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drug-induced prolongation of the QT interval

Etiology: 1) analeptics a) agents for ADHD - amphetamine/dextroamphetamine (Adderall, dexadrine) - lisdexamfetamine (Vyvanse) - atomoxetine (Strattera) - methylphenidate (Ritalin, Concerta) & dexmethylphenidate b) appetite suppressants - fenfluramine - sibutramine (Meridia) - phentermine (Fastin) 2) antiarrhythmic agents a) class IA agents 1] quinidine* 2] procainamide 3] disopyramide b) class 1B - moricizine c) class 1C 1] flecainide 2] propafenone 3] dofetilide (Tikosyn) d) class III agents 1] sotalol* 2] ibutilide 3] amiodarone# 4] dronedarone (Multaq) 3) antidepressants a) tricyclic antidepressants (TCA) 1] maprotiline 2] amitriptyline (Elavil) [3] - increasing doses associated with QT prolongation [10] 3] doxepin 4] imipramine 5] desipramine 6] clomipramine (Anafranil) 7] nortriptyline 8] protriptyline 9] Trimipramine b) SSRI 1] sertraline - sertraline is not associated with increased risk of QT prolongation (NEJM) [17] 2] fluoxetine 3] paroxetine 3] sibutramine (Meridia) 4] citalopram (Celexa) & escitalopram (Lexapro) - increasing doses associated with QT prolongation [10] c) venlaxafine & desvenlafaxine (Pristiq) d) mirtazapine (Remeron) e) trazodone 4) antiemetics a) dolasetron b) droperidol c) ondansetron d) domperidone e) granisetron f) palonosetron [8] g) promazine 5) antihistamines a) astemizole b) terfenadine c) diphenydramine d) hydroxyzine 6) antihypertensive agents - bepridil (Ca+2 channel blocker) 7) antineoplastic agents a) arsenic trioxide b) tamoxifen c) lapatinib (Tykerb) d) sunitinib (Sutent) e) toremifene (Fareston) f) dasatinib (Sprycel) g) nilotinib (Tasigna) h) vandetanib (Caprelsa) 8) antibiotics: a) macrolides: 1] erythromycin 2] clarithromycin 3] troleandromycin (TAO) 4] azithromycin b) trimethoprim-sulfamethoxazole c) pentamidine d) amantadine e) chloroquine f) anti-fungal agents 1] itraconazole 2] miconazole (Monistat) 3] fluconazole 4] ketoconazole 5] voriconazole (VFend) g) anti-retroviral agents 1] saquinavir 2] ritonavir 3] indinavir 4] Foscarnet (Foscavir) 5) atazanavir (Reyataz) h) quinolones 1] sparfloxacin 2] moxifloxacin (Avelox) [3] 3] grepafloxacin (Raxar) [3] 4] gatifloxacin 5] gemifloxacin 6] levofloxacin 7] ofloxacin 8] norfloxacin 9] ciprofloxacin i) telithromycin (Ketek) 9) bronchodilators a) albuterol, levalbuterol b) isoproterenol c) metaproterenol d) epinephrine e) terbutaline f) salmeterol (Serevent) g) salbutamol (Ventolin) 10) cardiac agents a) bepridil (Vascor) b) dopamine c) moexipril/HCTZ (Uniretic) d) norepinephrine e) epinephrine f) dobutamine g) isradipine (Dynacirc) h) nicardipine (Cardene) i) ranolazine (Ranexa) j) ephedrine k) isoproterenol 11) decongestants a) phenylephrine b) pseudoephedrine 12) psychotropic agents a) phenothiazines 1] thioridazine (Mellaril) 2] chlorpromazine 3] mesoridazine (Serentil) 4] fluphenazine [8] 5] perphenazine [5] b) haloperidol c) sertindole d) risperidone (Risperdal) [3] e) ziprasidone (Geodon) f) pimozide (Orap) g) clozapine (Clozaril) h) quetiapine (Seroquel) i) aripiprazole (Abilify) j) paliperidone (Invega) k) asenapine (Saphris) l) iloperidone (Fanapt) m) loxapine n) molindone o) olanzapine [8] p) risk least for haloperidol, risperidone, olanzapine [9] 13) triptans a) sumitriptan [8] b) zolmitriptan [8] 14) chemotherapy a) degarelix b) dosatinib c) nilotinib 15) urogenital agents - alfuzosin (Uroxatral) - solifenacin (Vesicare) - tolterodine (Detrol) - vardenafil 16) other - amantadine - apomorphine (Apokyn) - arsenic - chloral hydrate - chloroquine & hydroxychloroquine [14] - cisapride - cocaine - domperidone - donepezil - encainide - felbamate - FK506 - foscarnet - fosphenytoin - galantamine - halofantrine (Halfan) - indapamide (Lozol) - ketanserin - levomethadyl (Orlaam) - off market - lithium carbonate - Metoclopramide (Reglan) - methadone - midodrine - nefazodone - octreotide (Sandostatin) - orphenadrine (Norflex) - oxytocin (Pitocin) - pentamidine - probucol (off US market) - quinine - ritodrine - salmeterol (Serevent) - tacrolimus - terodiline - tizanidine (Zanaflex) * most common agents implicated in torsades de pointes # amiodarone is rarely associated with torsades de pointes

Related

QT interval

General

QT prolongation

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 151
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  3. Prescriber's Letter 8(4):19 2001
  4. Prescriber's Letter 11(11): 2004 Drugs That Prolong the QT Interval and/or Induce Torsades de Pointes Detail-Document#: 201115 Detail-Document#: 201111 (subscription needed) http://www.prescribersletter.com
  5. Prescriber's Letter 17(4): 2010 Drug-induced Long QT Interval CHART: Drug-induced Long QT Interval COMMENTARY: QT Prolongation, Torsades de Pointes, & Medication Safety Detail-Document#: 260421 (subscription needed) http://www.prescribersletter.com
  6. Prescriber's Letter 18(9): 2011 CHART: Drug-induced Long QT Interval COMMENTARY: QT Prolongation, Torsades de Pointes, & Medication Safety Detail-Document#: 270905 (subscription needed) http://www.prescribersletter.com
  7. Prescriber's Letter 19(1): 2012 Drug-Induced Long QT Interval Detail-Document#: 280111 (subscription needed) http://www.prescribersletter.com
  8. Geriatrics at your Fingertips, 13th edition, 2011 Reuben DB et al (eds) American Geriatric Society
  9. Campbell N, Boustani MA, Ayub A, et al. Pharmacological management of delirium in hospitalized adults- a systematic evidence review. J Gen Intern Med 2009; 24:848-853 PMID: 19424763
  10. Castro VM et al. QT interval and antidepressant use: A cross sectional study of electronic health records. BMJ 2013 Jan 29; 346:f288. PMID: 23360890
  11. Isbister GK, Page CB. Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice. Br J Clin Pharmacol. 2013 Jul;76(1):48-57 PMID: 23167578
  12. Wenzel-Seifert K, Wittmann M, Haen E. QTc prolongation by psychotropic drugs and the risk of Torsade de Pointes. Dtsch Arztebl Int. 2011 Oct;108(41):687-93. Review. PMID: 22114630 Free PMC Article
  13. CredibleMeds (MKSAP suggested reference) https://crediblemeds.org
  14. Lou N Heart Groups: Clear Risks With HCQ for COVID-19 - AHA/ACC/HRS caution on malaria drug plus antibiotic. MedPage Today April 9, 2020 https://www.medpagetoday.com/infectiousdisease/covid19/85870 - Roden DM, Harrington RA, Poppas A, Russo AM. Considerations for drug interactions on QTc in exploratory COVID-19 (coronarvirus disease 2019) treatment. Circulation 2020. April 8 PMID: 32267732 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.047521
  15. Yap YG, Camm AJ. Drug induced QT prolongation and torsades de pointes Heart. 2003 Nov;89(11):1363-72 PMID: 14594906 PMCID: PMC1767957 Free PMC article
  16. Roden DM Drug-Induced Prolongation of the QT Interval N Engl J Med 2004;350:1013-22 PMID: 14999113 https://www.nejm.org/doi/pdf/10.1056/NEJMra032426
  17. NEJM Knowledge+ Psychiatry