ZU-C 500

Vitamin C Chewable Tablets 500

Each uncoated chewable tablets contains:

Ascorbic Acid IP 50 mg

Sodium Ascorbate IP equivalent to Ascorbic Acid 400 mg '

Ascorbyl Palmitate IP 120 mg '

L- Lysine Hydrochloride USP 7.49 mg

'equivalent to L- Lysine 6 mg

Excipients q.s.

Colour: Sunset of Yellow FCF

Oral, Chewable Tablets, 500 mg

4.1 Therapeutic indication

For the prevention and treatment of Vitamin C deficiency

4.2 Posology and method of administration

Method of administration

Vitamin C Chewable Tablets are to be chewed before swallowing.

Posology

• Adults and Children > 12 years: 1-2 tablets per day (equivalent to 500 or 1000 mg/day) until symptoms subside.
• Children 6-12 years: 1 tablet per day (equivalent to 500 mg/day) until symptoms subside.
• Vitamin C Chewable Tablets are not recommended for children under 6 years.

4.3 Contraindications

• Hypersensitivity to the active substance or to any of the excipients.
• Ascorbic acid should not be given to patients with hyperoxaluria.
• Oxalate urolithiasis and iron storage diseases (thalassaemia, haemochromatosis, sideroblastic anaemia) or other medical conditions that predispose individuals to iron overload.

4.4 Special warnings and precautions for use

a. Increased intake of ascorbic acid over a prolonged period may result in an increased renal clearance of ascorbic acid, and deficiency may result if the intake is reduced or withdrawn rapidly.

b. Exceeding the recommended dose should be avoided as there have been isolated reports of severe haemolysis in patients with erythrocytic glucose-6-phosphate dehydrogenase deficiency when taking high doses (> 4000 mg/day) of ascorbic acid. Do not exceed the recommended dose.

c. Caution is required and use the minimum recommended dose in patients with renal impairment.

d. Patients with rare hereditary fructose intolerance, glucose-galactose malabsorption or sucraseisomaltase deficiency should not take ascorbic acid.

e. Interference with serological testing

• Ascorbic acid may interfere with tests and assays for urinary glucose, giving false-negative results with methods utilising glucose oxidase with indicator and false-positive results with neocuproine methods.
• Estimation of uric acid by phosphotungstate or uricase with copper reduction and measurement of creatinine in non-deproteinised serum may also be affected.
• High doses of ascorbic acid may give false-negative readings in faecal occult blood tests.
• Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Drugs interactions

• Ascorbic acid increases the renal excretion of amphetamine.
• The plasma concentration of ascorbate is decreased by smoking and oral contraceptives.
• Ascorbic acid increases the absorption of iron. This should be borne in mind in the case of iron replacement.
• Concomitant administration of aspirin and ascorbic acid may interfere with absorption of ascorbic acid. Renal excretion of salicylate is not affected and does not lead to reduced anti-inflammatory effects of aspirin.
• Concomitant administration of aluminium-containing antacids may increase urinary aluminium elimination. Concurrent administration of antacids and ascorbic acid is not recommended, especially in patients with renal insufficiency.
• Co-administration with amygdalin (a complementary medicine) can cause cyanide toxicity.
• Concurrent administration of ascorbic acid with desferrioxamine enhances urinary iron excretion. Cases of cardiomyopathy and congestive heart failure have been reported in patients with idiopathic haemochromatosis and thalassaemias receiving desferrioxamine who were subsequently given ascorbic acid. Ascorbic acid should be used with caution in these patients and cardiac function monitored.
• Ascorbic acid may interfere with biochemical determinations of creatinine, uric acid and glucose in samples of blood and urine.

4.6 Use in special populations

Pregnancy

For ascorbic acid no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Pregnant women should exercise caution.

Breast-feeding

Ascorbic acid is excreted in breast milk. Though again caution should be exercised, no evidence exists suggesting such excretion is hazardous to the infant.

4.7 Effects on ability to drive and use machines

On the basis of the product's pharmacodynamic profile and reported adverse events, ascorbic acid has no known effect on an individual's ability to drive or operate machinery.

4.8 Undesirable effects

• Nervous system disorders: headache.
• Vascular disorders: flushing.
• Gastrointestinal disorders: Nausea, vomiting and stomach cramps. Large doses of ascorbic acid may cause diarrhoea.
• Skin and subcutaneous tissue disorders: redness of skin.
• Renal and urinary disorders: Patients known to be at risk of hyperoxaluria should not ingest ascorbic acid doses exceeding 1g daily as there may be increased urinary oxalate excretion. However, such risk has not been demonstrated in normal, non-hyper oxaluric individuals. Ascorbic acid has been implicated in precipitating haemolytic anaemia in certain individuals deficient of glucose-6-phosphate dehydrogenase. Increased intake of ascorbic acid over a prolonged period may result in increased renal clearance of ascorbic acid, and deficiency may result if the intake is reduced or withdrawn rapidly. Doses of more than 600mg daily have a diuretic effect.
• 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: https://www.zuventus.com/drug-safety-reporting By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Symptoms: At doses of over 3g per day unabsorbed ascorbic acid is mainly excreted unmetabolised in the faeces. Absorbed ascorbic acid additional to the body's needs is rapidly eliminated. Large doses of ascorbic acid may cause diarrhoea and the formation of renal oxalate calculi. Symptomatic treatment may be required. Ascorbic acid may cause acidosis or haemolytic anaemia in certain individuals with a deficiency of glucose 6-phosphate dehydrogenase. Renal failure can occur with massive ascorbic acid overdosage.

Management: Gastric lavage may be given if ingestion is recent otherwise general supportive measure should be employed as required.

Pharmacotherapeutic group: Vitamins – Ascorbic acid (vitamin C) ATC code: A11GA01

5.1 Mechanism of Action

Ascorbic acid, coupled with dehydroascorbic acid to which it is reversibly oxidised, has a variety of functions in cellular oxidation processes.

5.2 Pharmacodynamicproperties

5.3 Pharmacodynamic properties

Ascorbic acid is required in several important hydroxylations, including the conversion of proline to hydroxyproline (and thus collagen formation e.g. for intercellular substances and during wound healing); the formation of the neurotransmitters 5-hydroxytryptamine from tryptophan and noradrenaline from dopamine, and the biosynthesis of carnitine from lysine and methionine. Ascorbic acid appears to have an important role in metal ion metabolism, including the gastrointestinal absorption of iron and its transport between plasma and storage organs. There is evidence that ascorbic acid is required for normal leucocyte functions and that it participates in the detoxification of numerous foreign substances by the hepatic microsomal system. Deficiency of ascorbic acid leads to scurvy, which may be manifested by weakness, fatigue, dyspnoea, aching bones, perifollicular hyperkeratosis, petechia and ecchymosis, swelling and bleeding of the gums, hypochromic anaemia and other haematopoietic disorders, together with reduced resistance to infections and impaired wound healing. In addition, an ascorbic acid deficiency impairs the immune defence reactions, especially chemotaxis, complement activation and interferon production. Ascorbic acid improves the absorption of iron salts by reducing ferric ions and forming iron chelates. It blocks the chain reactions triggered by oxygen radicals in aqueous compartments of the body. The anti-oxidative functions form a close biochemical interaction with those of vitamin E, vitamin A and carotenoids.

5.4 Pharmacokinetic properties

Absorption

Ascorbic acid is well absorbed from the gastrointestinal tract. As the unit dose increases the bioavailability falls to 60-75% after 1 g, to approximately 40% after 3 g and down to 16% after 12 g. The unabsorbed proportion is broken down by the flora in the large intestine, predominantly to CO2 and organic acids.

Distribution

Ascorbic acid is widely distributed to all tissues. Body stores of ascorbic acid normally are about 1.5g. The concentration is higher in leucocytes and platelets than in erythrocytes and plasma.

Metabolism

In healthy adults the maximum metabolic turnover of 40 to 50 mg/day is achieved at plasma concentrations of 0.8 to 1.0 mg/dl. The total daily turnover is about 1 mg/kg. At extremely high oral doses plasma concentrations of up to 4.2 mg/dl are achieved for a short time after about 3 hours

Elimination

Ascorbic acid additional to the body's needs, generally amounts above 200mg daily, is rapidly eliminated; unmetabolised ascorbic acid and its inactive metabolic products are chiefly excreted in the urine. The amount of ascorbic acid excreted unchanged in the urine is dose-dependent and may be accompanied by mild diuresis.

6.1 Animal Toxicology or Pharmacology

There are no other preclinical data of relevance to the prescriber which are additional to that already included in other sections of the prescribing information.

Vitamin C Chewable Tablets 500 is a blend of water soluble ascorbic acid (450mg) along with 120 mg Ascorbyl palmitate, a fat-soluble derivative of ascorbic acid. Ascorbyl palmitate is approximately 42.5% of Vitamin C (ascorbic acid). Considering this 120 mg Ascorbyl palmitate will provide approximately 50 mg of ascorbic acid. Therefore, each Vitamin C Chewable 500 Tablets provide tablet provides total 500 mg of ascorbic acid (Vitamin C).

Ascorbyl Palmitate (120 mg):

• Ascorbyl palmitate is also known as "vitamin C ester" because it is an ester formed from ascorbic acid and palmitic acid. It is used either as a fat-soluble form of vitamin C, or as an antioxidant food additive.
• Ascorbyl palmitate possesses all the benefits of vitamin C. Ascorbyl palmitate is highly bioavailable, fat-soluble derivative of ascorbic acid and is able to be stored in the lipid cell membrane until the body is ready to put it to use.
• Ascorbyl palmitate is an amphipathic molecule (fat as well as water soluble form of vitamin C) which is better absorbed than ascorbic acid (water-soluble form). This dual solubility allows it to be incorporated into cell membranes.
• The fat-soluble aspect of ascorbyl palmitate extends vitamin C free radical protection (free radical protection) into the fat parts of the body.
• When incorporated into the cell membranes of human red blood cells, ascorbyl palmitate has been found to protect them from oxidative damage and to protect alpha-tocopherol (a fat-soluble antioxidant) from oxidation by free radicals.

L-Lysine:

L-Lysine is an essential amino acid, necessary building block for all proteins in the body. Amino acids such as L-lysine and vitamin C are crucial for the body’s production of collagen and the protection of the endothelium of the artery walls.

8.1 Incompatibilities

None.

8.2 Shelf-life

18 months

8.3 Packaging information

20 strips of 15 tablets in each strip

1 strip of 15 chewable tablets

8.4 Storage and handing instructions

Store at a temperature not exceeding 25°C.

Protect from Light.

Keep out of reach of children.

Chew the tablets carefully before swallowing. Always take this medicine exactly as your doctor has told you. Do not take Ascorbic Acid Tablets if:

• You are allergic to Ascorbic Acid or any of the other ingredients of this medicine.
• You suffer from hyperoxaluria (excretion of urine containing large amounts of calcium oxalate crystals).

Talk to your doctor before taking Ascorbic Acid Tablets:

• If you are to undergo any blood or urine tests as ascorbic acid can interfere with some blood and urine tests.
• If you are a regular smoker.
• If you have kidney failure as ascorbic acid enhances aluminium absorption (present in antacids) which may reach toxic levels.

Tell your doctor if you are taking, have recently taken or might take any other medicines. This is particularly important if you are taking any of the following:

• Amphetamines.
• Contraceptives.
• Aspirin.
• Iron-containing medicines.
• Amygdalin (Vitamin B17) - can cause cyanide toxicity

Ascorbic Acid Tablets should not be taken for the first month after starting desferrioxamine treatment

If you stop taking Ascorbic Acid Tablets:

Keep taking this medicine until your doctor tells you to stop. You may need to stop taking the tablets slowly as they may alter your kidney function.