4.1. Therapeutic indications

Treatment and prophylaxis of vitamin D deficiency in adults and adolescents over 12 years with an identified risk.

In addition to specific osteoporosis treatment of patients who are at risk of vitamin D deficiency.

4.2. Posology and method of administration

Posology Recommended dose: One capsule per day.

Higher doses can be necessary in treatment of vitamin D deficiency, where the dose should be adjusted dependent upon desirable serum levels of 25- hydroxycolecalciferol (25(OH)D), the severity of the disease and the patient´s response to treatment.

The daily dose should not exceed 4,000 IU (5 capsules per day).

Dosage in hepatic impairment

No dose adjustment is required.

Dosage in renal impairment

Fultium-D3 is contraindicated in patients with severe renal impairment (see section 4.3).

Paediatric population

Fultium-D3 is not recommended in children under 12 years of age

Method of administration

The capsules should be swallowed whole with water.

4.3. Contraindications

Hypersensitivity to vitamin D or any of the excipients in the product

Hypervitaminosis D

Nephrolithiasis

Nephrocalcinosis

Diseases or conditions resulting in hypercalcaemia and/or hypercalciuria

Severe renal impairment

4.4. Special warnings and precautions for use

Patients with pseudohypoparathyroidism, sarcoidosis, and patients taking thiazide diuretics or cardiac glycosides must be referred to their doctor and not supplied this as a Pharmacy medicine.

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).

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 hypercalciuria (exceeding 300 mg (7.5 mmol)/24 hours) or signs of impaired renal function the dose should be reduced or the treatment discontinued Fultium-D3 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.

Allowances should be made for vitamin D supplements from other sources.

The need for additional calcium supplementation should be considered for individual patients. Calcium supplements should be given under close medical supervision. In such cases, it is necessary to monito serum calcium levels and unrinary calcium excretion frequently.

Medical supervision is required whilst on treatment to prevent hypercalcaemia.

During long-term treatment with a daily dose exceeding 1,000 IU vitamin D the serum calcium values must be monitored.

Fultium-D3 should not be given to children.

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

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.

Concomitant treatment with phenytoin or barbiturates can decrease the effect of vitamin D because of metabolic activation. Concomitant use of glucocorticoids can decrease the effect of vitamin D.

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.

Glucocorticoid steroids may increase vitamin D metabolism and elimination. During concomitant use, it may be necessary to increase the dose of the tablets. 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

There are no or limited amount of data from the use of colecalciferol in pregnant women. 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

Vitamin D and its metabolites are excreted in breast milk. Overdose in infants induced by nursing mothers has not been observed, however, when prescribing additional vitamin D to a breast-fed child the practitioner should consider the dose of any additional vitamin D given to the mother.

4.7. Effects on ability to drive and use machines

Fultium-D3 has no 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), rare (>1/10,000, <1/1,000) or not known (cannot be estimated form the available data).

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 the 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

Overdose can lead to hyper-vitaminosis D. An excess of vitamin D causes abnormally high levels of calcium in the blood, which can eventually severely damage the soft tissues, and kidneys. Tolerable Upper Intake Level for vitamin D3 (colecalciferol) is set at 4000 IU (100 µg) per day. Vitamin D3 should not be confused with its active metabolites, colecalciferol. Symptoms of hypercalcaemia may include anorexia, thirst, nausea, vomiting, constipation, abdominal pain, muscle weakness, fatigue, mental disturbances, polydipsia, 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. Treatment of hypercalcaemia: The treatment with vitamin D must be discontinued. Treatment with thiazide diuretics, lithium, vitamin A, and cardiac glycosides must also be discontinued. Rehydration, and, according to severity, 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.