Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2017 Publisher: LEO Laboratories Limited, Horizon, Honey Lane, Hurley, Maidenhead, Berkshire, SL6 6RJ, UK
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypercalcaemia, metastatic calcification.
During treatment with One-Alpha, serum calcium and serum phosphate levels should be monitored regularly especially in children, patients with renal impairment and patients receiving high doses. PTH, alkaline phosphatase and calcium phosphates should be monitored as clinically indicated.
Hypercalcaemia might appear in patients treated with One-Alpha. For this reason, patients should be informed about the clinical symptoms connected with hypercalcaemia. Signs of hypercalcaemia are muscle and bone pain, muscle weakness, confusion, dehydration, anorexia, fatigue, nausea and vomiting, constipation, polyuria, sweating, headache, polydipsia, hypertension and somnolence.
Hypercalcaemia can be rapidly corrected by stopping treatment until plasma calcium levels return to normal (in about one week). One-Alpha may then be restarted at a reduced dose (half the previous dose) with monitoring of calcium.
Prolonged hypercalcaemia may aggravate arteriosclerosis, cardiac valve sclerosis or nephrolithiasis and therefore prolonged hypercalcaemia should be avoided when One-Alpha is used in these patients. Transient or even long-lasting deterioration of kidney function has been observed. One-Alpha should also be used with caution in patients with calcification of pulmonary tissue as this may result in cardiac disease.
In patients with renal bone disease or severely reduced renal function, a phosphate binding agent could be used simultaneously with alfacalcidol to prevent increased serum phosphate and potential metastatic calcification.
One-Alpha should be used with caution in patients with granulomatous diseases such as sarcoidosis where the sensitivity to vitamin D is increased due to increased hydroxylation activity.
Concurrent use of digitalis glycosides in the presence of hypercalcaemia due to vitamin D administration increases the potential for cardiac arrhythmias.
One-Alpha capsules contain sesame oil as an excipient. Sesame oil may rarely cause severe allergic reactions.
Concurrent use of thiazide diuretics or calcium containing preparations may enhance the risk of hypercalcaemia. Calcium levels should be monitored.
Concurrent use of other vitamin D containing preparations may enhance the risk of hypercalcaemia. Use of multiple vitamin D analogues should be avoided.
Anticonvulsants (e.g. barbiturates, phenytoin, carbamazepine or primidone) have enzyme-inducing effects resulting in an increased metabolism of alfacalcidol. Patients taking anticonvulsants may require larger doses of One-Alpha.
Absorption of magnesium-containing antacids may be enhanced by One-Alpha, increasing the risk of hypermagnesaemia.
One-Alpha may increase the serum concentration of aluminium. Patients taking aluminium-containing preparations (e.g. aluminium hydroxide, sucralfate) should be monitored for signs of aluminium related toxicities.
Concomitant oral administration of bile acid sequestrants such as cholestyramine may impair the intestinal absorption of oral One-Alpha formulations. One-Alpha should be administered at least 1 hour before, or 4 to 6 hours after the intake of the bile acid sequestrant in order to minimise the potential risk of interaction.
There is a limited amount of data from the use of alfacalcidol in pregnant women. Studies in animals have shown reproductive toxicity at high doses.
Therefore, One-Alpha is not recommended during pregnancy and in women of child-bearing potential not using contraception.
Although it has not been established, it is likely that increased amounts of 1,25-dihydroxyvitamin D will be found in the milk of lactating mothers treated with One-Alpha. This may influence calcium metabolism in the infant.
Consequently, breast-fed infants of alfacalcidol-using mothers should be monitored closely for hypercalcaemia.
There are no clinical studies on the effect of One-Alpha on fertility. A pre-clinical study did not show an effect on fertility in rats.
Alfacalcidol has no or negligible direct influence on the ability to drive and use machines. However, the patient should be informed that dizziness may occur during treatment and take this into account while driving or using machines.
The estimation of the frequency of undesirable effects is based on a pooled analysis of data from clinical studies and spontaneous reporting.
The most frequently reported undesirable effects are various skin reactions such as pruritus and rash, hypercalcaemia, gastrointestinal pain/discomfort and hyperphosphataemia.
Renal failure has been reported post-marketing.
Undesirable effects are listed by MedDRA system organ class (SOC) and the individual undesirable effects are listed starting with the most frequently reported one. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Very common ≥1/10
Common ≥1/100 to <1/10
Uncommon ≥1/1,000 to <1/100
Rare ≥1/10,000 to <1/1,000
Very rare <1/10,000
Not known (cannot be estimated from the available data)
Common: Hypercalcaemia, Hyperphosphataemia
Not known: Confusional state
Uncommon: Headache
Rare: Dizziness
Common: Abdominal pain and discomfort
Uncommon: Diarrhoea, Vomiting, Constipation, Nausea
Common: Rash*, Pruritus
* Various types of rash such as erythematous, maculo-papular and pustular have been reported
Not known: Urticaria
Uncommon: Myalgia
Common: Hypercalciuria
Uncommon: Nephrolithiasis/Nephrocalcinosis
Not known: Renal impairment (including acute renal failure)
Uncommon: Fatigue/asthenia/malaise, Calcinosis
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.
Not applicable.
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