Summary of Product Characteristics (SmPC) - Colecalciferol 20 000 IU soft capsules
1 NAME OF THE MEDICINAL PRODUCT
Colecalciferol 20,000 IU Capsules, Soft
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains: 20,000 IU Colecalciferol (equivalent to 500 mcg of vitamin D3)
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Capsule, soft
Light yellow coloured, transparent oval shaped, soft gelatin capsules containing clear colorless liquid fill and bearing the designation “58”.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment and prophylaxis 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.
Target populations:
- Adults, elderly and adolescents over 12 years of age.
- Pregnant women
4.2 Posology and method of administration
Adults and elderly
Prevention of vitamin D deficiency and as an adjunct to specific therapy for osteoporosis:
Recommended dose is 20,000 IU/month (1 capsule), higher doses may be required in certain situations
Treatment of vitamin D deficiency:
Recommended dose is 40,000 IU/week (2 capsules) for 7 weeks, followed by maintenance therapy (equivalent to 1,400-2,000 IU/day, such as 2-3 capsules per month, may be required.
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.
Adolescents:
Prevention of vitamin D deficiency 12-18 years:
20,000 IU (1 capsule) every 6 weeks
Treatment of vitamin D deficiency 12-18 years:
20,000 IU (1 capsule) once every 2 weeks for 6 weeks
Paediatric
Colecalciferol Capsules 20,000 IU 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.
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 or equivalent weekly or monthly dose (60,000 IU (3 capsules) per month)].
Hepatic impairment
No dose adjustment is required.
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.
Certain populations are at high risk of Vitamin D3 deficiency, and may require higher doses and monitoring of serum 25(OH)D:
- Institutionalised or hospitalised individuals
- Dark skinned individuals
- Individuals with limited effective sun exposure due to protective clothing or consistent use of sunscreen
- Obese individuals
- Patients being evaluated for osteoporosis
- Use of certain concomitant medications (e.g., anticonvulsant medications, glucocorticoids)
- Patients with malabsorption, including inflammatory bowel disease and coeliac disease
- Those recently treated for Vitamin D3 deficiency, and requiring maintenance therapy.
Method of administration
Oral - The capsules should be swallowed whole (not chewed) with water. In order to enhance absorption, it is recommended to take Colecalciferol capsule with a meal.
4.3 Contraindications
- Hypersensitivity to the active substance(s) or to any of the excipients.
- Hypercalcaemia and/or hypercalciuria.
- Nephrolithiasis and/or Nephrocalcinosis
- Serious renal impairment
- Hypervitaminosis D
- Pseudohypoparathyroidism as the vitamin D requirement may be reduced due to phases of normal vitamin D sensitivity, involving the risk of prolonged overdose.
4.4 Special warnings and precautions for use
Patients with Sarcoidosis, Pseudohypoparathyroidism and Certain Medications
Patients with sarcoidosis, Pseudohypoparathyroidism and patients taking thiazide diuretics or cardiac glycosides must be referred to their doctor and not supplied this as a Pharmacy medicine. Colecalciferol capsules should be prescribed with caution in patients with sarcoidosis, due to a possible increase in the metabolism of Vitamin D3 in its active form. In these patients the serum and urinary calcium levels should be monitored.
Renal Impairment
Vitamin 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.
Cardiovascular Disease
Caution required in patients receiving treatment for cardiovascular disease (see section 4.5 Interaction with other medicinal products and other forms of interaction – cardiac glycosides including digitalis).
Additional Vitamin D3 Sources
Allowances should be made for the total dose of Vitamin D3 in cases associated with treatments already containing Vitamin D3, foods enriched with Vitamin D3, cases using milk enriched with Vitamin D3, and the patient’s level of sun exposure.
Risk of Renal Stones
There is no clear evidence for causation between Vitamin D3 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.
High- Dose Vitamin D3 administration
Oral administration of high-dose Vitamin D3 (500,000 IU by single annual bolus) was reported to result in an increased risk of fractures in elderly subjects, with the greatest increase occurring during the first 3 months after dosing.
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 the serum calcium values must be monitored.
Paediatric population
Colecalciferol Capsules should not be given to children under 12 years.
4.5 Interaction with other medicinal products and other forms of interaction
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 D3.
In cases of treatment with drugs containing digitalis and other cardiac glycosides, the administration of Vitamin D3 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 D3.
The cytotoxic agent actinomycin and imidazole antifungal agents interfere with Vitamin D3 activity by inhibiting the conversion of 25- hydroxy vitamin D3 to 1,25- dihydroxy vitamin D3 by the kidney enzyme, 25-hydroxyVitamin D3-1-hydroxylase.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are no or limited amount of data from the use of Colecalciferol Capsules in pregnant women. Studies have shown safe use of doses up to 4000 IU during pregnancy
although 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.
Breastfeeding
Vitamin D3 and metabolites pass into breast milk. Vitamin D3 can be prescribed while the patient is breast-feeding if necessary. This supplementation does not replace the administration of Vitamin D3 in the neonate.
Fertility
There are no data on the effect of Colecalciferol Capsules 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
Colecalciferol Capsules has no or negligible 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).
Immune system disorders
Not known (cannot be estimated from the available data): Hypersensitivity reactions such as angio-oedema or laryngeal oedema.
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 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
Symptoms of overdose
Ergocalciferol (vitamin D2) and colecalciferol (vitamin D3) have a relatively low therapeutic index. The threshold for vitamin D intoxication is between 40,000 and 100,000 IU daily for 1 to 2 months in adults with normal parathyroid function. Infants and small children may react sensitively to far lower concentrations. Therefore, it is warned against intake of vitamin D without medical supervision.
vitamin D3 have a relatively low therapeutic index. The threshold for vitamin D intoxication is between 40,000 and 100,000 IU daily for 1 to 2 months in adults with normal parathyroid function. Infants and small children may react sensitively to far lower concentrations. Therefore, it is warned against intake of vitamin D without medical supervision.
Overdose leads to increased serum and urinary phosphorus levels, as well as hypercalcaemic syndrome and consequently calcium deposits in the tissues and above all in the kidneys (nephrolithiasis, nephrocalcinosis) and the vessels.
uently calcium deposits in the tissues and above all in the kidneys (nephrolithiasis, nephrocalcinosis) and the vessels.
Discontinue Colecalciferol Capsule 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.
Chronic overdosage may lead to vascular and organ calcification, as a result of hypercalcaemia.
The symptoms of intoxication are little characteristic and manifest as nausea, vomiting, initially also diarrhoea, later constipation, loss of appetite, weariness, headache, muscle pain, joint pain, muscle weakness, persistent sleepiness, azotaemia, polydipsia and polyuria and, in the final stage, dehydration. Typical biochemical findings include hypercalcaemia, hypercalciuria, as well as increased serum 25 hydroxy colecalciferol concentrations.
Treatment of overdose
Symptoms of chronic vitamin D overdosage may require forced diuresis as well as administration of glucocorticoids or calcitonin.
Overdosage requires measures for treating the - often persisting and under certain circumstances life- threatening - hypercalcaemia.
The first measure is to discontinue the vitamin D preparation. Treatment with thiazide diuretics, lithium, vitamin A, and cardiac glycosides must also be discontinued; it takes several weeks to normalize hypercalcemia caused by vitamin D intoxication.
Depending on the degree of hypercalcaemia, measures include a diet that is low in calcium or free of calcium, abundant liquid intake, increase of urinary excretion by means of the drug furosemide, as well as the administration of glucocorticoids and calcitonin.
If kidney function is adequate, calcium levels can be reliably lowered by infusions of isotonic sodium chloride solution (3–6 liters in 24 hours) with addition of furosemide and, in some circumstances, also 15 mg/kg body weight/hour sodium edentate accompanied by continuous calcium and ECG monitoring. In oligoanuria, in contrast, haemodialysis (calcium-free dialysate) is necessary.
No special antidote exists.
It is recommended to point out the symptoms of potential overdose to patients under chronic therapy with higher doses of vitamin D (nausea, vomiting, initially also diarrhoea, later constipation, anorexia, weariness, headache, muscle pain, joint pain, muscle weakness, persistent sleepiness, azotaemia, polydipsia and polyuria).
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 is well known.
Absorption
Vitamin D is well absorbed from the gastro-intestinal tract in the presence of bile
Distribution and biotransformation
It is hydroxylated in the liver to form 25-hydroxycolecalciferol and then undergoes further hydroxylation in the kidney to form the active metabolite 1, 25 dihydroxycolecalciferol (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.
5.3 Preclinical safety data
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 calcinuria and decreased phosphaturia and proteinuria. Hypercalcemia has been reported in high doses. In a state of prolonged hypercalcemia, histological alterations (calcification) were more frequently borne by the kidneys, heart, aorta, testes, thymus and intestinal mucosa.
Colecalciferol has been shown to be teratogenic at high doses in animals.
At doses equivalent to those used therapeutically, colecalciferol has no teratogenic activity.
Colecalciferol has no potential mutagenic or carcinogenic activity.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Capsule Content
Vitamin E preparation (D-alpha tocopherol & Soyabean oil, Refined)
Triglycerides medium chain
Capsule Shell
Gelatin
Glycerol
Purified water
6.2 Incompatibilities
Not applicable
6.3 Shelf life
36 months
6.4 Special precautions for storage
This medicinal product does not require any special temperature storage conditions. Keep the blister in the outer carton in order to protect from light.
6.5 Nature and contents of container
Each carton contains 10, 20, 28, 30, 56, 60, 84 and 100 capsules packed in PVC/PVDC-AL blister strips.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Any unused product should be disposed of in accordance with the local requirements.
7 MARKETING AUTHORISATION HOLDER
Crescent Pharma Limited
Key House
Sarum Hill, Basingstoke
RG21 8SR
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 20416/0804
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
14/04/2025
10 DATE OF REVISION OF THE TEXT
14/04/2025