D-SEUL^® is indicated for:

· Prevention of vitamin D deficiency in infants and children

· Prevention of vitamin D deficiency in pregnant and breast-feeding women

Posology and method of administration:

1 drop contains 400 IU vitamin D3.

• Paediatric posology

-       Prevention of deficiency 0-1 years 400 IU/day (one drop)

-       Prevention of deficiency 1-18 years 600 IU/day (1-2 drops)

• Pregnancy and breast-feeding posology

-       Prevention of deficiency 400 IU/day (one drop)

• Special populations

-       Patients with renal impairment: no specific adjustment is required

-       Other conditions: in obese patients, patients with malabsorption syndromes, and patients on medications affecting vitamin D metabolism, higher doses are required for the treatment and prevention of vitamin D deficiency (2 - 3 times higher).

Route of administration: Orally.

Patients should be advised to take D-SEUL^® preferably with a meal.

D-SEUL^® can be taken as is or to facilitate the intake it can also be mixed with a spoonful or a small amount of cold or lukewarm food immediately prior to use. The patient should be sure to take the entire dose.

In children, D-SEUL^® can be mixed with a small amount of children's foods, yogurt, milk, cheese or other dairy products.

The parents should be warned not to mix D-SEUL^® into a bottle of milk or container of soft foods in case the child does not consume the whole portion, and does not receive the full dose. The parents should ensure that their child takes the entire dose. In children who are not breast-feeding, the prescribed dose should be administered with a meal.

·       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.

·       D-SEUL^® 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.

·       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.

Pregnancy

There are no or limited amount of data from the use of cholecalciferol in pregnant women. 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 2 000 IU/day - 10 drops). 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.

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.

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.

There are no data on the effects of D-SEUL^® Drops on the ability to drive. However, an effect on this ability is unlikely.

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 effect(s):

·       Saudi Arabia:

-   Other GCC States:

Discontinue D-SEUL^® when calcaemia exceeds 10.6 mg/dl (2.65 mmol/l) or if the calciuria exceeds 300 mg/24 hours in adults or 4-6 mg/kg/day in children. An overdose manifests as hypercalcaemia and hypercalciuria, the symptoms of which include the following: nausea, vomiting, thirst, constipation, polyuria, polydipsia and dehydration.

Chronic overdosage may lead to vascular and organ calcification, as a result of hypercalcaemia.

Treatment in cases of overdose

Discontinue administration of D-SEUL^® and initiate rehydration.

Pharmacotherapeutic group: Vitamin D and analogues, cholecalciferol.

ATC code: A11CC05

In its biologically active form, vitamin D 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 vitamin D. PTH secretion is inhibited additionally by the increased calcium uptake in the small intestine under the influence of biologically active vitamin D.

The pharmacokinetics of vitamin D is well known.

Absorption

Vitamin D is well absorbed from the gastro-intestinal tract in the presence of bile, so the administration with the major meal of the day might therefore facilitate the absorption of Vitamin D.

Distribution and biotransformation

It is hydroxylated in the liver to form 25-hydroxy-cholecalciferol and then undergoes further hydroxylation in the kidney to form the active metabolite 1, 25- dihydroxycholecalciferol (calcitriol).

Elimination

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.

Characteristics in Specific Groups of Subjects or Patients

A 57% lower metabolic clearance rate is reported in subjects with renal impairment as compared with that of healthy volunteers. Decreased absorption and increased elimination of vitamin D occurs in subjects with malabsorption. Obese subjects are less able to maintain vitamin D levels with sun exposure, and are likely to require larger oral doses of vitamin D to replace deficits.

Pre-clinical studies conducted in various animal species have demonstrated that toxic effects occur in animals at doses much higher than those required for therapeutic use in humans.

In toxicity studies at repeated doses, the effects most commonly reported were increased calciuria and decreased phosphaturia and proteinuria.

Hypercalcaemia has been reported in high doses. In a state of prolonged hypercalcaemia, histological alterations (calcification) were more frequently borne by the kidneys, heart, aorta, testes, thymus and intestinal mucosa.

Cholecalciferol has been shown to be teratogenic at high doses in animals.

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

Cholecalciferol has no potential mutagenic or carcinogenic activity.

Not applicable.

Store in cold place 2 - 8°C.           

Discard the content after one month from first opening.

D-Seul^® 2,000IU Oral Solution Drops packed in roll neck amber glass vial with an adhesive label & Sano dropper labeled with adhesive label, in a carton box with a multi folded leaflet.

Pack size: 10ml/Pack

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