Cholecalciferol Granules

Each sachet of 1gm contains:

Cholecalciferol IP 60000 IU.

Excipients q.s.

Granules, 60000 IU per sachet

4.1 Therapeutic indication

For the treatment of Vitamin-D3 deficiency.

4.2 Posology and method of administration

1/4 to 1 sachet with milk or as directed by the physician

4.3 Contraindications

• Hypersensitivity to vitamin D or any of the excipients in the product
• Hypervitaminosis D
• Nephrolithiasis
• Diseases or conditions resulting in hypercalcaemia and/or hypercalciuria
• Severe renal impairment

4.4 Special warnings and precautions for use

• Patients with gastrointestinal malabsorption syndromes may require higher doses of vitamin D3 supplementation and measurement of 25-hydroxyvitamin D should be considered.
• Vitamin D3 supplementation may worsen hypercalcemia and/or hypercalciuria when administered to patients with diseases associated with unregulated overproduction of 1,25 dihydroxyvitamin D (e.g., leukaemia, lymphoma, sarcoidosis). Urine and serum calcium should be monitored in these patients.
• It should be used with caution in patients with renal impairment or calculi, or heart disease, who might be at increased risk of organ damage if hypercalcaemia occurred.
• Plasma phosphate concentrations should be controlled during vitamin D3 therapy to reduce the risk of ectopic calcification.
• It is advised that patients receiving pharmacological doses of vitamin D3 should have their plasma-calcium concentration monitored at regular intervals, especially initially or if symptoms suggest toxicity.

4.5 Drugs interactions

• Olestra, mineral oils, orlistat, and bile acid sequestrants (e.g., cholestyramine, colestipol) may impair the absorption of vitamin D3.
• Anticonvulsants, cimetidine, and thiazides may increase the catabolism of vitamin D.
• There is an increased risk of hypercalcaemia if vitamin D3 is given with thiazide diuretics, calcium, or phosphate. Plasma-calcium concentrations should be monitored in such situations.
• Some antiepileptics may increase vitamin D3 requirements (e.g. carbamazepine, phenobarbital, phenytoin, and primidone).
• Rifampicin and isoniazid may reduce the effectiveness of vitamin D3.
• Corticosteroids may counteract the effect of vitamin D3.

4.6 Use in special populations

Pregnancy

No data are available for cholecalciferol (vitamin D3). There are no studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.

Nursing Mothers

Cholecalciferol and some of its active metabolites pass into breast milk. Infants should be closely monitored for hypercalcemia or clinical manifestations of vitamin D toxicity if the mother is taking pharmacological doses of vitamin D3.

Infants

Vitamin D3 should be used with caution in infants, who may have increased sensitivity to its effects.

4.7 Effects on ability to drive and use machines

It is not expected that Vitanova sachet would affect your ability to drive or to operate machinery.

4.8 Undesirable effects

Major & minor side effects for Vitanova D3 Sachet

• Increased blood calcium levels
• Increased calcium levels in urine
• Constipation
• Skin rash, hives, or itching
• Chest pain
• Shortness of breath

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 email to: medico@zuventus.com
• Website: http://www.zuventus.co.in/safety.aspx
• By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

There is limited information regarding doses of cholecalciferol associated with acute toxicity, although intermittent (yearly or twice yearly) single doses of ergocalciferol (vitamin D2) as high as 600,000 IU have been given without reports of toxicity. Signs and symptoms of vitamin D toxicity include hypercalcemia, hypercalciuria, anorexia, nausea, vomiting, polyuria, polydipsia, weakness, and lethargy. Serum and urine calcium levels should be monitored in patients with suspected vitamin D toxicity.

Treatment

Standard therapy includes restriction of dietary calcium, hydration, and systemic glucocorticoids in patients with severe hypercalcemia. Dialysis to remove vitamin D would not be beneficial.

5.1 Mechanism of Action

The mechanism of action of 1,25(OH)2D(calcitriol) is mediated by the interaction of calcitriol with the vitamin D receptor (VDR). Calcitriol binds to cytosolic VDRs within target cells, and the receptor-hormone complex translocates to the nucleus and interacts with DNA to modify gene transcription. The VDR belongs to the steroid and thyroid hormone receptor supergene family. Calcitriol also exerts nongenomic effects that may require the presence of a functional VDR.

5.2 Pharmacodynamic properties

Vitamin D3 is converted to 25-hydroxyvitamin D3 in the liver. Conversion to the active calcium-mobilizing hormone 1, 25-dihydroxyvitamin D3 (calcitriol) in the kidney is stimulated by both parathyroid hormone and hypophosphatemia. The principal action of 1,25-dihydroxyvitamin D3 is to increase intestinal absorption of both calcium and phosphate as well as regulate serum calcium, renal calcium and phosphate excretion, bone formation and bone resorption.

Vitamin D is required for normal bone formation. Vitamin D insufficiency develops when both sunlight exposure and dietary intake are inadequate. Insufficiency is associated with negative calcium balance, increased parathyroid hormone levels, bone loss, and increased risk of skeletal fracture. In severe cases, deficiency results in more severe hyperparathyroidism, hypophosphatemia, proximal muscle weakness, bone pain and osteomalacia.

5.3 Pharmacokinetic properties

Absorption

Vitamin D substances are well absorbed from the gastrointestinal tract. The presence of bile is essential for adequate intestinal absorption; absorption may be decreased in patients with decreased fat absorption.

Distribution

Following absorption, vitamin D3 enters the blood as part of chylomicrons. Vitamin D3 is rapidly distributed mostly to the liver where it undergoes metabolism to 25-hydroxyvitamin D3, the major storage form. Lesser amounts are distributed to adipose tissue and stored as vitamin D3 at these sites for later release into the circulation. Circulating vitamin D3 is bound to vitamin D-binding protein.

Metabolism

Vitamin D3 is rapidly metabolized by hydroxylation in the liver to 25-hydroxyvitamin D3, and subsequently metabolized in the kidney to 1,25-dihydroxyvitamin D3, which represents the biologically active form. Further hydroxylation occurs prior to elimination. A small percentage of vitamin D3 undergoes glucuronidation prior to elimination.

Excretion

When radioactive vitamin D3 was intravenously administered to healthy subjects, the mean urinary excretion of radioactivity after 48 hours was 2.4% of the administered dose, and the mean fecal excretion of radioactivity after 48 hours was 4.9% of the administered dose. In both cases, the excreted radioactivity was almost exclusively as metabolites of the parent. The mean half-life of vitamin D3 in the serum following an oral dose is approximately 14 hours.

6.1 Animal Toxicology or Pharmacology

No known animal toxicology data

Vitanova D3 contains cholecalciferol (Vitamin D3). Vitamin D3 is essential for the proper growth and development of the body. It is synthesized within the body after exposure to sunlight and is essential for many important functions of the human body. Vitamin D3 in Vitanova D3 also increases the Calcium absorption from the intestines.

8.1 Incompatibilities

Not applicable.

8.2 Shelf-life

Refer on pack

8.3 Packaging information

4 sachets of 1 gram each

8.4 Storage and handing instructions

Store protected from light & moisture at a temperature not exceeding 25°C. Keep out of reach of children.

• Take exactly as directed by your doctor or on the label. Do not increase the dosage or take for longer than is recommended.
• Vitanova-D3 Sachets 1 gm may interfere with cholesterol tests, hence please inform your physician and laboratory staff that you are taking Vitanova-D3 Sachets 1 gm before undergoing blood tests.
• Clinical monitoring of serum electrolyte concentrations and cardiac function is recommended.

Cholecalciferol (Vitamin-D3) Capsules

Each soft gelatin capsules contains:

Cholecalciferol (Vitamin D3) IP 1500 mcg

equivalent to 60,000 IU

Excipients q.s.

Appropriate overages of vitamin added to compensate the loss on storage.

Soft Gelatin Capsules

60,000 IU

4.1 Therapeutic indication

For the treatment of vitamin D3 deficiency

4.2 Posology and method of administration

Adults and adolescent: One Vitanova-D3 SG Capsules (60,000 IU) to be given once a week for a period of 8 weeks, followed by one Vitanova-D3 SG Capsules (60,000 IU) once a month or daily maintenance dose as directed by the physician.

Certain populations are at high risk of vitamin D deficiency, and may require higher doses and monitoring of serum 25(OH)D:

• Institutionalised or hospitalised individuals
• Dark skinned individuals
• Individuals with limited effective sun exposure due to protective clothing or consistent use of sun screens
• Obese individuals
• Patients being evaluated for osteoporosis
• Use of certain concomitant medications (e.g., anticonvulsant medications, glucocorticoids)
• Patients with malabsorption, including inflammatory bowel disease and coeliac disease
• Those recently treated for vitamin D deficiency, and requiring maintenance therapy.

Infants and young children (0-12 years)

Vitanova-D3 SG Capsules should not be given to children under 12 years due to the risk of choking.

Method of administration

This medicine is taken orally.

The Vitanova-D3 SG capsule should be swallowed whole with water, preferably with the main meal of the day.

4.3 Contraindications

• Hypersensitivity to vitamin D or any of the excipients in the product
• Hypervitaminosis D
• Nephrolithiasis
• Diseases or conditions resulting in hypercalcaemia and/or hypercalciuria
• Severe renal impairment

4.4 Special warnings and precautions for use

• Vitamin D should be used with caution in patients with impairment of renal function and the effect on calcium and phosphate levels should be monitored. The risk of soft tissue calcification should be taken into account. In patients with severe renal insufficiency, vitamin D in the form of Cholecalciferol is not metabolised normally and other forms of vitamin D should be used.
• Caution is required in patients receiving treatment for cardiovascular disease.
• Vitanova-D3 should be prescribed with caution to patients suffering from sarcoidosis because of the risk of increased metabolism of vitamin D to its active form. These patients should be monitored with regard to the calcium content in serum and urine.
• Allowances should be made for vitamin D supplements from other sources.
• The need for additional calcium supplementation should be considered for individual patients. Calcium supplements should be given under close medical supervision.
• Medical supervision is required whilst on treatment to prevent hypercalcaemia.

4.5 Drugs interactions

• Concomitant treatment with phenytoin or barbiturates can decrease the effect of vitamin D because of metabolic activation. Concomitant use of glucocorticoids can decrease the effect of vitamin D.
• The effects of digitalis and other cardiac glycosides may be accentuated with the oral administration of calcium combined with Vitamin D. Strict medical supervision is needed and, if necessary monitoring of ECG and calcium.
• Simultaneous treatment with ion exchange resins such as cholestyramine or laxatives such as paraffin oil may reduce the gastrointestinal absorption of vitamin D.
• The cytotoxic agent actinomycin and imidazole antifungal agents interfere with vitamin D activity by inhibiting the conversion of 25-hydroxyvitamin D to 1,25- dihydroxyvitamin D by the kidney enzyme, 25-hydroxyvitamin D-1-hydroxylase.

4.6 Use in special populations

Pregnancy

No data are available for cholecalciferol (vitamin D3). There are no studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.

Nursing Mothers

Cholecalciferol and some of its active metabolites pass into breast milk. Infants should be closely monitored for hypercalcemia or clinical manifestations of vitamin D toxicity if the mother is taking pharmacological doses of vitamin D3.

Infants

Vitamin D3 should be used with caution in infants, who may have increased sensitivity to its effects.

4.7 Effects on ability to drive and use machines

Vitanova D3 has no 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: uncommon (>1/1,000, <1/100) or rare (>1/10,000, <1/1,000).

Metabolism and nutrition disorders

Uncommon: Hypercalcaemia and hypercalciuria. Skin and subcutaneous disorders

Rare: Pruritus, rash and urticaria.

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 email to: medico@zuventus.com
• By reporting side effects, you can help provide more information on the safety of this medicine.

4.8 Overdose

The most serious consequence of acute or chronic overdose is hypercalcaemia due to vitamin D toxicity. Symptoms may include nausea, vomiting, polyuria, anorexia, weakness, apathy, thirst and constipation. Chronic overdoses can lead to vascular and organ calcification as a result of hypercalcaemia.

Treatment should consist of stopping all intake of vitamin D and rehydration. Rehydration, and, according to severity, isolated or combined treatment with loop diuretics, bisphosphonates, calcitonin and corticosteroids should be considered. Serum electrolytes, renal function and diuresis must be monitored.

5.1 Mechanism of Action

In its biologically active form vitamin D3 stimulates intestinal calcium absorption, incorporation of calcium into the osteoid, and release of calcium from bone tissue. In the small intestine it promotes rapid and delayed calcium uptake. The passive and active transport of phosphate is also stimulated. In the kidney, it inhibits the excretion of calcium and phosphate by promoting tubular resorption. The production of parathyroid hormone (PTH) in the parathyroids is inhibited directly by the biologically active form of vitamin D3. PTH secretion is inhibited additionally by the increased calcium uptake in the small intestine under the influence of biologically active vitamin D3.

5.2 Pharmacodynamic properties

Vitamin D3 is converted to 25-hydroxyvitamin D3 in the liver. Conversion to the active calcium-mobilizing hormone 1, 25-dihydroxyvitamin D3 (calcitriol) in the kidney is stimulated by both parathyroid hormone and hypophosphatemia. The principal action of 1,25-dihydroxyvitamin D3 is to increase intestinal absorption of both calcium and phosphate as well as regulate serum calcium, renal calcium and phosphate excretion, bone formation and bone resorption.

Vitamin D is required for normal bone formation. Vitamin D insufficiency develops when both sunlight exposure and dietary intake are inadequate. Insufficiency is associated with negative calcium balance, increased parathyroid hormone levels, bone loss, and increased risk of skeletal fracture. In severe cases, deficiency results in more severe hyperparathyroidism, hypophosphatemia, proximal muscle weakness, bone pain and osteomalacia.

5.3 Pharmacokinetic properties

The pharmacokinetics of vitamin D is well known. Vitamin D is well absorbed from the gastro-intestinal tract in the presence of bile. It is hydroxylated in the liver to form 25-hydroxyCholecalciferol and then undergoes further hydroxylation in the kidney to form the active metabolite 1, 25 dihydroxy Cholecalciferol (calcitriol). The metabolites circulate in the blood bound to a specific α - globin, Vitamin D and its metabolites are excreted mainly in the bile and faeces.

6.1 Animal Toxicology or Pharmacology

Vitamin D is well known and is a widely used material and has been used in clinical practice for many years. As such toxicity is only likely to occur in chronic overdosage where hypercalcaemia could result.

Cholecalciferol has been shown to be teratogenic in high doses in animals (4-15 times the human dose). Offspring from pregnant rabbits treated with high doses of vitamin D had lesions anatomically similar to those of supravalvular aortic stenosis and offspring not showing such changes show vasculotoxicity similar to that of adults following acute vitamin D toxicity.

Vitanova D3 contains cholecalciferol (Vitamin D3). Vitamin D3 is essential for the proper growth and development of the body. It is synthesized within the body after exposure to sunlight and is essential for many important functions of the human body. Vitamin D3 in Vitanova D3 also increases the Calcium absorption from the intestines.

8.1 Incompatibilities

Not applicable.

8.2 Shelf-life

Refer on the pack

8.3 Packaging information

10 Blister strips of 4 capsules each

8.4 Storage and handing instructions

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

Keep out of reach of children

Capsule should be swallowed whole & not to be opened, chewed or crushed

• Take exactly as directed by your doctor or on the label.
• Do not increase the dosage or take for longer than is recommended.
• Vitanova-D3 Capsules may interfere with cholesterol tests, hence please inform your physician and laboratory staff that you are taking Vitanova-D3 Capsules before undergoing blood tests.
• Clinical monitoring of serum electrolyte concentrations and cardiac function is recommended.

Pancreatin

ENZELO 10000

Each hard gelatin capsule contains:

Pancreatin IP 170 mg

(As enteric coated pellets)

Declared enzyme activity

Amylase (Ph.Eur.U)/U 8000

Lipase (Ph.Eur.U)/U 10000

Protease (Ph.Eur.U)/U 600

Approved Colours used in capsule shell

ENZELO 25000

Each hard gelatin capsule contains: Pancreatin IP 350 mg

(As enteric coated pellets)

Declared enzyme activity

Amylase (Ph.Eur.U)/U 18000

Lipase (Ph.Eur.U)/U 25000

Protease (Ph.Eur.U)/U 1000

Approved Colours used in capsule shell

Capsule

Pancreatin 170 mg / 350 mg

4.1 Therapeutic Indication

For the treatment of pancreatic exocrine insufficiency

4.2 Posology and method of administration

Adults (including the elderly) and children:

Initially one or two capsules during each meal. Dose increases, if required, should be added slowly, with careful monitoring of response and symptomatology.

It is important to ensure adequate hydration of patients at all times whilst dosing Enzelo 25000.

Fibrosing colonopathy has been reported in patients with cystic fibrosis taking in excess of 10,000 units of lipase/kg/day

Method of administration

Oral use.

Capsule should be swallowed whole & not to be opened, chewed or crushed.

4.3 Contraindications

Hypersensitivity to Pancreatin of porcine origin or to any of the excipients

4.4 Special warnings and precautions for use

Strictures of the ileo-caecum and large bowel (fibrosing colonopathy) have been reported in patients with cystic fibrosis taking high doses of pancreatin preparations. As a precaution, unusual abdominal symptoms or changes in abdominal symptoms should be medically assessed to exclude the possibility of fibrosing colonopathy, especially if the patient is taking in excess of 10,000 units of lipase/kg/day.

4.5 Drugs interactions

No interaction studies have been performed.

4.6 Use in special populations

Pregnancy

For pancreatic enzymes no clinical data on exposed pregnancies are available.

Animal studies show no evidence for any absorption of porcine pancreatic enzymes. Therefore, no reproductive or developmental toxicity is to be expected.

Caution should be exercised when prescribing to pregnant women.

Nursing Mothers

No effects on the suckling child are anticipated since animal studies suggest no systemic exposure of the breast-feeding woman to pancreatic enzymes. Pancreatic enzymes can be used during breast-feeding.

If required during pregnancy or lactation Enzelo should be used in doses sufficient to provide adequate nutritional status.

4.7 Effects on ability to drive and use machines

Enzelo has no or negligible influence on the ability to drive or use machines.

4.8 Undesirable effects

*Gastrointestinal disorders are mainly associated with the underlying disease. Similar or lower incidences compared to placebo were reported for abdominal pain and diarrhoea.

Strictures of the ileo-caecum and large bowel (fibrosing colonopathy) have been reported in patients with cystic fibrosis taking high doses of pancreatin preparations, see section 4.4 Special warnings and precautions for use.

Allergic reactions mainly but not exclusively limited to the skin have been observed and identified as adverse reactions during post-approval use. Because these reactions were reported spontaneously from a population of uncertain size, it is not possible to reliably estimate their frequency.

Paediatric population

No specific adverse reactions were identified in the paediatric population. Frequency, type and severity of adverse reactions were similar in children with cystic fibrosis as compared to adults.

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 email to: medico@zuventus.com

4.9 Overdose

Extremely high doses of pancreatin have been reported to be associated with hyperuricosuria and hyperuricaemia.

Supportive measures including stopping enzyme therapy and ensuring adequate rehydration are recommended.

5.1 Mechanism of Action

The capsules dissolve rapidly in the stomach releasing plenty of minimicrospheres, a multidose principle which is designed to achieve good mixing with the chyme, emptying from the stomach together with the chyme and after release, good distribution of enzymes within the chyme.

When the minimicrospheres reach the small intestine the coating rapidly disintegrates (at pH > 5.5) to release enzymes with lipolytic, amylolytic and proteolytic activity to ensure the digestion of fats, starches and proteins. The products of pancreatic digestion are then either absorbed directly, or following further hydrolysis by intestinal enzymes.

5.2 Pharmacodynamic properties

Treatment with enzelo markedly improves the symptoms of pancreatic exocrine insufficiency including stool consistency, abdominal pain, flatulence and stool frequency, independent of the underlying disease.

5.3 Pharmacokinetic properties

Pharmacokinetic data are not available as the enzymes act locally in the gastro-intestinal tract. After exerting their action, the enzymes are digested themselves in the intestine.

6.1 Animal Toxicology or Pharmacology

Not applicable.

Pancreatin is a pancreatic enzyme supplement, containing Lipase, Amylase, Protease

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on Pack

8.3 Packaging information

10 Blister strips of 10 capsules each

8.4 Storage and handing instructions

Store below 25°C.

Protect from light & moisture.

Keep out of reach of children.

• Capsule should be swallowed whole & not to be opened, chewed or crushed.
• Capsule should be taken with the first bite of a meal
• Should be taken with sufficient fluid, adequate hydration should be ensured
• Dosage should not be changed or increased without the physician direction
• Sporadic doses (not taken with food) should be avoided
• Do not take this medicine, if you are allergic to porcine pancreatin.
• Signs of an allergic reaction include a rash, itching or shortness of breath.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
• If you have any further questions, ask your doctor or pharmacist.

Amikacin injection

La-Mika® 100 Injection

Each vial (2ml) contains:

Amikacin Sulphate IP

equivalent to Amikacin 100 mg,

Methylparaben IP (as preservatives) 0.08 % w/v

Propylparaben IP (as preservatives) 0.02 % w/v

Water for Injection IP q.s.

LaMika® 250 Injection

Each vial (2ml) contains:

Amikacin Sulphate IP

equivalent to Amikacin 250 mg,

Methylparaben IP (as preservatives) 0.08 % w/v

Propylparaben IP (as preservatives) 0.02 % w/v

Water for Injection IP q.s.

LaMika® 500 Injection

Each vial (2ml) contains:

Amikacin Sulphate IP equivalent to Amikacin 500 mg,

Methylparaben IP (as preservatives) 0.08 % w/v

Propylparaben IP (as preservatives) 0.02 % w/v

Water for Injection IP q.s.

Injection 125 mg/250 mg/500 mg

4.1 Therapeutic indications

Treatment of serious infections due to amikacin sensitive organisms.

4.2 Posology and method of administration

Adults and adolescents over 12 years

The recommended intramuscular or intravenous dose for adults and adolescents with normal renal function (creatinine clearance ≥50 mg/min) is 15 mg/kg/day given either as a single daily dose or as several equal doses (e.g. 7.5 mg/kg all 12 hours, or 5 mg/kg every 8 hours). The total daily dose should not exceed 1.5 g. For endocarditis and febrile neutropenic patients, dosing should be done twice a day, as there is insufficient data for once-daily dosing.

Children from 4 weeks to 12 years

The recommended intramuscular or intravenous (slow intravenous infusion) dosage for children with normal renal function is 15-20 mg/kg/day, given either as a single daily dose of 15-20 mg/kg or divided into two doses of 7.5 mg/kg every 12 hours.

For endocarditis and febrile neutropenic patients, dosing should be done twice a day, as there is insufficient data for once-daily dosing.

Neonates

An initial dose of 10 mg/kg, then 7.5 mg/kg every 12 hours.

Preterm infants

The recommended dose for preterm infants is 7.5 mg/kg every 12 hours.

Dosage in elderly patients (≥ 65 years)

Renal function should be taken into account in elderly patients.

Life-threatening infections and/or those caused by Pseudomonas

The adult dose may be increased to 500 mg every eight hours but should neither exceed 1.5 g/day nor be administered for a period longer than 10 days. A maximum total adult dose of 1.5 g should not be exceeded.

Urinary tract infections (other than pseudomonal infections)

7.5 mg/kg/day in two equally divided doses (equivalent to 250 mg twice daily in adults). As the activity of amikacin is enhanced by increasing the pH, a urinary alkalizing agent may be administered concurrently.

Other routes of administration

Amikacin in concentrations of 0.25 % (2.5 mg/ml) may be used satisfactorily as an irrigating solution in abscess cavities, the pleural space, the peritoneum and the cerebral ventricles.

Intraperitoneal use

Following exploration for established peritonitis, or after peritoneal contamination due to faecal spill during surgery, Amikacin may be used as an irrigant after recovery from anaesthesia in concentrations of 0.25 % (2.5 mg/ml). If instillation is desired in adults, a single dose of 500 mg is diluted in 20 ml of sterile distilled water and may be instilled through a polyethylene catheter sutured into the wound at closure. If possible, instillation should be postponed until the patient has fully recovered from the effects of anaesthesia and muscle-relaxing drugs.

Monitoring

The renal function status should be evaluated by measuring the serum creatinine concentration or preferably by estimation of creatinine clearance. Blood urea nitrogen (BUN) is far less reliable for this purpose. Assessment of renal function should be performed at the start of therapy and should be re-evaluated at regular intervals during treatment.

Amikacin concentrations in serum should be measured in all patients receiving parenteral amikacin and must be measured in obesity, if high doses are being given, the elderly and in cystic fibrosis. Both peak and trough serum concentrations should be measured intermittently during therapy to ensure adequate but not excessive serum levels. In patients receiving multiple daily dosing peak concentrations (30-90 minutes after injection) of above 35 μg/ml and trough concentrations (just before the next dose) of above 10 μg/ml should be avoided.

In patients receiving once daily (or extended interval) dosing pre-dose ('trough') concentration should be less than 5 mcg/ml. Peak concentrations (approximately 60 minutes after administration) may exceed 35 mcg/ml.

If the pre-dose ('trough') concentration is high, the interval between doses must be increased. If the post-dose ('peak') concentration is high, the dose must be decreased.

Auditory and vestibular function should also be monitored during treatment, in particular if longer treatment duration (>7-10 days) is considered.

Dosage in renal impairment

In patients with impaired renal function (creatinine clearance <50 ml/min) the recommended dose has to be decreased and adjusted to the renal function. This can be achieved by increasing the dose interval and/or reducing the dose.

In all patients with renal impairment, serum amikacin peak and trough concentration and renal function must be monitored regularly and the dose regimen altered as necessary.

Once daily/extended interval dosing

Patients with renal impairment in whom once daily dosing would be considered appropriate if their renal function were normal may receive extended interval dosing.

The initial dose may be the same as in normal renal function. The dose interval should be at least 24 hours and extended according to the degree of renal impairment and the results of serum amikacin level measurements.

In severe renal impairment, the initial dose may have to be reduced in addition.

Once daily or extended interval dosing should be avoided in patients with a creatinine clearance less than 20 ml/minute.

A once daily/extended interval dose regimen should be avoided in children over 1 month of age with a creatinine clearance less than 20 ml/minute/1.73 m2.

Reduced dose at fixed intervals

If patients with renal impairment are given amikacin at fixed time intervals, the dose must be reduced. In these patients, the serum amikacin concentration should be measured to ensure accurate administration and to avoid excessive serum concentrations. If a determination of serum concentration is not possible and the patient's condition is stable, serum creatinine and creatinine clearance rates are the most readily available indicators of the extent of renal dysfunction and the consequent reduction in dose.

As renal function may alter appreciably during therapy, the serum creatinine should be checked frequently and the dosage regimen modified as necessary.

Multiple daily dosing

In patients with renal impairment in whom multiple daily dosing at fixed intervals would be considered appropriate if their renal function were normal, the dose must be reduced while the dose interval is maintained. Serum amikacin concentrations should be measured and creatinine clearance should be estimated regularly.

Treatment duration

At recommended dosages, infections caused by susceptible pathogens should respond to therapy within 24-48 hours. If clinical response does not occur within 3-5 days, therapy should be discontinued and the antibiotic susceptibility pattern of the invading organism should be rechecked. If necessary, alternative therapy should be considered. Failure of therapy may be due to the resistance of the organism or to septic locus requiring surgical drainage.

The average duration of treatment is 7-10 days. For all routes of administration, the maximum daily dose should not exceed 15-20 mg/kg/day. If prolonged treatment is required, it should be carried out after reviewing the necessity of using amikacin, determination of serum amikacin concentrations and additionally monitoring of renal, auditory and vestibular functions as closely as possible daily.

Method of administration

IM use or IV use after dilution.

4.3 Contraindications

• Hypersensitivity to the active substance or other aminoglycoside antibiotics.
• Due to the known cross sensitivities in this class of drugs, a history of hypersensitivity or serious toxic reactions to aminoglycosides may be a contraindication to all aminoglycosides.
• Because of its sulphate content, Amikacin must not be used in asthmatics with sulphate hypersensitivity.

4.4 Special warnings and precautions

Neuromuscular toxicity

Neuromuscular blockade and respiratory paresis have been reported following parenteral injection, topical lavage (such as orthopaedic and abdominal irrigation, or with local empyema treatment) or after oral administration of aminoglycosides. The risk of respiratory paresis when administering aminoglycosides irrespective of the route of administration should be considered, especially in patients receiving anaesthetics or neuromuscular blockers. Antidote in neuromuscular blockade: supply of calcium in ionized form (to relieve respiratory paralysis) and neostigmine. Mechanical ventilation may be necessary. In animal studies, neuromuscular blocks and myoparesis were found after administration of high doses of amikacin.

Aminoglycosides should be used with extreme caution in patients with myasthenia gravis as the curare-like effect on the neuromuscular junction may increase myasthenia with the potential for respiratory failure.

Aminoglycosides should be used with caution in patients with muscular disorders such as parkinsonism, since these drugs may aggravate muscle weakness because of their potential curare-like effect on the neuromuscular junction.

Nephrotoxicity and Ototoxicity

Amikacin is potentially nephrotoxic and ototoxic; therefore, patients must be carefully monitored clinically. Particular caution should be applied to patients with pre-existing renal insufficiency, or pre-existing hearing or vestibular damage. Safety for treatment periods which are longer than 14 days has not been established.

Precautions regarding the dose should be observed and adequate hydration maintained. Neurotoxicity occurring in patients treated with aminoglycosides is manifested as vestibular and/or bilateral ototoxicity.

Ototoxicity:

The risk of aminoglycoside-induced ototoxicity is greater in patients with impaired renal function, and in those who receive high doses, or in those whose therapy is prolonged over 5-7 days. High frequency deafness usually occurs first and can be detected only by audiometric testing. Vertigo or dizziness may occur and may be evidence of vestibular injury.

Other manifestations of neurotoxicity include numbness, tingling of the skin, muscle twitching and muscle spasms. At the first sign of hearing and/or balance disorders, therapy with amikacin should be discontinued.

The risk of ototoxicity due to aminoglycosides increases with the level of exposure either through consistently high peak serum concentrations or high serum trough concentrations. Patients who develop auditory or vestibular damage may not have any symptoms during therapy that may alert them to eighth nerve damage, and total or partial irreversible bilateral deafness or disabling vertigo may occur after the drug has been discontinued.

Aminoglycoside-induced ototoxicity is usually irreversible.

Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears and hearing loss) or nephrotoxicity requires discontinuation of the drug or dosage adjustment.

The use of amikacin in patients with a history of allergy to aminoglycosides or in patients who may have subclinical renal or eighth nerve damage induced by prior administration of nephrotoxic and/or ototoxic agents such as streptomycin, dihydrostreptomycin, gentamicin, tobramycin, kanamycin, bekanamycin, neomycin, polymyxin B, colistin, cephaloridine, or viomycin should be considered with caution, as toxicity may be additive.

In these patients amikacin should be used only if, in the opinion of the physician, therapeutic advantages outweigh the potential risks.

Nephrotoxicity

Aminoglycosides are potentially nephrotoxic. Renal toxicity appears independent of plasma obtained at the peak (Cmax). The risk of nephrotoxicity is increased in patients with impaired renal function and in patients receiving high doses or prolonged drug therapy.

Patients should be well hydrated during treatment and renal function should be assessed by the usual methods prior to starting therapy and daily during the course of treatment. A reduction of dosage is required if evidence of renal dysfunction occurs, such as presence of urinary casts, white or red cells, albuminuria, decreased creatinine clearance, decreased urine specific gravity, increased BUN, serum creatinine, or oliguria. If azotemia increases, or if a progressive decrease in urinary output occurs, treatment should be stopped.

Aminoglycosides may be inactivated by betalactams. Inactivation may continue in samples (serum, cerebrospinal fluid, etc.) taken for laboratory testing and then interfere with aminoglycoside level assays. The samples should therefore be adequately treated after collection (immediate determination, storage in the freezer or addition of beta-lactamase).

Concurrent and/or sequential systemic, oral, or topical use of other neurotoxic or nephrotoxic products, particularly bacitracin, cisplatin, amphotericin B, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides, should be avoided. Other factors that may increase risk of toxicity are advanced age and dehydration.

Other

Aminoglycosides are quickly and almost totally absorbed when they are applied topically, except to the urinary bladder, in association with surgical procedures.

Irreversible deafness, renal failure and death due to neuromuscular blockade have been reported following irrigation of both small and large surgical fields with an aminoglycoside preparation.

Prolonged antibiotic use may occasionally lead to overgrowth of resistant pathogens. The patient should be constantly monitored in this regard. Should a superinfection occur during therapy, appropriate measures must be taken.

Macular infarction sometimes leading to permanent loss of vision has been reported following intravitreous administration (injection into the eye) of amikacin.

Paediatric use

Aminoglycosides should be used with caution in premature and neonatal infants because of the renal immaturity of these patients and the resulting prolongation of serum half-life of these drugs.

4.5 Interaction with other medicinal products and other forms of interaction

Concurrent or serial use with other neurotoxic, ototoxic or nephrotoxic agents, particularly bacitracin, cisplatin, amphotericin B, cyclosporine, tacrolimus, cephaloridine, paromomycin, viomycin, colistimethate/colistin, vancomycin, or other aminoglycosides should be avoided both systemically and topically because of the potential for additive effects. Increased nephrotoxicity has been reported following concomitant parenteral administration of aminoglycoside antibiotics and cephalosporins. Concomitant cephalosporin use may spuriously elevate creatinine serum level determinations.

The risk of ototoxicity is increased when amikacin is used in conjunction with rapidly acting diuretic drugs, particularly when the diuretic is administered intravenously.

Diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue. Such agents include furosemide and ethacrynic acid which is itself an ototoxic agent. Irreversible deafness may result.

There is an increased risk of nephrotoxicity and possible ototoxicity when aminoglycosides are co-administered with platinum compounds.

The use of amikacin is not recommended in patients receiving anaesthetics or musclerelaxing drugs (such as volatile anaesthetics, d-tubocurarine, succinylcholine, decamethonium, atracurium, rocuronium, vecuronium) or in patients receiving massive transfusions of citrate-anticoagulated blood) as neuromuscular blockade and consequent respiratory depression may occur. If blockade occurs, calcium salts may reverse this phenomenon.

Indomethacin may increase the plasma concentration of amikacin in neonates.

In patients with severely impaired renal function, a reduction in activity of aminoglycosides may occur with concomitant use of penicillin-type drugs.

In vitro admixture of aminoglycosides with beta-lactam antibiotics (penicillins or cephalosporins) may result in significant mutual inactivation. A reduction in serum activity may also occur when an aminoglycoside or penicillin-type drug is administered in vivo by separate routes. Inactivation of the aminoglycoside is clinically significant only in patients with severely impaired renal function.

Inactivation may continue in specimens of body fluids collected for assay, resulting in inaccurate aminoglycoside readings. Such specimens should be properly handled (assayed promptly, frozen, or treated with beta-lactamase).

There is an increased risk of hypocalcaemia when aminoglycosides are administered with bisphosphonates.

There is an increased risk of nephrotoxicity and possibly of ototoxicity when aminoglycosides are administered with platinum compounds.

Concomitantly administered thiamine (vitamin B1) may be destroyed by the reactive sodium metabisulfite component of the amikacin sulphate formulation.

Sulphate is a very reactive compound. Therefore, mixtures with other medicinal products should be avoided.

4.6 Use in special populations

Pregnancy

Amikacin should be used in pregnant women and newborns only if clearly indicated and under medical supervision.

There is limited data on the use of aminoglycosides in pregnancy. Aminoglycosides can affect the development of the embryo/foetus in the womb. Aminoglycosides cross the placental barrier and there have been many reports of total, irreversible, bilateral congenital deafness in children whose mothers were treated with streptomycin during pregnancy.

Although adverse reactions to the unborn or neonate in pregnant women who have been treated with other aminoglycosides have not been reported, there is potential for harm.

If a pregnant patient is to be treated or becomes pregnant during treatment, medical advice should be provided on the risk of the potential hazard to the fetus.

Breast-feeding

It is not known if amikacin passes into the breast milk. The decision should be made to either stop breastfeeding or stop the therapy.

Fertility

In reproduction toxicity studies in mice and rats, no effects on fertility or foetal toxicity were reported.

4.7 Effects on ability to drive and use machines

No studies on the ability to drive and the use of machines have been performed. However, the occurrence of some side effects may affect the ability to drive vehicles and operate machinery.

4.8 Undesirable effects

All aminoglycosides have oto-, nephro- and neurotoxic potential.

The risk of these side effects is greater in patients with already impaired renal function, in patients receiving more than the recommended doses, prolonged therapy and in patients treated with other ototoxic or nephrotoxic drugs.

* Changes in renal function are usually reversible at the end of therapy. ** Amikacin is not intended for administration to the vitreous body. When amikacin was injected directly into the eye, maculopathies were observed, occasionally leading to complete loss of vision.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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 email to: medico@zuventus.com

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Significant risk of overdose is a potential nephro, oto and neurotoxic (neuromuscular blockade) effect. Respiratory neuromuscular blockade should be appropriately treated, including the administration of calcium in ionised form (for example as gluconate or lactobionate in 10-20 % solution). In case of overdose or toxic reactions, amikacin can be removed by peritoneal or hemodialysis. Continuous arteriovenous hemofiltration also leads to a reduction of amikacin. In neonates an exchange transfusion may be considered.

5.1 Mechanism of action / Pharmacodynamic properties

The mechanism of action of amikacin is due to a disruption of protein biosynthesis on the bacterial ribosome by interaction with the rRNA and subsequent inhibition of translation. This results in a bactericidal effect.

5.2 Pharmacokinetic Properties

After IM injection, amikacin is well tolerated locally and rapidly absorbed. After administration of 250 mg amikacin IM average serum peak concentrations of 11 μg/ml are achieved within one hour when amikacin 21 μg/ml is administered. I.V. short infusion of 500 mg amikacin results in an average serum concentration of 38 μg/ml (end of infusion). After 1 hour, 18 μg/ml were still detectable. In elderly patients (with mean creatinine clearance of 64 ml/min) the blood levels are 55 μg/ml after a 30-minute infusion of 15 mg/kg, 5.4 μg/ml after 12 hours and 1.3 μg/ml after 24 hours.

Serum half-life in patients with normal renal function is 2.4 hours, with an average volume of distribution of 24 litres and about 28 % of body weight. Plasma protein binding ranges from 0-11 %. The average serum clearance rate is 100 ml/min; The renal clearance rate in normal renal function is 94 ml/min. Amikacin is not metabolized and excreted almost exclusively by glomerular filtration. In normal renal function, approximately 91 % of the IM administered dose is excreted within the first 8 hours via urine in active form and 98 % within 24 hours.

Amikacin is removable by both peritoneal dialysis and hemodialysis. By peritoneal dialysis (patients without infection) about 20 % of the administered amikacin dose could be removed within 8-12 hours. Hemodialysis is much more effective. Depending on the dialysis method, either 50 % (range 29-81 %) of the administered dose was removed within 4 hours or 40-80 % was removed within 8 hours.

6.1 Animal toxicology or pharmacology

No long-term studies have been performed to evaluate the carcinogenic or mutagenic potential. Studies in rats have shown that daily doses up to 10 times recommended dose for humans did not cause any adverse effects on male and female fertility.

Amikacin, (as the sulphate) is a semi-synthetic aminoglycoside antibiotic derived from kanamycin.

D-Streptamine,O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→6)-O-[6-amino-6-deoxy-α-D-glucopyranosyl-(1→4)]-N1-(4-amino-2-hydroxy-1-oxobutyl)-2-deoxy-, (S)-, sulphate (1:2) (salt).

Chemical Structure: C₂₂H₄₃N₅O₁₃ • 2H2SO4

Molecular weight: 781.75

8.1 Incompatibilities

Aminoglycosides such as amikacin should not be combined with other medicines, but must be administered separately.

8.2 Shelf-life

Refer on package

8.3 Packaging information

2ml Injection vial containing amikacin

125 mg/250 mg/500 mg

8.4 Storage and handing instructions

Store below 300C. Protect from light and moisture. Don’t freeze. Keep out of reach of children. Do not use if solution is not clear or has particulate matter in vial.

Patients should be counselled that antibacterial drugs including amikacin sulphate injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When amikacin sulphate injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by amikacin sulphate injection or other antibacterial drugs in the future.

Patients should be counselled that diarrhoea is a common problem caused by antibiotics, and it usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Ferrous Ascorbate Suspension

Each 5 ml contains:

Ferrous Ascorbate

equivalent to Elemental Iron 30 mg

Excipients q.s.

Colour : Caramel USP-NF

Suspension

30mg/5ml, 150 ml bottle

4.1 Therapeutic indication

Prophylaxis and treatment of iron deficiency anemia.

4.2 Posology and method of administration

Prevention of iron deficiency:

Adults and elderly:

Feronia XT Suspension one 5 ml spoonful two to three times a day.

Paediatric population:

6-24 months of age: 12.5mg/day

2-5 years of age: 20-30mg/day

6-11 years of age: 30-60mg/day

Older children: 60mg/day

Premature infants: 5mg elemental iron per 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:

Adults and elderly:

Paediatric population:

Feronia XT Suspension 10 ml three times a day

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.
• Active peptic ulcer. Repeated blood transfusions. Regional enteritis and ulcerative colitis. Must not be used in anaemias other than those due to iron deficiency.

4.4 Special warnings and precautions for use

• Some post-gastrectomy patients show poor absorption of iron. Care is required when treating patients with iron deficiency anaemia who have treated or controlled peptic ulceration.
• 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.
• Paediatric population
• Feronia XT suspension should be kept out of the reach of children.
• Long-term treatment with Feronia XT suspension may increase the risk of dental caries. 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 suspension is 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.

4.6 Use in special populations

Pregnancy

Ferrous ascorbate can be used during pregnancy if clinically indicated.

Lactation

No adverse effects of ferrous ascorbate have been shown in breastfed infants of treated mothers. Feronia XT suspension can be used during breast-feeding if clinically indicated.

4.7 Effects on ability to drive and use machines

The medicine is considered unlikely to impair the ability to drive or to operate machinery safely.

4.8 Undesirable effects

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 diarrhoea). 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.

Reporting of side effects

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 email to: medico@zuventus.com

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.

Serum Iron

< 3 mg/L (55 micromol/L)

3-5 mg/L (55-90 micromol/L)

> 5 mg/L (90 micromol/L)

Severity

Mild toxicity

Moderate toxicity

Severe toxicity

Early signs and symptoms include nausea, vomiting, abdominal pain and diarrhoea. 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 hypovolaemia 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. If metabolic acidosis persists despite correction of hypoxia and adequate fluid resuscitation, an initial dose of 50 mmol sodium bicarbonate may be given and repeated as necessary, for adults guided by arterial blood gas monitoring (aim for a pH of 7.4). 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 anaemias. 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.

5.2 Pharmacokinetic properties

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, faeces, hair, skin, sputum, nails, and mucosal cells, and through blood loss.

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

Animal Toxicology or Pharmacology

As per the toxicity reports, designed to determine the acute oral toxicity of ferrous ascorbate Complex to Sprague Dawley rats. No signs of intoxication were observed in animals treated at the dose level of 2000 mg/kg of the test substance. All animals survived through the study period of 14 days. Animals from control and 2000 mg/kg dose group exhibited normal body weight gain on day 7 and day 14. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

Ferrous Ascorbate is a synthetic molecule of ascorbic acid and iron and is used as a source of iron for iron deficiency anaemia.

8.1 Incompatibilities

Not applicable

8.2 Shelf life

24 months

8.3 Packaging Information

Amber glass bottle with polypropylene, child resistant, tamper evident closure with PET faced Aluminium foil/EPE wads. Pack size: 1 x 150 ml

8.4 Special precautions for storage

Store below 30°C. Protect from light.

8.5 Storage and handing Instructions

No special requirements for disposal. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Do not administer Feronia XT suspension

• if the patient is allergic to active substances or any of the other ingredients of this medicine.
• if the patient suffers from Vitamin B12 deficiency.
• if the patient suffers from a blood disorder.
• if the patient had or is having repeated blood transfusions.
• if the patient has a stomach ulcer or other digestive conditions such as regional enteritis or ulcerative colitis.
• 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 suspension

• 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 suspension

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.
• Penicillamine (used for rheumatoid arthritis).
• Sulfasalazine (used for rheumatoid arthritis and bowel disease, e.g. Crohn’s disease).
• Cholestyramine (used for reducing blood cholesterol or control diarrhoea).
• Thyroxine (used for thyroid disease).
• Bisphosphonates (used for bone disease).
• Aminopterin and Methotrexate (used for certain cancers).
• Pyrimethamine (used for malaria).
• Trientine (used for Wilson’s disease).
• Methyldopa (used for high blood pressure).
• Zinc.
• Any other medicine, including medicines obtained without a prescription

Feronia XT suspension with food and drink

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