Colextra-D3 25000 IU Tablets

Each tablet contains 25000 IU Colecalciferol (Vitamin D₃) equivalent to 625micrograms.

Excipient(s) with known effect: sucrose, 43.75 mg

For a full list of excipients see section 6.1.

Tablet

White, or almost white, oval, biconvex tablet, plain on both sides with dimensions 17 mm x 8 mm.

Prevention and treatment of vitamin D deficiency in adults and adolescents with an identified risk.

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

Posology

The dosage of vitamin D depends on severity of the disease, as well as patient's response to treatment. Based on patient's needs, capabilities and preferences daily, weekly or monthly dosing regimens can be offered. Lower dosage forms (e.g. 400 IU, 500 IU, 800 IU and 1,000 IU) are suitable for daily vitamin D supplementation, while higher dosage forms like 20,000 IU contain amounts equal to the weekly and monthly vitamin D doses respectively, which should be taken into consideration. The dosage and the frequency of administration has to be established individually by a physician.

The following may apply as dosage recommendation

Adults

Prevention of vitamin D deficiency and as an adjunct to specific therapy for osteoporosis: Recommended dose range is 600 IU- 800 IU per day.

Treatment of vitamin D deficiency:

800 IU per day. Higher doses should be adjusted dependent upon desirable serum levels of 25-hydroxycolecalciferol (25(OH)D), the severity of the disease and the patient´s response to treatment.

The daily dose should not exceed 4,000 IU.

Adolescents:

The dose should be adjusted dependent upon desirable serum levels of 25 hydroxycolecalciferol (25(OH)D), the severity of the disease and the patient´s response to treatment.

The daily dose should not exceed 4,000 IU per day.

Alternatively, national posology recommendations in prevention and treatment of vitamin D deficiency can be followed.

Paediatric population:

Colextra-D3 25,000 IU tablets should not be given to children under 12 years of age due to the risk of choking. Instead, it is advisable to use drops or dissolvable tablets.

• Special Populations

o Dosage in hepatic impairment

No dose adjustment is required.

o Dosage in renal impairment

Patients with mild or moderate renal impairment: no specific adjustment is required

Colecalciferol must not be used in patients with severe renal impairment.

o Dosage in pregnancy

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).

o Other conditions: such as 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.

Method of administration

Oral.

The tablet should be swallowed whole (not chewed) with water.

Hypersensitivity to vitamin D or any of the excipients in the product.

Hypervitaminosis D.

Nephrolithiasis.

Diseases or conditions resulting in hypercalcaemia and/or hypercalciuria.

Severe renal impairment.

Colextra-D3 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).

Colextra-D3 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.

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 hypercalcaemia.

During long-term treatment with a daily dose exceeding 1,000 IU vitamin D, calcium values must be monitored.

Colextra-D3 25000 IU Tablets should not be given to children under 12 years.

This medicine contains 43.75 mg of sucrose in each tablet. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency 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-dihydroxyvtiamin D by the kidney enzyme, 25-hydroxyvtiamin D-1- hydroxylase.

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 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.

Breast-feeding

Vitamin D and its metabolites are excreted in breastmilk. 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 available on the effect of colecalciferol on fertility.

Colextra-D3 25000 IU Tablets have 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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the risk/benefit balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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 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 are 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-hydroxycolecalciferol and then undergoes further hydroxylation in the kidney to from the active metabolite 1, 25- dihydroxycolcecalciferol (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 has 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.

modified food starch

medium chain Triglycerides

dl-alpha-Tocopherol

sodium ascorbate crystalline

sucrose

microcrystalline Cellulose

hydroxypropylcellulose, low-substituted silica,

colloidal anhydrous

silicon dioxide

Not applicable.

Blisters: 24 months

Container: 18 months

Blisters: Store below 25°C. Keep the blister in the outer carton in order to protect from light.

Container: Store below 25°C. Store in the original package in order to protect from light.

PVC/PVdC/Al blister pack: Pack sizes: 4, 6 and 12 tablets.

Polyethylene Container and Polypropylene lid pack: 1000 tablets.

Not all pack sizes may be marketed.

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

Synergy Biologics Limited

Unit 1, The Stamp Factory

Wednesbury Road

Walsall

West Midlands

WS1 3QY

United Kingdom

PL 50484/0004

05/01/2022

05/01/2022