The format of this leaflet was determined by the Ministry of health and its content was

checked and approved on November 2017

ALPHA D3®
Capsules
Composition

Alpha D3 Capsules 0.25 mcg

Each soft gelatin capsule contains:

Capsule Content
Active Ingredient
Alfacalcidol (1-OHD3) 0.25 mcg

Other Ingredients
Arachis oil (peanut oil), dehydrated alcohol, Propyl gallate, dl-alpha-tocopherol,
citric acid anhydrous.

Soft Gelatin Capsule Shell

Gelatin, glycerol, Anidrisorb 85/70 (sorbitol, mannitol, sorbitan, hydrogenation
products of partly hydrolyzed starch, water), red iron oxide (E 172), priting ink black,
water.

Alpha D3 Capsules 0.5 mcg

Each soft gelatin capsule contains:

Capsule Content
Active Ingredient
Alfacalcidol (1-OHD3) 0.5 mcg

Other Ingredients
Arachis oil (peanut oil), dehydrated alcohol, Propyl gallate, dl-alpha-tocopherol,
citric acid anhydrous.

Soft Gelatin Capsule Shell

Gelatin, glycerol, Anidrisorb 85/70 (sorbitol, mannitol, sorbitan, hydrogenation
products of partly hydrolyzed starch, water), titanium dioxide (E171), red iron oxide
(E172), printing ink black, water.

Alpha D3 Capsules 1 mcg

Each soft gelatin capsule contains:

Capsule Content
Active Ingredient
Alfacalcidol (1-OHD3) 1 mcg

Other Ingredients
Arachis oil (peanut oil), dehydrated alcohol, Propyl gallate, dl-alpha-tocopherol,
citric acid anhydrous.

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Soft Gelatin Capsule Shell
Gelatin, glycerol, Anidrisorb 85/70 sorbitol, mannitol, sorbitan, hydrogenation
products of partly hydrolyzed starch, water), titanium dioxide (E171), yellow iron
oxide (E172), priting ink black, water.

Therapeutic Indications

Alpha D3 is used for treating:

 Renal bone disease (renal osteodystrophy)
 Hypoparathyroidism
 Hyperparathyroidism (with bone disease)- primary and tertiary.
 Rickets and osteomalacia.
 Osteoporosis

Dosage and Administration

General
The dosage and administration of Alpha D3 should be adjusted according to the
indication-specific notes which follow.
Alpha D3 capsules are not recommended for children under 20 kg bodyweight.

The initial dosage for all indications, excepting osteoporosis, is as follows:

Adults and children 20 kg and over bodyweight: 1 mcg/day

Elderly patients: 0.5 mcg/day

The recommended dosage in osteoporosis is 0.5 mcg/day. It should not be

exceeded.
The dose should subsequently be adjusted to avoid hypercalcemia, according to
the biochemical response. Plasma calcium levels (preferably corrected for protein
binding) should initially be measured weekly. The dose of Alpha D3 can be increased
by increments of 0.25 to 0.5 mcg/day. Most adults respond to doses of 1 to
3 mcg/day. Once the dose is stabilised, calcium levels may be measured every 2-
4 weeks.

Indices of response, in addition to a rise in plasma calcium, may include an 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 2 microgram/day. Should
hypercalcaemia occur, AlfaD should be stopped until plasma calcium returns to
normal (usually about a week) then restarted at one half of the previous dose.

Renal Bone Disease (Renal Osteostrophy)

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 hypercalcemia may further impair renal
function.
Before and during Alpha D3 treatment, the use of phosphate binding agents to
prevent hyperphosphatemia may also be considered.
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Hypoparathyroidism
Low plasma calcium levels may be restored to normal more quickly with Alpha D3
than with parent Vitamin D. Severe hypocalcemia is corrected more rapidly with
higher doses of Alpha D3 (e.g., 3-5 mcg) together with calcium supplements.

Hyperparathyroidism
In patients needing surgery for primary or tertiary hyperparathyroidsim, pre-
operative treatment with Alpha D3 for 2-3 weeks can reduce bone pain and myopathy
without aggravating hypercalcemia. To decrease the risk of post-operative
hypocalcemia, Alpha D3 should be continued until the plasma alkaline phosphatase
falls to normal or hypercalcemia occurs.

Nutritional and Malabsorptive Rickets and Osteomalacia

Malabsorptive osteomalacia, which responds to large doses of I.M. or I.V. parent
Vitamin D, will respond to small oral doses of Alpha D3. Nutritional rickets and
osteomalacia can also be rapidly cured with Alpha D3.

Hypophosphatemic Vitamin D-Resistant Rickets and Osteomalacia

Normal doses of Alpha D3 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 Type I) Rickets and Osteomalacia

As with the nutritional conditions, similar oral doses of Alpha D 3 are effective in
circumstances which would require high doses of parent Vitamin D.

Osteoporosis
Serum calcium and creatinine levels should be determined at 1, 3 and 6 months, and
at 6 monthly intervals thereafter.
The dose of Alpha D3 should be carefully adjusted for each patient according to the
biological response so as to avoid hypercalcaemia.

Use in Children
Alfa D3 capsules are not indicated in children under 20kg as the dosage cannot be
titrated adequately.

Use in Elderly
The clinical manifestations of hypo- or hyper calcaemia should be considered
especially in elderly patients with pre-existing renal or heart conditions.

Contraindications
 Hypercalcemia,
 Metastatic calcification.
 Alfacalcidol should not be used in patients with evidence of Vitamin D toxicity
or known hypersensitivity to the effects of Vitamin D or any of its analogues.
 Alpha D3 capsules should not be used in patients with peanut allergy or
hypersensitivity to alfacalcidol or any of the other ingredients.

Special wanings & precautions for use

Alfacalcidol should be used with caution for:
• patients being treated with cardioactive glycosides or digitalis as hypercalcaemia
may lead to arrhythmia in such patients (see Drug Interactions).

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• patients with nephrolithiasis.

Alfacalcidol increases the intestinal absorption of calcium and phosphate, serum

levels of which should be monitored, particularly in children, patients with renal
failure 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.

Hypercalcemia 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

If hypercalcaemia or hypercalciuria occur this can be rapidly corrected by stopping

treatment with Alpha D3 and any calcium supplements until plasma calcium levels
return to normal, usually in about week. Alpha D3 treatment may then be restarted at
half the last dose used {see also Precautions}.

Response to alfacalcidol may be impaired if the diet is markedly deficient in calcium.

Healing of bone lesions often indicates a decreased requirement for Alpha D3 in
which case appropriate dose adjustments should be made (see method of
administration).

Alpha D3 capsules contain arachis oil (peanut oil) and should not be taken by
patients known to be allergic to peanut. As there is a possible relationship between
allergy to peanut and allergy to soya, patients with soya allergy should also avoid this
medicine.

Interaction with other medicinal products and other forms of interaction

Digitalis Glycosides: Hypercalcemia in patients taking digitalis preparations may
precipitate cardiac arrhythmias. Patients taking digitalis concurrently with alfacalcidol
must therefore be closely monitored.
Barbiturates/Enzyme-inducing Anticonvulsant Drugs: Patients on barbiturates or other
anticonvulsants such as carbamazepine, phenytoin or primidone, may require an
increased dose of Alpha D3 to produce the desired effect.
Drugs Affecting Intestinal Absorption: Absorption of alfacalcidol may be impaired by
concurrent use of mineral oil (prolonged use), colestyramine, colestipol, sucralfate or
large amounts of aluminium-based antacids.
Magnesium: Caution should be exercised in the use of magnesium based antacids or
laxatives for patients taking alfacalcidol who are on chronic renal dialysis.
Hypermagnesemia may occur.
Calcium/Thiazides: The risk of hypercalcemia is increased in patients taking calcium-
containing preparations or thiazide diuretics concurrently with alfacalcidol.
Vitamin D and Derivatives: 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 hypercalcemia.

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Pregnancy and lactation
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,
Alpha D3 should only be used during pregnancy if treatment is essential and no better
alternative is available. Caution should be taken when prescribing to pregnant
women as hypercalcemia during pregnancy may produce congenital disorders in the
offspring.

Use in 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.

Effects on ability to drive and use machines

Alfacalcidol has no influence on the ability to drive or use machines

Adverse Reactions
The frequencies of adverse events are ranked according to the following: 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).

The most frequently reported undesirable effects are hypercalcemia and various
skin reactions.
Adverse effects generally relate to abnormally elevated serum calcium levels leading
to symptoms of anorexia, lassitude, nausea, vomiting, diarrhea, weight loss, polyuria,
sweating, headache, thirst, vertigo, and raised plasma and urine concentrations of
calcium and phosphate.

Hypercalcemia can be rapidly corrected by stopping treatment until plasma calcium

levels return to normal (about 1 week). Alpha D3 treatment may then be re-started at
half the previous dose.

In the case of renal impairment, elevated serum phosphate levels may be induced by
Alpha D3 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 or very rare being approximately 1:10,000 patients treated.

Metabolism and Nutrition Disorders

 Hypercalcemia
 Hyperphosphatemia

Skin and Subcutaneous Tissue Disorders

Pruritus
Rash
Urticaria

Renal and Urinary Disorders

Nephrocalcinosis

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
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reactions to the Ministry of Health according to the National Regulation by using an
online form
(http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffe
[email protected] ) or by email ([email protected] ).

Overdosage
Manifestations
Excessive intake of Vitamin D leads to the development of hypercalcaemia.
Administration of Alpha D3 should be stopped if hypercalcaemia occurs; symptoms
of which include anorexia, lassitude, nausea, vomiting, diarrhea, 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.

Keep the patient well hydrated by i.v. infusion of saline (force diuresis), measure
electrolytes, calcium and renal function indices; assess electrocardiographic
abnormalities, especially in patients on digitalis. More specifically, treatment with
glucocorticosteroids, loop diuretics, 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 fecal elimination.

Mechanism of Action

Pharmacodynamic properties
ATC Code: A11C C03 (Vitamin A and D, incl. combinations of the two, vitamin D
and analogues).
Alfacalcidol is converted rapidly in the liver to 1,25dihydroxyvitamin D. This is the
metabolite of vitamin D which acts as a regulator of calcium and phosphate
metabolism. Since this conversion is rapid, the clinical effects of Alpha D3 and 1,25-
dihydroxyvitamin D are very similar.
When 1-alpha hydroxylation by the kidneys is impaired, endogenous 1,25-
dihydroxyvitamin D3 production is reduced. Disorders in which this can occur
include renal bone disease, hypoparathyroidism, neonatal hypocalcaemia and
Vitamin D-dependent rickets. Such conditions require high doses of Vitamin D for
their correction but will respond to small doses of Alpha D3, which does not depend
on the renal 1-alpha hydroxylation process.

When using parent Vitamin D, the high dose and variable response time makes
dosage adjustment difficult. This can lead to unpredictable hypercalcaemia which
may take many weeks, sometimes months, to reverse.
With Alpha D3, the more rapid onset of response allows better titration of dose and, if
hypercalcemia does occur, it can be reversed within days of stopping treatment.

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.
In patients with renal failure, 1-5 μg/day of 1α-hydroxyvitamin D (1α-OHD3)
increased intestinal calcium and phosphorus absorption in a dose-related manner.
This effect was observed within 3 days of starting the drug and conversely, it was
reversed within 3 days of its discontinuation.
In patients with nutritional osteomalacia, increases in calcium absorption were noted
within 6 hours of giving 1 μg 1α-OHD3 orally and usually peaked at 24 hours. 1α-
OHD3 also produced increases in plasma inorganic phosphorus due to increased

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intestinal absorption and renal tubular re-absorption. This latter effect is a result of
PTH suppression by 1α-OHD3. The effect of the drug on calcium was about double
its effect on phosphorus absorption.
Patients with chronic renal failure have shown increased serum calcium levels within
5 days of receiving 1α-OHD3 in a dose of 0.5 -1.0 μg/day. As serum calcium rose,
PTH levels and alkaline phosphatase decreased toward normal.

Preclinical safety data

There are no-preclinical data of relevance to the prescriber which are additional to
that provided in other sections of the SPC.

Registration Numbers:
Alpha D3 Capsules 0.25 mcg: 125 64 30474
Alpha D3 Capsules 0.5 mcg : 122 51 30212
Alpha D3 Capsules 1 mcg: 125 65 30475

Nature and contents of the container

Alpha D3 Capsules 0.25 mcg:
Oval, opaque, reddish-brown, elastic, soft gelatin capsule imprinted “0.25” on one
side with black ink, containing a pale yellow oily solution.

Alpha D3 Capsules 0.5 mcg

Oval, opaque, pale pink, elastic, soft gelatin capsule imprinted “0.5” on one side with
black ink, containing a pale yellow oily solution.

Alpha D3 Capsules 1 mcg:

Oval, opaque, creamy to invory, elastic, soft gelatin capsule imprinted “1” on one side
with black ink, containing a pale yellow oily solution.

Packs of
Alpha D3 Capsules 0.25 mcg:
Aluminium Blisters 10, 20, 30, 40, 50, 60, 100 Capsules
Securitainer Plastic Bottles: 20, 30, 40, 50, 60, 100 Capsules

Alpha D3 Capsules 0.5 mcg

Aluminium Blisters 10, 30 Capsules
Securitainer Plastic bottles: 30, 50, 100 Capsules

Alpha D3 Capsules 1 mcg:

Aluminium Blisters: 10, 20, 30, 40, 50, 60, 100 Capsules
Securitainer Plastic bottles : 20, 30, 40, 50, 60, 100 capsules.

Not all pack sizes and types may be marketed.

Storage
Store in a dark place below 25C.

Manufacturer and Licence Holder

Teva Pharmaceutical Industries Ltd
P.O.Box 3190, Petach Tikva.

Alpha D3, MoH 11.2017 SZ - LK