4.1. Therapeutic indications

Prevention and treatment of vitamin D deficiency.

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

Colecalciferol is indicated in adults, the elderly and adolescents from 12 years of age.

4.2. Posology and method of administration

Posology

Adults

Vitamin D deficiency

For vitamin D deficiency in adults and the elderly (serum levels <25 nmol/l (<10 ng/ml)), 1 - 4 capsules (800-3200 IU) daily for up to 12 weeks dependent upon the severity of the disease and the patient's response to treatment.

Vitamin D insufficiency

For vitamin D insufficiency in adults and the elderly (serum levels 25 – 50 nmol/l (10-20 ng/mL)), long term maintenance therapy following treatment of deficiency in adults and the elderly and prevention of vitamin D deficiency, 1- 2 Capsules (800-1600 IU) daily.

Osteoporosis

As an adjunct to specific therapy for osteoporosis, 1 capsule daily.

Dosage in hepatic impairment

No dose adjustment is required.

Dosage in renal impairment

Colecalciferol should not be used in patients with severe renal impairment (see section 4.3).

Paediatric population

Vitamin D deficiency or insufficiency

Vitamin D deficiency or insufficiency in children over 12 years – 1 capsule daily depending on the severity of the disease and the patient's response to treatment. Should only be given under medical supervision.

Colecalciferol should not be used in children under 12 years.

During pregnancy and breast-feeding

Treatment of vitamin D deficiency

1 – 5 capsules (800 – 4000 IU) daily.

Long term maintenance therapy following treatment of deficiency

1 – 2 capsules (800 – 1600 IU) daily.

Method of administration

Oral

The capsules should be swallowed whole (not chewed) with water. The capsules should not be chewed in order to facilitate the swallowing of the capsule content. In order to enhance absorption, it is recommended to take vitamin D with a meal.

4.3. Contraindications

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

• Hypervitaminosis D

• nephrolithiasis

• Diseases or conditions resulting in hypercalcaemia and/or hypercalciuria Severe renal impairment

4.4. Special warnings and precautions for use

In the case of therapeutic treatment the dose should be established on an individual basis for the patients by regular checking of plasma calcium levels. During long-term treatment with a daily dose exceeding 1,000 IU vitamin D, the serum calcium level, urinary calcium excretion and renal function should be monitored by measuring the serum creatinine level. Monitoring is especially important for elderly patients who concomitantly take cardiac glycosides or diuretics (see section 4.5), and in the case of hyperphosphataemia, as well as for patients with an increased risk of lithiasis. In case of hypercalciuria (exceeding 300 mg (7.5 mmol)/24 hours) or signs of impaired renal function the dose should be reduced or the treatment discontinued.

Renal impairment

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).

Caution is required in patients receiving treatment for cardiovascular disease (see Section 4.5 – cardiac glycosides including digitalis).

Monitoring in children whose mother receives treatment with vitamin D

Similar monitoring is necessary for children whose mother receives treatment with vitamin D in pharmacological amounts. Some children may react with increased sensitivity to the effect of vitamin D.

Pseudohypoparathyroidism

Vitamin D3 capsules should not be taken if pseudohypoparathyroidism is present (the need for vitamin D may be reduced by the sometimes normal sensitivity to vitamin D, with a risk of long term overdose). In such cases, more manageable vitamin D derivatives are available.

Sarcoidosis

Colecalciferol 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.

Use of additional supplements

Allowances should be made for vitamin D supplements from other sources. The concomitant use of multivitamin products and dietary supplements containing vitamin D should be avoided.

The need for additional calcium supplementation should be considered for individual patients. Calcium supplements should be given under close medical supervision. Medical supervision is required whilst on treatment to prevent hypercalcaemia.

Paediatric population

Colecalciferol should not be given to children <12 years of age.

Sodium

This medicine contains less than 1 mmol sodium (23 mg) per 800 IU, that is to say essentially 'sodium-free'.

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

Concomitant use with calcium containing products administered in large doses may increase the risk of hypercalcaemia. Thiazide diuretics reduce the urinary excretion of calcium. Due to the increased risk of hypercalcaemia, serum calcium should be regularly monitored during concomitant use of thiazide diuretics or with calcium containing products taken in large doses.

Concomitant treatment with anticonvulsants (like phenytoin), hydantoin or barbiturates can decrease the effect of vitamin D because of metabolic activation. Concomitant use of glucocorticoids can decrease the effect of vitamin D. Systematic corticosteroids inhibit the absorption of calcium. Long- term use of corticosteroids may offset the effect of vitamin D.

Products containing magnesium (like antacids) may not be taken during vitamin D treatment because of the risk of hypermagnesaemia.

Concomitant use of calcitonin, etidronate, gallium nitrate, pamidronate or plicamycin with vitamin D may antagonise the effect of these products in hypercalcaemia treatment.

Products containing phosphor used in large doses, given concomitantly may increase the risk of hyperphosphataemia.

The effects of digitalis and other cardiac glycosides may be accentuated with the oral administration of calcium combined with Vitamin D. Strict medical supervision is needed and, if necessary monitoring of ECG and calcium.

Simultaneous treatment with ion exchange resins such as cholestyramine or laxatives 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.

Orlistat may potentially impair the absorption of colecalciferol as it is fat-soluble.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no or limited amount of data from the use of colecalciferol in pregnant women. Studies have shown safe use of doses up to 4000 IU during pregnancy although studies in animals have shown reproductive toxicity (see section 5.3). The recommended daily intake for pregnant women is 400 IU, 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.

Breast-feeding

Vitamin D3 and its metabolites are excreted in breast milk. No adverse events have been observed in infants. Colecalciferol can be used at recommended doses during lactation in case of a vitamin D deficiency. This should be considered when giving additional vitamin D to the child.

Fertility

There are no data on the effect of colecalciferol 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

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

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).

Immune system disorders

Not known (cannot be estimated from the available data): hypersensitivity reactions such as angio-oedema or laryngeal oedema.

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 at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

The most serious consequence of acute or chronic overdose is hypervitaminosis, hypercalcaemia and hyperphosphatemia due to vitamin D toxicity. Symptoms may include nausea, vomiting, polyuria, anorexia, weakness, apathy, thirst, constipation, abdominal pain, muscle weakness, confusion, polydipsia, bone pain, calcification in the kidneys, kidney stones, vertigo, and cardiac arrhythmia in severe cases. Chronic overdoses can lead to vascular and organ calcification as a result of hypercalcaemia. Hypercalcaemia in extreme cases may lead to coma or even death. Persistently high levels of calcium may cause irreversible renal impairment and soft tissue calcification.

Treatment should consist of stopping all intake of vitamin D. At the same time, the use of thiazide diuretics, lithium, vitamin D and A as well as cardiac glycosides should also be discontinued. In the case of patients with impaired consciousness gastric emptying is also necessary. Rehydration and mono- or combined therapy with loop diuretics, bisphosphonates, calcitonin and corticosteroids may be used depending on the severity of the overdose. Serum electrolyte levels, renal function and diuresis should be monitored. In severe cases ECG and central venous pressure monitoring may be necessary.