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Assessing Cardiac Safety of Second-generation Antihistamines

Assessing Cardiac Safety of Second-generation Antihistamines. Badrul A. Chowdhury, MD, PhD Antihistamines First-generation Antihistamines Second-generation Antihistamines. US Marketing History of Second Generation Antihistamines.

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Assessing Cardiac Safety of Second-generation Antihistamines

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  1. Assessing Cardiac Safety of Second-generation Antihistamines • Badrul A. Chowdhury, MD, PhD • Antihistamines • First-generation Antihistamines • Second-generation Antihistamines

  2. US Marketing History of Second Generation Antihistamines

  3. PK interaction and QT effects of selected second-generation antihistamines

  4. Yes Risk Factors for Serious Cardiac Arrhythmia

  5. Coadministration of drugs that block delayed rectifier potassium current, IKr

  6. Intentional or accidental overdose • In vivo animal cardiac safety studies • In vitro tissue studies • Clinical studies • In vitro ion channel studies

  7. Cloned human channels, such as HERG, Kv1.5, expressed in a human cell line • Any dose dependent prolongation of cardiac repolarization duration by an antihistamine and pharmacokinetic interaction with drugs that can increase its plasma concentration are serious concerns • Patients at risk of serious cardiac arrhythmia and magnitude of QT prolongation that can cause such arrhythmia cannot be predicted

  8. US experience demonstrated failure of label warnings and educational efforts to prevent serious cardiac arrhythmia and death due from improper use of some second generation antihistamines • Any risk for cardiac arrhythmia and death with an antihistamine is unacceptable because of non-serious nature of the indication - allergic rhinitis, and availability of safer alternatives

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