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Pregaday Tablets

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Pregaday 322mg/0.35mg film-coated Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains;

Ferrous Fumarate EP 322.00mg and Folic Acid EP 0.35mg For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Film-coated tablet

Brownish-pink dragee-shaped tablets, engraved on one side with the name PREGADAY.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Pregaday Tablets are indicated during the second and third trimester of pregnancy for prophylaxis against iron deficiency and megaloblastic anaemia of pregnancy. Pregaday Tablets are not intended as a treatment for established megaloblastic anaemia.

There is evidence that a daily intake of 100mg of elemental iron in the ferrous form is adequate to prevent development of iron deficiency in expectant mothers. If a mild iron deficiency is present when Pregaday Tablets administration is started, this will be corrected by increased absorption of iron.

The daily folate requirement rises steeply during the final trimester of pregnancy, and evidence of maternal depletion may be found. To ensure normal tissue folate levels in the mother after delivery a daily supplement of about 300 micrograms is required during the second and third trimester of pregnancy. This does not obscure the blood picture of addisonian pernicious anaemia.

4.2 Posology and method of administration

Adults

It is usual to begin therapy with Pregaday Tablets about the thirteenth week of pregnancy (see precautions) either as routine prophylaxis or selectively if the haemoglobin concentration is less than 11g/100ml (less than 75% normal).

One tablet should be taken daily by mouth.

Paediatric Population

There is no relevant use of Pregaday Tablets in the paediatric population.

4.3 Contraindications

Hypersensitivity to the active substances or any of the excipients listed is section 6.1.

Known hypersensitivity to the product, Vitamin B12 deficiency, paroxysmal nocturnal haemoglobinuria, haemosiderosis, haemochromatosis, active peptic ulcer, repeated blood transfusion, regional enteritis and ulcerative colitis.

Pregaday Tablets must not be used in the treatment of anaemias other than those due to iron deficiency.

4.4 Special warnings and precautions for use

The label will state

“Important warning: Contains Iron. Keep out of reach and sight 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.

Some post-gastrectomy patients show poor absorption of iron. Care is needed when treating iron deficiency anaemia in patients with treated or controlled peptic ulceration. Caution should be exercised when administering folic acid to patients who may have folate dependent tumours.

Since anaemia due to combined iron and vitamin B12 or folate deficiencies may be microcytic in type, patients with microcytic anaemia resistant to therapy with iron alone should be screened for vitamin B12 or folate deficiency.

Paediatric population

Pregaday Tablets should be kept out of the reach of children.

4.5 Interaction with other medicinal products and other forms of interaction

Iron reduces the absorption of penicillamine. Iron compounds impair the bioavailability of fluoroquinolones, levodopa, carbidopa, thyroxine and bisphosphonates.

Absorption of both iron and antibiotic may be reduced if Pregaday is given with tetracycline.

Absorption of both iron and zinc are reduced if taken concomitantly. Concurrent administration of antacids may reduce absorption of iron. Co-trimoxazole, chloramphenicol, sulphasalazine, aminopterin, methotrexate, pyrimethamine or sulphonamides may interfere with folate metabolism. Serum levels of anticonvulsant drugs may be reduced by administration of folate.

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

Some inhibition of iron absorption may occur if it is taken with cholestyramine, trientine, tea, eggs or milk.

Administration of oral iron may increase blood pressure in patients receiving methyldopa.

Coffee may be a factor in reducing iron bioavailability. Neomycin may alter the absorption of iron.

4.6 Fertility, pregnancy and lactation

Pregnancy

The use of Pregaday Tablets may be considered during first trimester of pregnancy, if necessary.

There are no or limited amount of data from the use of Folic Acid in pregnant women therefore a minority of them are not protected by physiological doses. The development of anaemia despite prophylaxis with Pregaday Tablets calls for investigation.

Breast-feeding

It is unknown whether Ferrous Fumarate and Folic Acid / metabolites are excreted in human milk.

A risk to the newborns/infants cannot be excluded.

Fertility

No fertility data is available

4.7 Effects on ability to drive and use machines

Pregaday Tablets has no influence on the ability to drive and use machines.

4.8 Undesirable effects

Very rare (<1/10,000)

Very rare (<1/10,000):

Rarely allergic reactions may occur.

Not known (cannot be estimated from the available data)

Not known: Gastrointestinal disorders

Gastro-intestinal discomfort, anorexia, nausea, vomiting, constipation, diarrhoea.

Not known: Renal and urinary disorders Darkening of the stools may occur.

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 on the MHRA website (www.mhra.gov.uk/yellowcard).

4.9 Overdose

Symptoms

Symptoms and signs of abdominal pain, vomiting and diarrhoea appear within 60 minutes. Cardiovascular collapse with coma may follow. Some improvement may occur after this phase which, in some patients, is followed by recovery. In others, after about 16 hours, deterioration may occur involving diffuse vascular congestion, pulmonary oedema, convulsions, anuria, hypothermia, severe shock, metabolic acidosis, coagulation abnormalities and hypoglycaemia.

Management

Vomiting should be induced immediately, followed as soon as possible by parenteral injection of desferrioxamine mesylate, and then gastric lavage. In the meantime, it is helpful to give milk and/or 5% sodium bicarbonate solution by mouth.

Dissolve 2g desferrioxamine mesylate in 2 to 3ml of water for injections and give intramuscularly. A solution of 5g desferrioxamine in 50 to 100ml of fluid may be left in the stomach. If desferrioxamine is not available, leave 300ml of 1 % to 5 % sodium bicarbonate in the stomach. Fluid replacement is essential.

Recovery may be complicated by long-term sequelae such as hepatic necrosis, pyloric stenosis or acute toxic encephalitis which may lead to CNS damage.

Paediatric population

Acute overdose of oral iron requires emergency treatment. In young children 200-250mg/kg Ferrous Fumarate is considered to be extremely dangerous.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group - Iron in combination with Folic Acid ATC code - B03AD

There is evidence that a daily dose of 100mg of elemental iron in the ferrous form is adequate to prevent development of iron deficiency in expectant mothers. If a mild iron deficiency is present when Pregaday Tablets administration is started, this will be corrected by increased absorption of Iron. The daily folate requirement rises steeply during the final trimester of pregnancy, and evidence of maternal depletion may be found. To ensure normal tissue folate levels in the mother after delivery a daily supplement of about 300 micrograms is required during the second and third trimester of pregnancy. This does not obscure the blood picture of addisonian pernicious anaemia.

5.2    Pharmacokinetic properties

Absorption

Iron is absorbed chiefly in the duodenum and jejunum.

Folic Acid is absorbed mainly from the proximal part of the small intestine. Distribution

The amounts of Folic Acid absorbed from normal diets are rapidly distributed in body tissues.

Biotransformation

Absorption being aided by the acid secretion of the stomach and being more readily effected when the iron is in the ferrous state.

Folate polyglutamates are considered to be de-conjugated to monoglutamates during absorption. Folic acid rapidly appears in the blood, where it is extensively bound to plasma proteins.

When larger amounts are absorbed, a high proportion is metabolised in the liver to other active forms of folate and a proportion is stored as reduced and methylated folate.

Elimination

Larger amounts of folate are rapidly excreted in the urine and about 4 to 5 micrograms is excreted in the urine daily.

5.3    Preclinical safety data

Not stated

6.1 List of excipients

The tablet core contain:

Maize Starch EP Sodium Lauryl Sulphate EP Gelatin EP Liquid Paraffin EP

The film coat contain:

Either:

Hydroxypropylmethyl Cellulose EP (E464) Acetylated Monoglyceride Opaspray Pink

Or:

Hydroxypropylmethyl Cellulose EP (E464) Propylene Glycol EP Opaspray Pink

Opaspray Pink contains:

Hydroxypropyl Cellulose (E463)

Red Iron Oxide (E172)

Titanium Dioxide (E171)

6.2 Incompatibilities

Not applicable.

6.3    Shelf life

36 months.

6.4    Special precautions for storage

Store below 25°C.

Keep the blister in the outer carton in order to protect from light.

6.5    Nature and contents of container

Each carton contains 28 (2 calendar blister packs of 14) film-coated tablets prepared from 250pm PVC base with aluminium foil 20pm and PVC 30pm lidding.

6.6 Special precautions for disposal

No special requirements for disposal.

7 MARKETING AUTHORISATION HOLDER

RPH Pharmaceuticals AB,

Lagervagen 7,

136 50 Jordbro,

Sweden

8    MARKETING AUTHORISATION NUMBER(S)

PL 36301/0020

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 23 February 1993 Date of latest renewal: 13 October 2005

10 DATE OF REVISION OF THE TEXT

22/12/2014