Calcium Biotika Injection

SUMMARY OF PRODUCT CHARACTERISTICS 

1.  NAME OF THE MEDICINAL PRODUCT 

                                    CALCIUM Biotika 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
Active substance:          Calcium gluconate monohydrate 960 mg, 
                                    Calcium saccharate tetrahydrate 36 mg in 10 ml. 
                                    Calcium content in 10 ml of product: 90.3 mg, this corresponds to 2.25 mmol.

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM 
Solution for injection 
Clear, colourless to slightly yellow colored solution.

4. CLINICAL PARTICULARS
4. 1 Therapeutic indications 
Hypocalcemia of different origin (hypoparathyroidism, decreased intake of calcium, vitamin D deficiency, malabsorption, diuretic therapy, hypocalcemia in newborns), primarily symptomatic hypocalcemia (tetany, spasmophylia, bronchospasm, laryngeal spasm)
Hypocalcemia prevention as a part of the infusion solutions, or orally to breast milk enrichment for premature osteopenia in premature babies.
Hyperkalemia and hypermagnesemia
Fluoride poisoning, fluorine poissoning, hydrofluoric acid, oxalic acid and its salts poisoning
Reduced myocardial contractility in calcium entry blocker or beta-blockers overdose and during cardiovascular resuscitation
Auxiliary treatment in acute allergic conditions, in itchy dermatose, in oozing and generalized eczema
This medicine is used to treat adults and children

4.2 Posology and method of administration 
a) Dosage for children: 
Dose depends on age, type of diet and calcemia values.  Single dose for newborns and children under 1 year is 100-200 mg (1-2 ml) in 5 ml of isotonic sodium chloride solution or 5% glucose solution, for children 1-6 years 200-500 mg (2-5 ml) and for children 6-15 years 500-1000 mg (5-10 ml). Solution for injection should be administered strictly intravenously, because in children tissue necrosis may easily develop.  In the prevention of oral osteopenia in prematures 9 ml of Biotika Calcium inj.  and 50 mg of phosphorus per 100 ml of breast milk is administered.
b) Dosage for adults: 
 Dosage in the prevention and treatment of hypocalcemia is individual according to the needs of the patient. In acute symptomatic hypocalcemia in adults 10-20 ml over 10-15 minutes is administered strictly intravenously, then followed by a maintenance infusion of calcium 1-2 mg / kg / h in 5% glucose solution (30-50 ml Biotika Calcium inj. in 500 ml 5% glucose solution).  Infusion duration depends on calcemia values. In other indications usually 10-20 ml are administered intravenously or intragluteally daily or every second or third day. 
 Injections should be applied warmed up to body temperature, very slowly, especially when applied intravenously. The speed of administration should not be higher than 5 ml per minute (45 mg of calcium per minute). 

4.3 Contraindications 
Hypercalcemia, hypercalciuria (eg hyperparathyroidism, vitamin D overdose, tumors causing decalcification such as plasmocytoma, bone metastases), immobilization-induced osteoporosis in patient, digitalisation (with the exception of severe symptomatic hypocalcemia), severe renal insufficiency, galactosemia, signs of shock (such as anaphylactic). 

4.4 Special warnings and precautions for use 
 During intravenous administration of Calcium Biotika inj.  it is necessary to monitor the concentration of calcium and other electrolytes in serum and ECG monitoring. As soon as the acute condition is stabilized, the switch to oral calcium supplementation shall be done. The product is not suitable for long-term therapy in neonates and infants. 
 Except of applications in case of emergency, the injection shall be warmed up to body temperature before administration. 
 Due to the possibility of crystal appearance in the solution for injection, which may arise after a certain time, it is necessary to pay attention to the appearance of the solution before use. Before each use, it is necessary to visually check whether the vial contains crystals or cloudiness.  In this case, the injection is not allowed to be administered. 

4.5 Interactions with other medicinal products and other forms of interaction
 Calcium gluconate may potentiate the emergence of cardiac arrhythmias during the treatment with cardioglycosides. Thiazide diuretics decrease the excretion of calcium (a potential risk of hypercalcemia).  Calcium gluconate may when co-administered with furosemide cause nephrocalcinosis in newborn. 
 When co-administered with pentagastrine in thyroid cancer diagnostic, development of atrial fibrillation has been described.  Coadministration of verapamil in treatment of supraventricular tachycardia is recommended. In addition the antiarrhythmic effect of verapamil is not affected and its negative inotropic effect is inhibited. 
 Intravenously administered calcium may potentiate the effect of intravenously administered epinephrine. The effect of intravenously administered magnesium sulphate might be inhibited by the subsequent administration of calcium containing preparation. 
 Calcium administered intravenously may affect myorelaxation substances. The effect of nondepolarizing neuromuscular blocking agents (except succinylcholine) may be increased or extended. 
 Effect of d-tubokurarinu may be increased or extended. 

4.6 Pregnancy and lactation 
Calcium crosses the placenta and is excreted into breast milk, while its absorption in infants is limited by phosphorus content in breast milk.  Data on teratogenicity and embryotoxicity have not been published in literature.

4.7 Effects on ability to drive and use machines 
Calcium Biotika has no effect on ability to drive or operate machinery

4.8 Undesirable effects 
 Too rapid intravenous administration of the calcium containing preparation leads to many symptoms as redness of the face, hot flushes, peripheral vasodilation, hypotension or hypertension, irregular heartbeat, nausea, vomiting, change in taste in mouth.  Burning, pain, redness and rash at the injection site may be a manifestation of extravasal transfer of the injected substance.  Subcutaneous, intramuscular or extravascular administration may lead to tissue calcification or necroses.  Particularly prone to side effects are newborns. 

4.9. Overdose 
 Overdose causes hypercalcemia.  Hypercalcemia symptoms are: hot heat, taste disturbances, peripheral vasodilation, hypotension or hypertension, anorexia, nausea, vomitus, abdominal pain, muscle weakness, mental disturbances, polydipsia, polyuria.  In severe cases, cardiac arrhythmia, coma and cardiac arrest in systole might appear. 
 Laboratory symptoms are: kalcemia above 2.6 mmol / l, in severe cases, more than 3.5 mmol / l. In addition there aere elevated levels of total calcium, elevated values of ionized calcium and ECG changes - shortening of Q-Ic interval and ST segment shortening.
 Treatment:  consists of saluretics administration (furosemide or ethacrynic acid). Potassium-sparing diuretic may be applied at the same time.  Thiazide diuretics are contraindicated.  Circulating fluid volume and adequate hydration is maintained by infusion of isotonic solution.  Regular monitoring of serum electrolytes is necessary.  In a very serious condition with cardiac symptoms, hemodialysis may be used. 

5. PHARMACOLOGICAL PROPERTIES 
5.1 Pharmacodynamic propertie
Pharmacotherapeutic group: Ion product. 
ATC code: A12AA03
Mechanism of effect 
 Calcium Biotika is calcium preparation for intravenous administration with a low-irritant effect.  Calcium ions have direct physiological effect .  Anion has no pharmacological effect. The advantage of calcium sacharate and calcium gluconate are that in comparisson with the other calcium salts (mainly chlorides)are less locally irritating, which is important in accidental paravenous injection.  Ionized calcium is an essential ion, which is inevitably required for the normal function of many biological processes of an organism, such as the management of nerve impulses, synaptic transmission, hormone secretion, cardiac automaticity, mitotic activity, excitation-contraction connection  in heart, striated and smooth muscle.  Ionized calcium is the main mediator, which is needed for full enzyme activity. It increases contractility of cardiac and smooth muscle, increases the secretion of gastric juices, ACTH, corticosteroids, aldosterone, reduces parathyroid hormone and renin secretion. 

5.2 Pharmacokinetic properties 
 After intravenous administration of sodium gluconate and calcium saccharate there is an increase in plasma ionized calcium, whose level depends on the dose and speed of administration.  Within a few minutes there is a redistribution to the various compartments of the body.  Concentration of calcium ions in extracellular fluid and in plasma varies very little, which makes  possible to maintain physiological levels of intracellular calcium.  Physiological plasma calcium levels are in range from 8.6 to 10.6 mg / dl. 
 Approximately half of the total calcium concentration in plasma is as ionized form: 40-45% of calcium is bound to proteins, primarily to albumin and 10-15% creates nonionized ultraviolet complexes such as calcium carbonate. The balance between the ionized form and protein bound calcium fraction depends on pH.  Alkalosis increases protein bound calcium fraction and reduces the concentration of ionized calcium, while the acidosis has the opposite effect.  Calcium is excreted in the urine, in faeces and later on in milk.

5.3 Preclinical safety data
Embryotoxic, cytotoxic, teratogenic and carcinogenic effects of calcium gluconate and calcium saccharate are not known. 

6. PHARMACEUTICAL PARTICULARS 
6.1 List of excipients 
Water for injection 

6.2 Incompatibilities 
Solution of calcium gluconate is incompatible with many drugs, with which creates slightly soluble salts. They are carbonates, bicarbonates, phosphates, oxidizing substances, amphotericin B, tobramycin, clindamycin, cefalotin, cefurozin, ceftiazid, novobiocine, streptomycine, tetracycline. In principle Calcium gluconate shall not be administered with other agents. 
 Calcium Biotika inj.  can be diluted with isotonic sodium chloride or 5% glucose solution. 

6.3 Shelf life 
3 years

6.4 Special precautions for storage 
 Stored at 10 ° C - 25 ° C 

6.5 Nature and contents of container 
Clear glass with a label, insert a PVC box 
 Package size: 10 ampoules of 10 ml 

6.6 Special precautions for disposal
No special requirements.

7. MARKETING AUTHORISATION HOLDER 
BB Pharma Pod Višňovkou 1662/21, 140 00 Prague 4, Czech Republic

8. MARKETING AUTHORISATION NUMBER(S) 
 39/774/92-S/C 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 December 14th, 1992 / July 14th, 1999

10. DATE OF LAST REVISION OF THE TEXT
August 24th, 2005