Cardiovascular Medicine Book

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Prolonged QT Interval due to Medication

Aka: Prolonged QT Interval due to Medication, Drug-Induced Torsades de Pointes
  1. See Also
    1. Prolonged QT
    2. Torsades de Pointes
  2. Risk Factors: Medication-Induced Torsades de Pointes
    1. Female gender
    2. Elderly
    3. Hypokalemia
    4. Hypocalcemia
    5. Severe Hypomagnesemia
    6. Hepatic or renal dysfunction
    7. Bradycardia
    8. Atrial Fibrillation Cardioversion recently
    9. Congestive Heart Failure
    10. Left Ventricular Hypertrophy
    11. Myocardial Infarction
    12. Concurrent Digoxin use
    13. Concurrent Diuretic use
    14. Baseline QT Prolongation or subclinical Long QT
    15. Multiple concurrent agents that prolong QT
    16. Rapid infusion of agents known to cause Prolonged QT
    17. Higher doses of predisposing drug raise risk
  3. Causes: Cardiovascular agents
    1. Diuretics
    2. Vasodilators
    3. Antiarrhythmics
      1. Amiodarone
      2. Procainamide
      3. Dofetilide
      4. Sotalol
  4. Causes: Antiemetics
    1. Phenothiazines
    2. Ondansetron (Zofran)
    3. Dolasetron (Anzemet)
    4. Granisetron
    5. If QTc is already prolonged, Metoclopramide (Reglan), Palonosetron (Aloxi), Prochlorperazine are safe alternatives
    6. 5HT3 agents are unlikely to cause harm (even at highest dose, Ondansetron prolongs QTc only 20 ms)
      1. Freedman (2014) Ann Emerg Med 64(1): 19-25 +PMID:24314899 [PubMed]
      2. Moffett (2016) Acad Emerg Med 23(1): 102-5 +PMID: 26720490 [PubMed]
  5. Causes: Psychiatric Agents
    1. Antipsychotics
      1. Highest risk: Thioridazine, pimozide, Haloperidol, chlorperazine
      2. Some risk: Geodon, Fanapt, Invega, Saphris, Seroquel
      3. Consider lower risk agents: Abilify, Latuda, Zyprexa
    2. Antidepressants
      1. Highest risk
        1. Tricyclic Antidepressants (Amitriptyline, Desipramine)
        2. Trazodone
        3. Citalopram (especially in combination with Cytochrome P450 2C19)
          1. Limit Citalopram to 20-40 mg/day
          2. Limit Escitalopram to 10-20 mg/day
      2. Some risk
        1. Venlafaxine
        2. SSRIs in general (e.g. Fluoxetine)
      3. Consider lower risk agents: Bupropion, Duloxetine, Mirtazapine
  6. Causes: Antimicrobials
    1. Fluoroquinolones
      1. Class effect (includes Levofloxacin, Moxifloxacin)
      2. Consider lower risk agent: Ciprofloxacin
    2. Macrolides
      1. Includes Clarithromycin, Erythromycin, Azithromycin
      2. Three fold increased risk of Sudden Cardiac Death while on Azithromycin
        1. Ray (2013) N Engl J Med 366(20): 1881-90 [PubMed]
    3. Antifungals
      1. Fluconazole
      2. Ketoconazole
      3. Itraconazole
    4. Other agents
      1. Protease Inhibitors
      2. Quinine
      3. Pentamidine
  7. Causes: Miscellaneous Agents
    1. Antihistamines and other Anticholinergics
      1. Hydroxyzine (associated more with QT Prolongation than other Antihistamines)
      2. Diphenhydramine
    2. Opioids
      1. Highest risk agents: Methadone, Buprenorphine, Oxycodone
      2. Consider lower risk agents: Morphine
    3. Sympathomimetics
      1. Amphetamines
      2. Decongestants
  8. Causes: Medications that more commonly cause Torsades
    1. Bepridil
    2. Disopyramide
    3. Dofetilide
    4. Ibutilide
    5. Procainamide
    6. Methadone
    7. Quinidine
    8. Sotalol
  9. Causes: Medications that less frequently cause Torsades
    1. Amiodarone
    2. Arsenic trioxide
    3. Chlorpromazine
    4. Cisapride
    5. Clarithromycin
    6. Domperidone
    7. Droperidol
    8. Erythromycin
    9. Halofantrine
    10. Haloperidol
    11. Lidoflazine
    12. Mesoridazine
    13. Pentamidine
    14. Pimozide
    15. Sparfloxacin
    16. Thioridazine
  10. Labs
    1. Basic metabolic panel
    2. Serum Magnesium
  11. Imaging
    1. Consider Echocardiogram
      1. Excludes structural heart disease
  12. Management
    1. Stop offending agent
    2. Correct electrolyte abnormalities, considering 5H5T causes (esp. Potassium abnormalities)
    3. Consider Magnesium Sulfate 1-2 grams prophylactically
    4. Indications to consider telemetry admission
      1. QTc Interval >500 ms
      2. QTc interval increased 60 ms over baseline
      3. T-Wave alternans
      4. Atrioventricular Block
      5. QRS Widening
      6. Syncope
    5. Manage Torsades de Pointes
      1. See Torsades de Pointes
      2. Electrical cardioversion (Nonsynchronized)
      3. Magnesium Sulfate 2 grams
        1. May be repeated in 5-15 minutes
        2. May be continued as infusion Magnesium 3 to 20 mg/min IV for Prolonged QTc
      4. Overdrive pacing
        1. Set at rate >100 bpm
      5. Other measures
        1. Isoproterenol has been used historically and is generally not recommended
          1. Dosing was bolus and infusion with titrate to Heart Rate >100 bpm
  13. References
    1. Glauser and Peters (2016) Crit Dec Emerg Med 30(4): 17-27
    2. Drew (2017) J Am Coll Cardiol 55(9): 934-47 +PMID:20185054 [PubMed]
    3. Roden (2004) N Engl J Med 350:1013-22 [PubMed]
    4. Wexler (2011) Am Fam Physician 84(1): 63-9 [PubMed]

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