COLEXTRA-D3 800 IU CAPSULES SOFT - summary of medicine characteristics

Colextra-D3 800 IU capsules, soft

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contain: 800 IU colecalciferol (equivalent to 20 micrograms Vitamin D3).

Excipient(s) with known effect: sorbitol 5.28mg.

For a full list of excipients see section 6.1

3 PHARMACEUTICAL FORM

Capsule, soft

Blue coloured transparent, round shaped soft gelatin capsule containing a clear, colourless liquid

Capsule size (diameter): 6.9mm

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

The 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.

4.2 Posology and method of administration

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 800 IU- 1600 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 800 IU capsules 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 D3 deficient a higher dose may be required (up to 2,000 IU/day)

o Other conditions (see above): such as obese patients, patients with malabsorption syndromes, and patients on medications affecting vitamin D3 metabolism, higher doses are required for the treatment and prevention of vitamin D3 deficiency

Method of administration

Oral

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

4.3 Contraindications

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

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, 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 capsules should not be given to children under 12 years.

This medicine contains 5.28mg sorbitol in each capsule.

4.5 Interaction with other medicinal products and other forms of interaction

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.

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 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.

4.7 Effects on ability to drive and use machines

Colextra-D3 capsules have no influence on the ability to drive and use machines

4.8 Undesirable effects

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.

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. 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 D and analogues

ATC code: A11CC05

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 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 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 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.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Capsule content:

Triglycerides, medium chain

all-rac-a-Tocopheryl acetate

Capsule shell:

gelatin

glycerol

sorbitol (E420)

brilliant Blue FCF (E133)

purified Water

6.2 Incompatibilities

Not applicable

6.3 Shelf life

24 months

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

PVC/PVdC/Al blister pack

Pack sizes: 30, and 100. Not all pack sizes may be marketed.

6.6 Special precautions for disposal

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

7 MARKETING AUTHORISATION HOLDER

Synergy Biologics Limited

Unit 1, The Stamp Factory

Wednesbury Road

Walsall

West Midlands

WS1 3QY

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 50484/0001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

28/09/2021