D-Seul^® is indicated for:

The treatment and prevention of vitamin D deficiency. D-Seul^® is indicated in adolescents and adults

• Posology

 Prevention (Prophylaxis) vitamin D deficiency in children (12-18):

• 400-1000 IU/DAY (up to 4000IU/DAY) (duration varies according to cases) 25000 IU/ every 6 to 8 weeks

Prevention (Prophylaxis) vitamin D deficiency in adults:

• Up to 2000IU/day
• Up to 25000IU/month

Treatment of vitamin D deficiency in children:

• Up to 2000IU/day for 6 weeks followed by maintenance dose.

Treatment of vitamin D deficiency in adults:

• Up to 50000IU/week for up to 8 weeks followed by maintenance dose.

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.

Method of administration

This medicine is taken orally.

The capsules should be swallowed whole (not chewed) with water. Preferably with the main meal of the day.

D-Seul^® 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 cholecalciferol is not metabolised normally and other forms of vitamin D have to be used.

D-Seul^® should not be taken by patients with a tendency to form calcium-containing renal calculi.

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

D-Seul^® 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 pregnancy, D-Seul^® should be taken only when strictly indicated and dosed only as it is absolutely necessary to correct vitamin D deficiency (see section 4.6).

Allowances should be made for vitamin D supplements, other vitamin D containing medicines or from other sources.

The need for additional calcium supplementation should be considered for individual patients. Calcium supplements should be given under close medical supervision.

During treatment with an equivalent daily dose, exceeding 1,000 IU vitamin D the serum and renal calcium levels must be monitored and renal function checked via serum creatinine determination. Such monitoring is particularly important in elderly patients and during concomitant treatment with cardiac glycosides or diuretics (see section 4.5). This also applies to patients who are particularly susceptible to the formation of kidney stones that contain calcium.

Paediatric population

D-Seul^® should not be used in infants or young children (under 12 years) as they may not be able to swallow the capsules and might choke. Instead, it is advisable to use drops or dissolvable tablets. Due to the lack of data on posology the administration in adolescents between the ages of 12-18 years is not recommended.

Patients treated with cardiac glycosides may be susceptible to high calcium levels and should have ECG parameters and calcium levels monitored. 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).

Simultaneous administration of benzothiadiazine derivatives (thiazide diuretics) increases the risk of hypercalcaemia because they decrease the calcium excretion in the urine. The calcium levels in plasma and urine should therefore be monitored for patients undergoing long-term treatment.

If cholecalciferol is combined with metabolites or analogues of vitamin D careful monitoring of serum calcium levels is recommended.

Calcium Supplements (see section 4.4)

Anti-convulsants e.g. phenytoin, phenobarbital, primidone may diminish the effect of cholecalciferol due to hepatic enzyme induction.

Rifampicin may reduce the effectiveness of cholecalciferol due to hepatic enzyme induction.

Isoniazid may reduce the effectiveness of cholecalciferol due to inhibition of the metabolic activation of cholecalciferol.

Drugs leading to fat malabsorption, e.g. orlistat, liquid paraffin, cholestyramine, may impair the absorption of cholecalciferol.

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.

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

Pregnancy

D-Seul^® 10 000 IU Capsules should not be used during pregnancy unless the clinical condition of the woman requires treatment with cholecalciferol, at a dose necessary to overcome the deficiency.

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.

Based on human experience and animal studies, vitamin D overdose causes physical and mental disability and congenital heart and eye conditions, due to hypercalcaemia, when administered during pregnancy.

Breast-feeding

D-Seul^® 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.

D-Seul^® S.G Capsules No studies on the effects on the ability to drive or use machines have been performed. D-Seul^® has no known side effects that are likely to affect the ability to drive and use or operate machines.

The frequency of possible side effects listed below are defined as:

Very common (≥ 1/10), Common (≥ 1/100 to <1/10), Uncommon (≥ 1/1,000 to <1/100)

Rare (≥ 1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data)

Metabolism and nutrition disorders:

Uncommon: hypercalcaemia and hypercalciuria.

Skin and subcutaneous disorders:

Rare: Pruritus, rash and urticaria.

To report any side effect(s):

·       Saudi Arabia:

-   Other GCC States:

Acute or chronic overdose of D-Seul^® 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 normalization 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.

Pharmacotherapeutic group: Vitamin D. ATC code: A11CC05.

Absorption: Cholecalciferol is easily absorbed in the small intestine.

Cholecalciferol is produced within the skin under the influence of UV radiation including sunlight. In its biologically active form, cholecalciferol 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 parathyroids is inhibited directly by the biologically active form of cholecalciferol. PTH secretion is inhibited additionally by the increased calcium uptake in the small intestine under the influence of biologically active cholecalciferol.

Elimination: Cholecalciferol and other forms of vitamin D are excreted in faeces and urine.

The pharmacokinetics of cholecalciferol have been widely studied and are well-known. Cholecalciferol from nutritional sources is almost completely absorbed from within the gastro-intestinal tract in the presence of dietary lipids and bile acids. Cholecalciferol is stored in fat cells and its biological half-life is approximately 50 days.

Cholecalciferol is metabolised by microsomal hydroxylase to form 25-hydroxycholecalciferol (25(OH) D3, calcidiol), the primary storage form of vitamin D3. 25(OH) D3 undergoes a secondary hydroxylation within the kidney to form the predominant active metabolite 1, 25-hydroxycholecalciferol (1, 25(OH) 2D3, calcitriol). The metabolites circulate in the blood bound to a specific α-globin.

After a single oral dose of cholecalciferol, the maximum serum concentrations of the primary storage form are reached after approximately 7 days. 25(OH) D3 is then slowly eliminated with an apparent half-life in serum of about 50 days.

Cholecalciferol and its metabolites are excreted mainly in the bile and faeces.

After high doses of cholecalciferol, serum concentrations of 25(OH) D3 may be increased for months. Overdose-induced hypercalcaemia may persist for weeks.

D-Seul^® is a well-known and established product and has been used in clinical practice for many years. No further specific toxicological hazard for humans is expected other than in chronic overdosage where hypercalcaemia could be seen.

Cholecalciferol overdosage in animals has been shown to induce malformations in rats, mice and rabbits at doses significantly higher than the human dose. The malformations included skeletal defects, microcephaly and cardiac malformations.

At doses equivalent to those used therapeutically, cholecalciferol has no teratogenic activity.

Cholecalciferol has no potential mutagenic or carcinogenic activity.

Not applicable.

Do not Store above 30^oC, protect from light.

D-Seul^® 10,000IU S.G Capsules are packed in HDPE jars with PP screw cap with induction sealing foil. With desiccant bag (silica gel granules) labeled with adhesive label in a carton box with a multi folded leaflet.

Pack size: 30 S.G. Capsules /Jar.

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