This information is intended for use by health professionals

1. Name of the medicinal product

CALCEOS 500mg/400IU Chewable Tablets.

2. Qualitative and quantitative composition

Calcium Carbonate 1250mg (equivalent to 500mg of elemental calcium).

Colecalciferol (Vitamin D3) 400IU (equivalent to 10μg).

Excipients with known effects (per tablet): 475mg sorbitol, 0.3mg partially hydrogenated soya bean oil, 1.52mg sucrose.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Chewable tablets.

Square, white-grey tablets.

4. Clinical particulars
4.1 Therapeutic indications

Vitamin D and calcium deficiency correction in the elderly. Vitamin and calcium supplement as an adjunct to specific therapy for osteoporosis and in patients at high risk of vitamin D and calcium combined deficiencies.

4.2 Posology and method of administration

Oral use. For adults only. One tablet, twice per day. Chew the tablets and drink a glass of water.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. Hypercalcaemia as a result of hyperparathyroidism (primary or secondary), hypercalciuria, calcium lithiasis, tissue calcification (nephrocalcinosis). Vitamin D overdose. Myeloma and bone metastases. Renal insufficiency (creatinine clearance less than 20ml/min). Calceos 500mg/400IU Chewable Tablets are also contraindicated in patients where prolonged immobilisation is accompanied by hypercalcaemia and/or hypercalciuria. In these cases, treatments should only be resumed when the patient becomes mobile.

This product contains partially hydrogenated soybean oil. Patients should not take this medicinal product if they are allergic to peanut or soya.

4.4 Special warnings and precautions for use

Calculate the total Vitamin D intake in case of treatment with another drug containing this vitamin.

The following may be important in patient monitoring: plasma calcium and urinary calcium determinations.

During long term treatment, it is advisable to monitor serum and urinary calcium levels and kidney function (serum creatinine levels). It is advisable to reduce or interrupt treatment temporarily if urinary calcium exceeds 7.5mmol/24h (300mg/24h). This monitoring is particularly important in the elderly, in cases of combined treatment with cardiac glycosides or diuretics (see section 4.5) and in patients who are frequently subject to the formation of kidney stones. In the presence of hypercalcaemia or signs of problems with renal function, the dose must be reduced or treatment interrupted.

The product should be used with caution in patients with renal insufficiency and the effects on calcium and phosphate homeostasis should be monitored. The risk of soft tissue calcification must be taken into account. In patients with severe renal insufficiency, vitamin D3 in the form of colecalciferol is not metabolised in the normal way and other forms of vitamin D3 must be used (see section 4.3).

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

This product contains sorbitol (E420) and sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

The sucrose in this product may be harmful to teeth if taken chronically, e.g. for two weeks or more.

4.5 Interaction with other medicinal products and other forms of interaction

Combinations requiring precautions for use:

Cardiac glycosides

Risk of cardiac dysrhythmia. Clinical surveillance is required and possibly electrocardiographic and plasma calcium monitoring are recommended.

Thiazide diuretics

Thiazide diuretics reduce the renal elimination of calcium. It is recommended that the calcium levels in plasma are monitored regularly.

Tetracyclines, etidronate, fluoride and iron

Calcium may impair the absorption of tetracyclines, etidronate, fluoride and iron. At least three hours should intervene between taking Calceos 500mg/400IU Chewable Tablets and these agents.

Strontium

Calcium may reduce the absorption of strontium. Risk of a 60 to 70% reduction in strontium bioavailability on concomitant administration of calcium-containing products. It is recommended to avoid taking Calceos 500mg/400IU Chewable Tablets immediately before and after taking strontium-containing medications.

Estramustine and Thyroid hormones

Calcium may reduce the absorption of estramustine and levothyroxine. It is recommended that these medicines should be taken at least two hours before or after Calceos 500mg/400IU Chewable Tablets.

Orlistat

Treatment with orlistat may potentially reduce the absorption of Vitamin D.

Food

Possible interaction with food, for example foods containing oxalic acid (e.g. spinach, rhubarb, sorrel, cocoa, tea), phosphate (e.g. ham, sausages, cheese spread) or phytic acid (e.g. pulses, whole cereals, chocolate). These types of foods may reduce the absorption of calcium. It is therefore recommended that meals containing these foods be taken some time (e.g. two hours) before or after ingestion of the product.

4.6 Fertility, pregnancy and lactation

This product may be used during pregnancy and lactation. However, the daily intake should not exceed 1500mg calcium and 600IU vitamin D3.

Pregnancy

In pregnancy, an overdose of colecalciferol must be avoided:

- overdoses of vitamin D during pregnancy have shown teratogenic effects in animals.

- in pregnant woman: 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 however several case reports of administration of very high doses in hypoparathyroidism in the mother, with no adverse effect on the infant.

Lactation

Vitamin D and its metabolites pass into the breast milk. This should be considered when giving additional vitamin D to the child.

4.7 Effects on ability to drive and use machines

None known.

4.8 Undesirable effects

Adverse reactions are listed below, by system organ class and frequency. Frequencies are defined as: uncommon (≥1/1,000 to <1/100) or rare (≥1/10,000 to <1/1,000).

Immune system disorders:

Cases of hypersensitivity reactions such as angioedema or laryngeal oedema have been reported.

Metabolism and nutrition disorders

Uncommon: hypercalcaemia and hypercalciuria

Gastrointestinal disorders

Uncommon: injury to teeth

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

Skin and subcutaneous tissue 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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

4.9 Overdose

Clinical signs: Anorexia, intense thirst, nausea, vomiting, polyuria, polydipsia, dehydration, hypertension, vasomotor disorders, constipation.

Laboratory signs: Hypercalcaemia, hypercalciuria, impaired renal function tests.

Emergency treatment:

- Stop all calcium and vitamin D supplements.

- Rehydration and, according to the severity of the intoxication, isolated or combined use of diuretics, corticosteroids, calcitonin, peritoneal dialysis.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Vitamin D Calcium supplement

ATC code: A12AX

Calceos 500mg/400IU Chewable Tablets are a fixed combination of calcium and vitamin D. The high calcium and vitamin D concentration in each dose unit facilitates absorption of a sufficient quantity of calcium with a limited number of doses. Vitamin D is involved in calcium-phosphorus metabolism. It allows active absorption of calcium and phosphorus from the intestine and their uptake by bone.

5.2 Pharmacokinetic properties

Calcium Carbonate:

Absorption:

In the stomach, calcium carbonate releases calcium ion as a function of pH. Calcium is essentially absorbed in the proximal part of the small intestine. The rate of absorption of calcium in the gastrointestinal tract is of the order of 30% of the dose ingested.

Elimination:

Calcium is eliminated in sweat and gastrointestinal secretions. The urinary calcium excretion depends on the glomerular filtration and rate of tubular resorption of calcium.

Vitamin D3:

Vitamin D3 is absorbed from the intestine and transported by protein binding in the blood to the liver (first hydroxylation) and to the kidney (second hydroxylation).

Non-hydroxylated Vitamin D3 is stored in reserve compartments such as muscle and adipose tissues. Its plasma half-life is of the order of several days; it is eliminated in faeces and urine.

5.3 Preclinical safety data

None stated.

6. Pharmaceutical particulars
6.1 List of excipients

Xylitol

Sorbitol (E420)

Povidone

Lemon flavouring*

Magnesium stearate

* Composition of the lemon flavouring: essential oils of lemon, orange and litsea cubeba, maltodextrin, acacia gum and sodium citrate.

The colecalciferol is present as a concentrate powder that also contains:

DL-alpha-Tocopherol

Partially hydrogenated soybean oil

Gelatin

Sucrose

Corn starch

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

36 months.

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

Polypropylene tube and polyethylene stopper with silica gel desiccant containing 10, 15, 30, 60 and 100 tablets. Packs of 1, 2, 4 or 10 tubes in card outers.

6.6 Special precautions for disposal and other handling

None.

7. Marketing authorisation holder

Laboratoire Innotech International

22 avenue Aristide Briand

94110 Arcueil

France

8. Marketing authorisation number(s)

PL 19152/0001

9. Date of first authorisation/renewal of the authorisation

31 October 2001

10. Date of revision of the text

31 March 2015