absorbed, and that which reaches the bloodstream is eliminated by both glomerular filtration and tubular excretion.

5.3 Preclinical safety data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Methyl parahydroxybenzoate (E218)

Propyl parahydroxybenzoate (E216)

Saccharin Sodium

Glycerol

Sorbitol liquid (E420)

Ethanol

Black cherry flavour

Ponceau 4R (E124)

Citric acid monohydrate

Water

6.2 Incompatibilities

None known

6.3 Shelf life

Unopened: 3 years.

Opened: 3 months from date of opening

6.4 Special precautions for storage

Store in the original package in order to protect from light.

6.5 Nature and contents of container

Amber glass bottle with a white child resistant tamper evident plastic cap. Each bottle contains 500ml of Sodium Feredetate oral solution.

6.6 Special precautions for disposal

No special requirements for disposal Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Mercury Pharmaceuticals Ltd,

Dashwood House,

69 Old Broad Street,

London, EC2M 1QS,

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 12762/0537

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

14/01/2025

10 DATE OF REVISION OF THE TEXT

14/01/2025