Pfizer Consumer Healthcare

CALTRATE 600 mg/400 IU, film-coated tablet

Each tablet contains:

600 mg of calcium (as calcium carbonate)

10 micrograms of cholecalciferol (equivalent to 400 I.U. vitamin D₃)

Excipients: sucrose, partially hydrogenated soya bean oil.

For a full list of excipients see section 6.1.

Film-coated tablet.

Capsule-shaped grey/beige tablets. One side is scored and engraved with “D” on the left and “600” on the right of the score. The other side is engraved with “Caltrate”.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

Correction of combined vitamin D and calcium deficiencies in the elderly.

Supply of vitamin D and calcium as an adjunct to specific treatments for osteoporosis, in patients where combined vitamin D and calcium deficiencies have been diagnosed or those at high risk of such deficiency.

Adults and elderly

One tablet twice a day (e.g. one tablet in the morning and one tablet in the evening). Dose reduction should be considered as necessary following the monitoring of calcium levels as indicated in section 4.4 and 4.5.

Pregnant women

One tablet a day (see section 4.6).

Posology in cases of hepatic insufficiency

The dose does not require adjustment.

The tablet should be swallowed with a large glass of water.

• Hypersensitivity to one of the active substances or to one of the excipients.

• The product contains partially hydrogenated soya bean oil and is contraindicated for patients hypersensitive to peanut or soya.

• Renal failure.

• Hypercalciuria and hypercalcaemia and diseases and/or conditions, which lead to hypercalcaemia and/or hypercalciuria (e.g. myeloma, bone metastases, primary hyperparathyroidism).

• Kidney stones (nephrolithiasis, nephrocalcinosis).

• Hypervitaminosis D.

In the event of prolonged treatment, checking calcaemia and renal function by assaying serum creatinine is justified. 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.

Caltrate must be prescribed with caution to patients who are immobilized and suffering from osteoporosis, because of the increase in the risk of hypercalcaemia.

Take into account the intake of vitamin D and calcium from all other sources before prescribing Caltrate. As this product already contains vitamin D, the additional administration of vitamin D or calcium must be carried out under strict medical supervision with regular monitoring of calcaemia and calciuria. It is advisable to reduce or interrupt treatment temporarily if urine calcium exceeds 7.5 mmol/24 h (300 mg/24 h).

Caltrate must be used with caution in patients suffering from sarcoidosis because of a possible increase in vitamin D₃ metabolism to its active form. In these patients, calcaemia and calciuria must be monitored.

Caltrate must be used with caution and phosphate-calcium levels monitored in patients presenting with a decrease in renal function. The risk of soft tissue calcification must be taken into account. In patients with severe renal insufficiency, vitamin D₃ in the form of cholecalciferol is not metabolised in the normal way and other forms of vitamin D₃ must be used (see section 4.3).

Post-marketing cases of asphyxiation due to tablet choking have been reported. It is always recommended to take tablets with a large glass of water (200 ml). In order to facilitate intake by patients, especially elderly or patients with known difficulties in swallowing, the breakable tablet may be divided into two parts before taking them with a large glass of water.

This product contains sucrose, therefore patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

This product contains partially hydrogenated soya bean oil which can cause hypersensitivity reactions (urticaria, anaphylactic shock). It is therefore contraindicated for patients hypersensitive to peanut or soya (see section 4.3).

Caltrate is not intended for use in children and adolescents.

Thiazide diuretics reduce calcium excretion in the urine. Because of the increased risk of hypercalcaemia, calcium monitoring is recommended in cases when thiazide diuretics are given simultaneously.

Systemic corticosteroids reduce calcium absorption. In the case of concomitant administration of corticosteroids, it might be necessary to increase the dose of Caltrate.

Orlistat, combined ion-exchange resin treatment such as cholestyramine or laxatives such as paraffin oil can reduce the gastrointestinal absorption of vitamin D₃.

Calcium carbonate can alter tetracycline absorption when given simultaneously. It is recommended that taking tetracycline be staggered by at least 2 hours before or 4 to 6 hours after taking calcium by mouth.

Hypercalcaemia can increase the toxicity of cardiac glycosides in the case of simultaneous administration with calcium and vitamin D. Consequently patients must be monitored regularly (ECG check and calcaemia).

Phenytoin or barbiturates may reduce the activity of vitamin D₃, since they increase the rate of its metabolism.

Calcium salts may decrease the absorption of iron, zinc or strontium. Consequently, the iron, zinc or strontium preparation should be taken at a distance of two hours from the calcium preparation.

Calcium salts may reduce the absorption of the estramustin or thyroid hormones. It is recommended that taking Caltrate be spaced at least 2 hours from these medicines.

In the case of concomitant bisphosphonate, sodium fluoride or fluoroquinolone administration, it is recommended that taking Caltrate Vitamin D₃ be spaced by at least 3 hours, as their absorption during digestion may be reduced.

Oxalic acid (found in spinach and rhubarb) and phytic acid (found in wholegrain cereals) can inhibit calcium absorption by forming insoluble compounds with calcium ions. Patients must not take calcium containing-products in the two hours after the consumption of foods rich in oxalic acid and phytic acid.

There are no data relating to the effect of this medicinal product on the ability to drive vehicles. However there is little likelihood of an effect.

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

Metabolism and nutrition disorders

Uncommon: hypercalcaemia and hypercalciuria.

Gastrointestinal disorders

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

Skin and subcutaneous tissue disorders

Rare: pruritis, rash and urticaria.

Renal and urinary disorders

Not known: nephrolithiasis.

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

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

Treatment of hypercalcaemia: All calcium and vitamin D₃ treatments must be stopped. Treatment with thiazide diuretics, lithium, vitamin A and cardiac glycosides must also be stopped. Gastric lavage should be performed on patients with problems affecting consciousness. Rehydrate and, depending on severity, isolated or combined treatment with loop diuretics, bisphosphonates, calcitonin and corticosteroids should be considered. Serum electrolytes, kidney function and diuresis must be monitored. In severe cases, ECG and calcaemia should be monitored.

Pharmacotherapeutic group: Calcium carbonate and cholecalciferol, ATC Code: A12 AX.

Vitamin D supplementation corrects an insufficient vitamin D intake. It increases the intestinal absorption of calcium. The optimal vitamin D dose in elderly subjects is 500 - 1000 I.U. per day. Calcium supplementation balances a dietary calcium deficiency. The usual calcium requirement of the elderly is 1500 mg/day. Vitamin D and calcium supplementation correct secondary senile hyperparathyroidism.

An 18-month, double-blind, placebo-controlled study carried out in 3270 women living in institutions, aged 84 ± 6 years and receiving a vitamin D₃ supplement (800 IU/day) and calcium phosphate (corresponding to 1200 mg/day of elemental calcium), showed a significant decrease in PTH secretion. After 18 months, following an “intention to treat” (ITT) analysis, 80 hip fractures were observed in the calcium-vitamin D₃ group and 110 hip fractures in the placebo group (p=0.004). In a follow-up study after 36 months, 137 women with at least one fracture of the hip were observed in the calcium-vitamin D3 group (n = 1176) versus 178 women in the placebo group (n = 1127) (p ≤0.02).

Calcium

Absorption: in the stomach, calcium carbonate releases calcium ions depending upon pH. The amount of calcium absorbed by the gastrointestinal tract is in the order of 30% of the ingested dose.

Distribution and metabolism: 99% of calcium is stored in the hard matter of bones and teeth. The remaining one percent is found in intra and extracellular liquids. Approximately 50% of total blood calcium is found in the physiologically active ionised form, of which approximately 10% in complexes with citrate, phosphate or other anions with 40% remaining bound to proteins, mainly albumin.

Elimination: calcium is eliminated in the faeces, urine and in sweat. Kidney excretion depends on glomerular filtration and on calcium reabsorption by the tubules.

Vitamin D

Absorption: vitamin D is easily absorbed by the small intestine.

Distribution and metabolism: cholecalciferol and its metabolites circulate in the blood, linked to a specific alpha globulin. Cholecalciferol is metabolised in the liver by hydroxylation to its active form, 25-hydroxycholecalciferol. It is then metabolised in the kidneys to 1,25-dihydroxycholecalciferol. 1,25-dihydroxycholecalciferol is the metabolite responsible for the increase in calcium absorption. The vitamin D₃ that is not metabolised is stored in adipose and muscle tissue.

Elimination: vitamin D3 is excreted via the faeces and urine.

Calcium carbonate and cholecalciferol did not show mutagenic potential in vitro (Ames test).

A teratogenic effect has been observed in animal studies at very much higher doses than human therapeutic doses.

Tablet Core:

Microcrystalline cellulose

Povidone

Crospovidone type A

Sodium laurilsulphate

Sodium croscarmellose

Magnesium stearate

DL-α-tocopherol

Partially hydrogenated soya bean oil

Sucrose

Bovine gelatin hydrolyzed

Corn starch

Silicon dioxide

Tablet Coat:

Light liquid paraffin

Talc

OPADRY OY-S-27203:

methylhydroxypropylcellulose

titanium dioxide (E171)

light liquid paraffin

sodium laurilsulphate

red iron oxide (E172)

black iron oxide (E172)

yellow iron oxide (E172)

Not applicable.

2 years.

Store below 25°C. Keep the bottle tightly closed in order to protect from moisture.

Opaque white high density polyethylene bottles with a polypropylene cap and induction sealed foil liner.

Bottles contain 20, 30, 60, 90 or 180 tablets.

Not all pack sizes may be marketed.

No special requirements.

Pfizer Healthcare Ireland,

9 Riverwalk,

National Digital Park,

Citywest Business Campus,

Dublin 24,

Ireland.

P.A.822/173/001

Date of first authorization: 24 April 2009

April 2015