The treatment of vitamin D3 deficiency.

Posology
1 capsule contains 50,000 IU vitamin D3.
▪ Paediatric posology
- Due to lack of clinical data, BLUM-D is not recommended.
▪ Pregnancy and breastfeeding
- Due to lack of clinical data, BLUM-D is not recommended.
▪ Adults
Higher doses may be required in certain situations, see below.
- Treatment of vitamin D3 deficiency (<25 nmol/l) 50,000 IU/week (1 Tablet) for 6-8 weeks,
followed by maintenance therapy (1400-2000 IU/day may be required, such as 1 Tablet per
month; 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.)

 ▪ Certain populations are at high risk of Vitamin D3 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 sunscreens.
- Obese individuals.
- Patients being evaluated for osteoporosis.
- Use of certain concomitant medications (eg, anticonvulsant medications, glucocorticoids).
- Patients with malabsorption, including inflammatory bowel disease and coeliac disease.
- Those recently treated for Vitamin D3 deficiency and requiring maintenance therapy.
Special Populations
Renal Impairment
BLUM-D 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
Oral – The Tablet should be swallowed whole with water.
Patients should be advised to take BLUM-D preferably with a meal (see section 5.2
Pharmacokinetic properties - “Absorption”).

• 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. • Pregnancy • Children and adolescents (under 18 years of age)

Vitamin D3 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).
BLUM-D should be prescribed with caution in patients with sarcoidosis, due to a possible
increase in the metabolism of Vitamin D3 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 D3 in cases associated with
treatments already containing Vitamin D3, foods enriched with Vitamin D3, cases using milk
enriched with Vitamin D3, and the patient's level of sun exposure.
There is no clear evidence for causation between Vitamin D3 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 D3 (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 D3.
In cases of treatment with drugs containing digitalis and other cardiac glycosides, the
administration of Vitamin D3 may increase 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 D3.
The cytotoxic agent actinomycin and imidazole antifungal agents interfere with Vitamin D3
activity by inhibiting the conversion of 25-hydroxyVitamin D3 to 1,25- dihydroxy Vitamin
D3 by the kidney enzyme, 25-hydroxyVitamin D3-1-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 D3 deficient a higher dose may be required (up to 2000 IU/day- 10
drops with the oral drops presentation).
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 D3 and its metabolites are excreted in breast milk.
Breastfeeding
Vitamin D3 can be prescribed while the patient is breast-feeding if necessary. This
supplementation does not replace the administration of Vitamin D3 in the neonate.
Fertility
There is no data regarding treatment with vitaminD3 and its effects on fertility.

There are no data on the effects of BLUM-D on the ability to drive. However, an effect on
this ability is unlikely.

Metabolism and nutrition disorders
Uncommon: Hypercalcaemia and hypercalciuria
Skin and subcutaneous disorders:
Rare: pruritus, rash, and urticaria.
Reporting of suspected adverse reactions
To Report Any Side Effects
• Saudi Arabia
The National Pharmacovigilance Centre (NPC):
• Fax: +966-11-205-7662
• Call NPC at +966-11-2038222, Ext 2317-2356-2340
• SFDA Call Center: 19999
• E-mail: npc.drug@sfda.gov.sa
• Website: www.sfda.gov.sa/npc
• Other GCC States:
• Please contact the relevant competent authority.

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).

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 BLUM-D 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 hydroxy cholecalciferol 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 and analogues, cholecalciferol ATC Code:
A11CC05.
In its biologically active form Vitamin D3 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 parathyroid 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 D3.

The pharmacokinetics of Vitamin D3 is well known.
Absorption
Vitamin D3 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 D3.
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-dihydroxy- cholecalciferol
(calcitriol).
Elimination
The metabolites circulate in the blood bound to a specific α – globin, Vitamin D3 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 D3 occurs in subjects with
malabsorption.
Obese subjects are less able to maintain Vitamin D3 levels with sun exposure and are likely
to require larger oral doses of Vitamin D3 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. 

Cholecalciferol 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.

Composition of BLUM-D 50,000 I.U. film coated tablet
CORE MATERIALS
Avicel DG
Croscarmellose Sodium
Colloidal Sillcone Dioxide
Magnesium Stearate
SEALING COATING
Hydroxy Propyl Methyl Cellulose
Polyethylene Glycol
Talc
Titanium Dioxide
Ethyl Alcohol absolute
Purified water
Coat Material (Opadry II 32k220011 yellow)
Opadry Ys-1-7027 white
Ethyl Alcohol absolute
Purified water

Not applicable.

2 years (24 Months).

Store below 30°C, Store in the original package in order to protect from light

BLUM-D 50,000 I.U. Film Coated Tablets are packed in 2 Blister as 10 tablets per blister

Any unused medicinal product or waste material should be disposed of in accordance with
local requirements, Keep out of the reach & sight of children