D-CURE Oral solution Ref.[116019] Active ingredients: Vitamin D3

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).

D-Cure 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.

In patients with idiopathic infantile hypercalcaemia (e.g. CYP24A1 mutation or SLC34A1 mutation), the risk of hypercalcaemia and secondary effects (e.g. hypercalciuria, nephrocalcinosis, nephrolithiasis) is increased due to accumulation of active vitamin D. Idiopathic infantile hypercalcaemia may be asymptomatic and undiagnosed at the beginning of vitamin D therapy and may be unmasked and become clinically apparent after vitamin D supplementation.

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.

In pregnancy and lactation, the high strength formulation is not recommended and a low strength formulation should be used.

Pregnancy

There are no or limited amount of data from the use of cholecalciferol in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3 Preclinical safety data). 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 (up to 2000 IU/day).

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 of vitamin D must be avoided during pregnancy, as prolonged hypercalcemia can lead to physical and mental retardation, supravalvular aortic stenosis and retinopathy of the child.

Breast-feeding

Vitamin D can be prescribed while the patient is breast-feeding if necessary. This supplementation does not replace the administration of vitamin D in the neonate.

Not relevant.

Injury, poisoning and procedural complications are the result of an incorrect route of drug administration, accidental overdose or exposure, or underdose.

The following adverse events can be observed (based on the post-marketing data source):

Psychiatric disorders

Confusional state, aggression, insomnia

Gastrointestinal disorders

Nausea, abdominal pain, diarrhoea, vomiting, gastrointestinal disorder, dyspepsia

Nervous system disorders

Dizziness, flushing

Metabolism and nutrition disorders

Hypercalcaemia, hypercalciuria, decreased appetite, tetany

Skin and subcutaneous disorders:

Pruritus, urticaria, rash, hyperhidrosis

The side effects are the result of overdose. Depending on the dose and duration of treatment, severe and prolonged hypercalcaemia with its acute (cardiac arrhythmias, nausea, vomiting, psychic symptoms, disturbances of consciousness) and chronic (increased urgency to urinate, increased thirst, loss of appetite, weight loss, kidney stones, kidney calcification, calcification in tissues outside the skeleton) consequences can occur. A fatal outcome has been reported in very rare cases. (see also section 4.4 'Special warnings and precautions for use' as well as section 4.5 'Interaction with other medicinal products and other forms of interaction'. Furthermore, refer also to section 4.9 'Overdose').

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 advice to report any suspected adverse reactions to the Product Registration Holder.

Not applicable.