CALRECIA Solution for infusion Ref.[27904] Active ingredients: Calcium chloride

Calcium chloride infusion should be used with caution in patients treated with Digitalis-Glycosides. In patients considered at risk to develop cardiac arrhythmia, continuous monitoring of the electrocardiogram should be considered during citrate anticoagulation and calcium infusion (see section 4.5).

Comorbidities affecting calcium metabolism and calcium excretion such as but not limited to nephrocalcinosis, hypercalciuria and overdose of vitamin D should carefully be considered when prescribing Calrecia. Dose adaptations might be required and blood calcium levels should be closely monitored. Preexisting hypercalcaemia should be considered by reducing initial calcium infusion rate and close monitoring of blood calcium levels. Pre-existing hypocalcaemia should be corrected prior to starting citrate anticoagulation. Pre-existing hyperchloremia might be corrected by adequate dialysis conditions; alternatively adjusted application of chloride-poor infusion solutions can be considered.

The precautions during use of the applied extracorporeal blood purification therapy must be adhered to. The electrolyte and acid-base balance must be regularly controlled during citrate-anticoagulated extracorporeal blood purification treatments. When infused into the extracorporeal circuit, the site of Calrecia infusion should regularly be inspected for signs of locally developing clotting and if observed a change of the extracorporeal circuit should be considered.

During the application of Calrecia, the serum ionised calcium concentration must be regularly checked. The calcium status of the patient and its trend during blood purification therapy must be considered. If hypocalcaemia is present or tends to develop, starting or increasing the supplementation of calcium may be required. If hypercalcaemia is present or tends to develop (e.g. caused by accumulation of calcium due to inefficient blood purification resulting from a clogged membrane or due to overdose) decreasing the supplementation of calcium may be required. Hypocalcaemia and an unexpectedly high need of Calrecia infusion to stabilise the systemic ionised calcium in the desired range might be caused by citrate accumulation: Citrate anticoagulation mostly will result in a moderate increase of the systemic citrate concentration and of systemically present calcium-citrate chelate complexes. In case of impaired citrate metabolism, citrate accumulation can result. A ratio of systemic total calcium to systemic ionised calcium above 2.25 can be a sign of clinically relevant citrate accumulation and strategies to reduce the systemic citrate exposure should be evaluated or a complete stop of the citrate anticoagulated extracorporeal blood purification treatment should be considered. In addition to monitoring systemic ionised calcium, monitoring of parathyroid hormone levels and other parameters of bone metabolism should be considered, specifically if treatment duration is prolonged (i.e. longer than 2 weeks) or citrate-anticoagulated treatments are repetitively applied.

After the stop of the citrate anticoagulated extracorporeal blood purification treatment, citrate metabolism will continue and calcium released from calcium-citrate chelate complexes might lead to ionised hypercalcaemia.

Calcium chloride injection is irritating to the 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 infusion into perivascular tissues. In case of perivascular infiltration, intravenous administration at that site should be discontinued at once. Uncontrolled infusion must be avoided (i.e. use a pump dedicated for calcium infusion) to minimise risks related to dosing inaccuracy.

Additional applications of calcium due to other infusion solutions or medicinal products need to be considered for dosing.

No other substance or solution must be added to Calrecia. In case Calrecia is applied not via the extracorporeal circuit but via a separate central venous catheter, the respective catheter lumen must not be used for any other infusion in parallel. Of note, calcium chloride solution has been demonstrated to be incompatible with various other solutions containing, e.g. inorganic phosphate, carbonates, tetracycline antibiotics, ceftriaxone and others.

Patients treated with Digitalis glycosides may show signs of Digitalis overdose after application of calcium containing solutions (see section 4.4).

Thiazide diuretics decrease urinary calcium excretion. Caution is therefore required if such drugs are administered with both calcium chloride and other calcium-containing preparations.

Pregnancy

There are no or limited amount of data from the use of calcium chloride in pregnant women.

Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Calrecia is not recommended during pregnancy unless the clinical condition of the woman requires CRRT, SLEDD or TPE.

Breastfeeding

Calcium is excreted in human milk, but at therapeutic doses of calcium chloride no effects on the breastfed newborns/infants are anticipated. Calrecia can be used during breast-feeding unless no other concern arises from the clinical condition of the mother.

Fertility

No human data on the effect of calcium chloride on fertility are available.

Not relevant.

The following adverse reactions can be anticipated for the treatment mode:

General disorders and administration site conditions:

• Hypothermia

Metabolism and nutrition disorders:

• Hyper- or hypohydration
• Hypercalcaemia at a dose of Calrecia considered appropriate. In this case, accumulation of calcium due to inefficient blood purification resulting from a clogged membrane should be considered (see section 4.4)
• Hypocalcaemia due to underdosing of Calrecia. In this case, citrate accumulation related to the use of citrate anticoagulation for CRRT, SLEDD and TPE should be considered (see section 4.4)
• Metabolic acidosis or alkalosis
• Other electrolyte disturbances (e.g. hypokalaemia, hypophosphataemia)

Vascular disorders:

• Hypotension.

The following undesirable effects have to be considered specifically related to the application of Calrecia:

Injury, poisoning and procedural complications:

• Application of Calrecia via other than the intended routes (i.e. infusion into the extracorporeal circuit or central venous infusion). In this context irritation at the site of infusion can occur. Extravasation can cause burning, necrosis and sloughing of tissue, cellulitis and soft tissue calcification disorders

Metabolism and nutrition disorders:

• Hypercalcaemia due to overdose of Calrecia (see section 4.9).

The exact frequency of such events is not known (cannot be estimated from the available data).

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. For substances known to be incompatible with calcium refer also to section 4.5.