Summary of Product Characteristics (SmPC) - Folic Acid 0.4 mg tablets

1 NAME OF THE MEDICINAL PRODUCT

Folic Acid 0.4 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 0.4 mg of Folic Acid (as Folic acid hydrate).

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablets

Off-white to yellowish, round, bevelled-edged, convex tablet with a diameter of 7 mm.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Folic Acid is indicated for the prevention of first occurrence neural tube defects in the foetus.

For use by women who are planning a pregnancy.

4.2 Posology and method of administration

Posology

Adult females

One tablet (0.4 mg) daily.

Supplementation should begin by taking one tablet (0.4 mg) daily prior to conception and be continued for at least the first 12 weeks of pregnancy.

Method of administration

Oral

The tablets should be swallowed with water.

4.3 Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

Folic acid should not be given alone in the treatment of Addisonian pernicious anaemia and other vitamin B₁₂deficiency states, as this may precipitate the onset of subacute combined degeneration of the spinal cord. Patients with malignant disease, unless megaloblastic anaemia due to folic acid deficiency. It should not be taken by people with folate dependant tumours.

Long-term folate therapy is contraindicated in any patient with untreated cobalamin deficiency. This can be untreated pernicious anaemia or other cause of cobalamin deficiency, including lifelong vegetarians. In elderly people, a cobalamin absorption test should be done before long-term folate therapy. Folate given to such patients for 3 months or longer has precipitated cobalamin neuropathy. No harm results from short courses of folate

4.4 Special warnings and precautions for use

Folic acid should not be administered for treatment of pernicious anaemia or undiagnosed megaloblastic anaemia without sufficient amounts of cyanocobalamin (vitamin B12) as folic acid alone will not prevent and may precipitate development of subacute combined degeneration of the spinal cord. Therefore a full clinical diagnosis should be made before initiating treatment.

Folate should not be routinely used in patients receiving coronary stents.

Women with pre-existing diabetes, obesity, family history of neural tube defects, or previous pregnancy affected by neural tube defect have an increased risk of having a pregnancy affected by a neural tube defect and higher doses should be considered.

Caution should be exercised when administering folic acid to patients who may have folate dependent tumours.

Folic acid is removed by haemodialysis.

4.5 Interaction with other medicinal products and other forms of interaction

Folic acid status may be affected by a number of drugs:

Antiepileptics: Folic acid can reduce plasma concentrations of anticonvulsants, particularly phenytoin, phenobarbital and primidone and therefore patients on antiepileptic therapy may need to have their dose adjusted at regular intervals and should be under the supervision of a physician while taking folic acid supplements
Antibacterials: chloramphenicol and co-trimoxazole may interfere with folate metabolism
Sulfasalazine: can reduce the absorption of folic acid
Preparations containing folic acid or its derivatives may decrease the effectiveness of methotrexate.

Patients with hypersensitivity to folic acid have been demonstrated to have antibodies that cross react with other folic acid analogues, including methotrexate, folinic acid and aminopterin.

Green and black tea may reduce folic acid bioavailability, therefore they should be avoided during treatment with folic acid

Folic acid may interfere with the toxic and therapeutic effects of methotrexate. Methotrexate and trimethoprim are specific anti-folates and the folate deficiency caused by their prolonged use cannot be treated by Folic Acid Tablets BP.

Folate supplements enhance the efficacy of lithium therapy.

Folinic acid should be used.

Nitrous oxide anaesthesia may cause an acute folic acid deficiency.

Both ethanol and aspirin increase folic elimination.

Food: The effects of green or black tea on the pharmacokinetics of folic acid were reported in healthy volunteers. At the 0.4mg folic acid dose, green and black tea reduced the mean area under the curve from time zero to infinity (AUC0-∞) of folic acid by 26.6% and 17.9% and, the maximum concentration(Cmax) of serum folate by 39.2% and 38.6%, respectively. At the 5 mg folic acid dose, green tea reduced the mean AUC0-∞ of folic acid by 39.9% and the mean Cmax of serum folate by 27.4% (Alemdaroglu NC et al, 2008).

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no known hazards to the use of folic acid in pregnancy, supplements of folic acid are often beneficial.

Non-drug - induced folic acid deficiency, or abnormal folate metabolism, is related to the occurrence of birth defects and some neural tube defects. Interference with folic acid metabolism or folate deficiency induced by drugs such as anticonvulsants and some antineoplastics early in pregnancy results in congenital anomalies. Lack of the vitamin or its metabolites may also be responsible for some cases of spontaneous abortion and intrauterine growth retardation.

Breast-feeding

Folic acid is actively excreted in human breast milk. Accumulation of folate in milk takes precedence over maternal folate needs. Levels of folic acid are relatively low in colostrum but as lactation proceeds, concentrations of the vitamin rise. No adverse effects have been observed in breast fed infants whose mothers were receiving folic acid.

No adverse effects have been observed in breast-fed infants whose mothers were receiving folic acid.

4.7 Effects on ability to drive and use machines

No effect on concentration or co-ordination.

4.8 Undesirable effects

Folic acid is generally well tolerated.

Rare (≥1/10,000 to

<1/1,000)

Not known (cannot be estimated from the available data)

Gastrointestinal disorders

Anorexia, nausea,

abdominal distension and flatulence

Immune system disorders

Allergic reactions, comprising erythema, rash, pruritus, urticaria, dyspnoea.

anaphylactic 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.

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

4.9 Overdose

There are no specific symptoms of overdosage and similarly no emergency treatment or antidotes. Metabolism and excretion can be rapid.

Overdose is not normally a problem. Folic acid is stored in the liver and cerebrospinal fluid. Any excess to requirement is excreted in the urine.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Folic acid and derivatives, ATC code: B03BB01

Folic Acid is essential in preventing megaloblastic anaemia especially if it is deficient in poor nutritional states, pregnancy or anti-epileptic patients. Folic Acid has been demonstrated to prevent recurrence of neural tube defects, as well as to prevent first occurrence neural tube defects when taken in different doses of 5 mg and 0.4 mg respectively.

Folic acid is a member of the vitamin B group. Folic acid is reduced in the body to tetrahydrofolate, which is a coenzyme for various metabolic processes including the synthesis of purine and pyrimidine nucleotides, and hence in the synthesis of DNA; it is also involved in some amino-acid conversions, and in the formation and utilisation of formate.

5.2 Pharmacokinetic properties

Absorption

Folic acid is absorbed mainly from the proximal part of the small intestine. The naturally occurring folate polyglutamates are largely deconjugated and reduced prior to absorption. It is the 5-methyltetrahydrofolate, which appears in the portal circulation, where it is extensively bound to plasma proteins.

Distribution

Via portal circulation. 5MTHF from naturally occurring folate is extensively plasma bound. The principle storage site of folate is in the liver; it is also actively concentrated in the CSF. Folate is distributed into the breast milk.

Elimination

There is an enterohepatic circulation for folate; about 4 to 5 micrograms is excreted in the urine daily. Administration of larger doses of folic acid leads to proportionately more of the vitamin being excreted in the urine. Folic acid is distributed into breast milk.

Metabolism

Therapeutically given folic acid is converted into the metabolically active form 5MTHF in the plasma and liver. There is an enterohepatic circulation for folate.

Elimination

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 haemodialysis.

5.3 Preclinical safety data

Folic Acid is a drug on which extensive clinical experience has been obtained. Folic acid is not mutagenic. large doses in rats and in rabbits (100mg/kg upwards) produced precipitation of folate crystals in the neural tubules, particularly the proximal tubules and in the ascending limb of the Loop of Henle. Tubular necrosis is followed by recovery.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Hydroxypropylcellulose

Croscarmellose sodium

Cellulose, microcrystalline

Silica, colloidal anhydrous

Stearic acid

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 years

Shelf life after first opening of the HDPE containers: 100 days

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Folic Acid 0.4 mg Tablets are available in HDPE bottle pack and blister pack of PVC/PVdC and Aluminium foil. Such bottles and blisters are packaged into cardboard carton.

Carton containing 20, 28, 30, 50, 56, 60, 90 and of 100 tablets in blister. Carton containing 100 tablets in HDPE bottle.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal