CACIT VITAMIN D3 500 mg/440 IU, effervescent granules for oral solution in sachet

One sachet of 4 g contains :

Calcium carbonate 1250 mg (equivalent to calcium element 500 mg or 12.5 mmol)

Colecalciferol concentrate (powder form) 440 IU (equivalent to colecalciferol (Vitamin D₃) 11µg)

For excipients, see 6.1.

Effervescent white granules for oral solution.

- Correction of vitamin D and calcium combined deficiency in elderly people.

- Vitamin D and calcium supplementation as an adjunct to specific therapy for osteoporosis treatment in patients with established, or at high risk of vitamin D and calcium combined deficiencies.

- Posology:

One or two sachets per day.

- Method of administration:

Oral.

Pour the contents of the sachet into a glass, add a large quantity of water, then drink immediately.

• Diseases and/or conditions resulting in hypercalcaemia and/or hypercalciuria

• Nephrolithiasis

• Hypervitaminosis D

• Hypersensitivity to the active substances or to any of the excipients (in particular soya oil).

During long-term treatment, serum calcium levels should be followed and renal function should be monitored through measurements of serum creatinine. Monitoring is especially important in elderly patients on concomitant treatment with cardiac glycosides or diuretics (see section 4.5) and in patients with a high tendency to calculus formation. In case of hypercalcaemia or signs of impaired renal function the dose should be reduced or the treatment discontinued.

Vitamin D3 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 (see section 4.3, contraindications)

Cacit Vitamin D3 sachets should be prescribed with caution to patients suffering from sarcoidosis, due to the risk of increased metabolism of vitamin D into its active form. These patients, should be monitored with regard to the calcium content in serum and urine.

Calcium/vitamin D3 sachets should be used with caution in immobilised patients with osteoporosis due to the increased risk of hypercalcaemia.

The contentof vitamin D3 (440 IU) in Cacit Vitamin D3 sachets should be considered when prescribing other medicinal products containing vitamin D. Additional doses of calcium or vitamin D should be taken under close medical supervision. In such cases it is necessary to monitor serum calcium levels and urinary calcium excretion frequently.

Cacit Vitamin D3 sachets are not intended for use in children.

- Special warnings:

Cacit Vitamin D3 sachets contain sucrose.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

Concomitant use requiring precautions:

- Digitalis and other cardiac glycosides: the oral administration of calcium combined with vitamin D increases the toxicity of digitalis (risk of dysrythmia). Strict medical supervision, and if necessary, monitoring ECG and calcaemia are necessary.

- Bisphosphonate, sodium fluoride: it is advisable to allow a minimum period of two hours before taking the calcium (risk of reduction of the gastrointestinal absorption of bisphosphonate and sodium fluoride).

- Thiazide diuretics : reduce urinary elimination of calcium therefore supervision of calcaemia is recommended.

- Phenytoin or barbiturates : can decrease the effect of vitamin D because of metabolic inactivation.

- Glucocorticosteroid : can decrease the effect of vitamin D.

- Tetracyclines by oral route: it is advisable to delay taking the calcium by at least three hours (calcium salts reduce the absorption of tetracyclines).

- Possible interactions with food (e.g. containing oxalic acid, phosphate or phytinic acid).

The product may be used during pregnancy and lactation. However, the daily intake should not exceed

1500 mg calcium and 600 IU vitamin D3.

In pregnancy overdoses of colecalciferol must be avoided

- Overdoses of vitamin D have shown teratogenic effects in pregnant animals.

- In humans overdoses of colecalciferol must be avoided as permanent hypercalcaemia can lead to physical and mental retardation, supravalvular aortic stenosis and retinopathy in the child.

There are however several case reports of administration of very high doses in hypoparathyroidism in the mother, where normal children were born.

Vitamin D and its metabolites pass into the breast milk.

No remarkable findings. No effect expected.

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.

Gastrointestinal disorders

Rare : Constipation, flatulence, nausea, abdominal pain and diarrhoea.

Skin and subcutaneous disorders

Rare : Pruritus, rash and urticaria.

Consequence of overdose are hypercalciuria and hypercalcaemia. Symptoms include:

nausea, vomiting, thirst, polydipsia, polyuria, constipation.

Chronic overdoses can lead to vascular and organ calcifications as a result of hypercalcaemia.

Treatment:

Stop all intake of calcium and vitamin D, rehydration.

Vitamin D corrects an insufficient intake of vitamin D and increases intestinal absorption of calcium.

Calcium intake corrects a lack of calcium in the diet.

The commonly accepted requirement of calcium in the elderly is 1500 mg/day.

The optimal amount of vitamin D in the elderly is 500 - 1000 IU/day.

Vitamin D and calcium correct secondary senile hyperparathyroidism.

In a double blind placebo controlled study of 18 months, including 3270 women aged 84 ± 6 years with a low intake of calcium and living in nursing homes, had their diet supplemented with colecalciferol (800 UI/day) + Calcium (1.2 g/day). A significant decrease in PTH secretion has been observed.

After 18 months, results of the intend to treat analysis showed 80 hip fractures (5.7%) in the Calcium Vitamin D group and 110 hip fractures (7.9%) in the placebo group (p = 0.004). Therefore, in these study conditions, the treatment of 1387 women prevented 30 hip fractures. After 36 months of follow up, 137 women presented at least one hip fracture (11.6%) in the Calcium Vitamin D group (n = 1176) and 178 (15.8%) in the placebo group (n = 1127) (p 0.02).

During dissolution the calcium salt contained in CACIT VITAMIN D3 is transformed into calcium citrate.

Calcium citrate is well absorbed, approximately 30% to 40% of the ingested dose.

Calcium is eliminated in the urine and faeces and secreted in the sweat.

Vitamin D is absorbed in the intestine and transported by protein binding in the blood to the liver (first hydroxylation) then to the kidney (second hydroxylation).

The non-hydroxylated vitamin D is stored in reserve compartments such as adipose and muscle tissue. Its plasma half-life is several days; it is eliminated in the faeces and the urine.

No remarkable findings.

Citric acid anhydrous , Malic acid, Gluconolactone, Maltodextrin, Sodium cyclamate, Saccharin sodium, Lemon flavouring (containing: Sorbitol, Mannitol, D-gluconolactone, Dextrin, Gum arabic, Lemon oil), Rice starch, Potassium carbonate, -Tocopherol, Soya-bean oil hydrogenated, Gelatin, Sucrose, Corn starch.

Quantity of sodium per sachet: 5 mg or 0.22 mmol

Not applicable.

3 years.

Do not store above 25 °C.

4 g sachets (paper/aluminium/polyethylene); boxes of 20, 28, 30, 46, 50, 56, 60 or 100 sachets and sample pack of 10 sachets.

Not all pack sizes may be marketed.

No special requirements

Procter & Gamble Pharmaceuticals UK Limited.

Rusham Park,

Whitehall Lane,

Egham,

Surrey.

TW20 9NW, UK.

PL 0364/0060

03 March 2001 (Renewal)

February 2006