Calcium Chloratum Injection


SUMMARY OF PRODUCT CHARACTERISTICS 

1. NAME OF THE MEDICINAL PRODUCT 

                                                 CALCIUM CHLORATUM Biotika

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
Active substance: 
        Calcium chlorate hexahydrate 1 g in 10 ml. 
        10 ml contains 183 mg of calcium, this corresponds to 4.56 mmol. 
        10 ml contains 324 mg of chloride, this corresponds to 9.12 mmol
For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM 
Solution for injection 
Clear, colourless solution. 

4. CLINICAL PARTICULARS
4. 1 Therapeutic indications 
In low blood calcium (adjunctive therapy in rachitis, osteomalacia, osteoporosis, in healing of fractures, tetany, spasmophylia), in the pressure drop caused by the acute reduction of force of myocardial contraction (eg the effect of intravenous barbiturates in anesthesia). 
 Acute allergic disease - auxiliary treatment, chronic inflammatory diseases, itchy dermatoses, moist and generalized eczema. 

4.2 Posology and method of administration 
a) Dosage for children: 
 In children is adminesterd intravenously.  The dose is adjusted according to age, type of nutrition and calcemia values. 
 Daily dosage in children: 
 1 year: to 0.25 g 
 1 to 6 years: from 0.25 to 0.5 g 
 6 to 15 years: from 0.5 to 1 g. 
 When calcium is parenterally  administered the monitoring of patient's heartbeat is necessary. 
b) Dosage for adults: 
 In adults 5-10 ml strictly intravenously and very slowly are administered for 3-10 minutes.  The exception is cardiac resuscitation when intravenous bolus is administered very quickly.  In acute symptomatic hypocalcemia an adult is initially given calcium bolus strictly intravenously at a dose of 100-200 mg of elementar calcium within 10 minutes, then a sustaining infusion of elementar calcium 1-2 mg / kg / h is applied.  The serum level of calcium level usually within 6-12 hours gets in this mode to normal values and therefore the maintaining dose can be reduced to 0.3 to 0.5 mg / kg / h. Hypomagnesemia or hypermagnesic hypocalcaemia  react not well to calcium administration. During intravenous supportive therapy the recommended calcium dose is 4-7 mg / kg / day. 

4.3 Contraindications 
 Hypercalcemia, hypercalciuria (hyperparathyroidism, vitamin D overdose, decalcification tumors as plasmocytoma, bone metastases), severe kidney insufficiency, a sudden rise in calcium serum levels, in osteoporosis caused by immobilization patient galactosemia, anaphylactic reaction with symptoms of impending shock,cardioglycosides therapy (except of severe symptomatic hypocalcemia). 

4.4 Special warnings and precautions for use 
 Intravenous calcium preparations irritate veins, so it has to be diluted in 50-100 ml of 5% glucose solution.  Calcium should be administered with caution in patients who are treated with digitalis glycosides, because hypercalcemia acts as predisposing to digitalis toxicity.  Optimal therapy requires frequent monitoring of levels of calcium, magnesium, phosphorus, potassium and creatinine in serum and determination of electrocardiographic and hemodynamic status. 
 Calcium chloride is acidifying, therefore, not suitable for the treatment of hypocalcemia in patients with renal insufficiency and acidosis. 
 The product should not be given intramuscularly, respectively. paravenously,because of the risk of necrosis. 
 Calcium may cause liver necrosis in neonates, when administered in the umbilical vein

4.5 Interactions with other medicinal products and other forms of interaction
 Local anesthetics, including procaine, inhibit or suppress the transport of ionized calcium from water environment to the lipid phase.  This effect is not only limited  to local anesthetics, but also to other medications (propranolol, digitalis glycosides, CNS active drugs, including morphine and opioid analgesic drugs). In unexpected hypercalcemia the risk of toxicity in patients treated with digoxin increases. Thiazide diuretics increase renal calcium reabsorption, reduce its excretion in urine and may cause hypercalcemia.  Concomitant administration of furosemide and calcium preparations may cause nephrocalcinosis and hypercalciuria in newborns. 

4.6 Pregnancy and lactation 
Calcium crosses the placenta and is excreted in breast milk. Absorption in infants is limited by phosphorus content in milk. Data on teratogenicity and embryotoxicity has not been published. 

4.7 Effects on ability to drive and use machines 
No effect on attention. 

4.8 Undesirable effects 
 The product has a local extremly irritative effect and the extravasal application is painful and can cause necrosis. Too rapid intravenous injection causes vasodilation, feeling of hot flushes and burning chalky taste in the mouth. Calcium salts in high doses, administered alone or with vitamin D can cause hypercalcemia with symptoms of anorexia, nausea, vomiting, abdominal pain, muscle weakness, bone pain, polydipsia , polyuria, confusion, irritability, cardiac arrhythmias, weakness and cardiac arrest or coma.  In children, acidosis may occur. Hypercalcemia is reversible, but persistent high calcium levels can cause irreversible nephrocalcinosis, nephrolithiasis, and renal concentration ability failure. Less serious side effect of supplementation with calcium chloride is constipation.  In this case the diet rich in fiber and adequate fluid intake is recommended.
 A quick therapy with calcium containing products causes a sudden increase in calcium serum concentrations, resulting in bradycardia and cardiac arrhythmias. Extravasal trnsfer of calcium solution into the subcutaneous tissue can cause severe tissue necrosis.  This can occur when an infusion pump is used. 

4.9. Overdose 
Clinical symptoms depend on the calcium concentration in serum. In lighter conditions nausea, vomiting, fatigue and somnolence may appear. Hypercalcemia at higher concentrations (above 3.5 mmol / l),is manifested by hot flushes, micturition disorders, taste disturbances, peripheral vasodilatation, abdominal pain, psychiatric disorders, polydipsia,, polyuria and muscular weakness. 
 Treatment: Discontinuation of calcium supplementation and adequate hydration is sufficient in most cases. Malignant hypercalcemia requires active treatment. Saluretics and potassium-sparing diuretics are administered.  Thiazide diuretics are contraindicated. Serum electrolytes monitoring is needed.  In a very severe condition hemodialysis can be used. 
 Data on acute and chronic toxicity of the product have not been published.

5. PHARMACOLOGICAL PROPERTIES 

5.1 Pharmacodynamic properties 
Pharmacotherapeutic group:  Ion product. 
ATC code: A12AA07 
Mechanism of effect 
 Calcium is an essential ion, necessary for normal function of many biological processes of the body such as nerve impulses conduction, synaptic transmission, hormone secretion, heart automaticity, mitotic activity, muscle contraction-relaxation, blood clotting.  Calcium is also a major intracellular mediator required for full enzyme activity. With reference to these and other features it is important to maintain the concentration of calcium ions, because hypocalcemia may also be manifested by pathological conditions with severe course, that threaten the patient's life. 
 Calcium plays a role in the tissue excitability regulation, which is likely to regulate the permeability of cell membranes for Na + and K +. ions. Muscle action potential stimulates the release of calcium ions from the sarcoplasmic reticulum and activates contraction.
. Slight lowering of calcium concentrations may significantly reduce the threshold of irritation,and therefore appearance of tetanus spasms may. In some patients with hypocalcaemia the reduced concentration of calcium ions is manifested by paresthesia, spasms, and laryngeal spasm with tetany.  Intravenous supplementation of calcium mitigates the clinical picture and it adjusts during the time. 
Calcium ion is the essential ion for excitation-contraction coupling in cardiac muscle tissue, for conducting of electrical impulses in certain areas of the heart, especially in the AV node as well.  Myocardial fiber depolarization opens calcium channels that depends on voltage and causes a slow internal currents, which are formed via the action potential plateau. These currents allow the permeation of sufficient calcium ions to the release of other ions from the sarcoplasmic reticulum and thereby cause a contraction. The effect of hypocalcemia on cardiovascular system is manifested by symptoms such as: hypotension, cardiac insufficiency, dysrhythmias (bradycardia, ventricular fibrillation) and reduced response to drugs, mechanisms in which participates calcium (noradrenaline, digoxin, dopamine).  After slow intravenous administration of ionized calcium vascular tonus is restored and cardiac contractility in patients with hypocalcaemia is adjusted. 
 Calcium plays an important role in maintaining of the integrity of the mucous membranes, cell adhesion, but also in a function of cell membranes themselves. It is required for exocytosis and therefore has an important role in stimulating of secretion of most exocrine and endocrine glands. The release of catecholamines from the adrenal glands, neurotransmitters at synapses, histamine from mast cells, etc. depends on calcium ions. The application of calcium salts is indicated in states of shock, when the permeability of cell membranes is increased and therefore to release of calcium from the vascular system.  Reduced ability to mobilize skeletal calcium due to hypofunction of PTH or vitamin D deficiency contributes to the worsening state of shock. 

5.2 Pharmacokinetic properties 
The largest amount of absorbed calcium, approximately one-third is absorbed in the proximal segments of the small intestine.  Intestinal absorption of soluble, ionized forms of calcium is in two separate steps:
1) calcium intake per mucosa, and 2) the transition to the serous side of the intestinal epithelium.  Calcium is absorbed faster than chlorides in the form of carbonate, or glycerolphosphate orthophosphate. 
In humans only about 1000 mg of calcium is located extracellularly. The largest depot site of calcium is a skeleton, where about 1.2 kg of this element is located, from which 4000 mg is available for rapid exchange with the extracellular environment and for buffering of plasma calcium. The skeleton is a dynamic tissue that is the subject of daily transformation.
 In this process, approximately 500 mg of calcium is extracted from extracellular depot  to form a new bone and the same amount of old bone tissue is resolved.
 
Concentration of calcium ions in extracellular fluid and in plasma varies very little, which enables to maintain physiological levels of intracellular calcium.  Physiological levels of calcium in plasma are in the range 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.   
 Blood calcium levels are physiologically maintained in very narrow limits due to retroactive sensitive mechanism of regulation.  The three main organs - kidneys, gastrointestinal tract and skeleton, and the three main hormones (vitamin D, PTH parathyroid hormone and calcitonin CT) are involved in homeostasis of minerals and in calcium regulation. Calcium is primarily excreted in the urine, in faeces ,in pancreatic juice, in bile, in saliva and later on in milk.
 
5.3 Preclinical safety data
Embryotoxic, cytotoxic, teratogenic a cancerogenic effects of Calcium chlorate hexahydrate are not known. 

6. PHARMACEUTICAL PARTICULARS 

6.1 List of excipients 
Water for injection 

6.2 Incompatibilities 
Calcium salts should not be administered with bicarbonate because the precipitation occurs. 

6.3 Shelf life 
5 years

6.4 Special precautions for storage 
Store at temperatures between +10 ° C to + 25 ° C 

6.5 Nature and contents of container 
 Clear glass with a label, insert a PVC box 
 Package Size: 5 ampoules of 10 ml 

6.6 Special precautions for disposal
The drug is subject to medical prescription. 
 Any unused product or waste material should be disposed in accordance with local requirements. 

7. MARKETING AUTHORISATION HOLDER 
BB Pharma Pod Višňovkou 1662/21, 140 00 Prague 4, Czech Republic 
8. MARKETING AUTHORISATION NUMBER(S) 
39 / 775 / 92-S / C 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 December 14th, 1992
10. DATE OF LAST REVISION OF THE TEXT
December 14th, 2005