The prevention and treatment of vitamin D deficiency.
As an adjunct to specific therapy for osteoporosis in patients with vitamin D deficiency or at risk
of vitamin D insufficiency.
 

Posology
Paediatric posology:
- Prevention of deficiency 0-1 years 25000 IU (1 ampoule) every 8 weeks
- Prevention of deficiency 1-18 years 25000 IU (1 ampoule) every 6 weeks
- Treatment of deficiency 0-18 years 25000 IU (1 ampoule) once every 2 weeks for 6 weeks
(followed by maintenance therapy of 400-1000 IU/day)
Pregnancy and breastfeeding:
- The high strength formulation is not recommended
Adults:
- Prevention of vitamin D deficiency 25000 IU/month (1 ampoule), higher doses may be required
in certain situations, see below
- As an adjunct to specific therapy for osteoporosis: 25000 IU/month (1 ampoule)
- Treatment of vitamin D deficiency (<25 ng/ml) 50000 IU/week (2 ampoules) for 6-8 weeks,
followed by maintenance therapy (1400-2000 IU/day may be required; follow-up 25(OH)D
measurements should be made approximately three to four months after initiating maintenance
therapy to confirm that the target level has been achieved)
- The recommended dosage range for the treatment of hypoparathyroidism is 10,000 to 200,000
IU vitamin D daily. Depending on serum calcium levels the daily dose is 1 ampoule or 8
ampoules D- CURA 25.000 IU (equivalent to 25,000–200,000 IU vitamin D).
- For initiating the vitamin D therapy a loading dose up to 5 mg or 200.000 I.U (= 8 ampoules DCURA 25.000 IU) may be given.
Certain populations are at high risk of vitamin D deficiency, and may require higher doses and
monitoring of serum 25(OH)D:
- Institutionalised or hospitalised individuals
- Dark skinned individuals
- Individuals with limited effective sun exposure due to protective clothing or consistent use of
sun screens
- Obese individuals
- Patients being evaluated for osteoporosis
- Use of certain concomitant medications (e.g., anticonvulsant medications, glucocorticoids)
- Patients with malabsorption, including inflammatory bowel disease and coeliac disease
- Those recently treated for vitamin D deficiency, and requiring maintenance therapy.
Special populations
Renal impairment
D-CURA should not be used in combination with calcium in patients with severe renal
impairment.
Hepatic impairment
No posology adjustment is required in patients with hepatic impairment.
Method of administration
Patients should be advised to take D-CURA preferably with meal (see section 5.2
Pharmacokinetic properties - “Absorption”).
Administration to adults:
The full contents of the ampoule should be either emptied into the mouth and swallowed orally,
or emptied onto a spoon and taken orally. D-CURA can also be taken by mixing with a small
amount of cold or lukewarm food immediately prior to use.
Administration to children:
In children, D-CURA can be mixed with a small amount of children's foods, yogurt, milk, cheese
or other dairy products. The parents should be warned not to mix D-CURA into a bottle of milk
or container of soft foods in case the child does not consume the whole portion, and does not
receive the full dose. The parents should ensure that their child takes the entire dose. For children
who are not breast-feeding, the prescribed dose should be administered with a meal
See also section 6.6, Special precautions for handling and disposal.
 

• Hypersensitivity to the active substance(s) or to any of the excipients. • Hypercalcaemia and/or hypercalciuria. • Nephrolithiasis and/or nephrocalcinosis • Serious renal impairment • Hypervitaminosis D • Pseudohypoparathyroidism as the vitamin D requirement may be reduced due to phases of normal vitamin D sensitivity, involving the risk of prolonged overdose. Better-regulatable vitamin D derivatives are available for this.

Vitamin D should be used with caution in patients with impairment of renal function and the
effect on calcium and phosphate levels should be monitored. The risk of soft tissue calcification
should be taken into account.
Caution is required in patients receiving treatment for cardiovascular disease (see section 4.5
Interaction with other medicinal products and other forms of interaction - cardiac glycosides
including digitalis).
D-CURA should be prescribed with caution in patients with sarcoidosis, due to a possible
increase in the metabolism of vitamin D in its active form. In these patients the serum and
urinary calcium levels should be monitored.
Allowances should be made for the total dose of vitamin D in cases associated with treatments
already containing vitamin D, foods enriched with vitamin D, cases using milk enriched with
vitamin D, and the patient's level of sun exposure.
There is no clear evidence for causation between vitamin D supplementation and renal stones,
but the risk is plausible, especially in the context of concomitant calcium supplementation. The
need for additional calcium supplementation should be considered for individual patients.
Calcium supplements should be given under close medical supervision.
Oral administration of high-dose vitamin D (500,000 IU by single annual bolus) was reported to
result in an increased risk of fractures in elderly subjects, with the greatest increase occurring
during the first 3 months after dosing.
 

Concomitant use of anticonvulsants (such as phenytoin) or barbiturates (and possibly other drugs
that induce hepatic enzymes) may reduce the effect of vitamin D3 by metabolic inactivation.
In cases of treatment with thiazide diuretics, which decrease urinary elimination of calcium,
monitoring of serum calcium concentration is recommended.
Concomitant use of glucocorticoids can decrease the effect of vitamin D.
In cases of treatment with drugs containing digitalis and other cardiac glycosides, the
administration of vitamin D may increases the risk of digitalis toxicity (arrhythmia). Strict
medical supervision is needed, together with serum calcium concentration and
electrocardiographic monitoring if necessary.
Simultaneous treatment with ion exchange resin such as cholestyramine, colestipol
hydrochloride, orlistat or laxative such as paraffin oil may reduce the gastrointestinal absorption
of vitamin D.
The cytotoxic agent actinomycin and imidazole antifungal agents interfere with vitamin D
activity by inhibiting the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by the
kidney enzyme, 25-hydroxyvitamin D-1-hydroxylase.
 

In pregnancy and lactation the high strength formulation is not recommended and a low strength
formulation should be used.
Pregnancy
There are no or limited amount of data from the use of cholecalciferol in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3 Preclinical safety data). The
recommended daily intake for pregnant women is 400 IU, however, in women who are
considered to be vitamin D deficient a higher dose may be required (up to 2000 IU/day).
During pregnancy women should follow the advice of their medical practitioner as their
requirements may vary depending on the severity of their disease and their response to treatment
vitamin D and its metabolites are excreted in breast milk.
Breast-feeding
Vitamin D can be prescribed while the patient is breast-feeding if necessary. This
supplementation does not replace the administration of vitamin D in the neonate.
 

Not relevant.
 

a) Summary of safety profile
The most reported adverse reactions are uncommon or rare. The most uncommonly reported adverse
reactions are hypercalcaemia and hypercalciuria. (> 0.1 %).
b) Adverse reactions are listed below, by system organ class and frequency. Frequencies are
defined as: uncommon (≥1/1,000, <1/100) or rare (≥1/10,000, <1/1,000)

c) Description of selected adverse reaction
Depending on the dose and duration of treatment, severe and prolonged hypercalcaemia with its acute
(cardiac arrhythmias, nausea, vomiting, psychic symptoms, disturbances of consciousness) and chronic
(increased urgency to urinate, increased thirst, loss of appetite, weight loss, kidney stones, kidney
calcification, calcification in tissues outside the skeleton) consequences can occur.
d) Pediatric population
Frequency, type and severity of adverse reactions in children are similar to those seen in adults.
e) Other special population(s)
Not applicable

Symptoms of overdose
Ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) have a relatively low therapeutic
index. The threshold for vitamin D intoxication is between 40,000 and 100,000 IU daily for 1 to
2 months in adults with normal parathyroid function. Infants and small children may react
sensitively to far lower concentrations. Therefore, it is warned against intake of vitamin D
without medical supervision.
Overdose leads to increased serum and urinary phosphorus levels, as well as hypercalcaemic
syndrome and consequently calcium deposits in the tissues and above all in the kidneys
(nephrolithiasis, nephrocalcinosis) and the vessels.
Discontinue D-CURA when calcaemia exceeds 10.6 mg/dl (2.65 mmol/l) or if the calciuria
exceeds 300 mg/24 hours in adults or 4-6 mg/kg/day in children.
Chronic overdosage may lead to vascular and organ calcification, as a result of hypercalcaemia.
The symptoms of intoxication are little characteristic and manifest as nausea, vomiting, initially
also diarrhoea, later constipation, loss of appetite, weariness, headache, muscle pain, joint pain,
muscle weakness, persistent sleepiness, azotaemia, polydipsia and polyuria and, in the final
stage, dehydration. Typical biochemical findings include hypercalcaemia, hypercalciuria, as well
as increased serum 25 hydroxycholecalciferol concentrations.
Treatment of overdose
Symptoms of chronic vitamin D overdosage may require forced diuresis as well as
administration of glucocorticoids or calcitonin.
Overdosage requires measures for treating the - often persisting and under certain circumstances
life-threatening - hypercalcaemia.
The first measure is to discontinue the vitamin D preparation; it takes several weeks to normalise
hypercalcaemia caused by vitamin D intoxication.
Depending on the degree of hypercalcaemia, measures include a diet that is low in calcium or
free of calcium, abundant liquid intake, increase of urinary excretion by means of the drug
furosemide, as well as the administration of glucocorticoids and calcitonin.
If kidney function is adequate, calcium levels can be reliably lowered by infusions of isotonic
sodium chloride solution (3-6 liters in 24 hours) with addition of furosemide and, in some
circumstances, also 15 mg/kg body weight/hour sodium edetate accompanied by continuous
calcium and ECG monitoring. In oligoanuria, in contrast, haemodialysis (calcium-free dialysate)
is necessary.
No special antidote exists.
It is recommended to point out the symptoms of potential overdose to patients under chronic
therapy with higher doses of vitamin D (nausea, vomiting, initially also diarrhoea, later
constipation, anorexia, weariness, headache, muscle pain, joint pain, muscle weakness, persistent
sleepiness, azotaemia, polydipsia and polyuria).
 

Pharmacotherapeutic group: Vitamin D, cholecalciferol
ATC Code: A11CC05
In its biologically active form Vitamin D stimulates intestinal calcium absorption , incorporation
of calcium into the osteoid, and release of calcium from bone tissue. In the small intestine it
promotes rapid and delayed calcium uptake. The passive and active transport of phosphate is also
stimulated. In the kidney, it inhibits the excretion of calcium and phosphate by promoting tubular
resorption. The production of parathyroid hormone (PTH) in the parathyroids is inhibited
directly by the biologically active form of vitamin D3. PTH secretion is inhibited additionally by
the increased calcium uptake in the small intestine under the influence of biologically active
vitamin D.
 

The pharmacokinetics of vitamin D is well known.
Absorption
Vitamin D is well absorbed from the gastro-intestinal tract in the presence of bile, so the
administration with the major meal of the day might therefore facilitate the absorption of
Vitamin D.
Distribution and biotransformation
It is hydroxylated in the liver to form 25-hydroxy-cholecalciferol and then undergoes further
hydroxylation in the kidney to form the active metabolite 1, 25-dihydroxycholecalciferol
(calcitriol).
Elimination
The metabolites circulate in the blood bound to a specific α - globin, vitamin D and its
metabolites are excreted mainly in the bile and faeces.
Characteristics in Specific Groups of Subjects or Patients
A 57% lower metabolic clearance rate is reported in subjects with renal impairment as compared
with that of healthy volunteers.
Decreased absorption and increased elimination of vitamin D occurs in subjects with
malabsorption.
Obese subjects are less able to maintain vitamin D levels with sun exposure, and are likely to
require larger oral doses of vitamin D to replace deficits.
 

Pre-clinical studies conducted in various animal species have demonstrated that toxic effects
occur in animals at doses much higher than those required for therapeutic use in humans.
In toxicity studies at repeated doses, the effects most commonly reported were increased
calciuria and decreased phosphaturia and proteinuria.
Hypercalcaemia has been reported in high doses. In a state of prolonged hypercalcaemia,
histological alterations (calcification) were more frequently borne by the kidneys, heart, aorta,
testes, thymus and intestinal mucosa.
Colecalciferol has been shown to be teratogenic at high doses in animals.
At doses equivalent to those used therapeutically, cholecalciferol has no teratogenic activity.
Cholecalciferol has no potential mutagenic or carcinogenic activity.
 

Tocopherol acetate,
Polyglyceryl oleate (E475),
Olive oil,refined,
Sweet orange peel oil.
 

Not applicable
 

3 years

Store below 25°C.
Store in the original package, in order to protect from light.
 

Transparent PVC/PVDC/PE ampoules.
Original Pack with 4 ampoules.
 

No special requirements
Any unused product or waste material should be disposed of in accordance with local
requirements.