SUMMARY OF PRODUCT CHARACTERISTICS

NAME OF THE MEDICINAL PRODUCT

Slow Fe Folic Tablets.

QUALITATIVE AND QUANTITATIVE COMPOSITION

One Slow Fe Folic tablet contains 160.0 mg ferrous sulphate dried, USP (equivalent to 50 mg of elemental iron) and 0.4 mg folic acid EP.

Excipient with known effect: Lactose For the full list of excipients, see section 6.1.

PHARMACEUTICAL FORM

Slow release tablet.

Yellowish white, circular biconvex, film-coated tablet imprinted CIBA on one side and TP on the other side.

CLINICAL PARTICULARS Therapeutic indications

Slow-Fe Folic is indicated throughout pregnancy for prophylaxis of iron and folic acid deficiency. Slow-Fe Folic is designed to minimise the problems of gastrointestinal disturbance associated with most oral iron preparations, and contains 0.4mg of folic acid, a daily supplement which prevents the occurrence of megaloblastic anaemia due to folate deficiency.

4.2 Posology and method of administration

Posology:

Adults

The product is intended for oral administration, one tablet to be taken daily throughout pregnancy. In the case of multiple pregnancies the dosage should be increased to two tablets daily. The tablets should be swallowed whole and for preference taken after food.

Paediatric population

Not indicated.

Use in the Elderly

Not indicated.

Method of administration:

Slow Fe Folic is taken orally in tablet form.

The tablets should be swallowed whole and for preference taken after food.

For optimal iron absorption, avoid taking the tablets with beverages such as tea or coffee (see section 4.5).

4.3 Contraindications

Iron therapy is contraindicated in patients:

•    with hypersensitivity to ferrous sulphate, folic acid, or to any of the excipients listed in Section 6.1

•    with haemochromatosis, haemosiderosis and haemolytic anaemia.

•    receiving repeated blood transfusions

•    with anaemias not resulting from iron deficiency unless iron deficiency is also present

Oral and parenteral iron therapy should not be used together.

Special warnings and precautions for use

In epileptic patients who have become folate deficient (for instance during phenytoin treatment) folic acid supplementation can result in decreased anticonvulsant serum concentrations, which (unless the anticonvulsant dosage is adjusted), can lead to loss of seizure control.

Folic acid should never be given alone for pernicious anaemia and other vitamin B12 deficiency states as this may precipitate subacute combined degeneration of the spinal cord). Vitamin B12 should be administered concurrently.

As with all iron preparations, Slow Fe Folic should be used with care in patients with known or suspected gastrointestinal diseases, such as inflammatory bowel disease, gastrointestinal strictures or diverticulae.

Slow Fe Folic contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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

4.5 Interaction with other medicinal products and other forms of interaction Related to ferrous sulphate

Concurrent administration of antacids may reduce absorption of iron preparations. Iron chelates with tetracyclines and absorption of both agents may be impaired. Iron may reduce the absorption or penicillamine and zinc salts.

Iron compounds interact with fluoroquinolone antibiotics, causing their serum antibacterial levels become subtherapeutic. The extent of this interaction in descending order is as follows: norfloxacin, levofloxacin, ciprofloxacin, moxifloxacin, gatifloxacin, ofloxacin/sparfloxacin and lomefloxacin.

Bone marrow depression provoked by chloramphenicol can oppose the treatment of anemias with iron compounds.

Ferrous sulphate markedly reduces the absorption of cefdinir, producing a poorly absorbed complex.

Iron compounds may reduce the antihypertensive effects of methyldopa, and may reduce the bioavailability of levodopa and carbidopa, possibly reducing the control of Parkinson disease.

The oral absorption of bisphosphonates is reduced by iron preparations.

Ferrous sulphate causes a reduction in the effects of levothyroxine in patients treated for hypothyroidism.

Reduced iron absorption has been reported with beverages high in polyphenolics such as coffee and tea.

Related to folic acid

If folate supplements are given to treat folate deficiency, which can be caused by the use of antiepileptics (phenytoin, phenobarbital, primidone and possibly carbamazepine and pheneturide), the serum antiepileptic levels may fall, leading to decreased seizure control in some patients.

Patients given fluorouracil or capecitabine (a prodrug of fluorouracil) should not be given folic acid, in order to prevent fluorouracil toxicity.

Folic acid interferes with both the toxic and therapeutic effects of methotrexate.

Sulfasalazine reduces the absorption of folic acid, interferes with folate metabolism, and rarely is associated with blood dyscrasias due to folate deficiency.

4.6 Fertility, pregnancy and lactation

Pregnancy

Slow Fe Folic is indicated throughout pregnancy for prophylaxis of iron and folic acid deficiency.

Breast-feeding

Supplemental iron and folic acid are either not excreted in breast milk or are not absorbed by the infant. The product gives very low levels in the infant with no apparent effect.

Slow Fe Folic can therefore be used at therapeutic doses for prophylaxis of iron and folic acid deficiency during lactation.

4.7 Effects on ability to drive and use machines

Slow Fe Folic has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Adverse reactions are listed below by system organ class and frequency.

Frequencies are defined as: very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1,000 to < 1/100); rare (> 1/10,000 to < 1/1,000); very rare (< 1/10,000), or not known (can not to be estimated from available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Gastrointestinal disorders

Common:    Nausea, constipation, abdominal discomfort/pain, diarrhoea.

Uncommon:    Faeces discoloured, vomiting

Immune system disorders

Rare: Hypersensitivity reactions (such as rash, erythema, pruritus, urticaria and swelling face).

4.9 Overdose

Symptoms

Symptoms include abdominal pain, nausea and vomiting, diarrhoea and haematemesis.

Treatment

Gastric lavage or emesis should be carried out immediately. To chelate excess free iron in the gastro-intestinal tract, 5g desferrioxamine dissolved in 50ml water should be introduced into the stomach. To chelate excess free iron in the blood, desferrioxamine may be given parenterally; depending on the patient’s condition, 1g desferrioxamine given every 3 hours intramuscularly may be appropriate.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: iron preparations/ Iron in combination with folic acid; ATC code: B03AD03.

Slow-Fe Folic incorporates iron (as ferrous sulphate) and folic acid in a slow release preparation. Both are essential constituents of the body. Iron is necessary for haemoglobin formation and for the oxidative processes of the tissues. Folic acid undergoes reduction in the body to tetrahydrofolate which is a co-enzyme for various metabolic processes including DNA synthesis. Deficiency of iron causes microcytic hypochronuc anaemia; deficiency of folic acid leads to megaloblastic anaemia. Epidemiological work has shown that folic acid deficiency in pregnancy is associated with an increased risk of neural tube defect. A supplement of folic acid given from the time of conception to the 12^th week of pregnancy may reduce this risk. In the absence of supplementation of dietary iron and folic acid during pregnancy anaemia is likely to occur. Slow Fe Folic can be used for prophylaxis of anaemia of pregnancy.

5.2 Pharmacokinetic properties

Absorption

Both iron and folic acid are obtained in the diet. Iron is irregularly and incompletely absorbed from the gastrointestinal tract, the main sites of absorption being the duodenum and jejunum; only about 5% - 10% of the iron ingested with food is absorbed. Iron absorption is increased in conditions of deficiency and decreased when body stores are overloaded.

Absorption is aided by the acid secretion of the stomach and by some dietary acids (such as ascorbic acid) and occurs more readily when the iron is in the ferrous state or is part of the haem complex (haem-iron). There is no significant difference between the absorption of iron from ferrous sulphate tablets and from Slow Fe in healthy persons, in anaemia, following gastrectomy, or in coeliac disease.

In healthy men and non-menstruating women absorption of 1 mg/day is required. In menstruating women, this rises to 2mg/day and in pregnancy/lactation 3 mg/day is required.

Folic acid is rapidly absorbed mainly from duodenum and jejunum.

Distribution and Biotransformation

Most absorbed iron is bound to transferrin and transported to the bone marrow, where it is incorporated into hemoglobin; the remainder is contained within the storage forms, ferritin or hemosiderin, or as myoglobin, with smaller amounts occurring in haem-containing enzymes or in plasma bound to transferrin.

Dietary folates are stated to have about half the bioavailability of crystalline folic acid. The naturally occurring folate polyglutamates are largely deconjugated, and then reduced by dihydrofolate reductase in the intestines to form 5-methyltetrahydrofolate, which appears in the portal circulation, where it is extensively bound to plasma proteins. Folate undergoes enterohepatic circulation. Folic acid given therapeutically enters the portal circulation largely unchanged, since it is a poor substrate for reduction by dihydrofolate reductase. It is converted to the metabolically active form 5-methyltetrahydrofolate in the plasma and liver. The principal storage site of folate is the liver; it is also actively concentrated in the cerebrospinal fluid.

Elimination

Only very small amounts of iron are excreted, as the majority released after the destruction of the hemoglobin molecule is re-used. This conservation of body iron and lack of an excretory mechanism for excess iron is the reason for the development of iron overload with excessive iron therapy or repeated transfusions. Apart from hemorrhage, iron is lost from the body in: urine, hair, nails, skin and sweat. In therapy, hemoglobin levels return to normal after about 10 weeks. 3 to 6 months are required to replenish body stores.

Folate metabolites are eliminated in the urine and folate in excess of body requirements is excreted unchanged in the urine. Folic acid is removed by hemodialysis.

A combination of iron and folic acid acts more effectively against the anaemia of pregnancy than either substance alone.

5.3    Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development.

6.    PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose ep

Hydroxy propyl methyl cellulose 50 cps usp

Cetostearyl alcohol ep

Magnesium stearate bp

Hydroxy propyl methyl cellulose 3 cps usp

Purified talc special bp

Polysorbate 80 usp

Titanium dioxide e171 bp

Yellow iron oxide 17268 e172 hse.

6.2 Incompatibilities None known.

6.3 Shelf life 60 months.

6.4 Special precautions for storage Protect from moisture.

6.5 Nature and contents of container

PVC 250 micron, aluminium foil 20 micron blister pack in a cardboard carton, containing either 28 or 150 tablets.

6.6 Instruction for use and handling

None.

MARKETING AUTHORISATION HOLDER

Novartis Consumer Health UK Ltd

T/A Novartis Consumer Health

Wimblehurst Road

Horsham

West Sussex

RH12 5AB

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 00030/0182

9 Date of the first authorisation or renewal

02/09/2005

10 DATE OF REVISION OF THE TEXT

17/10/2012