Vitamin D3 600 000 IU/1 ml solution for injection in Pre-filled Syringe Taj Pharma
- NAME OF THE MEDICINAL PRODUCT
Vitamin D3 600 000 IU/1 ml solution for injection in Pre-filled Syringe Taj Pharma
- QUALITATIVE AND QUANTITATIVE COMPOSITION
1 Prefilled syringe with 1 ml of solution for injection contains:
15 mg cholecalciferol (vitamin D3) corresponding to 600 000 IU
- PHARMACEUTICAL FORM
Solution for injection for intramuscular use Clear to opalescent, slightly yellowish solution in a prefilled syringe
- CLINICAL PARTICULARS
4.1 Therapeutic indications
Prophylaxis of vitamin D deficiency symptoms due to malabsorption, e.g. caused by chronic intestinal diseases, biliary hepatocirrhosis, extended stomach or intestines resections, if an oral therapy is impossible or ineffective.
4.2 Posology and method of administration
Posology
Adults
Prophylaxis due to malabsorption: ½ – 1 Prefilled syringe as a single dose in individual intervals (normal case: every 3 months).
The serum calcium level should be monitored every 3 – 6 months and the dose should be adjusted according to the values.
Method of administration
The injection solution is administered by deep intramuscular injection.
In case of an intravenous injection the oily part of the solution can lead to embolisms and the solubilizer to hemolysis depending on the applied dosage.
Paediatric Population
There is no expert knowledge with children.
4.3 Contraindications
- hypersensitivity to the active substance or to any of the excipients listed in section 1
- hypercalcemia and/or hypercalciuria
- pregnancy and
4.4 Special warnings and precautions for use
D3-Vicotrat should not be administered to patients
with a tendency to the formation of kidney stones containing calcium, also in the anamnesis;
with pseudohypoparathyroidism (the demand of vitamin D can be reduced due to the temporarily normal vitamin D sensitivity with the risk of a long-lasting overdose). In this case easily controllable vitamin D derivatives are available.
D3-Vicotrat should be administered only with caution to patients
with impaired renal calcium and phosphate excretion, in case of treatment with benzothiadiazine derivatives and immobilized patients, e.g. due to a cast (risk of hypercalcemia, hypercalciuria);
suffering from sarcoidosis because the risk of transformation of vitamin D into its active metabo- lites is increased.
The calcium levels in serum and urine should be monitored in these patients.
During a long-term therapy with D3-Vicotrat the calcium levels in serum and urine should be moni- tored every 3 to 6 months, and the kidney function should be checked by measuring the serum cre- atinine. This check is particularly important in older patients and during a concomitant therapy with cardiac glycosides or diuretics. In case of hypercalcemia or symptoms of an impaired kidney func- tion the dosage must be reduced or the therapy be stopped. It is recommended to reduce the dos- age or to interrupt the therapy if the calcium level in the urine exceeds 7.5 mmol/24 hours (300 mg/24 hours).
If other drugs containing vitamin D are prescribed, the dosage of vitamin D from D3-Vicotrat must be taken into account. Additional administration of vitamin D or calcium should only be carried out under medical supervision. In such cases the calcium levels in serum and urine must be monitored.
In patients with renal insufficiency, that are treated with D3-Vicotrat, the effect on the calcium and phosphate level should be monitored.
D3-Vicotrat should not be administered to patients who suffer from the rare hereditary fructose in- tolerance.
4.5 Interaction with other medicinal products and other forms of interaction
Phenytoine or barbiturates can reduce the effect of vitamin D3.
Thiazide diuretics can lead to hypercalcemia due to the reduction of the renal calcium excretion. Therefore, the calcium levels in serum and urine should be monitored during a long-term therapy.
The simultaneous administration of glucocorticoids can reduce the effect of vitamin D3.
The toxicity of cardiac glycosides may be raised due to an increase of the calcium level during the therapy with vitamin D (risk of cardiac dysrhythmia). In these patients ECG and calcium level in se- rum and urine should be monitored.
Only in exceptional cases and under serum calcium controls D3-Vicotrat should be combined with metabolic products or analogues of vitamin D.
4.6 Fertility, pregnancy and lactation
Pregnancy and lactation
Overdose of vitamin D in pregnancy must be prevented since long-lasting hypercalcemia can lead to physical and mental retardation as well as to congenital heart and eye diseases of the child.
Therefore D3-Vicotrat may not be used during pregnancy and lactation.
If a vitamin D supplement should be required, a drug with a lower cholecalciferol content than D3- Vicotrat should be chosen.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and to use machines have been performed.
4.8 Undesirable effects
The side effects of vitamin D result from hypercalcemia due to overdose. Depending on dosage and duration of the therapy a severe and long-lasting hypercalcemia can appear with acute symp- toms (arrhythmia, nausea, vomiting, psychic symptoms, and impaired consciousness) and chronic symptoms (polyuria, polydipsia, anorexia, weight loss, kidney stone formation, nephrocalcinosis, extraosseous calcifications). In individual cases lethal courses have been described (see also sec- tion 4.9).
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.
4.9 Overdose
Symptoms of overdose
Ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) have a relative low therapeutic index. In adults with normal parathyroid function the threshold for vitamin D intoxication is between 40 000 and 100 000 IU per day during 1 to 2 months. Babies and infants may react severely to far lower concentrations. Therefore vitamin D should not be administered without medical control.
Overdose leads to an increase of phosphorus in serum and urine and to the hypercalcemia syn- drome, later also to calcium deposit in the tissues, primarily in the kidneys (nephrolithiasis, nephro- calcinosis) and the vessels.
The symptoms of an intoxication are nonspecific and may appear as nausea, vomiting, at first often as diarrhoea, later on as obstipation, anorexia, weakness, headache, muscle and joint pain, muscle weakness as well as persistent drowsiness, azotaemia, polydipsia and polyuria, finally as exsic- cosis. Typical laboratory test results are hypercalcemia, hypercalciuria as well as increased serum levels of 25-hydroxycholecalciferol.
Treatment of overdose
In case of an overdose measures for the treatment of the often long-lasting and potentially threat- ening hypercalcemia are required.
The first measure is to stop the administration of the vitamin D product; a normalization of the hy- percalcemia due to vitamin D intoxication lasts for several weeks.
Graduated according to the extent of the hypercalcemia low calcium or calcium free nutrition, plenty intake of fluids, forced diuresis by means of furosemide as well as the administration of glu- cocorticoids and calcitonine may be applied.
Infusions of isotonic NaCl solution (3-6 l in 24 hour) with addition of furosemide as well as possibly 15 mg/kg BW sodium edetate under continuous calcium and ECG-control have a quite reliable calcium lowering effect in patients with a sufficient kidney function. Hemodialysis (calcium free dialy- sis fluid) is indicated in case of oliguria.
A special antidote does not exist.
It is recommended to inform patients with long-term treatment with higher vitamin D doses about the symptoms of a possible overdose (nausea, vomiting, at the beginning often diarrhoeas, later obstipation, anorexia, weakness, headache, muscle and joint pain, muscle weakness, drowsiness, azotaemia, polydipsia and polyuria).
- PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Vitamins, vitamin D and analogues
Cholecalciferol (vitamin D3) is synthesized in the skin under the influence of UV rays and is then metabolized in two hydroxylation steps, at first in the liver (position 25) and next in the kidney tissue (position 1) into the biologically active form 1,25-dihydroxy-cholecalciferol. 1,25-dihydroxy-cholecal- ciferol is essentially involved in the regulation of the calcium and phosphate balance together with parathyroid hormone and calcitonine. In case of a vitamin D deficiency the calcification of the skele- ton does not occur (rickets) or bone decalcification may result (osteomalacia).
According to the formation, physiological regulation and mode of action the so-called vitamin D3 is to be considered as precursor of a steroid hormone. Besides the physiological production in the skin cholecalciferol can be supplied with nutrition or as drug product. When administered as a drug product the physiological inhibition of the cutaneous vitamin D synthesis will be avoided and over- doses and intoxications may occur. Ergocalciferol (vitamin D2) is formed in plants. In humans it is metabolically activated like cholecalciferol and has qualitatively and quantitatively similar effects.
Occurrence and coverage of need
Fish liver oil and fish are particularly rich in vitamin D, small quantities are found in meat, egg yolk, milk, dairy products and avocado.
The daily demand for adults is 5 µg, corresponding to 200 IU. Healthy adults can cover their requirements at sufficient sun exposure by own synthesis. The supply by food is only of minor importance. However, it can be important in critical conditions (climate, way of life).
Deficiency symptoms
Deficiency symptoms may appear for instance in immature premature babies, in infants exclusively breastfed for more than six months without supplementary food containing calcium, and in children on strict vegetarian diet. The rare vitamin D deficiency in adults may be caused by inadequate ali- mentary supply, insufficient UV exposure, malabsorption and maldigestion, hepatocirrhosis as well as renal insufficiency.
5.2 Pharmacokinetic properties
Absorption
In alimentary doses vitamin D is almost completely absorbed from the nutrition together with nutri- tion lipids and bile acids. Higher doses are absorbed with a resorption rate of about 2/3. In the skin vitamin D is synthesized under the influence of UV light from 7-dehydrocholesterol Biotransformation
By means of a specific transport protein vitamin D reaches the liver where it is metabolized by a microsomal hydroxylase to 25-hydroxy-cholecalciferol.
Elimination
The excretion of vitamin D and its metabolites is carried out biliary/faecal.
Vitamin D is stored in fatty tissue and has therefore a long biological half-life. After high vitamin D doses the 25-hydroxyvitamin D concentrations in serum can be increased for months. Hypercalce- mia caused by overdose can persist for weeks (see section 4.9).
5.3 Preclinical safety data
There are no further special toxicological risks to humans apart from these listed under the sections
4.6 and 4.9.
- PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium dihydrogen phosphate dihydrate; sodium hydroxide; sorbitol, liquid 70% (crystallizing); pol- ysorbate 80; triglycerides, medium-chain; water for injections.
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medici- nal products.
6.3 Shelf life
3 years
In D3-Vicotrat the fat-soluble vitamin D3 is dispersed with solubilizers in water. Hereby an opalescent “solution” develops, appearing more or less turbid in incident light (Tyndall effect). The turbidity of the solution may be influenced by concentration and temperature and the solution may tend to emulsify. However, an appearing turbidity does not influence the effectiveness of the prepara- tion.
6.4 Special precautions for storage
Do not store above 25°C.
After opening of the Prefilled syringe s any leftover content must be discarded.
6.5 Nature and contents of container
5 Prefilled syringe s with 1 ml of solution for injection each.
6.6 Special precautions for disposal and other handling
No special requirements.
Using Prefilled syringe
- Your healthcare provider or nurse should show you how to prepare and inject Prefilled syringe using the prefilled syringe. Do not inject yourself or someone else until you have been shown how to inject Prefilled syringe.
- Keep this Instructions for Use and refer to it as needed.
- Each Prefilled syringe is for one-time use only. Do not share or reuse your Prefilled syringe. You may give or get an infection
- Your healthcare provider may help you decide where on your body to inject your dose. You can also read the “Choose your injection site” section of these instructions to help you choose which area can work best for you.
7. Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com
