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may result in an increased renal clearance of ascorbic acid, and deficiency may result if the intake is reduced or withdrawn rapidly.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

Zinc Acetate Oral Solution USP

Each 5ml contains:

Zinc acetate USP (as dihydrate) equivalent to Elemental Zinc 20 mg

Colour: Sunset Yellow FCF.

In a mentholated flavoured syrup base.

Dosage form - Syrup

Dosage Strength –Elemental Zinc 20 mg/5 ml

4.1 Therapeutic indication

For the treatment of acute diarrhoea in children as an adjunct to oral rehydration.

4.2 Posology and method of administration

As per WHO/UNICEF recommendations zinc supplementation can be used orally, as an adjunct to Oral Rehydration Therapy in acute diarrhea in following dose regimen:

In infants (under six months): 2.5ml (10 mg of elemental Zinc) daily for 10–14 days after meals

In children (children older than six months): 5 ml (20 mg of elemental Zinc) daily for 10 –14 days after meals

4.3 Contraindications

• Hypersensitivity to zinc salts or any component of a zinc-containing supplement.
• Copper deficiency

4.4 Special warnings and precautions for use

Renal impairment: Accumulation of zinc may occur in cases of renal failure. Hence caution should be exercised in patients with renal impairment with careful patient monitoring

4.5 Drugs interactions

Copper: Zinc may inhibit the absorption of copper.

Tetracyclines: Zinc may reduce the absorption of concurrently administered tetracyclines, also the absorption of zinc may be reduced by tetracyclines; when both are being given an interval of at least three hours should be allowed.

Quinolone Antibacterials: Zinc may reduce the absorption of quinolones; ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin and ofloxacin.

Calcium Salts: The absorption of zinc may be reduced by calcium salts.

Iron: The absorption of zinc may be reduced by oral iron, also the absorption of oral iron may be reduced by zinc.

Penicillamine: The absorption of zinc may be reduced by penicillamine, also the absorption of penicillamine may be reduced by zinc. Trientine: The absorption of zinc may be reduced by trientine, also the absorption of trientine may be reduced by zinc.

4.6 Use in special populations

Pregnancy

The safety of this product in human pregnancy has not been established. Zinc crosses the placenta and is present in breast milk.

Lactation

Zinc is excreted in human breast milk and zinc-induced copper deficiency in the breast-fed baby may occur. Therefore, breast-feeding should be avoided during zinc therapy.

4.7 Effects on ability to drive and use machines

Zinconia® Syrup has no influence on the ability to drive and use machines.

4.8 Undesirable effects

Zinc salts may cause abdominal pain, dyspepsia, nausea, vomiting, diarrhoea, gastric irritation and gastritis. There have also been cases of irritability, headache and lethargy observed. Zinc may interfere with the absorption of copper, leading to reduced copper levels, and potentially copper deficiency. The risk of copper deficiency may be greater with long-term treatment (e.g. if zinc deficiency is no longer present) and/or with higher doses of zinc.

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.

4.8 Overdose

Zinc acetate is corrosive in overdosage. Symptoms are corrosion and inflammation of the mucous membrane of the mouth and stomach; ulceration of the stomach followed by perforation may occur. Gastric lavage and emesis should be avoided. Demulcents such as milk should be given. Chelating agents such as sodium calcium edetate may be useful.

5.1 Mechanism of Action

Zinc supplementation improves immunity. Various studies have quoted different mechanisms of action of zinc in persistent and infective diarrhea patients: Preclinical studies have shown that zinc inhibits cAMP induced, chloride dependent fluid secretion by inhibiting basolateral potassium (K) channels of ileal mucosa. Zinc also improves the absorption of water and electrolytes, improves regeneration of the intestinal epithelium, increases the levels of brush border enzymes, and enhances the immune response, allowing for a better clearance of the pathogens. Recent evidence demonstrate that zinc inhibits toxin induced cholera. Thus by different mechanisms zinc supplementation could be beneficial in diarrhea.

It is demonstrated that zinc supplementation could improve symptoms of acute respiratory illness. It may prevent premature cell destruction and promotes activity of enzymes that affect production of prostaglandin from essential fatty acids, and as a result, leads to decrement of inflammation in airways. It also can activate natural killer cells, macrophages and lymphocytes. Zinc administration has also been demonstrated to improve tachypnea during acute phase of Acute Lower Respiratory Tract Infections in hospitalized children.

Zinc has critical effect in homeostasis, in immune function, oxidative stress, apoptosis, and aging, and significant disorders of great public health interest are associated with zinc deficiency. In many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, autoimmune diseases, aging, age-related degenerative diseases, and Wilson's disease, the concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress, and lead to the generation of inflammatory cytokines. In these diseases, oxidative stress and chronic inflammation may play important causative roles.

5.2 Pharmacodynamic properties

Zinc is an essential trace element involved in many enzyme systems. Severe deficiency causes skin lesion, alopecia, diarrhoea, increased susceptibility to infections and failure to thrive in children. Symptoms of less severe deficiency include distorted or absent perceptions of taste and smell and poor wound healing.

5.3 Pharmacokinetic properties

Zinc is absorbed (20% to 30%) from the gastrointestinal tract and distributed throughout the body. The highest concentrations occur in hair, eyes, male reproductive organs and bone. Lower levels are present in liver, kidney and muscle. In blood 80% is found in erythrocytes. Plasma zinc levels range from 70 to 110μg/dL and about 50% of this is loosely bound to albumin. About 7% is amino-acid bound and the rest is tightly bound to alpha 2-macroglobulins and other proteins. The liver is the main storage for zinc and hepatic zinc levels are increased during maintenance therapy with zinc.

The plasma elimination half-life of zinc in healthy subjects is around 1 hour. The elimination of zinc results primarily from faecal excretion with relatively little from urine and sweat. The faecal excretion is in the greatest part due to the passage of unabsorbed zinc but it is also due to endogenous intestinal secretion.

None stated.

Zinc acetate as the dihydrate is a salt of zinc used for the treatment of acute diarrhoea in children as an adjunct to oral rehydration.

Zinc is an integral component of many metallo enzymes in the body; it is involved in the synthesis and stabilization of proteins, DNA and RNA, and plays a structural role in ribosomes and membranes. Zinc is involved in oxygen transport and protection against free radical damage. Zinc facilitates wound healing and helps maintain normal growth rates, normal skin hydration and senses of taste and smell. Zinc acts as an integral part of several enzymes important to protein and carbohydrate metabolism.

Its structural formula is

Zinc acetate dihydrate structure

Molecular Formula: C₄H₆O₄Zn.2H₂O

Molecular Weight: 219.5 g/mol

8.1 Incompatibilities

None.

8.2 Shelf-life

Refer to pack.

8.3 Packaging information

Amber-coloured bottle of 100 mL.

8.4 Storage and handing instructions

Store in a cool, dry place protected from light.

Keep out of reach of children.

Do not take Zinconia® Syrup

- if you are allergic (hypersensitive) to zinc acetate or any of the other ingredients.

- if you have copper deficiency

Talk to your doctor, before taking Zinconia® Syrup if you suffer from kidney disease. If this applies to you it is important that you tell your doctor or pharmacist before taking Zinconia® Syrup and they will decide what to do.

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

• Copper supplements
• Tetracycline antibiotics (such as oxytetracycline or doxycycline) used to treat certain bacterial infections
• Quinolone antibiotics (such as ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin and ofloxacin) used to treat certain bacterial infections
• Calcium Salt Preparations
• Penicillamine (used to treat rheumatoid arthritis, Wilson's disease, autoimmune hepatitis and cystinuria)
• Trientine (used in the treatment of Wilson's disease)

Zinconia® Syrup should be taken after meals. Patients should take Zinconia® Syrup two to three hours after meals. In the rare event of gastric intolerance of zinc, generally occurring with the morning dose, this dose may be taken between breakfast and lunch.

16th Oct. 2023

Vitamin-D3 (Cholecalciferol) Drops

Each ml contains:

Cholecalciferol IP 800 IU.

In a Flavoured base q.s.

Colour: Tartrazine Supra

Appropriate overages of vitamin added to compensate loss on storage.

Dosage Form: Oral Drops.

Dosage Strength: 800 IU per ml

4.1 Therapeutic indication

For the treatment of vitamin D3 deficiency

4.2 Posology and method of administration

Treatment vitamin D deficiency should be for up to 12 weeks dependent upon the severity of the disease and the patient's response to treatment, followed by the appropriate long term maintenance therapy.

Pediatric Posology

Infants aged 0 to 2 years

Treatment of vitamin D deficiency: 0.5 ml to 1.25 ml (400 – 1,000 IU) daily.

Long term maintenance therapy following treatment of Deficiency and Prevention of vitamin D deficiency: 0.25ml to 1.25 ml (200 – 1,000 IU) daily.

Children aged 2 years to 11 years

Treatment of vitamin D deficiency: 0.5 ml to 2.5ml (400 – 2,000 IU) daily. Long term maintenance therapy following treatment of deficiency AND Prevention of vitamin D deficiency: 0.5ml to 1.25 ml (400 – 1,000 IU) daily.

Adolescents aged 12 years to 18 years

Treatment of vitamin D deficiency: 0.5 ml – 5ml (400 – 4,000 IU) daily.

Long term maintenance therapy following treatment of deficiency AND Prevention of vitamin D deficiency: 0.5 ml to 2 ml (400 – 1,600 IU) daily.

Adults and the elderly

Treatment of vitamin D deficiency: 1 ml – 5 ml (800 – 4,000 IU) daily. Long term maintenance therapy following treatment of deficiency AND Prevention of vitamin D deficiency: 1 ml – 2 ml (800 – 1,600 IU) daily. As an adjunct to specific therapy for osteoporosis: 1ml (800 IU) daily.

During Pregnancy and Breast-feeding

Treatment of vitamin D deficiency: 1ml – 5ml (800 – 4000 IU) daily.

Long term maintenance therapy following treatment of deficiency: 1ml – 2 ml (800 – 1600 IU) daily.

Table summarising the Posologies of different indications against patient population

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

There are no or limited amount of data from the use of cholecalciferol in pregnant women. Studies in animals have shown reproductive toxicity. The recommended daily intake for pregnant women is 400 IU, however, in women who are considered to be vitamin D deficient a higher dose may be required. During pregnancy women should follow the advice of their medical practitioner as their requirements may vary depending on the severity of their disease and their response to treatment.

Nursing Mothers

Vitamin D and its metabolites are excreted in breast milk. Overdose in infants induced by nursing mothers has not been observed, however, when prescribing additional vitamin D to a breast-fed child the practitioner should consider the dose of any additional vitamin D given to the mother.

Infants

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

Geriatric Patients

Elderly patients may be given the same dose as recommended for adults. However, studies have shown that the elderly people may have greater requirement for vitamin D due to a possible decrease in the capacity of skin to produce pro-vitamin D3, or a decrease in exposure to the sun, or impaired renal function, or impaired vitamin D absorption.

Renal impairment

Cholecalciferol should be used with caution in patients with renal impairment 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 impairment cholecalciferol is not metabolized normally thus, another form of vitamin D should be used. Use of cholecalciferol is contraindicated in patients with severe renal impairment.

Hepatic Impairment

Liver disease may impair the absorption of cholecalciferol. Thus, cholecalciferol should be used with caution in patients with hepatic impairment.

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
• Website: http://www.zuventus.co.in/safety.aspx

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

4.8 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.

Symptoms:

Acute or chronic overdose of vitamin D can cause hypercalcaemia. Symptoms of hypercalcemia are tiredness, psychiatric symptoms (e.g., euphoria, dazedness, disturbed consciousness), nausea, vomiting, lack of appetite, weight loss, thirst, polyuria, formation of renal calculi, nephrocalcinosis, extraosseous calcification and kidney failure, changes in ECG, arrhythmias, and pancreatitis. In isolated cases their course has been described as fatal.

Treatment:

If a massive dose has been ingested ventricular emptying may be considered, together with the administration of carbon. Sunlight and further administration of vitamin D or calcium should be avoided. Rehydration and treatment with diuretics, e.g. furosemide to ensure adequate diuresis. In hypercalcemia biphosphonates or calcitonin and corticosteroids may be given. The treatment is directed to symptoms.

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 25hydroxyvitamin 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 1,25dihydroxyvitamin 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

Vitamin D and its metabolites circulate in the blood, bound to a specific alpha-globulin. Vitamin D can be stored in adipose and muscle tissue for long periods of time. It is slowly released from such storage sites and from the skin where it is formed in the presence of sunlight or ultraviolet light. Cholecalciferol has a slow onset and a long duration of action.

Metabolism

Cholecalciferol is converted in the liver by hydroxylation to the active form 25-hydroxycholecalciferol. It is then further converted in the kidneys to 1,25-dihydroxycholecalciferol. 1,25-dihydroxycholecalciferol is the metabolite responsible for increasing calcium absorption. Vitamin D that is not metabolized is stored in adipose and muscle tissues.

Excretion

Vitamin D compounds and their metabolites are excreted mainly in the bile and faeces, with only small amounts appearing in the urine. There is some enterohepatic recycling but it is considered to have a negligible contribution to vitamin D status. Certain vitamin D substances may be distributed into breast milk.

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.  Chemical name- (1S,3Z)-3-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexan-1-ol

Chemical formula- C₂₇H₄₄O

Molecular weight- 384.6.

8.1 Incompatibilities

Not applicable.

8.2 Shelf-life

24 months.

8.3 Packaging information

Amber-coloured bottle glass (15 mL) with silver cap and dropper.

8.4 Storage and handing instructions

Store below 25°C. Keep out of reach of children.

Any unused product should be disposed of in accordance with local requirements.

Take exactly as directed by your doctor or on the label. Do not increase the dosage or take for longer than is recommended.

Instruct patients on the following points when administering the drug. Inform the patient not to take Cholecalciferol if they have

• allergic to vitamin D or any of the other ingredients of this medicine
• high levels of vitamin D in your blood
• kidney stones or serious kidney problems
• high levels of calcium in your blood and/or urine

Remind patients to inform their healthcare provider immediately before taking Cholecalciferol if they have

• problems with kidneys
• sarcoidosis
• they are already taking other medicines or supplements containing vitamin D.

Cholecalciferol Injection IP

Each ml contains:

Cholecalciferol IP 6,00,000 IU (15mg)

Ethyl Oleate IP q.s.

Ampoule, 6,00,000 IU

For intramuscular use only.

4.1 Therapeutic Indication

Indicated for the treatment of Vitamin D3 deficiency

4.2 Posology and method of administration

Vitamin D3 injection is administered intramuscularly as a single dose of 6,00,000 IU once only or repeated after 6 months to 1 year, depending upon clinical response and requirements. The serum calcium levels should be checked every 3 - 6 months and the dose adapted according to the values.

4.3 Contraindications

• Hypersensitivity to the active substance(s) or to any of the excipients.
• Hypercalcaemia, evidence of vitamin D toxicity, hypervitaminosis D, decreased renal function, metastatic calcification.

4.4 Special warnings and precautions for use

• Adequate dietary calcium is necessary for clinical response to Cholecalciferol therapy.
• Caution should be used when the injectable forms are used in patients with vitamin D resistant rickets as the range between the toxic and therapeutic dosage is narrow.
• Vitamin D should be administered with caution to infants and patients who may have an increased sensitivity to its effects. Use with care in patients with renal impairment, renal calculi or heart disease or arteriosclerosis who might be at increased risk of organ damage if hypercalcaemia were to occur.
• Cholecalciferol is not recommended for use in hypoparathyroidism. In the event of hypoparathyroidism when Cholecalciferol is used, calcium, parathyroid hormone or dihydrotachysterol may be required.
• Dosage should be individualised. Frequent serum and urinary calcium, phosphate and urea nitrogen determinations should be carried out. Adequate fluid intake should be maintained.
• Should hyperglycaemia develop, Cholecalciferol should be discontinued immediately.
• Because of the effect on serum calcium, Cholecalciferol should only be administered to patients with renal stones when potential benefits outweigh possible hazards.
• Vitamin D3 supplementation may worsen hypercalcemia and/or hypercalciuria when administered to patients with diseases associated with unregulated overproduction of calcitriol (e.g., leukemia, 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, heart disease, sarcoidosis, pseudo hypoparathyroidism and who might be at increased risk of organ damage if hypercalcemia occurred.
• Plasma calcium and phosphate concentrations should be controlled during vitamin D3 therapy to reduce the risk of ectopic calcification.

4.5 Drugs interactions

• Rifampicin and isoniazid may reduce the effectiveness of vitamin D3.
• Corticosteroids may counteract the effect of vitamin D3. Cholecalciferol and
  • Magnesium-containing antacids: hypermagnesaemia may develop in patients on chronic renal dialysis.
  • Digitalis glycosides: hypercalcaemia in patients on digitalis may precipitate cardiac arrhythmias.
  • Verapamil: atrial fibrillation has recurred when supplemental calcium and Cholecalciferol have induced hypercalcaemia.
  • Anti-convulsants: Vitamin D requirements may be increased in patients taking anti-convulsants (e.g. carbamazepine, phenobarbital, phenytoin and primidone).
  • Thiazide diuretics: hypoparathyroid patients on Cholecalciferol may develop hypercalcaemia.

4.6 Use in special populations

• Pregnancy :- There are no or limited amount of data from the use of ergocalciferol in pregnant women. Cholecalciferol Injection should not be used in pregnancy unless the potential benefit outweighs the potential hazards to the foetus.
• Nursing Mothers :- Vitamin D3 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.
• Elderly: Requirements of vitamin D3 are increased in the elderly patients.
• Renal Insufficiency:- Patients with renal insufficiency will have decreased ability to form calcitriol metabolite, the effect on the calcium and phosphate balance should be supervised.

4.7 Effects on ability to drive and use machines

Cholecalciferol injection have no influence on the ability to drive and use machines. If patient feels drowsiness, affected patients should not drive or operate machinery.

4.8 Undesirable effects

Adverse events are generally associated with excessive intake of Cholecalciferol leading to the development of hypercalcaemia.

Signs and symptoms of vitamin D intoxication associated with hypercalcemia include muscle weakness, apathy, headache, anorexia, nausea, vomiting, bone pain, ectopic calcification, proteinuria, hypertension and cardiac arrhythmias. Chronic hypercalcemia can lead to generalized vascular calcification, nephrocalcinosis, and rapid deterioration of renal function.

*In clinical studies on hypoparathyroidism and pseudohypopathyroidism, hypercalcaemia was noted on at least one occasion in about 1 in 3 patients and hypercalciuria in about 1 in 7. Elevated serum creatinine levels were observed in about 1 in 6 patients (approximately one half of whom had normal levels at baseline).

§ Possible early symptoms of hypercalcaemia

†Possible late symptoms of hypercalcaemia

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: www.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

Symptoms

Administration to patients in excess of their daily requirement can cause hypercalcaemia, hypercalciuria and hyperphosphataemia. Concomitant high intake of calcium and phosphate may lead to similar abnormalities.

Management

Treatment of chronic overdose with resulting hypercalcaemia consists of immediate withdrawal of the vitamin, a low calcium diet and generous fluid intake. Severe cases may require hydration with intravenous saline together with symptomatic and supportive treatment as indicated by the patient's clinical condition. Plasma calcium should 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.

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 (PTH) and hypophosphatemia. The known sites of action of calcitriol are intestine, bone, kidney and parathyroid gland. The principal action of calcitriol 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 PTH 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

After absorption, Vitamin D3 is rapidly distributed to the liver and lesser amount 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.

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

The mean urinary excretion of Vitamin D3 after 48 hours is 2.4% of the administered dose, and the mean fecal excretion after 48 hours is 4.9% of the administered dose as metabolites of the parent drug.

It was observed that, after intramuscular administration of 6,00,000 IU vitamin D3 in elderly patients, mean serum calcidiol concentration increases to 32.72±9.0 ng/ml at 6th week and up to 52.34±14.2 ng/ml at 12th week from baseline (11.76±7.6 ng/ml).

6.1 Animal Toxicology or Pharmacology

None stated.

Cholecalciferol is the naturally occurring form of vitamin D, also called vitamin D3. It is produced from 7-dehydrocholesterol, a sterol present in mammalian skin, after being exposed to ultraviolet radiation.

8.1 Incompatibilities

None stated.

8.2 Shelf-life

Refer on pack

8.3 Packaging information

3 ampoules of 1 ml each

8.4 Storage and handing instructions

Store below 25°C. Protect from light. After opening the residual must be discarded. Caution: Do not use if solution is not clear or has suspended matter.

• Vitanova-D3 6L injection may interfere with cholesterol tests, hence please inform your physician and laboratory staff that you are taking Vitanova-D3 6L injection before undergoing blood tests.
• Clinical monitoring of serum electrolyte concentrations and cardiac function is recommended.

Simethicone, Dill Oil and Fennel Oil Liquid

Each ml contains :

Simethicone Emulsion

equivalent to Simethicone USP 40 mg

Dill Oil BP 0.005 ml

Fennel Oil 0.0007 ml

In Syrupy Base

Oral drops

4.1 Therapeutic indication

Treatment of infantile colic

4.2 Posology and method of administration

For paediatric use only formulation.

Infants (below 6 months) : 5-10 drops 4 times daily, 15 minutes before feed.

Infants (6-12 months) : 10-20 drops 4 times daily, 15 minutes before feed.

Children (over 1 year) : 20 drops 4 times daily, 15 minutes before feed or as directed by the Physician.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients.

4.4 Special warnings and precautions for use

• Shake well before use.
• Cap should be tightly closed immediately after every use.
• Use calibrated dropper provided in this pack.

4.5 Drugs interactions

Levothyroxine may bind to Simethicone. Absorption of Levothyroxine may be impaired if the preparation is given concurrently to infants treated for thyroid disorders.

4.6 Use in special populations

For paediatric use only.

4.7 Effects on ability to drive and use machines

Not applicable

4.8 Undesirable effects

Simethicone does not have any serious side effects.

Minor adverse effects : Nausea, Mild diarrhea and Constipation. Rarely, hypersensitivity reactions such as rash, pruritis, facial oedema, tongue oedema and respiratory difficulty have been reported.

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

In the event of deliberate or accidental overdose, treat symptoms on appearance.

5.1 Mechanism of action

Excessive swallowing of air results in collection of gas in the intestine. This can be the result of too rapid eating, breast feeding babies where they inhale air along with the milk, excessive use of a pacifier (dummy), finger sucking or yelling. Simethicone, Dill Oil and Fennel Oil Liquid Relieves Infant Colic, Griping Pain & Flatulence When the swallowed air is in the intestine, bubbles are formed, which makes it more difficult for the gas to pass through the intestine canal, resulting in abdominal distension and pain.

Simethicone

Simethicone is used to relieve painful pressure caused by excess gas in the stomach and intestines. Simethicone is a surface active substance which changes the surface tension of the intestinal mucus allows gas bubbles in the stomach and intestines to come together. Thus, the air bubbles burst and the gas is released for easier passage of gas. The elimination of the gas, air or foam from the gastro-intestinal tract, relieves abdominal distension and dyspepsia.

Dill oil and fennel oil

Contains volatile oils that produce smooth muscle relaxation, an antispasmodic effect and increases intestinal motility. Dill and Fennel Oils are also used for digestion problems including intestinal gas (flatulence) and constipation.

5.2 Pharmacodynamic properties

Simethicone reduces surface tension and collapses gas bubbles, thus act as an 'antifoaming agent' and relieve flatulence. Dill Oil and Fennel Oil produce an antispasmodic effect and increases intestinal motility.

5.3 Pharmacokinetic properties

Physiologically the active ingredient Simethicone is a chemically inert. Simethicone is not absorbed from the gastrointestinal tract and is excreted unchanged in the faeces.

6.1 Animal toxicology or pharmacology

No known animal toxicology data

TumsUp drops is a fixed dose combination of Simethicone (40 mg) + Dill Oil (0.005 ml) + Fennel Oil (0.0007 ml) per ml. Simethicone is inert oil, which is tissue adherent and water repellent, it is therefore mucosal protective. Dill and Fennel Oils are essential oils extracted from the seeds or leaves/stems of Anethum Graveolens (Dill plant) and Foeniculum Vulgare respectively. Dill (Anethum Graveolens) has seeds containing volatile oils rich in carvone. Fennel (Foeniculum Vulgare) seeds hold another Volatile Oil, Anethole.

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

24 Months

8.3 Packaging information

A glass bottle of 30 ml.

8.4 Storage and handing instructions

Store below 25°C. Protect from light. Do not Freeze. KEEP AWAY FROM THE REACH OF CHILDREN.

• Ask the patient to report any adverse events.
• Not to exceed the stated recommended daily dose.

05 February 2022