SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Calcichew-D₃ Forte Strawberry and Watermelon 500 mg/400 IU chewable tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

One tablet contains:

Calcium carbonate equivalent to 500 mg calcium

Cholecalciferol concentrate (powder form) equivalent to 400 IU (10 microgram) cholecalciferol (vitamin D3)

Excipient(s) with known effect:

One tablet contains 1 mg aspartame (E951), 390 mg sorbitol (E420) and 0.7 mg sucrose

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Chewable tablet.

Round, white, uncoated and convex tablets of 16 mm. May have small specks.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Prevention and treatment of vitamin D and calcium deficiency.

Vitamin D and calcium supplement as an adjunct to specific osteoporosis treatment of patients who are at risk of vitamin D and calcium deficiency.

Posology and method of administration

Posology

Adults and elderly

One chewable tablet twice daily.

Dosage in hepatic impairment No dose adjustment is required

Dosage in renal impairment

Calcichew-D₃ Forte Strawberry and Watermelon should not be used in patients with severe renal impairment.

Paediatric population

Calcichew-D₃ Forte Strawberry and Watermelon is not intended for use in children. Method of administration

For oral use. The chewable tablet may be chewed or sucked.

Contraindications

•    Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

•    Severe renal impairment

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

•    Nephrolithiasis

•    Hypervitaminosis D

4.4 Special warnings and precautions for use

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

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

Calcichew-D₃ Forte Strawberry and Watermelon should be used cautiously in immobilised patients with osteoporosis due to increased risk of hypercalcaemia.

The content of vitamin D (400 IU) in Calcichew-D₃ Forte Strawberry and Watermelon 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. Milk-alkali syndrome (Burnett’s syndrome), i.e. hypercalcaemia, alkalosis and renal impairment, can develop when large amounts of calcium are ingested with absorbable alkali.

Calcichew-D₃ Forte Strawberry and Watermelon contains aspartame (E951, a source of phenylalanine). May be harmful for people with phenylketonuria.

Calcichew-D₃ Forte Strawberry and Watermelon 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.

4.5 Interaction with other medicinal products and other forms of interaction

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.

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 is used concomitantly, this preparation should be administered at least one hour before the intake of Calcichew-D₃ Forte Strawberry and Watermelon since gastrointestinal absorption may be reduced.

The efficacy of levothyroxine can be reduced by the concurrent use of calcium, due to decreased levothyroxine absorption. Administration of calcium and levothyroxine should be separated by at least four hours.

The absorption of quinolone antibiotics may be impaired if administered concomitantly with calcium. Quinolone antibiotics should be taken two hours before or six hours after intake of calcium.

Calcium salts may decrease the absorption of iron, zinc and strontium ranelate. Consequently, iron, zinc or strontium ranelate preparations should be taken at least two hours before or after Calcichew-D₃ Forte Strawberry and Watermelon.

Treatment with orlistat may potentially impair the absorption of fat-soluble vitamins (e.g. vitamin D₃).

4.6 Fertility, pregnancy and lactation

Pregnancy

During pregnancy the daily intake should not exceed 1500 mg calcium and 4000 IU vitamin D. Studies in animals have shown reproductive toxicity of high doses of vitamin D. In pregnant women, overdoses of calcium and vitamin D should be avoided as permanent hypercalcaemia has been related to adverse effects on the developing foetus. There are no indications that vitamin D at therapeutic doses is teratogenic in humans. Calcichew-D₃ Forte Strawberry and Watermelon can be used during pregnancy, in case of a calcium and vitamin D deficiency.

Breastfeeding

Calcichew-D₃ Forte Strawberry and Watermelon can be used during breast-feeding. Calcium and vitamin D₃ pass into breast milk. This should be considered when giving additional vitamin D to the child.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

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 (cannot be estimated from the available data): Hypersensitivity reactions such as angioedema or laryngeal oedema.

Metabolism and nutrition disorders Uncommon: Hypercalcaemia and hypercalciuria.

Very rare: Seen usually only in overdose (see section 4.9): Milk-alkali syndrome.

Gastrointestinal disorders

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

Skin and subcutaneous tissue disorders Very rare: Pruritus, rash and urticaria.

Other special population

Patients with renal impairment: potential risk of hyperphosphaetemia, nephrolithiasis and nephrocalcinosis. See section 4.4.

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

Overdose can lead to hypervitaminosis D and hypercalcaemia. Symptoms of hypercalcaemia may include anorexia, thirst, nausea, vomiting, constipation, abdominal pain, muscle weakness, fatigue, mental disturbances, polidipsia, polyuria, bone pain, nephrocalcinosis, renal calculi 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.

Milk-alkali syndrome may occur in patients who ingest large amounts of calcium and absorbable alkali. Symptoms are frequent urge to urinate, continuing headache, continuing loss of appetite, nausea or vomiting, unusual tiredness or weakness, hypercalcaemia, alkalosis and renal impairment.

Treatment: The treatment with calcium and vitamin D must be discontinued. Treatment with thiazide diuretics and cardiac glycosides must also be discontinued. Emptying of the stomach in patients with impaired consciousness. Rehydration, and, according to severity, isolated or combined treatment with loop diuretics, bisphosphonates, calcitonin and corticosteroids. Serum electrolytes, renal function and diuresis must be monitored. In severe cases, ECG and CVP should be followed.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmatherapeutic 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 1000 mg calcium and 800 IU vitamin D 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) (p<0.02).

5.2 Pharmacokinetic properties

Calcium

Absorption: The amount of calcium absorbed through the gastrointestinal tract is approximately 30% of the swallowed dose.

Distribution and biotransformation: 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

Absorption: Vitamin D is easily absorbed in the small intestine.

Distribution and biotransformation: Cholecalciferol and its metabolites circulate in the blood bound to a specific globulin. Cholecalciferol is converted in the liver by hydroxylation to the active form 25-hydroxycholecalciferol. It is then further converted in the kidneys to 1,25 dihydroxycholecalciferol. 1,25 dihydroxycholecalciferol 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.

5.3 Preclinical safety data

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

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Sorbitol (E420)

Povidone

Flavouring (strawberry-watermelon)

Maize maltodextrin Glyceryl triacetate (E1518)

Mono and diacetyl tartaric acid esters of mono-and deglycerides of fatty acids Magnesium stearate Aspartame (E951)

All-rac-alpha-tocopherol

Sucrose

Modified maize starch Triglycerides, medium-chain Sodium ascorbate Silica, colloidal anhydrous

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

HDPE tablet container: 30 months

Shelf life after first opening of the tablet container is 60 days.

6.4 Special precautions for storage

HDPE tablet container: Do not store above 30°C. Store in the original container in order to protect from light. Keep the container tightly closed in order to protect from moisture.

6.5 Nature and contents of container

The chewable tablets are packed in:

HDPE tablet containers with HDPE screw caps

Pack sizes: 20, 30, 50, 60, 90, 100, 120, 168 and 180 tablets

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Takeda UK Ltd.

Building 3

Glory Park Glory Park Avenue Wooburn Green High Wycombe HP10 0DF

8    MARKETING AUTHORISATION NUMBER(S)

PL 16189/0029

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

17/06/2015

10    DATE OF REVISION OF THE TEXT

14/12/2015