4.1. Therapeutic indications

Prophylaxis and treatment of vitamin D deficiency in adolescents (children ≥ 12 years) and adults with an identified risk.

As an adjunct to specific therapy for osteoporosis in patients with vitamin D deficiency or at risk of vitamin D deficiency.

4.2. Posology and method of administration

Posology

Dose should be established by a physician on an individual basis depending on the extent of the necessary vitamin D supplementation.

• Paediatric posology

• Doses of up to 1,000 IU/day may be required to prevent deficiency in some children.

• Treatment of deficiency 12-18 years: up to 2,000 IU (2 capsules) per day for 6 weeks, followed by maintenance therapy of up to 1,000 IU (1 capsule) per day, as directed by a doctor.

• Adults

• Treatment of vitamin D deficiency 1,000 IU – 4,000 IU/day for up to 12 weeks, followed by maintenance therapy of 1,000 IU – 2,000 IU/day (such as one to two 1,000 IU soft capsules per day), as directed by your doctor.

Prevention of vitamin D deficiency 1,000 IU (1 capsule) per day. Higher doses may be required in certain populations, see below:

“Follow- up 25(OH)D measurements should be made approximately three to four months after initiating maintenance therapy to confirm that the target level has been achieved”.

Certain populations are at high risk of vitamin D deficiency, and may require higher doses and more intensive monitoring of serum 25(OH)D:

• Institutionalised or hospitalised individuals

• Dark skinned individuals

• Individuals with limited effective sun exposure due to protective clothing or consistent use of sun screens

• Obese individuals

• Patients being evaluated for osteoporosis

• Use of certain concomitant medications (e.g., anticonvulsant medications, glucocorticoids)

• Patients with malabsorption, including inflammatory bowel disease and coeliac disease

• Those recently treated for vitamin D deficiency, and requiring maintenance therapy.

• As an adjunct to specific therapy for osteoporosis: 1,000 IU/day.

Method of administration

This medicine is taken orally.

The capsule should be swallowed whole with water, preferably with the main meal of the day.

4.3. Contraindications

• Hypersensitivity to the active substance(s) or to any of the excipients.

• Hypercalcaemia and/or hypercalciuria.

• Nephrolithiasis and/or nephrocalcinosis

• Serious renal impairment

• Hypervitaminosis D

• Pseudoparathyroidism as the vitamin D requirement may be reduced due to phases of normal vitamin D sensitivity, involving the risk of prolonged overdose. Better-regulatable vitamin D derivatives are available for this.

4.4. Special warnings and precautions for use

The capsule formulation should not be given to children under 12 years of age due to the risk of choking.

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.

Caution is required in patients receiving treatment for cardiovascular disease (see section 4.5 Interaction with other medicinal products and other forms of interaction ¬cardiac glycosides including digitalis).

Colecalciferol should be prescribed with caution in patients with sarcoidosis, due to a possible increase in the metabolism of vitamin D in its active form. In these patients the serum and urinary calcium levels should be monitored.

Allowances should be made for the total dose of vitamin D in cases associated with treatments already containing vitamin D, foods enriched with vitamin D, cases using milk enriched with vitamin D, and the patient's level of sun exposure.

There is no clear evidence for causation between vitamin D supplementation and renal stones, but the risk is plausible, especially in the context of concomitant calcium supplementation. The need for additional calcium supplementation should be considered for individual patients. Calcium supplements should be given under close medical supervision.

Oral administration of high-dose vitamin D (500,000 IU by single annual bolus) was reported to result in an increased risk of fractures in elderly subjects, with the greatest increase occurring during the first 3 months after dosing.

4.5. Interaction with other medicinal products and other forms of interaction

Concomitant use of anticonvulsants (such as phenytoin) or barbiturates (and possibly other drugs that induce hepatic enzymes) may reduce the effect of vitamin D3 by metabolic inactivation.

In cases of treatment with thiazide diuretics, which decrease urinary elimination of calcium, monitoring of serum calcium concentration is recommended.

Concomitant use of glucocorticoids can decrease the effect of vitamin D.

In cases of treatment with drugs containing digitalis and other cardiac glycosides, the administration of vitamin D may increase the risk of digitalis toxicity (arrhythmia).

Strict medical supervision is needed, together with serum calcium concentration and electrocardiographic monitoring if necessary.

Simultaneous treatment with ion exchange resin such as cholestyramine, colestipol hydrochloride, orlistat or laxative such as paraffin oil may reduce the gastrointestinal absorption of vitamin D.

The cytotoxic agent actinomycin and imidazole antifungal agents interfere with vitamin D activity by inhibiting the conversion of 25-hydroxyvitamin D to 1,25¬dihydroxyvitamin D by the kidney enzyme, 25-hydroxyvitamin D-1-hydroxylase.

4.6. Fertility, pregnancy and lactation

Pregnancy

Colecalciferol is not recommended during pregnancy as there are limited data from the use of colecalciferol in pregnant women and the recommended daily intake should not exceed 600 IU vitamin D. However, in women who are considered to be vitamin D deficient, a higher dose may be required. During pregnancy women should follow the advice of their medical practitioner as their requirements may vary depending on the severity of their disease and their response to treatment . Studies in animals have shown reproductive toxicity of high doses of vitamin D (see section 5.3). There are no indications that vitamin D at therapeutic doses is teratogenic in humans.

Breast-feeding

Vitamin-D can be used during breast-feeding if necessary. Vitamin D3 passes into breast milk. This should be considered when giving additional vitamin D to the child. Overdose in infants induced by nursing mothers has not been observed, however, when prescribing additional vitamin D3 to a breast-fed child the practitioner should consider the dose of any additional vitamin D3 given to the mother.

Fertility

There is no data regarding treatment with vitamin D3 and its effects on fertility. However, normal endogenous levels of vitamin D are not expected to have any adverse effects on fertility.

4.7. Effects on ability to drive and use machines

There are no data on the effects of Colecalciferol on the ability to drive. However, an effect on this ability is unlikely.

4.8. Undesirable effects

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

Uncommon: Hypercalcaemia and hypercalciuria

Skin and subcutaneous 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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store..

4.9. Overdose

Symptoms of overdose

Ergocalciferol (vitamin D2) and colecalciferol (vitamin D3) have a relatively low therapeutic index. Infants and small children may react sensitively to far lower concentrations. Therefore, it is warned against intake of vitamin D without medical supervision.

Acute or chronic overdose of Colecalciferol can cause hypercalcaemia, an increase in the serum and urinary concentrations of calcium. The symptoms of hypercalcaemia are not very specific and consist of nausea, vomiting, diarrhoea, often in the early stages, and later constipation, anorexia, fatigue, headache, muscle and joint pain, muscle weakness, polydipsia, polyuria, formation of renal calculi, nephrocalcinosis, kidney failure, calcification of soft tissues, changes in ECG measurements, arrhythmias and pancreatitis. In rare and isolated cases there are reports that hypercalcaemia is fatal.

Treatment of overdose

A normalisation of hypercalcaemia due to vitamin D intoxication lasts several weeks. The recommendation for the treatment of hypercalcaemia is the avoidance of any further administration of vitamin D, including supplements, dietary intakes and the avoidance of sunlight. A low calcium or calcium-free diet can also be considered.

Rehydration and the treatment with diuretics e.g. furosemide to ensure adequate diuresis should be considered. Additional treatment with calcitonin or corticosteroids can also be considered.

Phosphate infusions should not be administered to lower hypercalcaemia of hypervitaminosis D because of the dangers of metastatic calcification.