Stexerol-D3 1,000 IU Film-coated Tablets

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 therapy4.3 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 impairment4.4 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) | | | | | --- | --- | --- | | **System Organ Class** | **Frequency** | **Adverse Reaction** | | Immune system disorders | Not known | Hypersensitivity reactions | | Gastrointestinal disorders | Not known | Nausea, vomiting | | Metabolism and nutrition disorders | Uncommon | Hypercalcaemia, hypercalciuria | | Skin and subcutaneous disorders | Rare | Pruritus, rash, urticaria | 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.

5.1 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 α-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.

6.1 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-α-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 months6.4 Special precautions for storage Do not store above 25°C. 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 and other handling No special requirements.