ONE-ALPHA Solution for injection Ref.[7468] Active ingredients: Alfacalcidol

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 solution for injection contains 10 vol % ethanol (alcohol) as an excipient, i.e. up to 160 mg ethanol per dose (corresponding to 4 micrograms of alfacalcidol), equivalent to 4 ml beer or 1.7 ml wine. The alcohol content may be harmful for those suffering from alcoholism. The alcohol content must be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy.

One-Alpha solution for injection contains 0.14 mmol sodium per dose (corresponding to 4 micrograms of alfacalcidol). Products containing less than 1 mmol sodium (23 mg) per dose are considered essentially ‘sodium-free’.

Thiazide diuretics and calcium containing preparations

Concurrent use of thiazide diuretics or calcium containing preparations may enhance the risk of hypercalcaemia. Calcium levels should be monitored.

Other vitamin D containing preparations

Concurrent use of other vitamin D containing preparations may enhance the risk of hypercalcaemia. Use of multiple vitamin D analogues should be avoided.

Anticonvulsants

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.

Magnesium-containing antacids

Absorption of magnesium-containing antacids may be enhanced by One-Alpha, increasing the risk of hypermagnesaemia.

Aluminium-containing preparations

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.

Pregnancy

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.

Breast-feeding

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.

Fertility

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)

Metabolism and nutrition disorders

Common: Hypercalcaemia, Hyperphosphataemia

Psychiatric disorders

Not known: Confusional state

Nervous system disorders

Uncommon: Headache

Rare: Dizziness

Gastrointestinal disorders

Common: Abdominal pain and discomfort

Uncommon: Diarrhoea, Vomiting, Constipation, Nausea

Skin and subcutaneous tissue disorders

Common: Rash*, Pruritus

* Various types of rash such as erythematous, maculo-papular and pustular have been reported

Not known: Urticaria

Musculoskeletal and connective tissue disorders

Uncommon: Myalgia

Renal and urinary disorders

Common: Hypercalciuria

Uncommon: Nephrolithiasis/ Nephrocalcinosis

Not known: Renal impairment (including acute renal failure)

General disorders and administration site conditions

Uncommon: Fatigue/asthenia/malaise, Calcinosis

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.

None known.