SUMMARY OF PRODUCT CHARACTERISTICS

Transcription

1 SUMMARY OF PRODUCT CHARACTERISTICS 1

2 1. NAME OF THE MEDICINAL PRODUCT HELIOS IU, oral solution HELIOS IU, oral solution 2. QUALITATIVE AND QUANTITATIVE COMPOSITION HELIOS IU: 1 ml solution (1 Ampoule) contains mg cholecalciferol, equivalent to 25,000 IU vitamin D. HELIOS IU: 1 ml solution (1 Ampoule) contains 2.5 mg cholecalciferol, equivalent to IU vitamin D. For a full list of excipients, see section PHARMACEUTICAL FORM Oral solution Clear, sligthly yellow, oily liquid with an orange odor 4. CLINICAL PARTICULARS 4.1 Therapeutic indications - For starting treatment of vitamin D deficiency. 4.2 Posology and method of administration Posology The dosage must be determined individually by the treating doctor. For starting treatment of vitamin D deficiency and under medical supervision single dosage a cumulative dose of IU over 1 week is recommended. 1 Ampoule of Helios I.U may be given as a single dose or 4 ampoules of Helios IUweekly week may be given. ( I.U see 4.4). Additional necessary treatment with HELIOS must be decided by the treating doctor. Serum levels of 25- hydroxycalciferol and calcium should be monitored after initiation of treatment. The necessity of further monitoring can be individualised, guided by the dose administered and by the individual patient s needs. Starting treatment of vitamin D deficiency should be followed by a maintenance therapy dose of (chole)calciferol. Maintenance therapy requires lower strength cholecalciferol formulations. Special populations Renal impairment Helios should not be used in combination with calcium in patients with severe renal impairment. Hepatic impairment No posology adjustment is required in patients with hepatic impairment. Paediatric population (< 18 years old) There is no relevant use of Heliox in the paediatric population. 2

3 Method of administration The solution should be taken with a spoonful of liquid. The duration of use depends on the course of the disease. 4.3 Contraindications Hypersensitivity to the active substance(s) or to any of the excipients. Hypercalcaemia and/or hypercalciuria. Neprhrolithiasis. 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. Better-regulatable vitamin D derivatives are available for this. Paediatric population (< 18 years). 4.4 Special warnings and precautions for use During long-term treatment with HELIOS, the serum and urinary calcium levels should be monitored and the kidney function checked by measurement of serum creatinine. These checks are particularly important in elderly patients and in concomitant treatment with cardiac glycosides or diuretics. In the case of hypercalcaemia or signs of impaired kidney function, the dose must be reduced or treatment interrupted. It is recommended to reduce the dose or to interrupt treatment if the urinary calcium level exceeds 7.5 mmol/24 hours (300 mg/24 hours). HELIOS must be used with particular caution in patients with disturbed urinary excretion of calcium and phosphate, in treatment with benzothiadiazine derivatives and in immobilized patients (risk of hypercalcaemia and hypercalciuria). Plasma and urinary calcium levels should be monitored in these patients. HELIOS should be prescribed with caution to patients suffering from sarcoidosis, as there is the risk of increased conversion of vitamin D to its active metabolite. Serum and urinary calcium levels should be monitored in these patients. In patients with renal insufficiency who are treated with HELIOS, the effect on the calcium and phosphate metabolism should be monitored. If other vitamin D-containing medicines are prescribed, the dose of vitamin D contained in HELIOS must be taken into consideration. The additional administration of vitamin D or calcium should only be carried out under medical supervision. In such cases the serum and urinary calcium levels must be monitored (see above). 4.5 Interaction with other medicinal products and other forms of interaction Phenytoin or barbiturates may impair the effect of vitamin D. Thiazide diuretics can lead to hypercalcaemia due to reduced calcium excretion via the kidneys. Therefore, plasma and urinary calcium levels should be monitored during long-term treatment. Simultaneous administration of glucocorticoids can impair the effect of vitamin D. 3

4 The toxicity of cardiac glycosides may increase during treatment with vitamin D due to increased calcium levels (risk of cardiac arrhythmias). The ECG as well as plasma and urinary calcium levels should be monitored in such patients. 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-dihydroxyvitamin D by the kidney enzyme, 25- hydroxyvitamin D-1-hydroxylase. 4.6 Fertility, pregnancy and lactation Pregnancy HELIOS should only be taken during pregnancy if clearly needed and only at doses that are absolutely necessary to eliminate the deficiency. 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. Lactation Vitamin D and its metabolites pass into breast milk. Overdose in infants induced in this way has not been observed Fertility No effect on fertility in reproductive toxicity studies have been observed with colechalciferol. The potential benefit/risk for humans is unknown. 4.7 Effects on ability to drive and use machines Not relevant. 4.8 Undesirable effects The assessment of adverse reactions is based on the following frequency grouping: Very common ( 1/10) Common ( 1/100, < 1/10) Uncommon ( 1/1,000, < 1/100) Rare ( 1/10,000, < 1/1,000) Very rare (< 1/10,000) Not known (can not be estimated from the available data) The side effects are the result of overdose. Depending on the dose and duration of treatment, severe and prolonged hypercalcaemia with its acute (cardiac arrhythmias, nausea, vomiting, psychic symptoms, disturbances of consciousness) and chronic (increased urgency to urinate, increased thirst, loss of appetite, weight loss, kidney stones, kidney calcification, calcification in tissues outside the skeleton) consequences can occur. A fatal outcome has been reported in very rare cases. (see also section 4.4 'Warnings' as well as section 4.5 'Interaction'. Furthermore, refer also to section 4.9 'Overdose'). 4.9 Overdose Symptoms of overdose 4

5 Ergocalciferol (vitamin D2) and cholecalciferol (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. 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- hydroxycholecalciferol 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 lifethreatening - 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 (3 6 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). 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Vitamin D, cholecalciferol ATC Code: A11CC05 Cholecalciferol (vitamin D3) is formed in the skin on exposure to UV light and converted into its biologically active form, 1,25-dihydroxycholecalciferol, in two hydroxylation steps, first in the liver (position 25) and then in the renal tissue (position 1). Along with parathormone and calcitonin, 1,25- dihydroxycholecalciferol has a considerable impact on the regulation of calcium and phosphate metabolism. 5

6 In vitamin D deficiency the skeleton does not calcify (resulting in rickets) or decalcification of bones occurs (resulting in osteomalacia). According to production, physiological regulation and mechanism of action, vitamin D3 is to be considered as precursor of a steroid hormone. In addition to physiological production in the skin, cholecalciferol can be supplied via the diet or in the form of a drug. Since in the latter case the product inhibition of cutaneous vitamin D synthesis is circumvented, overdose and intoxications may occur. Ergocalciferol (vitamin D2) is synthesised by plants. Human beings activate it metabolically in the same way as cholecalciferol. It has the same qualitative and quantitative effects. Adults require 5 µg daily, equivalent to 200 IU. Healthy adults can cover their requirement by producing vitamin D on their own through sufficient exposure to the sun. Alimentary vitamin D supply plays a subordinate role, but can be important under critical conditions (climate, lifestyle). Fish liver oil and fish are particularly rich in vitamin D; small amounts are found in meat, egg yolk, milk, dairy products and avocado. Deficiency diseases can occur, among others, in immature pre-term new-born infants, infants exclusively breast-fed for more than six months without calcium-containing foods and children fed a strictly vegetarian diet. The causes of rarely occurring vitamin D deficiency in adults may be inadequate alimentary intake, insufficient exposure to UV light, malabsorption and maldigestion, liver cirrhosis as well as renal insufficiency. 5.2 Pharmacokinetic properties In alimentary doses vitamin D is almost completely absorbed from the food together with alimentary lipids. Higher doses are absorbed at a ratio of approx. 2:3. Skin exposed to UV light synthesises vitamin D from 7- dehydrocholesterol. Vitamin D is transferred to the liver via a specific transport protein. In the liver it is metabolised by a microsomal hydroxylase to 25- hydroxycholecalciferol. Vitamin D and its metabolites are excreted with bile and faeces. Vitamin D is stored in the fatty tissue and has therefore a long biological half-life. After high vitamin D doses, the 25-hydroxyvitamin D concentrations in the serum may be increased for several months. Hypercalcaemia due to overdose can persist over several weeks (see section 4.9 'Overdose'). Vitamin D is stored in the fatty tissue and has therefore a long biological half-life. After high vitamin D doses, the 25-hydroxyvitamin D concentrations in the serum may be increased for several months. Hypercalcaemia induced by overdose can persist for several weeks. 5.3 Preclinical safety data There are no further specific toxicological risks for human beings beyond those mentioned in the data sheet in sections 4.6 'Pregnancy and lactation' and 4.9 'Overdose'. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Tocopherol acetate, Polyglyceryl oleate (E475), Olive oil,refined, Sweet orange peel oil. 6.2 Incompatibilities 6

7 Not applicable. 6.3 Shelf life 3 years 6.4 Special precautions for storage Do not store above 30 C. Store in the original package, in order to protect from light. 6.5 Nature and contents of container Transparent PVC/PVDC/PE ampoules. Original Pack with 1 ampoule. Original Pack with 2 ampoules. Original Pack with 4 ampoules. Sample - not for sale with 1 ampoule. Not all pack sizes may be marketed. 6.6 Special precautions for disposal <and other handling> No special requirements Any unused product or waste material should be disposed of in accordance with local requirements. 7. MARKETING AUTHORISATION HOLDER Laboratoires SMB S.A. Rue de la pastorale Bruxelles BELGIUM Tel Fax MARKETING AUTHORISATION NUMBER(S) <[To be completed nationally]> 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION <{DD/MM/YYYY}> <{DD month YYYY}> <[To be completed nationally]> 10. DATE OF REVISION OF THE TEXT <{MM/YYYY}> <[To be completed nationally]> 7