Feronia XT Drops

Ferrous Ascorbate & Folic Acid Drops

Each ml contains:

Ferrous Ascorbate IP

equivalent to Elemental Iron 10 mg

Folic Acid IP 100 mcg

Excipients q.s.

Colour: Caramel USP-NF

Appropriate overages of vitamins added.

Drops, For pediatric use only.

10mg ferrous ascorbate + 100mcg folic acid per ml, 15 ml bottle

4.1 Therapeutic indication

Prophylaxis and treatment of iron deficiency anemia in pediatric patients

4.2 Posology and method of administration

Prevention of iron deficiency:

Paediatric population:

6-24 months of age: 1-2 ml/day

2-5 years of age: 2-3 ml/day

6-11 years of age: 3-6 ml/day

Older children: 6 ml/day

Premature infants: 0.5 ml/day. Iron supplementation in premature infants is only recommended in those of low birth weight who are solely breast fed. Higher doses up to 2mg/kg of elemental iron per day might be needed to cover the needs of growing exclusively breastfed infants. Supplementation should be commenced 4-6 weeks after birth and continued until mixed feeding is established.

Treatment of iron deficiency:

Paediatric population:

Full term infants and children: 3 to 6 mg elemental iron/Kg/day given in 2 to 3 divided doses. Total daily dose should not exceed 180 mg elemental iron.

Administration to infants and children should take place under medical advice.

Medical advice should be sought if symptoms do not improve after four weeks of use of this product as these symptoms may reflect an underlying disease process.

Method of administration: Oral

4.3 Contraindications

• Known hypersensitivity to the active substance or to any of the excipients of the product.
• Paroxysmal nocturnal haemoglobinuria. Haemosiderosis, haemochromatosis.
• Repeated blood transfusions. Must not be used in anaemias other than those due to iron deficiency.

4.4 Special warnings and precautions for use

General

Do not exceed the recommended dose. The type of anaemia and the underlying cause or causes should be determined before starting therapy with this medication. Since the anaemia may be a result of a systemic disturbance, such as recurrent blood loss, the underlying cause or causes should be corrected, if possible.

• Duration of treatment of uncomplicated iron deficiency anaemia should not usually exceed 6 months (3 months after reversal of the anaemia has been achieved).
• Because anaemia due to combined iron and Vitamin B12 or folate deficiencies may be microcytic in type, patients with microcytic anaemia resistant to treatment with iron alone should be screened for Vitamin B12 or folate deficiency.
• Feronia XT drops should be kept out of the reach of children.
• Long-term treatment with Feronia XT drops may increase the risk of dental caries in children. Adequate dental hygiene must be maintained.

4.5 Drugs interactions

Iron reduces the absorption of penicillamine, bisphosphonates, ciprofloxacin, entacapone, levodopa, levofloxacin, levothyroxine (thyroxine) (give at least 2 hours apart), moxifloxacin, mycophenolate, norfloxacin, ofloxacin, zinc. Absorption of both iron and antibiotic may be reduced if Feronia XT drops are given with tetracycline. Absorption of oral iron is reduced by calcium salts, magnesium salts (as magnesium trisilicate), Trientine. 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, tea, eggs or milk. Avoid concomitant use of iron with dimercaprol. Oral iron antagonises hypotensive effect of methyldopa.

Folic Acid

• The administration of the following with folic acids results in decreased effectiveness of the molecule: Fosphenytoin, phenytoin, pyrimethamine.
• The administration of the following with folate results in reduced folate absorption: Aminosalicylic acid, antacids, antibiotics, aspirin, carbamazepine, cholestyramine, colestipol, cycloserine, cimetidine, famotidine, nizatidine, ranitidine, pancrelipase, sulfasalazine, triamterene.
• The administration of the following with folate results in reduced serum folate levels: Oestrogens conjugated, oral contraceptives pills, methotrexate, methylprednisolone sodium succinate (noted in people with multiple sclerosis), intravenous pentamidine, phenobarbital and primidone, pyrimethamine.
• Chloramphenicol may antagonize some effects of folic acid on the blood (haematopoietic system). Limited data suggests that diuretics may increase excretion of folic acid.
• Reduced vitamin B12 and, to a lesser extent, folate levels occur in some people with diabetes and can contribute to hyperhomocysteinaemia, which adds to the already increased risk of cardiovascular disease. The reduced folate levels seen in diabetics have been linked to metformin use in some cases, possibly as a result of reduced folic acid absorption. Symptomatic folate deficiency is unlikely to occur with metformin, but people with diabetes may need folic acid supplements to reduce hyperhomocysteinaemia.
• Folate-dependent enzymes have been inhibited in laboratory experiments by ibuprofen, naproxen, indomethacin and sulindac.
• There is a general belief that folic/folinic acid supplements do not interfere with the therapeutic effects of trimethoprim. However, this view has been challenged, and failure of trimethoprim therapy has occurred rarely when folinic acid is given concurrently.

4.6 Pregnancy and lactation

Not applicable.

4.7 Effects on ability to drive and use machines

Not applicable

4.8 Undesirable effects

Ferrous ascorbate

The following adverse reactions are classified by system organ class and ranked under heading of frequency using the following convention:

Not known: frequency cannot be estimated from the available data

Gastrointestinal disorders:

The commonest side effects relate to gastrointestinal irritation (nausea, epigastric pain, constipation or diarrhea). In the event of these ADRs, it may be helpful to reduce the dose or switch to an alternative iron salt.

Darkening of stools, black discoloration of the teeth and allergic reactions (due to metabisulphite in the syrup vehicle) may also occur.

Folic Acid

Folate appears to be well-tolerated in recommended doses. Stomatitis, alopecia, myelosuppression and zinc depletion have been reported.

Erythema, urticaria, skin flushing, rash, itching, nausea, bloating, flatulence, cramps, bitter taste, and diarrhoea have been reported. The colour of the urine may become more intense.

Irritability, excitability, general malaise, altered sleep patterns, vivid dreaming, overactivity, confusion, impaired judgment, increased seizure frequency, and psychotic behaviour have been reported. Very high doses can cause significant central nervous system side effects. Supplemental folic acid might increase seizures in people with seizure disorders, particularly in very high doses.

Folic acid may mask the symptoms of pernicious, aplastic or normocytic anaemias caused by vitamin B12 deficiency and may lead to neurological damage.

Reporting of side effects

If the patient gets any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly at website: www.zuventus.co.in and click the “Safety Reporting” located on the top of the home page. By reporting side effects, you can help provide more information on the safety of this medicine. You can also report the side effect with the help of your treating physician.

4.9 Overdose

Symptoms:

Ingestion of 20 mg/kg elemental iron is potentially toxic and 200-250 mg/kg is potentially fatal. No single method of assessment is entirely satisfactory - clinical features as well as laboratory analysis must be taken into account. The serum iron taken at about 4 hours after ingestion is the best laboratory measure of severity.

Early signs and symptoms include nausea, vomiting, abdominal pain and diarrhea. The vomit and stools may be grey or black. In mild cases early features improve but in more serious cases there may be evidence of hypoperfusion (cool peripheries and hypotension), metabolic acidosis and systemic toxicity. In serious cases there can be recurrence of vomiting and gastrointestinal bleeding, 12 hours after ingestion. Shock can result from hypovolaemria or direct cardiotoxicity. Evidence of hepatocellular necrosis appears at this stage with jaundice, bleeding, hypoglycaemia, encephalopathy and positive anion gap metabolic acidosis. Poor tissue perfusion may lead to renal failure. Rarely, gastric scarring causing stricture or pyloric stenosis (alone or in combination) may lead to partial or complete bowel obstruction 2-5 weeks after ingestion.

Management:

Supportive and symptomatic measures include ensuring a clear airway, monitor cardiac rhythm, BP and urine output, establishing IV access and administering sufficient fluids to ensure adequate hydration. Consider whole bowel irrigation. Consider the use of desferrioxamine, if the patient is symptomatic (other than nausea), serum iron concentration is between 3-5 mg/L (55-90 micromol/L) and still rising. Haemodialysis does not remove iron effectively but should be considered on a supportive basis for acute renal failure as this will facilitate removal of the iron-desferrioxamine complex.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Iron bivalent, oral preparations

Iron is an essential constituent of the body, and is necessary for haemoglobin formation and the oxidative processes of living tissues. Iron and iron salts should be given for the treatment or prophylaxis of iron deficiency anaemia. Preparations of iron are administered by mouth, by intramuscular or intravenous injection.

Soluble ferrous salts are most effective by mouth. Ferrous ascorbate is an easily absorbed source of iron for replacement therapy. It is a salt of ferrous iron with an organic acid and is less irritant to the gastro-intestinal tract than salts with inorganic acids.

Folic acid is also known as vitamin B9. Folic acid is required for synthesis of nucleoprotein, purine nucleotides and the metabolism of some amino acids, normal growth and cell reproduction, nucleoprotein synthesis and the maintenance of normal erythropoiesis. It helps in the process of maturation of red blood cells (RBCs) inside the body.

5.2 Pharmacokinetic properties

Iron

Absorption

In the acid conditions of the gastric contents, ferrous ascorbate is dissociated and ferrous ions are liberated. These ions are absorbed in the proximal portion of the duodenum. The ferrous iron absorbed by the mucosal cells of the duodenum is oxidised to the ferric form, and this is bound to protein to form Ferritin.

Distribution

Ferritin in the mucosal cells releases iron into the blood, where it is bound to transferrin and passed into the iron stores - liver, spleen, and bone marrow.

These stores are a reserve of iron for synthesis of haemoglobin, myoglobin, and iron containing enzymes.

Elimination

Iron is lost from the body through loss of cells in urine, feces, hair, skin, sputum, nails, and mucosal cells, and through blood loss.

Ferrous ascorbate has the same pattern of absorption and excretion as dietary iron.

Folic acid

Absorption

The bioavailability of folic acid ranges from 76% to 93%. Folic acid is absorbed by a carrier-mediated process primarily in the proximal part of the small intestine. There is little absorption in the distal jejunum and practically none in the distal ileum.

Distribution

Folate derivatives are bound by plasma proteins. The greatest affinity for plasma protein-binding occurs with the non-methylated analogs. Other distribution sites include the liver (50%) and tissues. Once absorbed, folate and its derivatives are rapidly distributed to all body tissues.

Metabolism

Folic acid is metabolized in the liver to 7,8-dihydrofolic acid and, eventually, to 5,6,7,8-tetrahydrofolic acid with the aid of a reduced diphosphopyridine nucleotide (DPNH) and folate reductases. This conversion occurs primarily in the liver and not to any significant degree during absorption through the intestinal mucosa. Tetrahydrofolic acid derivatives are distributed to all body tissues, but are stored primarily in the liver.

Excretion

The kidneys excrete 30% of folic acid. After a single oral dose of 100 mcg of folic acid in a limited number of normal adults, only a trace amount of the drug appeared in the urine. The other route of excretion is bile. Following oral administration, folic acid is found in concentrations ranging from 15 - 400 ng/mL in the bile, with peak levels occurring in approximately 120 minutes.

6.1 Animal Toxicology or Pharmacology

No preclinical findings relevant to the prescriber have been reported.

Ferrous Ascorbate is a synthetic molecule of ascorbic acid and iron and is used as a source of iron for iron deficiency anaemia. Folic acid is used to treat anemia caused by folate deficiency.

8.1 Incompatibilities

Not applicable.

8.2 Shelf-life

Refer on pack.

8.3 Packaging information

15 ml bottle

8.4 Storage and handing instructions

Store at a temperature not exceeding 30°C. Protect from light.

Keep out of reach of children.

Do not administer Feronia XT drops

• if the patient is allergic to active substances or any of the other ingredients of this medicine.
• if the patient suffers from a blood disorder.
• if the patient had or is having repeated blood transfusions.
• if the patient is suffering from anemia that is not due to lack of iron.

If any of the above applies to the patient, talk to your doctor.

Talk to your doctor before starting Feronia XT drops

• if the patient has been or is being treated for a stomach ulcer.
• if the patient had or has folate dependent tumour.
• if the patient had all or part of the stomach removed.

Keep out of reach and sight of children, as overdose of iron may be fatal.

Other medicines and Feronia XT drops

Tell your doctor if the patient is taking any other medicines.

Antibiotics e.g. fluoroquinolones, cotrimoxazole, chloramphenicol, sulphonamides, tetracyclines, neomycin (used for infections).

• Anticonvulsant medicines (used for epilepsy).
• Antacids.
• Thyroxine (used for thyroid disease).
• Aminopterin and Methotrexate (used for certain cancers).
• Pyrimethamine (used for malaria).
• Trientine (used for Wilson’s disease).
• Zinc.
• Any other medicine, including medicines obtained without a prescription

Feronia XT drops with food and drink

If tea, coffee or milk or eggs are taken at the same time as Feronia XT drops, the body may absorb less of the iron supplement, which may reduce the effect of this medicine.