This information is intended for use by health professionals

1. Name of the medicinal product

Sytron 27.5 mg iron per 5 ml Oral Solution

2. Qualitative and quantitative composition

Each 5 ml of oral solution contains 207.5 mg of sodium feredetate trihydrate equivalent to 27.5 mg of iron.

Excipients with known effect:

Each 5 ml of Sytron solution contains: 5 mg of Methyl hydroxybenzoate (E218), 1 mg of Propyl Hydroxybenzoate (E216), 11.4 mg of sodium, 1400 mg of sorbitol, 0.015 ml of ethanol and 0.35 mg of Ponceau 4R (E124) - please refer to section 4.4 for further details.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Oral solution

Clear, red syrup, free of particles

4. Clinical particulars
4.1 Therapeutic indications

Sytron is indicated in adults, children and infants for iron deficiency anaemia:

• Notably in paediatrics;

• In pregnancy when other forms of oral iron may not be well tolerated;

• In anaemias secondary to rheumatoid arthritis.

4.2 Posology and method of administration

Posology

Treatment:

Adults and the elderly

(over 65 years):

5 ml increasing gradually to 10 ml three times daily.

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.

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

For instructions on dilution of the medicinal product before administration, see section 6.6.

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.

Contains Methyl hydroxybenzoate (E218), Ponceau 4R (E124) and Propyl hydroxybenzoate (E216) which may cause allergic reactions (possibly delayed).

This medicinal product contains small amounts of ethanol (alcohol), less than 100 mg in the maximum dose of 10 ml.

This medicine contains approximately 23 mg sodium in the maximum dose of 10 ml, equivalent to 1.2% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

At doses lower than the maximum, this medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.

This medicine contains 1400 mg sorbitol in each dosage unit (5 ml) which is equivalent to 280 mg/ml. Patients with hereditary fructose intolerance (HFI) should not take/be given this medicinal product. Sorbitol may cause gastrointestinal discomfort and mild laxative effect when taken orally at levels equal to, or over, 140 mg/kg/day. The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietery intake of sorbitol (or fructose) should be taken into account. The content of sorbitol in medicinal products for oral use may affect the bioavailability of other medicinal products for oral use administered concomitantly.

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 Sytron 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 Sytron 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 “unknown”.

Tabulated summary of adverse reactions

SYSTEM ORGAN CLASS (SOC)

FREQUENCY

ADVERSE REACTION

Immune system disorders

Unknown

Hypersensitivity

Gastrointestinal disorders

Unknown

Nausea, mild diarrhoea

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

4.9 Overdose

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

Treatment of overdosage

1. Administer an emetic.

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. Keep the patient under constant surveillance to detect possible aspiration of vomitus. Maintain suction apparatus and standby emergency oxygen in case of need.

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. 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. Less severe poisoning: im desferrioxamine should be administered (adults 50mg/kg to a maximum of 4g, children 1g 4 to 6 hourly).

7. 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 Sytron is not astringent and does not discolour teeth. 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. 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. 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 preclinical 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 hydroxybenzoate (E218)

Propyl hydroxybenzoate (E216)

Citric acid monohydrate

Saccharin sodium

Glycerol

Sorbitol solution

Ethanol 96%

Black cherry flavour

Ponceau 4R (E124)

Potable water

6.2 Incompatibilities

None known

6.3 Shelf life

Unopened: 36 months

Opened: 3 months from date of opening

If this product has been diluted with water use within 14 days of preparation.

6.4 Special precautions for storage

Store below 30°C

6.5 Nature and contents of container

Sytron is supplied in round amber glass bottles with a CRC cap. Each bottle contains either 125ml or 500ml or 2250ml of Sytron.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Water is the recommended diluent for this product.

7. Marketing authorisation holder

Kyowa Kirin Limited

Galabank Business Park

Galashiels

TD1 1QH

United Kingdom

8. Marketing authorisation number(s)

PL 16508/0059

9. Date of first authorisation/renewal of the authorisation

13 October 1993/18 February 2004

10. Date of revision of the text

November 2019