SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Calcium chloride 10% w/v Solution for Infusion

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

One ampoule of 10ml contains 1g of Calcium chloride dihydrate.

Each gram of calcium chloride dihydrate represents approximately 6.8 mmol (13.6 mEq) calcium and 13.6 mmol (13.6 mEq) chloride. Each mL of the 10 mL ampoule contains 0.68 mmol (1.36 mEq) calcium.

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Sterile solution for slow intravenous infusion.

Pale brown-yellow, clear solution with a pH of between 5 and 8.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Calcium chlorideis indicated for use in Cardio-pulmonary Resuscitation where there is also hyperkalaemia or hypocalcaemia or calcium channel block toxicity. It is also used for the treatment of hypocalcaemia and of calcium deficiency states (a decrease in plasma-calcium concentration below the normal range of 2.15-2.60 mmol/L) as a result of impaired or reduced absorption from the gastrointestinal tract, increased deposition in bone, or to excessive losses, for instance during lactation. Additionally, hypocalcaemia may develop during transfusions utilising citrated blood or during longterm parenteral nutrition unless prophylactic calcium supplementation is employed. Other causes of hypocalcaemia include decreased parathyroid hormone activity, vitamin D deficiency and hypomagnesaemia.

4.2 Posology and method of administration

For slow intravenous infusion only. Not for intramuscular use, or subcutaneous use. In Cardiopulmonary Resuscitation (CPR) a single dose of 10ml (10% w/v) should be considered, according to the algorithm recommended by the European Resuscitation Council & the Resuscitation Council (UK).

Adults in acute hypocalcaemia, a typical dose is 2.25 to 4.5 mmol (approximately 37ml of a 10% w/v solution) of calcium given by slow intravenous infusion and repeated as required.

Paediatric population

This drug is not recommended for use in children.

Patients with impaired renal function

Calcium salts should be given cautiously to patients with impaired renal function.

4.3 Contraindications

Parenteral calcium therapy is contra-indicated in patients receiving cardiac glycosides, because calcium enhances the effects of digitalis glycosides on the heart and may precipitate digitalis intoxication.

Calcium chloride, because of its acidifying nature, is unsuitable for the treatment of hypocalcaemia caused by renal insufficiency or in patients with respiratory acidosis or failure. It should not be administered to patients with hypercalcaemia or hypercalciuria.

4.4 Special warnings and precautions for use

Excessive amounts of calcium salts may cause hypercalcaemia. Careful monitoring of serum-electrolyte concentrations is essential throughout therapy.

Parenteral administration may cause local reactions at the injection site and soft tissue calcification. Calcium chloride is generally considered to be the most irritant of the commonly used calcium salts. Care should be taken to prevent extravasation during intravenous injection.

Calcium chloride, must be administered slowly through the vein. Too rapid intravenous injection may lead to symptoms of hypercalcaemia.

Calcium salts should be given cautiously to patients with impaired renal function, cardiac disease, or sarcoidosis.

4.5 Interaction with other medicinal products and other forms of interaction

Calcium salts have been reported to be incompatible with a wide range of drugs. Complexes may form resulting in the formation of a precipitate.

Calcium salts reduce the absorption of bisphosphonates (in the treatment of Paget’s disease or hypercalcaemia of malignancy) and must be given at least 12 hours apart.

Calcium salts reduce the absorption of tetracyclines.

Diuretics, such as thiazides increase the risk of hypercalcaemia.

Large intravenous doses of calcium can precipitate arrhythmias by interacting with cardiac glycosides (e.g. digitoxin and digoxin).

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of calcium chloride in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of Calcium chloride during pregnancy.

Breast-feeding

Calcium is excreted in human milk, but at therapeutic doses of Calcium chloride no effects on the breastfed newborns/infants are anticipated.

Calcium chloride can be used during breast-feeding.

Fertility

No human data on the effect of calcium chloride on fertility are available. Calcium chloride was shown to be non-toxic to rat spermatogenic cells.

4.7 Effects on ability to drive and use machines

No adverse effects have been reported.

4.8 Undesirable effects

Injection of calcium salts can produce irritation. Solutions of calcium chloride are extremely irritant and should not be injected intramuscularly or subcutaneously.

Soft tissue calcification has also been reported following parenteral administration of calcium salts.

Excessive amounts of calcium salts may lead to hypercalcaemia. Symptoms of hypercalcaemia may include anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, mental disturbances, polydipsia, polyuria, bone pain, nephrocalcinosis, renal calculi, and, in severe cases, cardiac arrhythmias and coma.

Too rapid intravenous injection of calcium salts may also lead to many of the symptoms of hypercalcaemia as well as a chalky taste, hot flushes and peripheral vasodilation.

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 via Yellow Card Scheme, Website: (www.mhra.gov .uk/yellowcard).

4.9 Overdose

An overdose of Calcium chloride would lead to hypercalcaemia and produce the signs and symptoms described above (see undesirable effects).

Initial management of hypercalcaemia should include rehydration by either the oral or intravenous route. In severe hypercalcaemia, administration of sodium chloride by intravenous infusion to expand the extracellular fluid may be necessary.

Intravenous rehydration may be given with, or followed by, frusemide or other loop diuretics to increase calcium excretion. Thiazide diuretics should be avoided as they may increase the renal absorption of calcium.

Other drugs which may be used if this treatment proves unsuccessful include calcitonins, the bisphosphonates and plicamycin.

Phosphates may be useful, but should be given by mouth and only to patients with low serum phosphate concentrations and normal renal function.

Haemodialysis may be considered as a last resort.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: I.V. solution additives, electrolyte solutions, ATC code: B05XA07

Calcium is the most abundant mineral in the body, and is an essential body electrolyte. Homeostasis is mainly regulated by the parathyroid hormone, by calcitonin, and by the activated form of vitamin D.

Parathyroid hormone is released when the calcium blood level is low. It stimulates osteoclasts to release calcium into the blood, and increases the absorption of calcium from the gastrointestinal tract.

Calcitonin, from the thyroid gland, decreases the blood level of calcium by stimulating osteoblasts and inhibiting osteoclasts. In the presence of calcitonin, osteoblasts remove calcium from the blood and deposit it in the bone.

Calcium is a structural component of bones and teeth. It is also required for blood clotting, neurotransmitter release, muscle contraction and normal heartbeat.

5.2 Pharmacokinetic properties

The body contains about 1200g of calcium (or 300 to 500 mmol per Kg body weight), approximately 99% of which is found in the skeleton. The normal concentration of calcium in plasma is between 2.15 to 2.60 mmol per litre.

Calcium is absorbed from the small intestine. The amount of calcium absorbed varies depending on several factors including the requirements of the body, but is normally only about 30% of the dietary intake.

The absorption of calcium is increased during periods of high physiological requirement such as during pregnancy and lactation.

The amount of dietary calcium required by an adult is about 700 to 800 mg (17.5 - 20 mmol) per day.

After absorption calcium is eventually incorporated into bones and teeth with 99% of the body’s calcium content being present in such skeletal tissue. The remaining calcium is present in both the intra- and extracellular fluids.

About 50% of the total blood-calcium content is in the physiologically active ionised form with 5% being complexed to citrate, phosphate or other anions and 45% being bound to proteins.

Excretion of calcium occurs in the urine although a large proportion is reabsorbed in the renal tubules. Excretion also occurs in the faeces, this consisting of unabsorbed

calcium as well as that secreted in the bile and pancreatic juice. Minor amounts are lost in the sweat. Calcium crosses the placenta and is also excreted in breast milk.

5.3 Preclinical safety data

Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use and development.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Water for injections

6.2    Incompatibilities

Calcium salts have been reported to be incompatible with a wide range of drugs (see section 4.5). Complexes may form resulting in the formation of a precipitate.

6.3    Shelf life

2 years.

6.4    Special precautions for storage

This medicinal product does not require any special storage conditions.

Nature and contents of container

Polypropylene ampoules containing 10ml of Calcium chloride 10% w/v Solution for infusion. One outer carton contains 10 or 50 ampoules.

6.6 Special precautions for disposal

For single use only.

The product should be used immediately after opening. Any unused solution should be discarded.

Do not use this medicine if you notice turbidity, precipitation or discoloration.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7    MARKETING AUTHORISATION HOLDER

DEMO SA Pharmaceutical Industry 21st km National Road Athens - Lamia 14568 Krioneri, Attiki, Greece Tel: +30 210 8161802 Fax: +30 210 8161587

8    MARKETING AUTHORISATION NUMBER(S)

PL 17589/0007

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

25/01/2016 25/01/2016