Summary of Product Characteristics (SmPC) - Vitamin D3 A.Forall Access 1000 IU soft capsules
1 NAME OF THE MEDICINAL PRODUCT
Vitamin D3 A.forall Access 1000 IU soft capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains colecalciferol (vitamin D3) 1000 IU.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Transparent, blue, oval, soft capsules, filled with light yellow viscous liquid.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
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 patients response to treatment. Based on patients 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-Hydroxy colecalciferol (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:
Vitamin D3 A.forall Access 1000 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
- Dosage in hepatic impairment
No dose adjustment is required.
- 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.
- 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 – 2 capsules of 1000 IU).
- 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.
4.3 Contraindications
- Hypersensitivity to the active substance or to any of the excipients mentioned in section 6.1
- Hypervitaminosis D
- Nephrolithiasis
- Disease or conditions resulting in hypercalcemia and/or hypercalciuria
- Severe Renal impairment
4.4 Special warnings and precautions for use
Renal impairment
Colecalciferol 1000 IU Capsules 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. Renal Insufficiency
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. Colecalciferol capsules should not be taken by patients with a tendency to form calcium-containing renal calculi.
Caution is required in patients receiving treatment for cardiovascular disease or diuretics (see section 4.5). Caution is also required with treatment with benzothiadiazine derivatives. In 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.
Sarcoidosis
Colecalciferol 1000 IU Capsules 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.
Calcium Supplements
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 1000 IU vitamin D the serum calcium values must be monitored and renal function should be monitored through measurements of serum creatinine.
Other Vitamin D sources
The content of vitamin D (1000 IU) in Vitamin D3 A.forall Access should be considered when prescribing other medicinal products containing vitamin D. Additional doses of vitamin D should be taken under close medical supervision. In such cases it is necessary to monitor serum calcium levels and urinary calcium excretion frequently.
Vitamin D is liposoluble and can accumulate in the body. Overdose and long-term treatment with high doses may cause toxic effects. Therefore, the recommended dosage should not be exceeded.
Oral administration of high dose vitamin D (500,000 IU by a single annual bolus) has been reported to increase the risk of fracture in the elderly, with the largest increase occurring during the first 3 months after administration.
Paediatric population
Colecalciferol 1000 IU Capsules should not be given to infants and children under the age of 12.
4.5 Interaction with other medicinal products and other forms of interaction
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.
Concomitant use of phenytoin or barbiturates may reduce the effect of vitamin D since the metabolism increases.
Excessive dosing 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.
Glucocorticoid steroids may increase vitamin D metabolism and elimination. During concomitant use, it may be necessary to increase the dose of colecalciferol.
Simultaneous treatment with ion exchange resins such as cholestyramine or laxatives such as paraffin oil may reduce the gastrointestinal absorption of vitamin D. Orlistat may potentially impair the absorption of colecalciferol as it is fat-soluble. Rifampicin may reduce the effectiveness of Colecalciferol due to hepatic enzyme induction.
Isoniazid may reduce the effectiveness of Colecalciferol due to inhibition of the metabolic activation of Colecalciferol.
The cytotoxic agent actinomycin and imidazole antifungal agents interfere with vitamin D activity by inhibiting the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by the kidney enzyme, 25-hydroxyvitamin D-1-hydroxylase.
4.6 Fertility, pregnancy and lactation
Pregnancy
Vitamin D deficiency is harmful for mother and child. There are no signals that recommended doses of vitamin D3 are harmful for the embryo/foetus. High doses of vitamin D have been shown to have teratogenic effects in animal experiments. Overdose of vitamin D must be avoided during pregnancy, as prolonged hypercalcaemia can lead to physical and mental retardation, supravalvular aortic stenosis and retinopathy of the child.
Colecalciferol can be used up to 2,000 IU/day only in case of a Vitamin D deficiency.
Colecalciferol is not recommended during pregnancy in patients without a vitamin D deficiency as the daily intake should not exceed 400 IU vitamin D.
Breastfeeding
Vitamin D3 and metabolites pass into the breast milk. No adverse events have been observed in infants. Vitamin D3 A.forall Access can be used at recommended doses during lactation in case of a vitamin D deficiency.
Fertility
There are no data on the effect of Colecalciferol on fertility. 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
There are no data about the effect of this product on driving capacity. An effect is, however, unlikely.
4.8 Undesirable effects
Adverse reactions frequencies are based on the following categories: 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 : 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.
Depending on the dose and duration of treatment, severe and prolonged hypercalcaemia may be associated with its acute (cardiac arrhythmias, nausea, vomiting, mental symptoms, dysphagia) and chronic (increased urination, increased thirst, loss of appetite, weight loss, kidney stones, renal calcification, calcification in tissues outside the bone) Consequences occur.
Very rarely have fatal outcomes been reported.
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 at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Overdose can lead to hyper-vitaminosis D. An excess of vitamin D causes abnormally high levels of calcium in the blood, which can eventually severely damage the soft tissues, and kidneys. Tolerable Upper Intake Level for vitamin D3 (colecalciferol) is set at 4000 IU (100 μg) per day. Vitamin D3 should not be confused with its active metabolites. Colecalciferol.
Symptoms of hypercalcaemia may include anorexia, thirst, nausea, vomiting, constipation, abdominal pain, muscle weakness, fatigue, mental disturbances, polydipsia, polyuria, bone pain, nephrocalcinosis, renal calculi and in severe cases, cardiac arrhythmias. Extreme hypercalcaemia may result in coma and death. Persistently high calcium levels may lead to irreversible renal damage and soft tissue calcification.
Treatment of hypercalcaemia: The treatment with vitamin D must be discontinued. Treatment with thiazide diuretics, lithium, vitamin A, and cardiac glycosides must also be discontinued. Rehydration, and, according to severity, isolated or combined treatment with loop diuretics, bisphosphonates, calcitonin and corticosteroids should be considered. Serum electrolytes, renal function and diuresis must be monitored. In severe cases, ECG and CVP should be followed.
Phosphate infusions should not be administered to lower hypercalcaemia of hypervitaminosis D because of the dangers of metastatic calcification.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Vitamin D and analogues
ATC Code: A11CC05
Absorption: Colecalciferol is easily absorbed in the small intestine.
Colecalciferol is produced within the skin under the influence of UV radiation including sunlight. In its biologically active form, Colecalciferol 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 Colecalciferol. PTH secretion is inhibited additionally by the increased calcium uptake in the small intestine under the influence of biologically active Colecalciferol.
Elimination: Coleclaciferol and other forms of vitamin D are excreted in faeces and urine.
5.2 Pharmacokinetic properties
The pharmacokinetics of Colecalciferol have been widely studied and are well known. Colecalciferol from nutritional sources is almost completely absorbed from within the gastro-intestinal tract in the presence of dietary lipids and bile acids. Colecalciferol is stored in fat cells and its biological half-life is approximately 50 days.
Colecalciferol is metabolised by microsomal hydroxylase to form 25-hydroxycolecalciferol (25(OH)D3, calcidiol), the primary storage form of vitamin D3. 25(OH)D3 undergoes a secondary hydroxylation within the kidney to form the predominant active metabolite 1,25-hydroxycolecalciferol (1,25(OH)2D3, calcitriol). The metabolites circulate in the blood bound to a specific α-globin.
After a single oral dose of Colecalciferol, the maximum serum concentrations of the primary storage form are reached after approximately 7 days. 25(OH)D3 is then slowly eliminated with an apparent half-life in serum of about 50 days. Colecalciferol and its metabolites are excreted mainly in the bile and faeces.
After high doses of Colecalciferol, serum concentrations of 25(OH)D3 may be increased for months. Overdose-induced hypercalcaemia may persist for weeks (see 4.9 "Overdose”).
A deficiency in vitamin D metabolism and excretion has been reported in patients with chronic renal failure.
5.3 Preclinical safety data
Colecalciferol is well known and established product and has been used in clinical practice for many years. No further specific toxicological hazard for humans is expected other than in chronic overdosage where hypercalcaemia could be seen. Colecalciferol overdosage in animals has been shown to induce malformations in rats, mice and rabbits at doses significantly higher than the human dose. The malformations included skeletal defects, microcephaly and cardiac malformations. 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 fill
Medium-chain triglycerides
Capsule shell
Gelatin (E 441)
Glycerol (E 422)
Patent blue V (E131)
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 blister in the outer carton.
6.5 Nature and contents of container
30, 40, 100, 120 capsules packed in Al/PVC/PVDC blisters.
Not all packs sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
A.forall Access Ltd.
Stephenstown Industrial Park,
Balbriggan Co. Dublin, K32 VR92
Ireland
8 MARKETING AUTHORISATION NUMBER(S)
PL 51316/0002
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
09/09/2022
10 DATE OF REVISION OF THE TEXT
12/12/2024