Alfacalcidol 1.0 Microgram Capsules
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Alfacalcidol 1.0 Microgram Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each soft gelatin capsule contains 1 microgram of alfacalcidol.
Each soft gelatin capsule also contains 98.8mg of Arachis oil (refined), 1.15mg ethanol and 4.53mg of sorbitol 70%.
For a full list of excipients, see 6.1.
3 PHARMACEUTICAL FORM
Capsule, soft.
Oval, opaque cream coloured, elastic soft gelatin capsule printed with “1.0” containing a clear, pale yellow, oily solution.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Alfacalcidol is used for treating conditions in which calcium metabolism is disturbed due to impaired 1a-hydroxylation and other disorders associated with Vitamin D resistance.
The main indications are:
- Renal osteodystrophy
- Hypoparathyroidism
- Hyperparathyroidism (with bone disease)
- Nutritional and malabsorptive rickets and osteomalacia
- Hypophosphataemic Vitamin-D resistant rickets and osteomalacia
- Pseudo-deficiency (D-dependent Type 1) rickets and osteomalacia
4.2 Posology and method of administration
All indications -
Starting dose: Children 20 kg and over: 1 microgram/day
Adults: 1 microgram/day
Elderly patients: 0.5 microgram/day
The dose should subsequently be adjusted according to the biochemical response to avoid hypercalcaemia. Plasma calcium levels (preferably corrected for protein binding) should initially be measured weekly. The dose of Alfacalcidol can be increased by increments of 0.25 to 0.5 micrograms/day. Most adults respond to doses of 1 to 3 micrograms/day. Once the dose is stabilised, calcium levels may be measured every 2-4 weeks. Indices of response, in addition to plasma calcium, may include alkaline phosphatase, parathyroid hormone levels, bone radiography and histological investigations. When there is biochemical or radiographic evidence of bone healing (or in hypoparathyroidism when calcium levels have normalised) the dose required for maintenance generally decreases to around 0.25 to 1 microgram/day. Should hypercalcaemia occur, Alfacalcidol should be stopped until plasma calcium returns to normal (usually about a week), and then restarted at one half of the previous dose.
Renal Osteodystrophy - Patients with already high plasma calcium levels may have autonomous hyperparathyroidism. In this situation they may not respond to alfacalcidol and other therapeutic measures may be indicated.
In patients with chronic renal disease it is particularly important to check the plasma calcium frequently because prolonged hypercalcaemia may further impair renal function.
Before and during Alfacalcidol treatment, the use of phosphate binding agents to prevent hyperphosphataemia may also be considered.
Hypoparathyroidism - Low plasma calcium levels may be restored to normal more quickly with Alfacalcidol than with parent Vitamin D. Severe hypocalcaemia is corrected more rapidly with higher doses of Alfacalcidol (e.g. 3-5 micrograms) together with calcium supplements.
Hyperparathyroidism - In patients needing surgery for primary or tertiary hyperparathyroidsim, pre-operative treatment with Alfacalcidol for 2-3 weeks can reduce bone pain and myopathy without aggravating hypercalcaemia. To decrease the risk of post-operative hypocalcaemia, Alfacalcidol should be continued until the plasma alkaline phosphatase falls to normal or hypercalcaemia occurs.
Nutritional and Malabsorptive Rickets and Osteomalacia - Malabsorptive osteomalacia, which responds to large doses of intramuscular or intravenous parent Vitamin D, will respond to small oral doses of AlfaD. Nutritional rickets and osteomalacia can also be rapidly corrected with AlfaD.
Hypophosphataemic Vitamin D-Resistant Rickets and Osteomalacia - Normal doses of Alfacalcidol rapidly relieve myopathy when present, and increase calcium and phosphate retention. Phosphate supplements may also be required in some patients. Neither large doses of parent Vitamin D nor phosphate supplements are entirely satisfactory in these conditions.
Pseudo-Deficiency (D-Dependent Typel) Rickets and Osteomalacia - As with the nutritional conditions, similar oral doses of Alfacalcidol are effective in circumstances which would require high doses of parent Vitamin D.
Use in Children
Alfacalcidol Soft Gelatin Capsules are not indicated in children under 20 kg as the dosage cannot be titrated adequately.
Use in Elderly
Initiation of therapy requires a lower dose in elderly patients. The clinical manifestations of hypo- or hypercalcaemia should be considered especially in elderly patients with pre-existing renal or heart conditions.
4.3 Contraindications
Hypercalcaemia, metastatic calcification.
Hypersensitivity to Alfacalcidol or other ingredients in the preparation.
Alfacalcidol should not be used by patients with evidence of Vitamin D toxicity or known hypersensitivity to the effects of Vitamin D or any of its analogues. Alfacalcidol Capsules contain arachis oil (peanut oil) and should not be used by patients with peanut allergy.
As there is a possible relationship between allergy to peanut and allergy to soya, patients with soya allergy should also avoid Alfacalcidol Capsules.
4.4 Special warnings and precautions for use
Alfacalcidol increases the internal absorption of calcium and phosphate, serum levels of which should be monitored, particularly in patients with renal failure.
If hypercalcaemia or hypercalciuria occur this can be corrected rapidly by stopping treatment with Alfacalcidol and any calcium supplements until plasma calcium levels return to normal, usually in about a week. Alfacalcidol may then be restarted at half the last dose used.
Response to alfacalcidol may be impaired if the diet is markedly deficient in calcium. Healing of bone lesions often indicates a decreased requirement for Alfacalcidol in which case appropriate dose adjustments should be made (see Posology and Method of Administration).
Alfacalcidol Capsules contain small amounts of ethanol (alcohol), approximately 1mg per capsule.
The capsule shell contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine. Sorbitol may cause gastro-intestinal disturbance.
Alfacalcidol should be used with caution for:
- patients being treated with cardioactive glycosides or digitalis as hypercalcaemia may lead to arrhythmia in such patients.
- patients with nephrolithiasis
During treatment with Alfacalcidol serum calcium and serum phosphate should be monitored regularly especially in patients with renal impairment and patients receiving high doses. To maintain serum phosphate at an acceptable level in patients with renal bone disease a phosphate binding agent may be used.
Hypercalcaemia may appear in patients treated with Alfacalcidol, the early symptoms are as follows:
- polyuria
- polydipsia
- weakness, headache, nausea, constipation
- dry mouth
- muscle and bone pain
- metallic taste
Paediatric population
During treatment with Alfacalcidol serum calcium and serum phosphate should be monitored regularly in children.
4.5 Interaction with other medicinal products and other forms of interaction
Hypercalcaemia in patients taking digitalis preparations may precipitate cardiac arrhythmias. Patients taking digitalis concurrently with alfacalcidol must therefore be closely monitored.
Patients on barbiturates or other anticonvulsants may require an increased dose of Alfacalcidol to produce the desired effect.
Absorption of alfacalcidol may be impaired by concurrent use of mineral oil (prolonged use), colestyramine, colestipol, sucralfate or large amounts of aluminium-based antacids.
Caution should be exercised in the use of magnesium-based antacids or laxatives for patients taking alfacalcidol who are on chronic renal dialysis. Hypermagnesaemia may occur.
The risk of hypercalcaemia is increased in patients taking calcium-containing preparations or thiazide diuretics concurrently with alfacalcidol.
Alfacalcidol is a potent derivative of Vitamin D. Pharmacological doses of Vitamin D or its analogues should not be given during alfacalcidol treatment because of the possibility of additive effects and an increased risk of hypercalcaemia.
Paediatric population
Drug interactions with Alfacalcidol are known to be similar in the paediatric age group and that in adults.
4.6 Fertility, pregnancy and lactation
Pregnancy
There is insufficient evidence on which to assess the safety of alfacalcidol use during pregnancy, although it has been widely used for many years without apparent adverse effects. Animal studies have not revealed any hazard but as with all drugs, The potential risks for humans are unknown. Alfacalcidol should only be used during pregnancy if treatment is essential and no better alternative is available as hypercalcaemia during pregnancy may produce congenital disorders in the offspring.
Breastfeeding
Although not definitely established, it is likely that increased levels of 1,25-dihydroxyvitamin D3 will be found in the breast milk of mothers treated with alfacalcidol. This might have an influence on calcium metabolism in a breast-fed infant.
Fertility
No fertility data is available for use of alfacalcidol
4.7 Effects on ability to drive and use machines
Alfacalcidol has no influence on the ability to drive or use machines.
4.8 Undesirable effects
Adverse effects generally relate to abnormally elevated serum calcium levels leading to symptoms of anorexia, lassitude, nausea, vomiting, diarrhoea, weight loss, polyuria, sweating, headache, thirst, vertigo and raised plasma and urine concentrations of calcium and phosphate.
In the case of renal impairment, elevated serum phosphate levels may be induced by Alfacalcidol therapy. The dosage should be adjusted to the patient’s requirements. Based on data from post-market use the total undesirable effect 'reporting rate' is rare (>1/10,000 to <1/1,000) or very rare (<1/10,000); being approximately 1:10,000 patients treated.
|
System Organ Class |
Adverse Drug Reactions |
|
Metabolism and Nutrition Disorders |
Hypercalcaemia |
|
Hyperphosphataemia | |
|
Skin and Subcutaneous Tissue Disorders |
Pruritus Rash Urticaria |
|
Renal and Urinary Disorders |
Nephrocalcinosis Renal impairment |
Paediatric population
Frequency and type of adverse reactions in children are the same as in adults.
4.9 Overdose
Excessive intake of vitamin D leads to the development of hypercalcaemia. Administration of Alfacalcidol should be stopped if hypercalcaemia occurs symptoms of which include anorexia, lassitude, nausea, vomiting, diarrhoea, weight loss, polyuria, sweating, headache, thirst, vertigo and raised plasma and urine concentrations of calcium and phosphate. Severe hypercalcaemia may require treatment with general supportive measures, with intravenous fluids, with a loop diuretic or with corticosteroids, measure electrolytes, calcium and renal function indices; assess electrocardiographic abnormalities, especially in patients on digitalis bisphosphonates, calcitonin and eventually haemodialysis with low calcium content should be considered.
In acute overdosage, early treatment with gastric lavage and/or the administration of mineral oil may reduce absorption and promote faecal elimination.
Paediatric population
Infants and children are generally more susceptible to the toxic effects of vitamin D.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC Code: A11C C03 (Vitamin A and D, incl. combinations of the two, vitamin D and analogues).
When 1 a-hydroxylation by the kidneys is impaired, endogenous 1,25-di-hydroxyvitamin D3 production is reduced. Disorders in which this can occur include renal bone disease, hypoparathyroidism and Vitamin D-dependent rickets. Such conditions require high doses of Vitamin D for their correction but will respond to small doses of Alfacalcidol, which does not depend on the renal 1-a-hydroxylation process.
When using parent Vitamin D, the high dose and variable response time can lead to unpredictable hypercalcaemia which may take many weeks, sometimes months, to reverse. With Alfacalcidol, the more rapid onset of response allows better titration of dose and, if hypercalcaemia does occur, it can be reversed within days of stopping treatment.
5.2 Pharmacokinetic properties
Alfacalcidol undergoes rapid hepatic conversion to 1,25-dihydroxy-vitamin D3, the Vitamin D3 metabolite which acts as a regulator of calcium and phosphate metabolism.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber, which are additional to that provided in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Capsule Contents
Citric Acid, Anhydrous (E330) Propyl Gallate (E310) a-Tocopherol (E307)
Ethanol, Anhydrous Arachis Oil (peanut oil)
Soft Gelatin Capsule Shell
Gelatin
Glycerol
Sorbitol
Titanium dioxide (E171) Yellow iron oxide (E172)
Printing Ink
Shellac
Black iron oxide Propylene glycol
Incompatibilities
6.2
Not applicable.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Do not store above 25°C. Store in the original package. Keep blister in the outer carton.
6.5 Nature and contents of container
Cold form aluminium-aluminium blister strips each with 10 capsules, in packs of 30, capsules.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
TEVA UK Limited Brampton Road,
Hampden Park,
Eastbourne,
East Sussex BN22 9AG UNITED KINGDOM
MARKETING AUTHORISATION NUMBER(S)
8
PL 00289/1557
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
28/10/2009
10 DATE OF REVISION OF THE TEXT
15/11/2012