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| The United Kingdom: Calcium chloride, calcium gluconate: potential risk of underdosing with calcium gluconate in severe hyperkalaemia (English only) |
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Medicines and Healthcare products Regulatory Agency (MHRA) announces to alert the potential risk of underdosing with calcium gluconate in severe hyperkalaemia. Calcium salts (either calcium chloride or calcium gluconate) are used to stabilise the myocardium and prevent cardiac arrest in patients experiencing severe hyperkalaemia. However, the two salts are not equivalent in terms of calcium dose. Ensure the correct dose is administered to avoid underdosing of calcium. If treated sub-optimally, hyperkalaemia can be fatal.
Treatment of severe hyperkalaemia (plasma concentration ≥6.5 mmol/l) is a medical emergency and treatment must not be delayed. Calcium gluconate is used to stabilise the myocardium and prevent arrythmias and cardiac arrest.
Calcium salts have previously been used off-label for the treatment of myocardial excitability in severe hyperkalaemia, but the MHRA recently authorised the use of calcium gluconate in acute severe hyperkalaemia and in cardiac resuscitation due to severe hyperkalaemia. Calcium gluconate therapy should be started only in cases of documented severe hyperkalaemia. It should not be routinely administered during cardiac arrest.
In the United Kingdom (UK), updated Clinical Practice Guidelines in the Treatment of Acute Hyperkalaemia in Adults were published in 2020. Calcium salts do not reduce the serum potassium but are given to protect the heart. The guideline recommends use of either calcium chloride or calcium gluconate. However, the salts are not equivalent in terms of calcium dose. To achieve the recommended calcium dose of 6.8 mmol, 30ml of calcium gluconate 10% or 10ml calcium chloride 10% must be used. Both calcium gluconate and calcium chloride preparations are available in 10ml vials at 10% (w/v) concentration, therefore 3 vials of calcium gluconate are required to reach the appropriate dose but only 1 vial of calcium chloride. The method of administration should be by slow intravenous injection, which may need to be repeated.
Electrocardiogram (ECG) changes may provide evidence of potassium toxicity but are not always present initially. ECG monitoring is advised for potassium levels above 6.0 mmol/L. Calcium gluconate should show an effect on ECG abnormalities within 3 minutes of administration and its action is expected to last for 30 to 60 minutes. A 30ml bolus dose of calcium gluconate 10% should be given by intravenous injection over 10 minutes. The effect of calcium salts is temporary so consider a repeat dose if ECG abnormalities remain within 5 to 10 minutes after the initial dose is complete.
Calcium salts do not lower potassium levels. The risk of arrythmias and cardiac arrest increases in proportion to severity of hyperkalaemia. Measures to lower potassium levels and to address underlying causes of hyperkalaemia must be taken immediately.
Tissue necrosis is a serious adverse event if extravasation occurs during administration of both intravenous (IV) calcium salts. Ensure reliable intravenous access and test with flush prior to administration.
Review of underdosing of calcium gluconate:
The MHRA has reviewed available UK data related to inappropriate use of calcium gluconate and identified isolated cases where medication errors have occurred, including one death, where 10ml of calcium gluconate was used during cardiopulmonary resuscitation (Yellow Card literature report). Reports from the National Reporting Learning System received since the guideline was updated indicate that 6 incidents showed incorrect calcium gluconate administration and monitoring in the context of severe hyperkalaemia and cardiac arrest (5 fatal, 1 unknown outcome). The safety concerns in these incidents related to calcium gluconate underdosing; lack of repeat dosing where indicated; lack of potassium-lowering treatment and lack of or inappropriate ECG monitoring.
Following a review by the MHRA and advice from the Commission on Human Medicines, the product information for these medicines will be updated to more clearly define the safe and effective administration of calcium gluconate for severe hyperkalaemia and to warn of the potential for underdosing.
The MHRA recently authorised use of calcium gluconate for the treatment of myocardial excitability in severe hyperkalaemia, which was previously off-label. Healthcare professionals are reminded that calcium gluconate is not usually recommended for the treatment of cardiac arrest except for where there is concomitant severe hyperkalaemia. Bolus injection is recommended in these circumstances.
Healthcare professionals are advised:
- calcium salts (either calcium chloride or calcium gluconate) are used to stabilise the myocardium and prevent cardiac arrest – these two products are not dose-equivalent
- be alert to the risk of inadvertent underdosing if calcium gluconate is used instead of calcium chloride and verify the calcium salt details before administration: 30ml of calcium gluconate 10% provides 6.8mmol of calcium (equivalent to 10ml of calcium chloride 10%)
- administration must be by slow intravenous injection of the whole dose over 10 minutes
- repeat doses may be required as the effect of calcium is temporary, lasting 30 to 60 minutes
Please refer to the following websites in MHRA for details:
http://www.gov.uk/drug-safety-update/calcium-chloride-calcium-gluconate-potential-risk-of-underdosing-with-calcium-gluconate-in-severe-hyperkalaemia
http://www.gov.uk/drug-device-alerts/national-patient-safety-alert-potential-risk-of-underdosing-with-calcium-gluconate-in-severe-hyperkalaemia-natpsa-slash-2023-slash-007-slash-mhra
In Hong Kong, there are four registered pharmaceutical products containing calcium gluconate as the single active ingredient for injection, namely Calcium Gluconate Kabi Solution for Injection/Infusion 1000mg/10ml (HK-66892), 10% Calcium Gluconate Inj (B Braun) (HK-37887), Calcium-Aguettant Solution for Injection/Infusion 10% w/v (HK-66062) and Calcium Gluconate-Hameln Solution for Injection 10% w/v (HK-66660); and there are three registered pharmaceutical products containing calcium chloride as the single active ingredient, namely Calcium Chloride Injection BP 10% w/v 1g/10mL (HK-66744), Calcium Chloride Demo Solution for Infusion 10% w/v 1g/10mL (HK-67621) and Calcium Chloride Injection USP 1000mg/10mL (HK-63078). They are all prescription-only medicines.
Amongst the abovementioned products, only Calcium Gluconate Kabi Solution for Injection/Infusion 1000mg/10ml (HK-66892), Calcium Chloride Injection BP 10% w/v 1g/10mL (HK-66744) and Calcium Chloride Demo Solution for Infusion 10% w/v 1g/10mL (HK-67621) are approved in Hong Kong for the hyperkalaemia; and their package inserts have already a warning for use with caution in patients with cardiac disease.
So far, the Department of Health (DH) has not received any adverse drug reaction (ADR) cases related to calcium gluconate injection or calcium chloride injection. In light of the above MHRA’s announcement, letters to inform local healthcare professionals will be issued. The matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/ Wednesday, June 28, 2023
Issued at HKT 18:45
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