The treatment and prevention of vitamin D deficiency.

As an adjunct to specific therapy for osteoporosis in patients with vitamin D deficiency.

DivaD^® capsules are indicated for use in adults, the elderly and adolescents.

Severe vitamin D deficiency: Loading doses 50,000 I.U. once weekly for 2 months. Maintenance dose: 800 to 2000 I.U. Once daily.

Vitamin D deficiency: 2000-5000 I.U. once daily or 10000 I.U. every other day for 2 months.

Vitamin D insufficiency: 2000-5000 I.U. once daily or 10000 I.U. every other day for 2 months.

Supplementation: 1000-2000 I.U. once daily

Follow-up measurements should be made approximately three to four months after initiating maintenance therapy to confirm that the target level has been achieved.

Infants and young children (0-12 years)

Not recommended for children under 12 years.

Pregnancy and breastfeeding

DivaD^® capsules are not recommended during pregnancy unless the clinical condition of the woman requires treatment.

Colecalciferol and its metabolites are excreted in breast milk. Overdose in infants induced by nursing mothers has not been observed but allowance for any maternal dose should be made when prescribing vitamin D products to a breast-fed child.

Method of administration

This medicine is taken orally.

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

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).

Vitamin D 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.

During long-term treatment with an equivalent daily dose exceeding 1,000 IU vitamin D the serum calcium values must be monitored. Renal function should also be checked by measuring serum creatinine. It is recommended to reduce the dose or interrupt treatment if the calcium content in the urine exceeds 7.5 mmol / 24 hours (300 mg / 24 hours).

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.

Medical supervision is required whilst on treatment to prevent hypercalcemia.

DivaD^® Capsules should not be given to children under 12 years.

DivaD^® 50000 I.U. capsules contain lactose: Patients with rare hereditary problems of galactose intolerance e.g. galactosaemia should not take this medicine.

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.

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.

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 in the United Kingdom 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.

DivaD^® has no influence on the ability to drive and use machines.

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.

To report any side effects:

National Pharmacovigilance and Drug Safety Centre (NPC)

o   Fax: + 966-11-205-7662

o   Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340

o   Toll free phone: 8002490000

o   Email: npc.drug@sfda.gov.sa

o   Website: www.sfda.gov.sa/npc

The most serious consequence of acute or chronic overdose is hypercalcaemia due to vitamin D toxicity. Symptoms may include nausea, vomiting, polyuria, anorexia, weakness, apathy, thirst and constipation. Chronic overdoses can lead to vascular and organ calcification as a result of hypercalcaemia. Treatment should consist of stopping all intake of vitamin D and rehydration.

Pharmacotherapeutic group: Vitamin D and analogues

ATC code: A11CC05

In its biologically active form vitamin D₃ stimulates intestinal calcium absorption, incorporation of calcium into the osteoid, and release of calcium from bone tissue. In the small intestine it promotes rapid and delayed calcium uptake. The passive and active transport of phosphate is also stimulated. In the kidney, it inhibits the excretion of calcium and phosphate by promoting tubular resorption. The production of parathyroid hormone (PTH) in the parathyroid is inhibited directly by the biologically active form of vitamin D₃. PTH secretion is inhibited additionally by the increased calcium uptake in the small intestine under the influence of biologically active vitamin D₃.

Vitamin D is well absorbed from the gastro-intestinal tract in the presence of bile. It is hydroxylated in the liver to form 25-hydroxycolecalciferol and then undergoes further hydroxylation in the kidney to form the active metabolite 1, 25 dihydroxycolecalciferol (calcitriol). The metabolites circulate in the blood bound to a specific α - globin, Vitamin D and its metabolites are excreted mainly in the bile and faeces.

Vitamin D is well known and is a widely used material and has been used in clinical practice for many years. As such toxicity is only likely to occur in chronic overdosage where hypercalcaemia could result.

Colecalciferol has been shown to be teratogenic in high doses in animals (4-15 times the human dose). Offspring from pregnant rabbits treated with high doses of vitamin D had lesions anatomically similar to those of supravalvular aortic stenosis and offspring not showing such changes show vasculotoxicity similar to that of adults following acute vitamin D toxicity.

DivaD^® 5000 and 10000 are: Microcrystalline cellulose and colloidal anhydrous silica.

DivaD^® 50 000 are: Lactose and Hydrated colloidal silica.

Not applicable.

Store in a dry place below 30°C.

DivaD^® 5000 Capsules are available in packs of 30 and 100 capsules.

DivaD^® 10000 Capsules are available in packs of 100 capsules.

DivaD^® 50000 Capsules are available in packs of 8, 100 capsules.

Not all pack sizes may be marketed.

Any unused product should be disposed of in accordance with local requirements.