SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Cacit D3 effervescent granules, 500 mg/440 IU

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Cacit D3 500 mg/440IU contains 1250 mg of calcium carbonate (equivalent to 500mg of elemental calcium) and 440IU of cholecalciferol (vitamin D3) per sachet of 4g.

3    PHARMACEUTICAL FORM

Effervescent granules for oral solution.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For correction of vitamin D and calcium combined deficiency in elderly people.

Cacit D3 may be used as an adjunct to specific therapy for osteoporosis, in patients with either established vitamin D and calcium combined deficiencies or in those patients at high risk of needing such therapeutic supplements.

4.2    Posology and method of administration Dosage:

One or two sachets of Cacit D3 effervescent granules, 500mg/440IU per day.

Method of administration:

Oral, after reconstitution.

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

4.3    Contraindications

-    hypercalcaemia, hypercalciuria

-    long-term immobilisation accompanied by hypercalciuria and/or hypercalcaemia

-    calci-lithiasis

-    hypersensitivity to one of the ingredients

4.4 Special warnings and precautions for use

With long-term treatment it is advisable to monitor serum and urinary calcium levels and kidney function, and reduce or interrupt treatment temporarily if urinary calcium exceeds 7.5mmol/24 hours (300mg/24 hours).

The product should be used with caution in patients with renal insufficiency and the effects on calcium and phosphate homeostasis should be monitored.

In the case of combined treatment with digitalis, bisphosphonate, sodium fluoride, thiazide diuretics, tetracyclines, see section 4.5 (interactions with other medicines).

Allowances should be made for vitamin D/calcium supplements from other sources. Additional administration of vitamin D or calcium should be carried out under strict medical supervision, with weekly monitoring of serum and urinary calcium.

The product should be prescribed with caution in patients with sarcoidosis because of possible increased metabolism of vitamin D to its active form. These patients should be monitored for serum and urinary calcium.

4.5 Interaction with other medicinal products and other forms of interaction

The effects of digitalis and other cardiac glycosides may be accentuated with the oral administration of calcium combined with vitamin D (increases the toxicity of digitalis and therefore the risk of dysrythmia). Strict medical supervision, and if necessary, monitoring ECG and calcaemia are necessary.

In case of concomitant treatment with a bisphosphonate or with 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 increase the renal absorption of calcium, so the risk of hypercalcaemia should be considered Strict medical supervision of calcaemia is recommended.

Concomitant treatment with phenytoin or barbiturates can decrease the effect of vitamin D because of metabolic inactivation.

Concomitant use of a glucocorticosteroid can decrease the effect of vitamin D. Calcium salts reduce the absorption of tetracyclines. It is advisable to delay taking Cacit D3 by at least three hours.

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

4.6 Fertility, pregnancy and lactation

The product may be used during pregnancy and lactation. However, the daily intake should not exceed 1500mg calcium and 600IU vitamin D.

Overdoses of vitamin D have shown teratogenic effects in pregnant animals. In humans overdoses of vitamin D must be avoided, as permanent hypercalcaemia can lead to physical and mental retardation, supravalvular aortic stenosis and retinopathy in the child. There are 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.

4.7    Effects on ability to drive and use machines

No data are known about the effect of this product on driving capacity. However, an effect is unlikely.

4.8    Undesirable effects

Constipation, flatulence, nausea, gastric pain, diarrhoea.

Hypercalciuria and in rare cases hypercalcaemia with long-term treatment at high doses.

Skin reactions such as pruritus, rash, urticaria (especially in patients with a past history of allergy).

4.9    Overdose

The most serious consequence of acute or chronic overdose would be hypercalciuria and hypercalcaemia due to vitamin D toxicity. Symptoms include nausea, vomiting, thirst, polydipsia, polyuria and constipation. Chronic overdoses can lead to vascular and organ calcifications as a result of hypercalcaemia. Treatment would consist of stopping all intake of calcium and vitamin D and rehydration.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Vitamin D corrects an insufficient intake of vitamin D and increases intestinal absorption of calcium. The optimal amount of vitamin D in the elderly is 500 -1000 IU/day.

Calcium corrects an insufficient intake of calcium in the diet.

The commonly accepted requirement of calcium in the elderly is 1500mg/day. Vitamin D and calcium correct secondary senile hyperparathyroidism.

In two double blind placebo-controlled clinical studies, a significant diminution of PTH was followed by a significant reduction of non-vertebral fractures. One study evaluated the benefit on hip fracture: a hip fracture reduction in elderly women treated by Calcium and Vitamin D was shown in a 3 year study, in 3270 women aged 84 ± 6 years living in nursing homes. After 18 months, results expressed in intend to treat analysis showed 80 hip fractures in the Calcium Vitamin D group and 110 hip fractures in the placebo group (p= 0.004). In the study condition, treatment of 1387 women prevented 30 hip fractures. After 36 months, the following results were obtained: 137 hip fractures in the Calcium Vitamin D group and 178 in the placebo group (p <0.02).

5.2    Pharmacokinetic properties

During dissolution the calcium salt contained in Cacit 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.

5.3    Preclinical safety data

No remarkable findings.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Citric acid, malic acid, gluconolactone, maltodextrin, sodium cyclamate, saccharin sodium, lemon flavouring (containing: sorbitol, mannitol, D-gluconolactone, dextrin, gum arabic, lemon oil), rice starch, corn starch, potassium carbonate, *-tocopherol, vegetable oils, gelatin, and sucrose

One sachet of Cacit D3 500mg/440IU contains a total of 0.22mmol of sodium (5mg).

6.2    Incompatibilities

None known.

6.3    Shelf life

3 years.

6.4    Special precautions for storage

Store below 25°C.

6.5    Nature and contents of container

Paper/aluminium/polyethylene sachets packed in boxes of 20*, 30, 46*, 50* or 100 and sample packs of 10 sachets.

*Not all pack sizes may be marketed.

6.6    Special precautions for disposal

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

7    MARKETING AUTHORISATION HOLDER

Warner Chilcott UK Limited Old Belfast Road Millbrook Road Larne

County Antrim BT40 2SH

8    MARKETING AUTHORISATION NUMBER(S)

PL 10947/0017

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

07/03/1996 / 06/03/2001

10    DATE OF REVISION OF THE TEXT

01/05/2010