Diseases caused by disturbances in the calcium metabolism in consequence of reduced endogenous production of 1.25-dihydroxyvitamin D3.
Renal osteodystrophy, postoperative or idiopathic hypoparathyroidism, pseudohypoparathyroidism, as an adjunct to the management of tertiary hyperparathyroidism, vitamin D-resistant rickets or osteomalacia, vitamin D-dependent rickets, neonatal hypocalcaemia or rickets, malabsorption of calcium, osteoporosis, malabsorptive and nutritional rickets, and osteomalacia.

Posology
Initial dose:
Adults and children above 20 kg weight: 1 μg daily.
Children under 20 kg body weight: 0.05 μg/kg/day.
Neonates and premature infants: 0.05 to 0.1 μg/kg/day.
It is important to adjust the dosage according to the biochemical responses to avoid hypercalcaemia. Indices of response include levels of serum calcium, alkaline phosphatase, parathyroid hormone, urinary calcium excretion as well as radiographic and histological investigations. Patients with marked bone disease (other than those with renal failure) may tolerate higher doses without developing hypercalcaemia. However, failure of the serum calcium to rise promptly in osteomalacic patients does not necessarily mean that a higher dose is required, since calcium from increased intestinal calcium absorption may be incorporated into demineralized bone.
Most patients will respond to doses between 1 and 3 μg daily.
The dose requirements generally decrease in patients with bone disease when there is biochemical or radiographic evidence of bone healing and in hypoparathyroid patients after normal serum calcium levels have been obtained. Maintenance doses are generally in the range of 0.25–2 μg daily.
Method of administration
The individual daily dose must be taken once daily. The soft gelatin capsules must, whenever possible, always be taken at the same time each day. The duration of use is determined individually by the physician.
During the period of treatment with One-Alpha® capsules, regular monitoring of serum calcium levels - in addition to phosphate and blood gas analyses - must be performed. These checks should be carried out at weekly to monthly intervals; more frequent measurements may be necessary at the start of treatment.
Prolonged use requires regular monitoring of the serum calcium level and Ca × P product. Long-term therapy is justifiable under these conditions; continuous courses of treatment for up to 5 years have been reported in the literature.

Serum calcium and serum phosphate levels must be checked regularly during treatment with One-Alpha®. PTH, alkaline phosphatase and the calcium × phosphate product must be monitored if clinically indicated.
Hypercalcaemia may occur in patients treated with One-Alpha®. For this reason, patients must be informed of the clinical symptoms associated with hypercalcaemia. Signs of hypercalcaemia are loss of appetite, fatigue, nausea and vomiting, constipation or diarrhoea, increased urinary urgency, sweating, headache, increased thirst, high blood pressure, drowsiness and dizziness.
Hypercalcaemia can be rapidly corrected by discontinuing treatment until plasma calcium levels return to normal values (about one week). Administration of One-Alpha® can then be continued at a reduced dose (half of the original dose) under monitoring of the calcium level.
Persistent hypercalcaemia can lead to worsening of arteriosclerosis, cardiac valve sclerosis or nephrolithiasis; persistent hypercalcaemia should therefore be avoided in such patients during administration of One-Alpha®. Temporary or even chronic worsening of renal function has been observed. One-Alpha® must also be used with caution in patients with lung tissue calcification, as this can lead to heart disease.
In patients with renal osteopathy or severely impaired renal function, alfacalcidol can be administered together with a phosphate-binding agent to prevent an increase in serum phosphate and potential metastatic calcification.
One-Alpha® capsules must be used with caution in patients with granulomatosis, e.g. sarcoidosis, as sensitivity to vitamin D is increased due to increased hydroxylation activity.

In the presence of hypercalcaemia due to vitamin D administration, concomitant use of digitalis glycosides increases the likelihood of cardiac arrhythmias.
One-Alpha® capsules contain sesame oil as an excipient. In rare cases, sesame oil can cause severe allergic reactions.

Thiazide diuretics and preparations containing calcium
Concomitant use of thiazide diuretics or preparations containing calcium can increase the risk of hypercalcaemia. Calcium levels must be monitored.
Other preparations containing vitamin D
Concomitant use of other preparations containing vitamin D can increase the risk of hypercalcaemia. Administration of several vitamin D analogues must be avoided.
Anticonvulsants
Anticonvulsants (e.g. barbiturates, phenytoin, carbamazepine or primidone) have enzyme-activating effects that lead to increased metabolism of alfacalcidol. Patients taking anticonvulsants may require higher doses of One-Alpha®.
Antacids containing magnesium
Absorption of magnesium-containing antacids can be increased by One-Alpha® capsules, which increases the risk of hypermagnesaemia.
Preparations containing aluminium
One-Alpha® capsules can increase the serum concentration of aluminium. Patients taking preparations containing aluminium (e.g. aluminium hydroxide, sucralfate) must be observed for signs of aluminium poisoning.
Bile acid sequestrants
Concomitant oral use of bile acid sequestrants such as cholestyramine can impair the intestinal absorption of oral One-Alpha® products. One-Alpha® must be administered at least 1 hour before, or 4 - 6 hours after taking bile acid sequestrants, in order to minimise any possible risk of interactions.

Pregnancy
There is only limited experience with the use of alfacalcidol in pregnant women. Studies in animals have shown reproductive toxicity.
One-Alpha® should not be used during pregnancy unless clearly necessary, as hypercalcaemia during pregnancy can induce congenital malformations in the newborn infant. Particular caution should be exercised in women of childbearing potential.
Breast-feeding
Alfacalcidol is excreted in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from One-Alpha® therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Breast-fed infants whose mothers are using alfacalcidol must be monitored closely for hypercalcaemia, taking into account possible vitamin D supplementation for the child.
Fertility
No clinical studies are available on the effect of One-Alpha® on fertility in humans.

Alfacalcidol has no or negligible direct influence on the ability to drive and use machines. However, patients should be informed that dizziness may occur during treatment. This should be taken into account when driving a car or using machines.

The estimation of the frequency of adverse reactions is based on a pooled analysis of data from clinical studies and spontaneous reports.
The most commonly reported adverse reactions are various skin reactions such as pruritus and rash, hypercalcaemia, gastrointestinal complaints, hyperphosphataemia.
There have been post-marketing reports of renal failure.
Adverse reactions are listed by MedDRA System Organ Class (SOC), with the individual adverse reactions listed by frequency, starting with the most commonly reported adverse reaction. Within any frequency grouping, undesirable effects are listed in order of decreasing seriousness.
Tabulated list of adverse reactions
Frequency categories are as follows:
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: Hypercalcemia, hyperphosphatemia,

Psychiatric disorders
Uncommon: Confusion

Nervous system disorders
Uncommon: Headache
Rare: Dizziness
Gastrointestinal disorders
Common: Gastrointestinal complaints
Uncommon: Diarrhoea, vomiting, constipation, nausea

Skin and subcutaneous tissue disorders
Common: Rash* Pruritus
*various types of rash have been reported, including erythematous, maculopapular and pustular rash
Musculoskeletal and connective tissue disorders
Uncommon: Myalgia
Renal and urinary disorders
Common: Hypercalciuria
Uncommon: Renal dysfunction (including acute renal failure), Renal calculi/calcification
General disorders and administration site conditions
Uncommon: Fatigue/weakness/malaise, calcinosis

Paediatric population
The observed safety profile is comparable in children and adults.

To report any side effect(s):
• Saudi Arabia

• The National Pharmacovigilance Centre (NPC)
- Fax: +966-11-205-7662
- SFDA Call Center: 19999
- E-mail: npc.drug@sfda.gov.sa
- Website: https://ade.sfda.gov.sa/

• Other GCC States:

Please contact the relevant competent authority.

Excessive use of One-Alpha® can lead to the development of hypercalcaemia. However, this effect can be rapidly reversed by discontinuing therapy.
In severe cases of hypercalcaemia, general supportive measures must be undertaken: Adequately hydrate the patient by infusion with saline solution (forced diuresis) and check electrolyte and calcium levels, as well as kidney function. Vigilance is required for ECG abnormalities, especially in patients using digitalis.
Targeted treatment with glucocorticosteroids, loop diuretics, bisphosphonates, calcitonin and, if necessary, haemodialysis with low calcium concentrations should be considered.

Pharmacotherapeutic group: Vitamin D and analogues
ATC code: A11CC03
Alfacalcidol is an essential factor in maintaining calcium homeostasis. In patients with impaired kidney function, it leads to an increase in the reduced absorption of calcium through the intestine, to normalisation of reduced blood calcium levels and to the eradication of bone and muscle pain associated with renal osteodystrophy.

Alfacalcidol is to be regarded as a pro-drug for 1α,25-dihydroxycholecalciferol. Its distribution in the body and conversion to 1α,25-dihydroxycholecalciferol has been shown in animal experiments and in humans with the radioactively labelled substance.
Bioavailability is to be assessed according to the effect on plasma calcium levels in the patient. The half-life for the decline in calcium levels after discontinuation of alfacalcidol is 4.5 - 4.8 days, regardless of the dose. Alfacalcidol is not a substance normally found in the body. Following oral and parenteral administration, it is rapidly converted to 1α,25(OH)2–D3 in the liver.

Protein binding, cerebrospinal fluid penetration, placenta penetration and transfer into breast milk are not known.

The preclinical toxicity of alfacalcidol is attributed to the known vitamin D effect of calcitriol on calcium homeostasis, which is characterised by hypercalcaemia, hypercalciuria and possible soft tissue calcification.
Alfacalcidol is not genotoxic.
No teratogenic effects were reported from embryotoxicity studies on rats and rabbits with a maximum of 0.9 μg alfacalcidol/kg BW/day. In rabbit foetuses, intrauterine growth retardation occurred from 0.3 μg alfacalcidol/kg BW/day. In fertility studies on rats, a dose of 0.9 μg alfacalcidol/kg BW/day resulted in a lower pregnancy rate and a reduction in litter size.
High doses of vitamin D are known to have a teratogenic effect on laboratory animals.

One-Alpha® 0.25 μg capsules
All-rac-alpha tocopherol
Refined sesame oil
Gelatin
Glycerol
Potassium sorbate (Ph. Eur.)
Titanium dioxide (E 171)

One-Alpha® 1 μg capsules
All-rac-alpha tocopherol
Refined sesame oil
Gelatin
Glycerol
Potassium sorbate (Ph. Eur.)
Iron oxide (E 172).

Not applicable

Do not store above 25 °C, as discolouration can occur at temperatures from 25 °C and the soft gelatin capsules may become deformed.

30 soft gelatin capsules, each with 0.25 μg alfacalcidol.
50 soft gelatin capsules, each with 0.25 μg alfacalcidol.
100 soft gelatin capsules, each with 0.25 μg alfacalcidol.
Hospital pack, each with 10 × 30 soft gelatin capsules

30 soft gelatin capsules, each with 1 μg alfacalcidol.
50 soft gelatin capsules, each with 1 μg alfacalcidol.
100 soft gelatin capsules, each with 1 μg alfacalcidol.
Hospital pack, each with 10 × 30 soft gelatin capsules

Not all pack sizes/ strengths are marketed

No special requirements.