Vitanova®-D3 800 IU Drops

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.