Calcichew-D₃ Forte Chewable Tablets

Per tablet: Calcium carbonate 1250 mg

(equivalent to 500 mg of elemental calcium)

Colecalciferol 400 IU

(equivalent to 10 micrograms vitamin D₃)

Contains sorbitol, 390mg; isomalt, 49.90mg; aspartame, 1mg; sucrose, 1.52mg; and soya bean oil, hydrogenated, 0.30mg. For a full list of excipients, see Section 6.1.

Chewable tablet.

Round, white, uncoated and convex tablets. May have small specks.

The treatment and prevention of vitamin D/calcium deficiency (characterised by raised serum alkaline phosphatase levels associated with increased bone loss, raised levels of serum PTH and lowered 25-hydroxyvitamin D) particularly in the housebound and institutionalised elderly subjects.

The supplementation of vitamin D and calcium as an adjunct to specific therapy for osteoporosis, in pregnancy, in established vitamin D dependent osteomalacia, and in other situations requiring therapeutic supplementation of malnutrition.

Oral.

Adults and elderly:

2 chewable tablets per day, preferably one tablet morning and evening.

The tablet may be chewed or sucked.

Dosage in hepatic impairment:

Dosage in renal impairment:

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

• Nephrolithiasis

• Hypervitaminosis D

• Hypersensitivity to soya or peanut

• Hypersensitivity to the active substances or to any of the excipients

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 D 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 colecalciferol is not metabolised normally and other forms of vitamin D should be used (see section 4.3, contraindications).

Calcichew-D₃ Forte Chewable Tablets should be prescribed with caution to patients suffering from sarcoidosis because of the risk of increased metabolism of vitamin D to its active form. These patients should be monitored with regard to the calcium content in serum and urine.

Calcichew-D₃ Forte Chewable Tablets should be used with caution in immobilised patients with osteoporosis due to the increased risk of hypercalcaemia.

The content of colecalciferol (400 IU) in Calcichew-D₃ Forte Chewable Tablets 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.

CalcichewD₃ ForteChewable Tablets contain aspartame (a source of phenylalanine) which may be harmful for people with phenylketonuria.

CalcichewD₃ ForteChewable Tablets contain sorbitol (E420), isomalt and sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

CalcichewD₃ ForteChewable Tablets are not intended for use in children.

Thiazide diuretics reduce the urinary excretion of calcium. Due to increased risk of hypercalcaemia, serum calcium should be regularly monitored during concomitant use of thiazide diuretics.

Systemic corticosteroids reduce calcium absorption. During concomitant use, it may be necessary to increase the dose of Calcichew-D₃ Forte Chewable Tablets.

Simultaneous treatment with ion exchange resins such as cholestyramine or laxatives such as paraffin oil may reduce the gastrointestinal absorption of vitamin D.

Calcium carbonate may interfere with the absorption of concomitantly administered tetracycline preparations. For this reason, tetracycline preparations should be administered at least two hours before, or four to six hours after, oral intake of calcium.

Hypercalcaemia may increase the toxicity of cardiac glycosides during treatment with calcium and vitamin D. Patients should be monitored with regard to electrocardiogram (ECG) and serum calcium levels.

If a bisphosphonate or sodium fluoride is used concomitantly, this preparation should be administered at least three hours before the intake of Calcichew-D₃ Forte Chewable Tablets since gastrointestinal absorption may be reduced.

Oxalic acid (found in spinach and rhubarb) and phytic acid (found in whole cereals) may inhibit calcium absorption through formation of insoluble calcium salts. The patient should not take calcium products within two hours of eating foods high in oxalic acid and phytic acid.

Pregnancy

Lactation

There are no data about the effect of this product on driving capacity. An effect is, however, unlikely.

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

Gastrointestinal disorders

Skin and subcutaneous disorders

Overdose can lead to hypercalcaemia. Symptoms of hypercalcaemia may include anorexia, thirst, nausea, vomiting, constipation, abdominal pain, muscle weakness, fatigue, mental disturbances, polydipsia, polyuria, bone pain, nephrocalcinosis, nephrolithiasis and in severe cases, cardiac arrhythmias. Extreme hypercalcaemia may result in coma and death. Persistently high calcium levels may lead to irreversible renal damage and soft tissue calcification.

Treatment of hypercalcaemia: The treatment with calcium must be discontinued. Treatment with thiazide diuretics, lithium, vitamin A, vitamin D and cardiac glycosides must also be discontinued. Treatment: rehydration, and, according to severity of hypercalcaemia, isolated or combined treatment with loop diuretics, bisphosphonates, calcitonin and corticosteroids should be considered. Serum electrolytes, renal function and diuresis must be monitored. In severe cases, ECG and CVP should be followed.

Pharmacotherapeutic group: Mineral supplements

ATC code: A12AX

Vitamin D increases the intestinal absorption of calcium.

Administration of calcium and vitamin D₃ counteracts the increase of parathyroid hormone (PTH), which is caused by calcium deficiency and which causes increased bone resorption.

A clinical study of institutionalised patients suffering from vitamin D deficiency indicated that a daily intake of two tablets of Calcichew-D₃ Forte chewable tablets for six months normalised the value of the 25-hydroxylated metabolite of vitamin D₃ and reduced secondary hyperparathyroidism and alkaline phosphatases.

An 18 month double-blind, placebo controlled study including 3270 institutionalised women aged 84+/- 6 years who received supplementation of vitamin D (800 IU/day) and calcium phosphate (corresponding to 1200 mg/day of elemental calcium), showed a significant decrease of PTH secretion. After 18 months, an "intent-to treat" analysis showed 80 hip fractures in the calcium-vitamin D group and 110 hip fractures in the placebo group (p=0.004). A follow-up study after 36 months showed 137 women with at least one hip fracture in the calcium-vitamin D group (n=1176) and 178 in the placebo group (n=1127) (p0.02).

Calcium

Distribution and metabolism: 99% of the calcium in the body is concentrated in the hard structure of bones and teeth. The remaining 1% is present in the intra- and extracellular fluids. About 50% of the total blood-calcium content is in the physiologically active ionised form with approximately 10% being complexed to citrate, phosphate or other anions, the remaining 40% being bound to proteins, principally albumin.

Elimination: Calcium is eliminated through faeces, urine and sweat. Renal excretion depends on glomerular filtration and calcium tubular reabsorption.

Vitamin D

Distribution and metabolism: Colecalciferol and its metabolites circulate in the blood bound to a specific globulin. Colecalciferol is converted in the liver by hydroxylation to the active form 25-hydroxycholecalciferol. It is then further converted in the kidneys to 1,25hydroxycholecalciferol; 1,25hydroxycholecalciferol is the metabolite responsible for increasing calcium absorption. Vitamin D, which is not metabolised, is stored in adipose and muscle tissues.

Elimination: Vitamin D is excreted in faeces and urine.

At doses far higher than the human therapeutic range teratogenicity has been observed in animal studies. There is no further information of relevance to the safety assessment in addition to what is stated in other parts of the SmPC.

Sorbitol E420

Povidone

Isomalt (E953)

Flavouring (lemon)

Fatty acid mono- and diglycerides

Aspartame (E951)

Magnesium stearate

Sucrose

Gelatin

Soya bean oil, hydrogenated

Tocopherol

Maize starch

Not applicable.

3 years.

Do not store above 30°C. Keep the container tightly closed.

White, high density polyethylene bottles containing 20, 30, 60, 90 or 100 tablets with tamper-evident seal.

Not all pack sizes may be marketed.

No special requirements.

Shire Pharmaceuticals Limited

Hampshire International Business Park

Chineham

Basingstoke

Hampshire RG24 8EP

United Kingdom

PL 08557/0029

26 March 1996

April 2007