This information is intended for use by health professionals

1. Name of the medicinal product

Calcium Chloride 10 millimoles in 10 ml Injection

2. Qualitative and quantitative composition

Calcium Chloride, Dihydrate 14.7% w/v

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Injection

Clear, bright, colourless liquid. Free from visible particulates.

4. Clinical particulars
4.1 Therapeutic indications

Hypocalcaemia or electrolyte imbalance

4.2 Posology and method of administration

Posology

For slow intravenous injection or, after dilution with at least 4 times its volume of Sodium Chloride Intravenous Infusion (0.9% w/v), by intravenous infusion.

Adults and the elderly

The precise dosage is determined by the requirements of the patient. Plasma Calcium must be monitored. An initial injection or infusion of up to 10 millimoles (at a rate not exceeding 1 millimole per minute) may be given. This may be continued by infusion of up to 10 millimoles per day.

Paediatric population

The precise dosage is determined by a paediatrician and is dependent on the requirements of the patient. Plasma calcium must be monitored.

Age 2 to 12 years

0.5 millimoles to 3.5 millimoles by intravenous infusion after dilution with at least 4 times its volume of Sodium Chloride Intravenous Infusion 0.9% w/v). The dose may be repeated everyone to three days.

Age: under 2 years

Less than 0.5 millimoles by intravenous infusion after dilution with at least 4 times its volume of Sodium Chloride Intravenous Infusion (0.9% w/v). The dose may be repeated every one to three days.

Method of administration

Intravenous injection or Infusion

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

Calcium chloride is also contraindicated in those patients with conditions associated with hypercalcaemia and hypercalcuria (e.g. some forms of malignant disease) or in those with conditions associated with elevated vitamin D levels (e.g. sarcoidosis) or in those with renal calculi or a history of calcium renal calculi.

Ceftriaxone is contraindicated in full-term newborns (up to 28 days of age) if they require (or are expected to require) IV calcium treatment, or calcium-containing infusions because of the risk of precipitation of ceftriaxone-calcium (see sections 4.4 and 4.5).

The treatment of asystole and electromechanical dissociation.

4.4 Special warnings and precautions for use

Cases of fatal reactions with calcium-ceftriaxone precipitates in lungs and kidneys in premature and full-term newborns aged less than 1 month have been described. At least one of them had received ceftriaxone and calcium at different times and through different intravenous lines. In the available scientific data, there are no reports of confirmed intravascular precipitations in patients, other than newborns, treated with ceftriaxone and calcium-containing solutions or any other calcium-containing products.

In patients of any age ceftriaxone must not be mixed or administered simultaneously with any calcium-containing IV solutions, even via different infusion lines or at different infusion sites. However, in patients older than 28 days of age ceftriaxone and calcium-containing solutions may be administered sequentially one after another if infusion lines at different sites are used, or if the infusion lines are replaced or thoroughly flushed between infusions with physiological salt-solution to avoid precipitation. In patients requiring continuous infusion with calcium-containing TPN solutions, healthcare professionals may wish to consider the use of alternative antibacterial treatments which do not carry a similar risk of precipitation. If use of ceftriaxone is considered necessary in patients requiring continuous nutrition, TPN solutions and ceftriaxone can be administered simultaneously, albeit via different infusion lines at different sites. Alternatively, infusion of TPN solution could be stopped for the period of ceftriaxone infusion, considering the advice to flush infusion lines between solutions.

A moderate fall in blood pressure due to vasodilation may attend the injection. Since calcium chloride is an acidifying salt, it is usually undesirable in the treatment of hypocalcaemia of renal insufficiency.

Calcium chloride injection is irritating to veins and must not be injected into tissues, since severe necrosis and sloughing may occur. Great care should be taken to avoid extravasation or accidental injection into perivascular tissues.

Should perivascular infiltration occur, IV administration at that site should be discontinued at once. Local infiltration of the affected area with 1 % procaine hydrochloride, to which hyaluronidase may be added, will often reduce venospasm and dilute the calcium remaining in the tissues locally. Local application of heat may also be helpful.

4.5 Interaction with other medicinal products and other forms of interaction

For interaction between calcium containing products and ceftriaxone, please see sections 4.3 and 4.4 above.

Calcium-containing products may decrease the effectiveness of calcium channel blockers.

Because of the danger involved in the simultaneous use of calcium salts and drugs of the digitalis group, a digitalized patient should not receive an intravenous injection of a calcium compound unless the indications are clearly defined.

Calcium salts should not generally be mixed with carbonates, phosphates, sulfates or tartrate in parenteral mixtures.

The effect of administered magnesium may be neutralised by calcium.

The absorption of tetracyclines is reduced by calcium.

Biphosphonates may interact with calcium chloride causing reduced absorption of biphosphates. Thiazide diuretics may increase the risk of hypercalcaemia.

4.6 Fertility, pregnancy and lactation

Studies on the effects of calcium chloride on pregnant women have not been carried out and problems have not been documented. Calcium crosses the placenta. The benefits of administration must outweigh any potential risk. Calcium is excreted in breast milk but there are no data on the effects, if any, on the infant.

4.7 Effects on ability to drive and use machines

Parenteral calcium can cause dizziness and drowsiness, if affected, patients should not drive or operate machinery.

4.8 Undesirable effects

Rapid intravenous injections may cause the patient to complain of tingling sensations, a calcium taste, and a sense of oppression or “heat wave”. Injections of calcium chloride are accompanied by peripheral vasodilation as well as a local burning sensation and there may be a moderate fall in blood pressure.

Necrosis and sloughing with subcutaneous or intramuscular administration or if extravasation occurs have been reported. Soft tissue calcification, bradycardia or arrhythmias have also been reported.

Hypercalcemia

Rarely, severe, and in some cases fatal, adverse reactions have been reported in preterm and full-term newborns (aged <28 days) who had been treated with intravenous ceftriaxone and calcium. Precipitations of ceftriaxone-calcium salt have been observed in lung and kidneys post-mortem. The high risk of precipitation in newborns is due to their low blood volume and the longer half-life of ceftriaxone compared with adults (see sections 4.3 and 4.4).

Parenteral calcium may cause:

• anorexia

• hypertension

• venous thrombosis

• vomiting

• constipation

• abdominal pain

• muscle weakness

• mental disturbances

• polydipsia

• polyuria

• bone pain

• nephrocalcinosis

• renal calculi

• drowsiness,

• flushing,

• nausea,

• sweating

• mild gastrointestinal disturbances and irritation can occur following intravenous injection.

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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Symptoms:

Symptoms: 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.

Treatment:

Withholding calcium administration will usually resolve mild hypercalcaemia in asymptomatic patients, provided renal function is adequate.

When serum calcium concentrations are greater than 12mg per 100ml, immediate measures may be required such as hydration, loop diuretics, chelating agents, calcitonin and corticosteroids. Serum calcium concentration should be determined at frequent intervals to guide therapy adjustments.

Cardiac arrhythmia and cardiac arrest may occur.

A diuretic such as bumetanide, ethacrynic acid or frusemide will assist in the excretion of excessive calcium, but in very severe cases, EDTA may be necessary.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Calcium is essential to the function of the nervous, muscular and skeletal systems. It also plays a part in cardiac function, renal function, respiration and blood coagulation.

Calcium ions increase the force of myocardial contraction. In response to electrical stimulation of muscle, calcium ions enter the sarcoplasm from the extracellular space. Calcium ions contained in the sarcoplasmic reticulum are rapidly transferred to the sites of interaction between the actin and myosin filaments of the sarcomere to initiate myofibril shortening. Thus, calcium increases myocardial function. Calcium's positive inotropic effects are modulated by its action on systemic vascular resistance. Calcium may either increase or decrease systemic vascular resistance. In the normal heart, calcium's positive inotropic and vasoconstricting effect produces a predictable rise in systemic arterial pressure.

5.2 Pharmacokinetic properties

Calcium is distributed throughout the body, but is in large amounts in the skeleton as the hydroxyapatite complex. Ca2+ is 45% plasma protein bound. Elimination is mainly faecal, with small amounts excreted in the urine.

5.3 Preclinical safety data

Not applicable since calcium chloride has been used in clinical practice for many years and its effects in man are well known.

6. Pharmaceutical particulars
6.1 List of excipients

Water for Injections

pH may be adjusted with Hydrochloric Acid.

6.2 Incompatibilities

Calcium salts should not be mixed with carbonates, phosphates, sulfates, tartrates or tetracycline antibiotics in parenteral mixtures.

6.3 Shelf life

36 months.

6.4 Special precautions for storage

None stated.

6.5 Nature and contents of container

5 or 10 ml in Type 1 colourless neutral glass ampoules. Fusion sealed.

Packed in cartons of 10 ampoules

6.6 Special precautions for disposal and other handling

None stated.

7. Marketing authorisation holder

Macarthys Laboratories

t/a Martindale Pharma

Bampton Road,

Harold Hill,

Romford

RM3 8UG

UK

8. Marketing authorisation number(s)

PL 01883/6174R

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 22-03-1990

10. Date of revision of the text

22/03/2018