Acidum Ascorbicum Biotika Injection 500mg


SUMMARY OF PRODUCT CHARACTERISTICS
 
1. TRADE NAME OF THE MEDICINAL PRODUCT 
 
                                    ACIDUM ASCORBICUM Biotika 

 2. QUALITATIVE AND QUANTITATIVE COMPOSITION
 Active ingredient: Acidum ascorbicum 500 mg per 5 ml. 

 3. PHARMACEUTICAL FORM 
 Solution for injection
 Product Description: clear, colorless to slightly yellow solution, with no mechanical foreign particles. 

 4. CLINICAL PARTICULARS 

 4.1 Therapeutic indications 
 Hypovitaminosis C. To prevent the increased need or insufficient intake of vitamin C in children during the first year, mainly in non-breastfed, during the rapid growth during pregnancy and lactation, in old age, in athletes during the period of maximum performance,in workers dealing with ionizing radiation, with heavy metals, to increase the immune resistance. For therapy of pre-scorbutic states, of influenza and other infections, especially in the beginning, in hypercholesterolemia, in liver disease during the period of metabolic dysfunction and during symptoms of cholestasis, in a lengthy healing of wounds, fractures and trophic ulcers in the varicose syndrome, in decubital defects, prolonged use of drugs such as ataractic drugs or salicylate preparations, in anemia and optic neuritis, in ophthalmology to drip into the conjunctival sac in aniline colors and lime burns, in nitrosamines, aniline colors and anilides, heavy metals poisoning.  Vitamin C supplementation during parenteral nutrition. 

 4.2 Posology and method of administration 
 a / Dosage for children: 
 Children should be applied on average 170mg / m 2 / 24 hours. 
 b / Dosage for adults: 
 1-2 ampoules intravenously (500-1000 mg) daily.  Subcutaneous and intramuscular injection only in case of impossibility of intravenous application (big pain). 
 Note: Acidum ascorbicum may be added to Sol.  sodium chlorate isotonic, Sol.  Lactic sodium, Sol.  glucose, Sol.  fructose 5%, Sol.  xylose, 5% and 10% Sol.  Sorbitol 10%. 

 4.3 Contraindications 
 Hypersensitivity to the ascorbic acid. 

 4.4 Special warnings and precautions for use 
 In patients with glucose-6-phosphate dehydrogenase may result in hemolysis.  High doses of ascorbic acid reduce the level of serum uric acid with effect on its clearance and thus may complicate the diagnosis of hyperuricemia and in predisposed individuals it can accelerate the emergence of acute arthritis.  In patients with urinary stones in the history is the increased risk of urolithiasis. 
 When administered simultaneously with desferoxamine it is necessary to determine the iron excretion before and after administration of ascorbic acid. 
 In case of sudden interruption of the prolonged treatment with high doses paradoxical symptoms of hypovitaminosis C and decrease in non-specific immunity may appear. 

 4.5 Interaction with other medicinal products and other forms of interaction 
 High doses of vitamin C can increase the absorption of vitamin B12, of iron, and of penicillin-V from the gastrointestinal tract, may affect the metabolism of vitamin B6, can increase plasma concentrations of oral contraceptives, reduce efficiency of anticoagulants , reduce the effect of heparin.  Ascorbic acid increases the excretion of oxalates in the urine and thus a risk of crystalluria with the use of sulfonamides, PAS acid. Vitamin C may increase the amount of unbiotransformed isoprenaline competing for metabolic sulphation, and this may lead to significant potentiation of pharmacological activity.  Aspirin reduces the bioavailability of ascorbic acid. 
 Ascorbic acid should not be mixed with a solution of digoxin, heparin, with hyaluronidase with insulin, norepinephrine, aminophylline and  with a solution containing sodium bicarbonate. 

 4.6 Pregnancy and lactation 
 Ascorbic acid crosses the placenta and is distributed into breast milk. It has no teratogenic effects. In newborns of mothers who received high doses during the pregnancy, ascorbic acid can lead to paradoxical expressions of hypovitaminosis. 

4.7 Effects on ability to drive and use machines 
 No effect on attention. 
 
4.8 Undesirable effects 
 Ascorbic acid is generally well tolerated.  High doses can cause side effects.  In newborns of mothers who have taken high doses of vitamin C scurvy symptoms or discontinuation syndrome may occur.  A similar phenomenon can occur in people who suddenly stop taking large doses of ascorbic acid. There may be an increased incidence of thrombotic episodes, in patients with lack of glucose-6-phosphate dehydrogenase it may cause hemolysis.  Formation of renal stones, hyperoxalemia, glucosuria.  In predisposed individuals it can accelerate the emergence of acute arthritis.  The rise of oxalates excretion in urine sometimes causes a burning sensation during urination, transient diarrhea and excretion into the intestine.  High doses may rarely cause anxiety, impaired sleep and aggression.  In allergic individuals skin reactions and asthma attack may experience.  Local pain at the s.c. and i.m. administration.

 4.9 Overdose
 Symptoms of acute overdose are not known. 
 During the long term use it is important to reduce the dose gradually to avoid symptoms of hypovitaminosis after the therapy. 

 5 PHARMACOLOGICAL PROPERTIES 
 5.1 Pharmacodynamic properties 
 Pharmacotherapeutic group 
 Vitamin. 
 ATC code:  A11GA01 
 Mechanism of action 
 Ascorbic acid is involved in oxido-reduction reactions, hydroxylation reactions, amidation reactions and other reactions in the body.  Scavenging reactive forms of oxygen, which play a role in the pathogenesis of atherosclerosis and ischemia-reperfusion injury of tissues.  Ascorbic acid causes a decrease in platelet and leukocyte adhesion to vascular endothelium, inhibits the catabolic enzyme arylsufatase B, inhibits lipid peroxidation, protects against oxidants present in cigarette smoke, regenerates alpha-tocopherol.  The antioxidant properties of ascorbic acid are also involved in the healing of replants, fractures and wounds, and also in radioprotective effect.  It participates in the catabolic conversion of cholesterol to bile acids.  It is important in the metabolism of bone and connective tissues, because it participates in collagen synthesis and the incorporation of sulfate into mucopolysaccharide. It  has cytotoxic effects on cancer cells, the probable mechanism of action is the activation of DNA-ase and destruction of DNA or prooxidation effect on these cancer cells deficient in catalase.  It increases the body's immune response. 

 5.2 Pharmacokinetic properties 
 Physical supplies of ascorbic acid in healthy individuals are about 1500 mg, the recommended daily intake of 60 mg of vitamin C means plasma concentration of about 0.8 mg / dl, ie 45  mol / l.  Ascorbic acid concentration is higher in leukocytes and platelets than in erythrocytes.  The concentration in leukocytes is similar to concentration in tissues.  White blood cells of healthy adults have a concentration of around 27  g per 10 8 cells.  Quantity of ascorbic acid in leukocytes is inversely related to their number and therefore there may be falsely low results in patients with leukocytosis. The increased income will increase plasma concentrations, in the early stages linearly.  Renal threshold for ascorbic acid is about 1.5 mg / dl plasma (85  mol / l), then it is is eliminated. In human and animal tissues, there are more or less specific transport systems for ascorbic acid.  Despite the fact that most tissues prefers reduced ascorbate to oxidized form - dehydro-ascorbic acid and have a high affinity for it, they have the transporters with a very high affinity for it, there are opposite examples, eg, glucose transporter (GLUT-1) and the sodium-dependent transport systems.  Vitamin C is transported in human B lymphocytes by two components: high-affinity, which is a concentration-and temperature-dependent, saturable and inhibited by ouabainem.  The second component hasn´t been kinetically determined.  More than 90% of intracellular ascorbic acid in the cytosol of B lymphocytes. 
 The most important metabolic pathway of vitamin C is its conversion into oxalate, which is excreted in the urine, the main intermediate is dehydroascorbate.  Another metabolite of vitamin C, that is present in the human urine is inactive 2-sulphate of the ascorbic acid.  Besides it, other ascorbic acid´ metabolite has been isolated from the human urine – conjugate of ascorbic acid and beta-D-glucuronic acid. 
 Ascorbic acid crosses the placenta and is distributed into the breast milk.  Removal is by hemodialysis. 
 
5.3 Preclinical safety data 
 Ascorbic acid is not embryotoxic, cytotoxic, teratogenic or carcinogenic. 
 
6. PHARMACEUTICAL PARTICULARS 
 6.1 List of excipients 
 Excipients: sodium bicarbonate, sodium hydroxymethansulfinate, dihydrate trisodium edetate, water for injection. 
 Sodium content in the plant: 16 025 mg / ml, corresponding to 0.696 mmol / ml. 

 6.2 Incompatibilities 
 Not known 

 6.3 Shelf life 
 3 years 

 6.4 Special precautions for storage 
 Store at 10-25 ° C. Store in the original package to protect from light. 

 6.5 Nature and content of container 
 Clear glass ampoules with a label, insert PVC, paper box. 
 Package Size: 5 ampoules a 5 ml 
                       50 ampoules a 5 ml 

6.6 Special precautions for disposal and other handling 
 Medicinal product is a subject to medical prescription. 
 Any unused product or waste material should be disposed of in accordance with local requirements. 

 7. MARKETING AUTHORISATION HOLDER 
 BB Pharma, Kovriginova 1416/6, 147 00 Praha 4, Czech Republic 
 8. MARKETING AUTHORISATION NUMBER
 86/799/92-S/C 
 9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION
 1992 / June 30th, 1999
 10. DATE OF REVISION OF THE TEXT 
 January 18th,2006