Calceos 500mg/400IU Chewable Tablets

CALCEOS is indicated only in adults for:
 - Vitamin D and calcium deficiency correction in the elderly.
 - Vitamin D and calcium supplement as an adjunct to specific therapy for osteoporosis and in patients at high risk of vitamin D and calcium combined deficiencies.

Posology

Adults

One tablet, twice per day.

Paediatric population

The safety and efficacy of CALCEOS in children has not been established. No data are available.

Method of administration

Oral use.

Chew the tablets and drink a glass of water.

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
- This product contains partially hydrogenated soybean oil. Patients should not take this medicinal product if they are allergic to peanut or soya.
- Hypercalcaemia, hypercalciuria and diseases and/or conditions, which lead to hypercalcaemia and/or hypercalciuria (e.g. myeloma, bone metastases, primary hyperparathyroidism).
- Calcium lithiasis, nephrocalcinosis.
- Vitamin D overdose.
- Severe renal impairment (glomerular filtration rate < 30 ml/min). In patients with severe renal impairment, Vitamin D₃ in the form of colecalciferol is not metabolised in the normal way and other forms of Vitamin D₃ must be used.

- The product should be prescribed with caution in patients with sarcoidosis because of possible increase of metabolism of vitamin D to its active form. These patients should be monitored for serum and urinary calcium.
- The product should be used with caution in renal impairment patients (glomerular filtration rate ≥ 30 ml/min) and with monitoring of calcium and phosphate homeostasis. The risk of soft tissue calcification must be taken into account.
- Calcium and alkali intake from other sources (foods, dietary supplements or other drugs) should be considered when prescribing CALCEOS. If very high doses of calcium are taken in combination with absorbable alkaline agents (such as carbonates), there is a risk of Burnett syndrome (or milk-alkali syndrome) consisting of hypercalcemia, metabolic alkalosis, renal failure, and soft tissue calcification. In this case, frequent monitoring of serum calcium and calciuria may be necessary.
- In case of prolonged immobilisation in patients with hypercalciuria and/or hypercalcaemia, vitamin D and calcium treatment should only be resumed when the patient becomes mobile.
- In case of 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.
- Additional administration of vitamin D or calcium should be carried out under strict medical supervision. In such situation, weekly monitoring of serum and urinary calcium is absolutely necessary.

Excipients:

CALCEOS contains sorbitol (E420).

Patients with hereditary fructose intolerance (HFI) should not take this medicine.

CALCEOS contains sucrose (sucrose is present in small quantities in colecalciferol concentrate).

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine. The sucrose may be harmful to teeth if this product is taken chronically, e.g. for two weeks or more.

Combinations requiring precautions for use:

Cardiac glycosides

Risk of serious dysrhythmia. Medical supervision and if necessary, monitoring electrocardiographic and calcaemia.

Bisphosphonates

Risk of decrease in the gastrointestinal absorption of bisphosphonates. It is advisable to take calcium salts apart from bisphosphonates (a minimum period of at least 2 hours)

Strontium

Reduction in strontium gastrointestinal absorption on concomitant administration of calcium-containing products. It is advisable to take calcium more than two hours apart from strontium-containing medications.

Tetracyclines orally

Possible reduction in the absorption of tetracycline. It is advisable to take calcium salts at least two hours apart from tetracyclines.

Rifampicin

Possible decrease in vitamin D concentrations. Vitamin D concentrations should be measured and supplementation provided if necessary.

Fluoroquinolones

Risk of reduction in the intestinal absorption of fluoroquinolones. It is advisable to take calcium more than two hours apart from fluoroquinolones.

Dolutegravir

Risk of reduction in the intestinal absorption of dolutegravir. It is advisable to take calcium at least 2 hours after or 6 hours before dolutegravir intake.

Ferrous salt

Risk of reduced gastrointestinal absorption of ferrous salt. It is advisable to allow a period of more than two hours between calcium and ferrous salt.

Zinc

Risk of reduced gastrointestinal absorption of zinc. It is advisable to allow a period of more than two hours between calcium and zinc.

Estramustine

Risk of reduction in the gastrointestinal absorption of estramustine. It is advisable to allow a period of more than two hours between calcium and estramustine.

Thyroid hormones

Risk of reduction in the gastrointestinal absorption of thyroid hormones. It is advisable to allow a period of more than two hours between calcium and thyroid hormones.

Enzyme-inducing antiepileptic drugs (AEDs) (carbamazepine, fosphenytoin, phenobarbital, phenytoin and primidone)

Possible decrease in vitamin D concentrations. Vitamin D concentrations should be measured and supplementation provided if necessary.

Roxadustat

The intake of divalent cation may decrease intestinal absorption and the efficacy of roxadustat when taken simultaneously.

Administration of calcium with roxadustat should be separated by more than 1 hour (if possible).

Combinations to be taken into account:

Orlistat

Treatment with orlistat may potentially reduce the absorption of Vitamin D₃.

Thiazide diuretics

Risk of hypercalcemia due to a decrease in the urinary excretion of calcium. It is recommended that the calcium levels in plasma are monitored regularly.

Food

Possible interaction with food, for example foods containing oxalic acid (spinach, rhubarb, sorrel, cocoa, tea), phosphate (pork, ham, sausages, processed cheese, dessert cream, beverages containing cola, etc.) or phytic acid (wholemeal cereals, dry vegetables, oleaginous seeds, chocolate, etc.). These types of foods may reduce the absorption of calcium. It is therefore recommended that meals containing these foods be taken some time before or after ingestion of the product.

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 (see section 5.3).
- 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.

Fertility

No data is available on the effects of CALCEOS on fertility. However, normal endogenous calcium and vitamin D levels are not expected to have undesired effects on fertility.

CALCEOS has no or negligible influence on the ability to drive and use machines.

Adverse reactions are listed below, by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to < 1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Immune system disorders:

Not known: Hypersensitivity reactions such as angioedema or laryngeal oedema.

Metabolism and nutrition disorders

Uncommon: Hypercalcaemia and hypercalciuria.

Not known: Milk-alkali syndrome (hypercalcaemia, alkalosis and renal impairment). Seen usually only in overdose (see sections 4.4 and 4.9).

Gastrointestinal disorders

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

An overdose can lead to hypervitaminosis and hypercalcaemia.

Symptoms

The symptoms of hypercalcaemia can include: anorexia, thirst, nausea, vomiting, constipation, abdominal pain, muscle weakness, fatigue, hypertension, mental disturbances, polydipsia, polyuria, skeletal pain, renal calcinosis, kidney stones, and in severe cases, cardiac arrhythmia. Extreme hypercalcaemia may lead to coma and death. Continuous high calcium levels may lead to irreversible damage to the kidneys and soft tissue calcification.

The risk of overdose may be increased if other calcium containing products or alkaline agents are taken (Milk-alkali syndrome). See Section 4.4 and 4.8.

Management

Treatment of hypercalcaemia: all calcium and Vitamin D₃ treatments must be stopped. The need to continue all other concomitant medicines should be reconsidered by the physician. Rehydrate and, depending on severity, isolated or combined treatment with loop diuretics, bisphosphonates, calcitonin and corticosteroids should be considered. Peritoneal dialysis should be considered in patients with renal failure or in patients refractory to other therapies.

Serum electrolytes, kidney function and diuresis must be monitored. In severe cases, ECG and calcaemia should be monitored.

Pharmacotherapeutic group: CALCIUM, COMBINATIONS WITH VITAMIN D AND/OR OTHER DRUGS, ATC code: A12AX

Vitamin D corrects an insufficient intake of vitamin D.

It increases intestinal absorption of calcium and its fixation on the osteoid tissue.

Calcium intake corrects a lack of calcium in the diet.

Vitamin D and calcium correct secondary senile hyperparathyroidism.

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.

Repeat-dose toxicity

Pre-clinical studies conducted in various animal species have demonstrated that toxic effects of calcium carbonate and vitamin D occur in animals at doses higher than those required for therapeutic use in humans.

Genotoxicity

Calcium carbonate and vitamin D were negative for genotoxicity in several tests.

Carcinogenicity

No dedicated regulatory compliant carcinogenicity studies in animals have been performed with calcium carbonate or vitamin D. However, neither calcium carbonate nor vitamin D are expected to have carcinogenic potential.

Reproductive and developmental toxicity

No treatment-related effects on reproductive and developmental toxicity have been reported with calcium carbonate. At very high doses, vitamin D3 has been found to be teratogenic in rabbits (at doses 4 to 15 times the recommended human dose), and to induce change in sexual behaviour in juvenile rats treated neonatally.

Xylitol

Sorbitol (E420)

Povidone

Lemon flavouring*

Magnesium stearate

* Composition of lemon flavouring: flavouring preparations, natural flavouring substances, maltodextrin, acacia, sodium citrate, citric acid, butylated hydroxyanisole.

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

DL-alpha- Tocopherol

Hydrogenated soybean oil

Gelatin

Sucrose

Corn starch

Silicon dioxide

Not applicable.

36 months.

Do not store above 25°C.

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.

None.