Rapid Response Report 2

Transcription

1 Rapid Response Report 2 Additional information to support the NPSA Rapid Response issued on 3 September 2007 Risk of confusion between non-lipid and lipid formulations of injectable amphotericin The NPSA is aware of two recent fatal incidents reported to the National Reporting & Learning System (NRLS) The patients were prescribed and given the non lipid formulation of amphotericin. However, in error, the dose was calculated from the lipid formulation (which is a higher dose) Details of injectable amphotericin products are shown in Table 1. There is international evidence of fatal incidents resulting from mis-selection and administration of the wrong formulation to patients (1-9) Up until the recent report of the two fatal incidents the NPSA had not received any reports of death or serious injury involving amphotericin injection. However reports have been received to indicate that the different formulations of amphotericin have been confused in practice and either administered to patients without apparent harm or the mis-selection error has been identified and corrected before the infusion was administered. A summary of incidents involving injectable amphotericin products is presented in Table 2. 1 of 5

2 Table 1: Amphotericin Products Listed in the British National Formulary 53, March 2007 Proprietary Name Manufacturer Formulation Test dose Normal dose range Maximum dose Fungizone Squibb Amphotericin Initial test dose of 1 mg 250 micrograms/kg 1.5 mg/kg daily or on deoxycholate over minutes daily, increasing alternate days 50mg vial slowly to 1 mg/kg daily Abelcet Zeneus/Cephalon Amphotericin as lipid Initial test dose 1 mg 5 mg/kg daily complex over 15 minutes 100mg/20ml vial AmBisome Gilead Amphotericin encapsulated in liposomes 50mg vial Initial test dose 1 mg over 10 minutes 1 mg/kg daily increasing slowly to 3 mg/kg daily 5 mg/kg daily [unlicensed dose] Amphocil Beacon Amphotericin as a complex with sodium cholesteryl sulphate 50mg and 100mg vials 2 mg over 10 minutes 1 mg/kg daily increasingly slowly to 3 4 mg/kg daily max. 6 mg/kg daily 2 of 5

3 Review of NRLS Incidents reported to the NPSA January 2004 July 2007 Table 2: Incidents associated with confusion in the selection, calculation, preparation and administration of amphotericin products Type of incident Sub-type Number of incidents Degree of harm Comment Mis-selection of amphotericin formulation Fungizone instead of Ambisone 6 2 death 1 low harm 3 no harm A dose of fungizone was administered in 3 incidents. Ambisome instead of Fungizone 8 1 low harm 7 no harm Doses of ambisome were administered in 4 incidents Ambisome for Abelcet 1 1 no harm A dose of ambisome was administered in this incident Not stated 2 2 no harm No doses administered Dose mis-calculation 7 7 no harm Involving both the test dose or treatment dose Dose preparation error 23 1 moderate 5 low harm 17 no harm Incompatible solution for dilution used, phosphate buffer not used, made up to the wrong final volume, failure to filter the solution. the light sensitive infusion was not protected from light Administration error 6 6 no harm Test dose not administered before treatment dose, Infused at the incorrect rate, IV line not flushed with glucose 5% Total 53 3 of 5

4 Potential action to reduce risks NHS organisations should review local systems and consider actions to reduce risks. The following safer practice recommendations are based on guidance issued by The Institute of Safe Medication Practice Canada (3) following similar incidents, and might be useful for local consideration as part of the risk assessment and management process: 1. When prescribing, communicating and dispensing amphotericin products use both the complete generic name and the proprietary name: non-lipid amphotericin (Fungizone) or liposomal amphotericin (AmBisome) or lipid complex amphotericin (Abelcet). 2. Verify the dose if you are unfamiliar with the drug and/or dose prior to prescribing, dispensing and/or administering the drug. 3. Ensure that detailed technical drug information is easily and readily accessible in clinical areas that use amphotericin products. 4. Add a warning statement to any I.V. guideline documents or drug charts produced by the hospital specifically describing the risks associated with these products. 5. Include details of the patient weight and dose calculation as part of the prescription. 6. Amphotericin products should ideally be restricted to dispensing and preparation in a pharmacy department. 7. Risk assess the storage of amphotericin products as stock in clinical areas. 8. Consider well differentiated or separate storage of different formulations of amphotericin within the Pharmacy. Consider the use of cautionary labels or another mechanism (e.g. warning sign) to remind staff about the differences between products. In addition to mis-selection errors, a number of incidents of miscalculated, wrongly prepared and wrongly administered doses of amphotericin have been reported to the NPSA. These incidents indicate that the NHS finds the use of these complex products difficult and error prone in practice. In March 2007 the NPSA issued Patient Safety Alert 20: Promoting safe use of injectable medicines. Available at In this alert the NPSA recommends the following action for the NHS and Independent sector in England and Wales: 1. Undertake a risk assessment of injectable medicine procedures and products in all clinical areas to identify high risks, and develop an action plan to minimise them. 2. Ensure there are up-to-date protocols and procedures for prescribing, preparing and administering injectable medicines in all clinical areas. 3. Ensure essential technical information on injectable medicines is available and accessible to healthcare staff in clinical areas at the point of use 4. Implement a purchasing for safety policy to promote procurement of injectable medicines with inherent safety features. 5. Provide training for, and supervision of, all healthcare staff involved in prescribing, administering and monitoring injectable medicines. 6. As part of the annual medicines management audit programme, healthcare organisations should include an audit of medication practice with injectable medicines. 4 of 5

5 References 1. Burke D, Lal R, Finkel KW, Samuels J, Foringer JR. Case report. Acute amphotericin B overdose. The Annals of Pharmacotherapy 2006; 40: Mohr JF, Hall AC, Ericsson CD, Ostrosky-Zeicher L. Fatal amphotericin B overdose due to the administration of nonlipid formulation instead of lipid formulation Pharmacotherapy. 2005; 25: Institute For Safe Medication Practices Canada. Safety Bulletin. Warning: Prevent Mix-ups between conventional amphotericin B (Fungizone) and lipid based amphotericin B products (Ambisome and Abelcet). Institute For Safe Medication Practices. Canada. Volume 2, Issue 6, June Smetzer J. Cohen M. editors. ISMP Medication Safety Alert. Institute for Safe Medication Practices. Volume 4, Issue 18, September 8, Cohen M. Special Alert! Medication Errors with Lipid-based Drug Products. ISMP Medication Safety Alert. Institute for Safe Medication Practices. August 18, Wiegman S. Cohen M. editors. ISMP Medication Safety Alert. Institute for Safe Medication Practices. Volume 2, Issue 23, November 19, Cleary JD, Hayman J, Sherman J, Lasala GP, Piazza-Hepp T. Amphotericin B overdose in pediatric patients associated with cardiac arrest. Annals of Pharmacotherapy 1993; 27: Perlman JM. Acarregui M. Gard JW. Fatal Overdose of Amphotericin B in Two Pre-term Infants. Developmental Pharmacology & Therapeutics. 17(3-4):187-90, Koren G. Lau A. Kenyon CF. Kroppert D. Klien J. Clinical Course and Pharmacokinetics Following a Massive Overdose of Amphotericin B in a neonate. Journal of Toxicology Clinical Toxicology. 28(3): 371-8, of 5