Ascorbic acid solution for injection 100 mg/ml Prefilled Syringe Taj Pharma.
1. NAME OF THE MEDICINAL PRODUCT
Ascorbic acid solution for injection/infusion
100 mg/ml Prefilled Syringe Taj Pharma.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml of solution contains 100 mg ascorbic acid (Acidum ascorbicum).
Each Prefilled Syringe of 5 ml contains 500 mg ascorbic acid.
Excipients with known effect:
Each Prefilled Syringe of 5 ml contains 500mg sodium sulfite, anhydrous. For the full list of excipients, see section 6.1.
3.PHARMACEUTICAL FORM
Solution for injection/infusion.
Clear, colourless to pale brownish-yellow solution free from visible particles, with a pH of 5.0-7.0. Osmolality: 1050-1200 mOsmol/kg, hypertonic solution.
4.CLINICAL PARTICULARS
4.1 Therapeutic indications
Ascorbic acid Prefilled Syringe100 mg/ml contains solution for injection/infusion is used for treatment of scurvy and for prophylaxis of ascorbic acid deficiency when oral use is not possible or absorption after oral intake is insufficient in all age groups.
4.2 Posology and method of administration
Posology
Adults (including elderly patients)
Treatment of scurvy
250 mg once or twice daily from 2 to 21 days (until skeletal changes and haemorrhagic disorders are reversed).
Prophylaxis of ascorbic acid deficiency The usual dose is: from 50 to 200 mg daily.
Duration of treatment should be individualized, based on the therapeutic response and severity of the disease.
Patients (adults, including elderly patients) with renal impairment
In patients with recurrent renal stone formation, the daily dose of vitamin C should not exceed 100 mg to 200 mg.
Patients with severe or terminal renal failure (dialysis patients) should receive no more than 50 mg to 100 mg daily (see section 4.4).
Paediatric population (neonates, infants, children and adolescents under 18 years of age)
Treatment of scurvy
The intramuscular/intravenous daily dose in children is from 100 mg to 300 mg in divided doses, for 7-10 days.
Prophylaxis of ascorbic acid deficiency 25 – 75 mg daily.
Duration of treatment should be individualized, based on the therapeutic response.
Paediatric patients with renal impairment
Patients should be treated with lower individually adapted dose (see section 4.4).
Method of administration
Ascorbic acid Prefilled Syringe contains solution for injection/infusion is administered intramuscularly or slowly intravenously. Intramuscular administration is recommended.
Preparation and administration of intramuscular injection
Withdraw the required dose of Ascorbic acid Prefilled Syringe100 mg/ml solution for injection/infusion. Inject slowly high into the gluteal muscle, 5 cm below the iliac crest. Rotate injection sites for subsequent injection
Preparation and administration of intravenous injection
Rapid intravenous injection of the drug can cause temporary dizziness and should be avoided.
Since undiluted solution is hypertonic, it is recommended to dilute Vitamin C Sopharma 100 mg/ml solution for injection/infusion before intravenous injection in at least an equal volume of diluent such as 9 mg/ml (0.9%) sodium chloride solution or 50 mg/ml (5%) glucose solution and to inject slowly intravenously.
Preparation and administration of intravenous infusion
Withdraw the required Ascorbic acid Prefilled Syringe100 mg/ml solution for injection/infusion dose and add to
100 ml 9 mg/ml (0,9%) sodium chloride solution or 50 mg/ml (5%) glucose solution. Give by intravenous infusion over 15 – 30 minutes.
The solution should be administered immediately after mixing.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hyperoxaluria.
Oxalate urolithiasis.
4.4 Special warnings and precautions for use
Large dose of ascorbic acid elevates urinary oxalate levels and may precipitate the formation of calcium oxalate urinary calculi. Patients with impaired renal function and/or history of renal stones can be more susceptible to this effect (see section 4.2).
In case of glucose-6-phosphate dehydrogenase deficiency, high doses can induce haemolysis (see section 4.9).
Intravenous administration of ascorbic acid can be painful and rarely can cause thrombophlebitis due to chemical irritation. Rapid venous injection of ascorbic acid should be avoided and care should be taken to avoid extravasation during the infusion (see section 4.2).
In patients with disorders of the venous vascular system, thrombophlebitis, on anticoagulant therapy and with predisposition to thrombosis, intramuscular administration of the product is recommended.
Ascorbic acid should be administered with caution to patients with iron overload (e.g. hemochromatosis, thalassemia, sickle cell anaemia, sideroblastic anaemia).
High doses of ascorbic acid has been associated with sickle-cell crisis in patients with sickle-cell anaemia.
There are rare reports of scurvy due to tolerance or resistance following cessation after long-term high- dose use, such as in infants born to mothers taking 400 mg/day or greater throughout their pregnancy (see section 4.6).
The excessive dose of vitamin C may interrupt pregnancy. Excipients
This medicinal product contains sodium sulfite, anhydrous (E221) as an excipient, which may rarely
cause severe hypersensitivity reactions and bronchospasm.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose of 100 mg (1ml), i.e. essentially sodium-free.
This medicinal product contains:
1,2 mmol (or 27,56 mg) sodium per dose of 200 mg (2ml);
1,8 mmol (or 41,3 mg) sodium per dose of 300 mg (3ml);
3 mmol (or 68,9 mg) sodium per dose of 500 mg (5 ml).
To be taken into consideration by patients on a controlled sodium diet.
4.5 Interaction with other medicinal products and other forms of interaction
Salicylates
In case of concomitant administration the amount of vitamin C in body may decrease because of possible reduced absorption of ascorbic acid and increased urinary excretion of it. Salicylates have been found to reduce the absorption of ascorbic acid by about a third.
Corticosteroids
Increase the oxidation of ascorbic acid.
Anticoagulants
Ascorbic acid may influence the intensity and duration of action of coumarin anticoagulants (for example, warfarin, bishydroxycoumarin).
Oral contraceptives
Oral contraceptives lower serum levels of ascorbic acid. When used concomitantly with estrogen containing medicinal products, ascorbic acid may increase estrogen concentration.
Iron-containing products
Ascorbic acid can increase iron absorption in the gastrointestinal tract.
Desferrioxamine
Ascorbic acid may increase the excretion of iron when given concomitantly with desferrioxamine. However, cases of cardiomyopathy and congestive heart failure have occurred in patients on concomitant treatment. It may be that ascorbic acid mobilises iron from spleen and other reticuloendothelial tissues resulting in increased iron deposition in visceral organs.
Isoprenaline
In concomitant administration with ascorbic acid, the chronotropic effect of isoprenaline decreases.
Alcohol
Alcohol reduces ascorbic acid levels.
Disulfiram
Chronic use or high doses of ascorbic acid may interfere with the disulfiram – alcohol interaction when used concurrently.
Mexiletine
The use of large doses of ascorbic acid may accelerate the urinary excretion of mexiletine.
Barbiturates or primidon
May increase urinary excretion of ascorbic acid when administered together with barbiturates or primidone.
Fluphenazine, other phenothiazine derivatives
Concomitant administration of ascorbic acid and fluphenazine and other phenothiazine derivatives leads to reduction of phenothiazine derivatives therapeutic effect.
Amphetamines and tricyclic anti-depressants
Ascorbic acid decreased renal tubule reabsorption of amphetamines and tricyclic anti-depressants.
Aluminium containing medicinal products
Ascorbic acid may enhance the absorption of aluminium and potentiate undesirable effects.
Influence of ascorbic acid in laboratory parameters
Because ascorbic acid is a strong reducing agent, it interferes with numerous laboratory tests based on oxidation-reduction reactions. The degree of interference with laboratory tests depends on several factors (e.g., the concentration of ascorbic acid, the resulting pH, the specific reagents used). Specialized references should be consulted for specific information on laboratory test interferences caused by ascorbic acid.
Ascorbic acid at high doses can compromise the test results of transaminases, lactatdehydrogenase, bilirubin.
Ascorbic acid, as a redox-compound, affects various oxidative-reduction tests for determination of glucose in urine and serum. Ascorbic acid administration should be discontinued 1-2 days before such test. Diabetic patients taking more than 500 mg vitamin C daily may obtain false readings of their urinary glucose test.
Ascorbic acid has been reported to interfere with screening tests for acetaminophen in urine, causing negative screening tests to occur in the presence of acetaminophen. Acetaminophen screening tests employing methods which are not based upon hydrolysis and formation of an indophenol blue chromogen should be used in patients receiving ascorbic acid. Alternatively, the addition of copper sulfate overcomes this interference.
Large doses of ascorbic acid (i.e., greater than 500 mg daily) may interfere in carbamazepine levels when measured by the Ames ARIS(R) method. A method of carbamazepine assay other than the Ames ARIS(R) method should be used in patients receiving ascorbic acid.
Use of ascorbic acid (greater than 1 g daily) may cause a false negative guaiac fecal occult blood test. Ascorbic acid should be discontinued if an interference with a guaiac test is suspected.
4.6 Fertility, pregnancy and lactation
Pregnancy
Ascorbic acid crosses the placenta.
With the ingestion of high doses (400 mg/day or greater) of ascorbic acid during pregnancy, the foetus can adapt and then develop a scorbutic illness after birth as a withdrawal reaction (see section 4.4).
Administration of Ascorbic acid Prefilled Syringe100 mg/ml solution for injection/infusion for pregnant woman should be considered only when it is absolutely necessary.
Breastfeeding
Ascorbic acid is excreted into breast milk, but there is no evidence of any hazard for breastfed infant. Nevertheless, administration in breastfeeding mothers should be done with precaution.
Fertility
There are no data about effect of ascorbic acid on fertility.
4.7 Effects on ability to drive and use machines
Ascorbic acid Prefilled Syringe100 mg/ml solution for injection/infusion has no influence on the ability to drive and use machines.
4.8 Undesirable effects
Undesirable effects are described below and are classified by organs and systems, and by frequency as follows: very common (³1/10), common (³1/100 to <1/10), uncommon (³1/1000 to <1/100), rare (³1/10000 to <1/1000), very rare (<1/10000) and not known (cannot be estimated from the available data).
Nervous system disorders
Not known: headache, insomnia, temporary faintness or dizziness as a result of too rapid intravenous administration.
Gastrointestinal disorders
Rare: nausea, vomiting, abdominal colic, diarrhoea.
Diarrhoea may occur after oral dosage of 1 g or more daily or greater.
Skin and subcutaneous tissue disorders
Rare: at high doses may provoke allergic reactions.
Renal and urinary disorders
Rare: polyuria, nephrolithiasis in some patient. Doses of 600 mg or more daily have a diuretic action.
Acidification of urine by large doses of ascorbic acid might cause precipitation of urate, oxalate or cystine stones or drugs in the urinary tract, especially since some ascorbate is metabolised to oxalate. Some patients with pre-existing renal disease have been reported to develop renal failure following treatment with high doses of ascorbic acid.
General disorders and administration site condition
Rare: transient mild soreness and hardening at the site of intramuscular injection.
Not known: hot flushes, fatigue, “rebound” effect in the form of vitamin C deficiency after discontinuation of high doses therapy.
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.
4.9 Overdose
Symptoms
Overdosage of ascorbic acid may cause acidosis and haemolytic anaemia in predisposed individuals e.g., in patients with glucose-6-phosphate dehydrogenase deficiency. In massive ascorbic acid overdosage, renal failure may occur due to excessive oxalate excretion.
At high doses vitamin C may provoke allergic reactions.
Treatment
In the event of severe or unusual untoward effects, ascorbic acid therapy should be terminated. Symptomatic or supportive measures should be taken.
5.0 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Vitamins, ascorbic acid (vitamin C), plain.
Mechanism of action
Ascorbic acid, a water-soluble vitamin, is essential for formation of collagen and intercellular material, and therefore necessary for the development of cartilage, bone, teeth and for the healing of wounds. It is also essential for the conversion from folic acid to folinic acid, facilitates iron absorption from the gastro-intestinal tract and influences haemoglobin formation and erythrocyte maturation.
5.2 Pharmacokinetic properties
Absorption
Ascorbic acid is rapidly and completely absorbed after parenteral administration.
Distribution
Ascorbic acid is distributed in all tissues with about 25% bound to plasma proteins. Ascorbic acid crosses the placenta.
Large concentrations of the vitamin C are found in the liver, leukocytes, platelets, glandular tissues,
and the lens of the eye, while low levels are found in plasma and saliva.
A plasma ascorbate concentration of 50 μmol/l is indicative of adequate status that corresponds to a body pool of about 1,5 g with metabolic losses of about 3,0% per day (or 40-50 mg/day).
Catabolic turnover varies widely, about 10 to 45 mg/day, over a wide range of dietary intakes due to body pool size.
Ascorbic acid plasma concentration below 10 μmol/l is associated with scurvy.
Biotransformation
Ascorbic acid is metabolized in the liver to dehydroascorbic acid, 2-3-diketogulonic acid and oxalic acid which are excreted with urine.
Elimination
Ascorbic acid is excreted with urine unchanged and in the form of metabolites. About 50% of the oxalates in urine are formed during ascorbic acid metabolism, but there are no data of oxalate concretion formation in the kidneys during prolonged therapy.
The quantity of unchanged ascorbic acid is dose-dependent – unmetabolized ascorbate is excreted with dietary intakes up to about 80 mg/day and that renal excretion of ascorbate increases proportionately with higher intakes.
Up to 40% of plasma ascorbic acid can be removed by haemodialysis.
5.3 Preclinical safety data
Non-clinical data do not reveal any specific risk for humans based on conventional pharmacological studies of safety, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive toxicity.
6.0 PHARMACEUTICAL PARTICULARS
6.1List of excipients
Sodium hydrogen carbonate Sodium sulfite, anhydrous, Edetic acid
Water for injections
6.2 Incompatibilities
Ascorbic acid is incompatible in solution with aminophyllyine, bleomycin, erythromycin, lactobionate, nafcillin, sodium nitrofurantoin, conjugated oestrogens, sodium bicarbonate, sulfafurazole diethanolamine, chloramphenicol sodium succinate, chlorothiazide sodium and hydrocortisone sodium succinate.
Ascorbic acidis rapidly oxidised in alkaline media, in the presence of copper and iron ions as well as other oxidants.
6.3 Shelf life
2 years.
6.4 Special precautions for storage
Store below 25ºC. Do not freeze.
6.5 Nature and contents of container
5 ml solution in Prefilled Syringe of colourless glass (Type І), with marking for Prefilled Syringe opening (a colour dot/ring). A self-adhesive label is attached on each Prefilled Syringe.
. Not all pack sizes may be marketed.
Special precautions for disposal and other handling
Ascorbic acid Prefilled Syringe100 mg/ml solution for injection/infusion should be used immediately after opening.
Ascorbic acid Prefilled Syringe100 mg/ml solution for injection/infusion should only be mixed with those infusion solutions which are recommended:
sodium chloride 9 mg/ml (0.9%) solution for infusion; glucose 50 mg/ml (5%) solution for infusion. For instructions on administration, see section 4.2.
Disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. MANUFACTURED IN INDIA BY:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com
