英国药监机构（MHRA）关于50mg/ml盐酸胺碘酮注射液潜在结晶问题沟通函（原文）
[关键字]： 药物警戒 盐酸胺碘酮注射液
讯：
Direct Healthcare Professional Communication
24thAugust2021
Amiodarone Hydrochloride50mg/ml Concentrate for Solution for Injection/Infusion - Potential for crystallisation
Dear Healthcare professional,
In agreement withthe Medicines and Healthcare products Regulatory Agency (MHRA), the UK MarketingAuthorisation Holders of products containingamiodaronehydrochloride 50 mg/ml concentrate,namely hameln pharmagmbh, BowmedIbisqus Limited/Ibigen S.r.l. Aventis Pharma Limited trading as Sanofi, would like to informyou ofthe following:
Reports have been received of visible crystals of amiodarone hydrochloride within thesolution of asmall number of ampoules of marketedproduct
Healthcare professionals are advised to:
Visuallyinspect ampoules of amiodarone for clarity,particulate matter, discolouration the integrity of the container
Onlyuse thesolution if it is clear the container is undamaged intact
Backgroundinformation
Amiodaronehydrochloride is an antiarrhythmicusedfor the management of life-threatening ventricular arrhythmias(tachycardiaor fibrillation) and supraventricular arrhythmias (fibrillation or flutter) and Wolff-Parkinson-White Syndrome.
The potential for amiodarone solutionsto crystallise and the associated potential for amiodarone- inducedphlebitis are known havebeenpreviously discussed in the scientific literature [1, 2].
Amiodaronein aqueous solutionis associated with crystallisationdueto poor solubility.To overcome this, the moleculeistypically solubilised as part of amicellar systemusing an excipient, such as polysorbate 80, which acts as asurfactant.Anybreakdown ofthis micellar system canlead to crystallisation of amiodarone in solution,whichhas been observed both at high concentrations of amiodarone(e.g.in ampoules of concentrate)andatlow concentrations (e.g.ininfusionbags during administration).
Whilethe potential for amiodarone solutionsto crystallise is known, following receipt of a small number of reports of crystallisationin ampoules from separate batches of product,andthesubsequentinvestigationsundertaken, the MarketingAuthorisationHolders would liketohighlight this potential for crystallisation tohealthcare professionals.
Adverse reactions
Asnotedin the prescribing information for the products, infusion phlebitis is listed as one ofthe most common adverse drug effects reported with intravenous amiodarone hydrochloride.
There has beenno identified increasein the reporting of adverse reactionsthat would be considered related tothe crystallisation ofamiodaroneduringinfusion (e.g. phlebitis,thrombophlebitis). Whilethisdoesn’texclude the possibility of adversehealth consequences,itfurther supportsthe overallprobability thatthe occurrence of such reactions is low.
Recommendations foruse
Toinform healthcare professionals ofthepotential for crystallisation,the MarketingAuthorisation Holders,in agreement withthe MHRA,have issued this Direct HealthcareProfessional Communication to provide additional information for healthcare professionals.
Healthcare professionalsshould continue to follow the advice below:
Before use, thesterile concentrateshouldbevisuallyinspected for clarity,particulate matter, discolourationtheintegrity ofthe container. Thesolutionshould onlybe usedif itis clear the container is undamaged intact.
Althoughtheuse of in-line filters isnotconsidered to be standardpracticeinthe UK for allinfusions of medicinal products, healthcare professionals may wishto considertheuse of in-line filters forinfusions of solutions that are knownto crystallise, including solutions ofamiodarone [1,2].
Call for reporting
Pleasecontinue to report suspected adverse drug reactions(ADRs)tothe MHRAthroughthe Yellow
Card Scheme. Please report:
all suspected ADRs that are serious or resultinharm. Serious reactions are those that are fatal,
life-threatening, disabling orincapacitating,those that cause a congenital abnormality or result in hospitalisation, andthosethat are considered medically significant foranyother reason;
all suspected ADRs associated with new drugsandvaccines identified by the black triangle▼.
Itis easiestquickestto report ADRs online viathe Yellow Card website -https://yellowcard.mhra.gov.uk/or viathe Yellow Card app available fromthe Apple App Store or GooglePlayStore.
Report via
the Yellow Card websitehttps://yellowcard.mhra.gov.uk/
the free Yellow Card app available from the Apple App Store or GooglePlay Store
some clinicalIT systems (EMIS, SystmOne, Vision, MiDatabank) for healthcare professionals. Suspected side effect can also be reported by calling 0800 731 6789 for free.
When reporting please provide as much information as possible, including information about medical history,anyconcomitant medication,onset, treatment dates, product brname.
Companycontacts
This letter concerns all amiodaronehydrochloride 50 mg/ml concentrate medicinal productsthat are licensed in the UK has been agreed by the below listed companies.
Marketing Authorisation Holder |
Registered Product Name |
Contact details |
hamelnpharma gmbh |
Amiodarone Hydrochloride 50 mg/ml Concentrate for Solution forInjection/Infusion |
hamelnpharmaltd Nexus,GloucesterBusiness Park Gloucester, GL3 4AG Tel: 01452 621 661 drug.safety@hameln- pharma.co.uk |
Bowmed Ibisqus Limited/ Ibigen S.r.l. |
Amiodarone 150 mg/3 ml Concentratefor Solutionfor Injection/Infusion |
Bowmed Ibisqus Limited The Old Dairy, Brynkinalt Business Centre Brynkinalt, Chirk, Tel: 01483 212 151 |
AventisPharmaLimited Trading as Sanofi |
Cordarone X 150 mg/3 ml Solution forInjection |
Sanofi 410 Thames Valley Park Drive Reading, Berkshire, RG6 1PT Tel: 0800 035 2525 |
Signed on behalf of the above MA Holders
Richard Wysocki MRPharmS
Medical Affairs Director,hameln pharma ltd
References
1)Phlebitis inIntravenous Amiodarone Administration:Incidenceand ContributingFactors.Crit Care Nurse(2019) 39 (1):e1–
e12https://aacnjournals.org/ccnonline/article/39/1/e1/20866/Phlebitis-in-Intravenous-Amiodarone-Administration
2)Phlebitisin AmiodaroneAdministration. Incidence, Contributing Factors, Clinical Implications.Am J Crit Care(2013)22 (6): 498-505https://medest118.files.wordpress.com/2013/12/phlebitis-in-amiodarone-administration.pdf