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FEROFOLIC Tablets

SCHEDULING STATUS
Unscheduled

PROPRIETARY NAME
(and dosage form)

FEROFOLIC Tablets

COMPOSITION
Controlled-released dose form of iron in a patented vehicle, the GRADUMET
Each tablet contains:
Ferrous sulphate

(equivalent to 105 mg elemental iron)	525 mg
Ascorbic acid (Vitamin C)	500 mg
Folic acid	350 micrograms

PHARMACOLOGICAL CLASSIFICATION
A 8.3 Erythropoietics (haematinics)

PHARMACOLOGICAL ACTION
Oral iron is absorbed better when administered between meals: however, conventional iron preparations often cause gastric irritation when taken on an empty stomach. Studies with GRADUMET iron have indicated that relatively little of the iron is released in the stomach, the major portion being released in the upper intestinal tract. It is an inert, porous, plastic matrix, in which ferrous sulphate is impregnated. Iron is leached from the GRADUMET as it passes through the gastro-intestinal tract, and the expended matrix is excreted harmlessly in the stool. Thus, the possibility of gastric irritation is minimised when iron is administered in the GRADUMET form in comparison with conventional oral iron preparations. Controlled-release iron, therefore, is beneficial to patients who have a demonstrated intolerance to oral iron preparations.
Some investigators have shown that large amounts of ascorbic acid administered orally with ferrous sulphate improve iron absorption. This appears to be related to the ability of ascorbic acid to prevent oxidation of ferrous iron to the less effectively absorbed ferric form.
The ascorbic acid and folic acid are released on dissolution. Folic acid and iron are absorbed in the proximal small intestine, particularly in the duodenum. Folic acid is absorbed maximally and rapidly at this site and iron is absorbed in a descending gradient from the duodenum distally.

INDICATIONS
FEROFOLIC is indicated in pregnancy for the prevention and treatment of iron deficiency anaemia and to supply a maintenance dosage of folic acid. It is also indicated for the general treatment of iron deficiency of concomitant folic acid deficiency in non-pregnant patients.

CONTRA-INDICATIONS
FEROFOLIC is contra-indicated in patients with pernicious anaemia.
The use of Fero-Folic-500 is contraindicated in the presence of intestinal diverticula or any intestinal obstruction.
Iron preparations are contraindicated in patients with hemochromatosis and hemosiderosis.
Iron is contraindicated in patients receiving repeated blood transfusions.
Oral iron preparations are contraindicated when used concomitantly with parenteral iron therapy.

WARNINGS
Acute iron poisoning occurs rarely in adults, however it could happen if children swallow this medication.
Ascorbic acid is essentially non-toxic in man, though exceptionally high doses may cause some side effects.

DOSAGE AND DIRECTIONS FOR USE
FEROFOLIC is administered orally and may be taken on an empty stomach.
Patients should be advised to swallow tablets whole.
Oral iron preparations are contraindicated when used concomitantly with parenteral iron therapy.
Adults
For treatment of iron deficiency and prevention of folic acid deficiency, the recommended dose is one tablet daily.
Pregnant women
For prevention and treatment of iron deficiency and to supply a maintenance dosage of folic acid, the recommended dose is one tablet daily.
Gastric intolerance to iron in the controlled-release GRADUMET vehicle is rare. Should it occur, the tablet may be taken after a meal, although this reduces iron absorption,

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Like other oral preparations FEROFOLIC should be stored out of reach of children to guard against accidental iron poisoning.
Iron given in therapeutic doses, may cause gastro-intestinal discomfort, diarrhoea and vomiting. However, these side effects are generally not severe enough to necessitate stopping the treatment. Continued administration may sometimes cause constipation.
Where anaemia exists, its nature should be established and underlying causes determined.
FEROFOLIC contains 350 micrograms of folic acid per tablet. Folic acid, especially in doses about 1,0 mg daily, may obscure pernicious anaemia, in that haematologic remission may occur while neurological manifestations remain progressive. Therefore, in older patients and those with conditions tending to lead to Vitamin B12 depletion, serum B12 levels should be regularly assessed during treatment with FEROFOLIC. Concomitant parenteral therapy with Vitamin B12 may be necessary in patients with deficiency of the Vitamin. Pernicious anaemia is rare in women of childbearing age, and the likelihood of its occurrence along with pregnancy is reduced by the impairment of fertility associated with Vitamin B12 deficiency.
Drug Interactions:
The following drug interactions have been reported:

1.	With Iron Salts
	Allopurinol potentiates iron absorption. Iron salts should not be given simultaneously. Haemosiderosis is caused when allopurinol blocks the enzyme that prevents the absorption of iron.
	Antacids containing carbonates inhibit the absorption of iron by forming insoluble iron carbonate.
	Phytic acid in cereals forms a complex with iron which prevents absorption.
	Dimercaprol increases the toxicity of ferrous sulphate and other iron salts (toxic Iron chelate formed).
	Eggs can inhibit the absorption of iron.
	Oestrogen and progestogens increase protein bound iron.
	Magnesium trisilicate inhibits the absorption of iron.
	Milk reduces the absorption of iron salt
	Iron salts may interfere with the absorption of tetracyclines.
	Hydroxyurea may delay the clearance of iron from the plasma and reduce the rate of iron utilisation by erythrocytes.
2.	With Folic Acid
	Diphenylhydantoin depresses folic acid levels in the body and potentiates folic acid antagonists.
	Malabsorption of folate has been associated with oral contraceptives.
3.	With Ascorbic Acid
	Vitamin C increases excretion of anti-pyrines (inhibition) and vice versa.
	Vitamin C increases excretion of atropine (inhibition) and vice versa.
	Vitamin C decreases excretion of barbiturates (potentiation of the sedative).
	Barbiturates increase the excretion of Vitamin C.
	Mineral oil may inhibit absorption of Vitamin C.
	Vitamin C inhibits quinidine by increasing its urinary excretion.
	Salicylates increase excretion of Vitamin C. Vitamin C decreases salicylate excretion (potentiation of analgesic).
	Vitamin C decreases excretion of sulphonamides (potentiation and sulphonamides increase excretion of Vitamin C (inhibition of the Vitamin).
4.	Laboratory Tests
	Iron preparations colour the faeces black, which may interfere with tests used for detection of occult blood in the stools. The guaic test occasionally yield false positive tests for blood.
	As a strong reducing agent, ascorbic acid may interfere with tests based on oxidation-reduction reactions.
	Ascorbic acid in the urine may produce false results in glycosuria determinations.
5.	Drug Interactions
	Iron absorption is inhibited by magnesium, therefore oral iron preparations should not be taken within one hour before or two hours after ingestion of antacids.
	Iron inhibits the absorption of tetracyclines from the gastrointestinal tract and tetracycline inhibits the absorption of iron. If both drugs must be given, tetracycline should be administered three hours after or two hours before oral iron supplements.
	Ascorbic acid may enhance the absorption of iron from the gastrointestinal tract.
	Iron can decrease gastrointestinal absorption of penicillamines. Therefore, administration should be at least two hours apart, if both drugs must be administered.
	Chloramphenicol may delay response to iron therapy.
	Concurrent administration of oral iron preparations may interfere with the oral absorption of some quinolone anti-infective agents (eg. ciprofloxacin, norfloxacin, ofloxacin) resulting in decreased serum and urine concentrations of the quinolones. Therefore, oral iron preparations should not be ingested with or within two hours of a dose of an oral quinolone.

The side effects reported with Fero-Folic-500 are similar to those associated with conventional iron preparations. They are as follows: nausea, vomiting, abdominal pain or discomfort, blackening of stools, diarrhoea and constipation.
Ascorbic acid is well tolerated. However, large doses are reported to cause diarrhoea and other gastrointestinal disturbances and are associated with the formation of renal calcium oxalate calculi.
Isolated cases of allergic reaction have been reported ranging from rash to anaphylaxis.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Iron poisoning is extremely rare in adults and it is considered unlikely in adults with ingestion of doses of ferrous sulphate below 50 g. However, serious acute poisoning in children can result from the ingestion of doses in excess of 1 g.
Signs and Symptoms of iron toxicity may occur within 30 minutes, or they may be delayed several hours. Most frequently, they are gastro-intestinal irritation and necrosis, often with nausea, vomiting and shock; they also include pallor of cyanosis, lassitude, drowsiness, haematemesis, diarrhoea of green and subsequently tarry stools, and cardiovascular collapse. The corrosive injury to the stomach may result in subsequent pyloric stenosis or severe gastric scarring. If death does not occur within 6 hours, there may be a transient period of apparent recovery followed by death in 12 to 48 hours.
Most importantly, signs of serious toxicity with FEROFOLIC may be delayed, because the iron is entrapped in the controlled-release vehicle. If overdosage occurs, efforts must be made to hasten the elimination of the GRADUMET tablets ingested.
Ascorbic Acid - Essentially nontoxic, unless exceptionally high doses (1 - 12 g) are ingested by man.
Folic Acid - Folic acid is essentially nontoxic in man.
Treatment of overdosage:
In overdosage, efforts should be made to hasten the elimination of the GRADUMET tablets ingested. An emetic should be administered as soon as possible, followed by gastric lavage if indicated.
Immediately following emesis, a large dose of saline cathartic should be used to speed passage through the intestinal tract. X-Ray examination may then be considered to determine the position and number of GRADUMET tablets remaining in the gastro-intestinal tract.
Supportive therapy must be instituted immediately and fluid loss should be replaced by I.V. administration of a Dextrose Saline solution with Sodium Lactate. It is essential to block further absorption from the alimentary tract by a chelating substance such as desferrioxamine. Other symptoms are treated systematically.

CONDITIONS OF REGISTRATION
None

IDENTIFICATION
Geranium-red, ovaloid, film-coated tablet.
Ferrous solfate is freely soluble in water and insoluble in alcohol.

PRESENTATION
Amber glass bottles containing 30 FERO-FOLIC tablets.
PVC/Al foil blister packs containing 20 FERO-FOLIC tablets.

STORAGE INSTRUCTIONS
Store in a cool (below 25°C) dry place. Keep tightly closed.
Keep out of reach of children.

REGISTRATION NUMBERS
B/8.3/181

NAME AND BUSINESS ADDRESS OF THE APPLICANT
Adcock Ingram Limited
Adcock Ingram Park
17 Harrison Avenue
Bryanston Ext. 77
Private Bag X69
Bryanston, 2021

New addition to this site: April 2004
Source: Pharmaceutical Industry
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