STEXEROL-D3 1 000 IU FILM-COATED TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Stexerol-D3 1,000 IU Film-coated Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 1,000 colecal­ciferol (equivalent to 25 micrograms of vitamin D3)

Excipients with known effect:

Each 1,000 IU tablet contains approximately 1.8 milligrams of sucrose and 2 milligrams of sodium. See Section 4.4 for further details.

For a full list of excipients see section 6.1

Film-coated Tablets

The 1,000 IU tablets are orange, oval shaped tablets of 8.5 mm

4.1 Therapeutic indications

Stexerol-D3 is indicated in adults, the elderly and adolescents for prevention and treatment of vitamin D deficiency.

As an adjunct to specific therapy for osteoporosis in patients with vitamin D deficiency or at risk of vitamin D insufficiency.

4.2 Posology and method of administration

Posology

Paediatric population

Stexerol-D3 is not recommended for children under 12 years.

Method of Administration

The tablets can be swallowed whole, or crushed. The tablets can be taken with food.

Treatment of deficiency (< 25 ng/ml):

Adults: 50,000 IU/week for 6 weeks or, 3,000 – 4,000 IU/day for 10–12 weeks

Adolescents 12 years and over: 25,000 IU once every 2 weeks for 6 weeks (i.e. total dose 75,000 IU), or 2,000 IU/day for 6 weeks

Maintenance therapy following treatment of deficiency:

Adults: 25,000 IU/month or 1,000 IU/day. In certain situations (see below) higher doses of up to 50,000 IU/month or up to 4,000 IU/day may be required if patients cannot be maintained at the lower doses.

Adolescents 12 years and over: 1,000 IU/day

25(OH)D should be measured approximately 3 to 4 months after beginning maintenance therapy to confirm that target level has been reached.

Prevention of deficiency:

Adults: 25,000 IU/month or 1,000 IU/day. In certain situations (see below) higher doses of up to 50,000 IU/month or up to 4,000 IU/day may be required if patients cannot be maintained at the lower doses.

Adolescents 12 years and over: 25,000 IU every 6 weeks

Adjunct to specific therapy for osteoporosis:

Adults: 25,000 IU/month or 1,000 IU/day

Certain populations are at higher risk of vitamin D deficiency and may require higher doses, e.g.:

– People who are institutionalised or hospitalised long term

– Darker skinned people, especially at higher latitudes

– People whose effective sun exposure is limited due to covering up with clothing or constant use of sun screens

– Obese people

– People using certain concomitant medications (e.g. anticonvulsants,

glucocorticoids)

– People with conditions causing malabsorption, including inflammatory bowel disease and coeliac disease

– People with osteoporosis

– People recently treated for vitamin D deficiency and requiring maintenance therapy

4.3 Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1

Hypervitaminosis D

Nephrolithiasis

Nephrocalcinosis

Diseases or conditions resulting in hypercalcaemia and/or hypercalciuria(e.g.

myeloma, bone metastases or other malignant bone disease, primary hyperparathyro­idism)

Severe renal impairment

4.4 Special warnings and precautions for use

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).

Stexerol-D3 should be prescribed with caution to patients suffering from sarcoidosis or other granulomatous disease because of the risk of increased metabolism of vitamin D to its active form. These patients should be monitored with regard to the calcium levels in serum and urine.

Treatment with vitamin D has the potential to unmask primary hyperparathyro­idism. Serum calcium levels should be monitored in susceptible patients. If calcium levels are raised then the potential for vitamin D treatment to have unmasked primary hyperparathyroidism should be considered.

During long-term treatment, serum calcium levels and renal function (through measurements of serum creatinine) should be monitored. Monitoring is especially important in elderly patients on concomitant treatment with cardiac glycosides or diuretics (see section 4.5) and in patients with an increased tendency to calculus formation. In the 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.

The total dose of vitamin D should be considered and adjusted accordingly when prescribing Stexerol-D3 with other medicinal products containing vitamin D.

The calcium status and dietary intake of individual patients should also be considered at the same time as starting vitamin D3 replacement or treatment.

Monitoring may be necessary in patients with increased sensitivity to vitamin D therapy.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction Concomitant use of phenytoin or barbiturates may reduce the effect of vitamin D due to increase in the rate of its metabolism.

Simultaneous treatment with ion exchange resins such as cholestyramine or laxatives such as paraffin oil may reduce the gastrointestinal absorption of vitamin D.

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

Increased levels of vitamin D can induce hypercalcaemia, which may increase the risk of digitalis toxicity and serious arrhythmias due to the additive inotropic effects. The electrocardiogram (ECG) and serum calcium levels of patients should be closely monitored.

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.

4.6 Fertility, pregnancy and lactation

Pregnancy

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 up to 600 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 deficiency and their response to treatment. There are no indications that vitamin D at therapeutic doses is teratogenic in humans.

Breast-feeding

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.

Fertility

There are no data on the effect of Stexerol-D3 on fertility. However, normal endogenous levels of vitamin D are not expected to have any adverse effects on fertility.

4.7 Effects on ability to drive and use machines

Stexerol-D3 has no influence on the ability to drive and use machines.

4.8 Undesirable effects

Adverse reactions frequencies are defined as: uncommon (>1/1,000, <1/100), rare (>1/10,000, <1/1,000) or not known (cannot be estimated from the available data)

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.

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

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, somnolence and vertigo. 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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Vitamin supplements

ATC-code: A11C C05

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 parathyroids 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.

5.2 Pharmacokinetic properties

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

5.3 Preclinical safety data

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

There are no reported teratogenicity or foetal toxicity studies of vitamin D3 in animal species. However, potential for vitamin D2 (in far higher doses than human therapeutic range) induced foetal teratogenesis has been suggested in small studies of pregnant animals.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

1,000 IU Tablet:

Tablet Core:

Microcrystalline cellulose

Croscarmellose sodium

Magnesium stearate

Modified maize starch

Colloidal anhydrous silica

Sucrose

Sodium ascorbate

Triglycerides, medium chain

Silicon dioxide, colloidal

all-rac-a-tocopherol

Film-coat:

Hypromellose

Talc

Macrogol 6000 (PEG)

Titanium dioxide (E171)

Yellow iron oxide (E172)

Red iron oxide (E172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

18 months

6.4 Special precautions for storage

Do not store above 25oC.

Store in the original packaging in order to protect from light and moisture.

6.5 Nature and contents of container

The 1,000 IU tablets are provided in, PVC-PE-PVDC/Aluminium blister packs of 28 tablets or High Density Polyethylene bottles with a polypropylene cap containing 56 tablets, inside cardboard cartons.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal No special requirements.

7. MARKETING AUTHORISATION HOLDER

Kyowa Kirin Ltd.

Galabank Business Park

Galashiels

TD1 1QH

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL16508/0047

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

19/11/2015