Summary of Product Characteristics Updated 17-Dec-2015 | Consilient Health Ltd
Paediatric posology:- Due to a lack of clinical data, invitaD3 is not recommended.
Pregnancy and breastfeeding:- Due to a lack of clinical data, invitaD3 is not recommended.
Adults:- Treatment of vitamin D deficiency (<25 nmol/l) 50,000 IU/week (1single-dose oral solution) for 6-8 weeks, followed by maintenance therapy (equivalent to 1400-2000 IU/day, such as 1 single-dose 50,000 IU oral solution per month) may be required; follow-up 25(OH)D measurements should be made approximately three to four months after initiating maintenance therapy to confirm that the target level has been achieved).
Certain populations are at high risk of vitamin D 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 sun screens- 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 D deficiency, and requiring maintenance therapy.
Renal impairmentinvitaD3 should not be used in combination with calcium in patients with severe renal impairment.
Hepatic impairmentNo posology adjustment is required in patients with hepatic impairment.
Method of administrationPatients should be advised to take invitaD3 preferably with meal (see section 5.2 Pharmacokinetic properties - Absorption).
Administration to adults:The single-dose oral solution should be either emptied into the mouth and swallowed orally, or emptied onto a spoon and taken orally. invitaD3 can also be taken by mixing with a small amount of cold or lukewarm food/drink immediately prior to use.See also section 6.6, Special precautions for handling and disposal.
PregnancyThere 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 Preclinical safety data). 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 2000 IU/day).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 vitamin D and its metabolites are excreted in breast milk.
Breast-feedingVitamin D can be prescribed while the patient is breast-feeding if necessary. This supplementation does not replace the administration of vitamin D in the neonate.
FertilityThere is no data regarding treatment with vitamin D3 and its effects on fertility.
Metabolism and nutrition disordersUncommon: 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 at: www.mhra.gov.uk/yellowcard.
Symptoms of overdoseErgocalciferol (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.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.Discontinue invitaD3 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 over doseSymptoms 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; it takes several weeks to normalise hypercalcaemia 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 (36 liters in 24 hours) with addition of furosemide and, in some circumstances, also 15 mg/kg body weight/hour sodium edetate 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).
Distribution and biotransformationIt is hydroxylated in the liver to form 25-hydroxy-colecalciferol and then undergoes further hydroxylation in the kidney to form the active metabolite 1, 25-dihydroxycolecalciferol (calcitriol).
EliminationThe metabolites circulate in the blood bound to a specific α globin, vitamin D and its metabolites are excreted mainly in the bile and faeces.
Characteristics in Specific Groups of Subjects or PatientsA 57% lower metabolic clearance rate is reported in subjects with renal impairment as compared with that of healthy volunteers. Decreased absorption and increased elimination of vitamin D occurs in subjects with malabsorption. Obese subjects are less able to maintain vitamin D levels with sun exposure, and are likely to require larger oral doses of vitamin D to replace deficits.
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