Prolonged QT Interval due to Medication

Aka: Prolonged QT Interval due to Medication, Drug-Induced Torsades de Pointes, Drug-Induced QTc Prolongation, Drugs That Prolong the QTc Interval, Medication Causes of QTc Prolongation

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II. 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 with Reduced Ejection Fraction (HFrEF)
  10. Left Ventricular Hypertrophy
  11. Recent 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

III. Causes: Cardiovascular agents

  1. Diuretics
  2. Vasodilators
  3. Antiarrhythmics (all are considered higher risk)
    1. Amiodarone
    2. Procainamide
    3. Dofetilide (Tikosyn)
    4. Sotalol (Betapace)
    5. Quinidine

IV. 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]

V. Causes: Psychiatric Agents

  1. Antipsychotics
    1. Highest risk: Thioridazine, Pimozide, Haloperidol, chlorperazine
    2. Some risk: Ziprasidone (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. Fluoxetine (Prozac)
      4. Citalopram and Escitalopram (especially in combination with Cytochrome P450 2C19)
        1. Limit Citalopram (Celexa) to 20-40 mg/day
        2. Limit Escitalopram (Lexapro) to 10-20 mg/day
    2. Some risk
      1. Venlafaxine
      2. SSRIs in general
    3. Consider lower risk agents: Bupropion, Duloxetine, Mirtazapine

VI. 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

VII. 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
  4. Seratonin Agonists
    1. Sumatriptan (Imitrex)
    2. Zolmitriptan (Zomig)

VIII. Causes: Medications that more commonly cause Torsades

  1. Bepridil
  2. Disopyramide
  3. Dofetilide
  4. Ibutilide
  5. Procainamide
  6. Methadone
  7. Quinidine
  8. Sotalol

IX. 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

X. Labs

  1. Basic metabolic panel
  2. Serum Magnesium

XI. Imaging

  1. Consider Echocardiogram
    1. Excludes structural heart disease

XII. 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

XIII. Prevention

  1. Avoid combining agents at risk for QTc Prolongation
  2. Exercise caution in prescribing agents that prolong QTc in patients with underlying risk factors
  3. Use the lowest effective dose for agents at risk of QTc Prolongation
  4. Consider baseline EKG prior to administering QTc prolonging agent
    1. Avoid these agents if elevated QTc (>450 to 460 ms)
    2. Stop these agent if QTc increases >60 ms or QTc >500 ms

XIV. References

  1. (2022) Presc Lett 29(8): 44-5
  2. Glauser and Peters (2016) Crit Dec Emerg Med 30(4): 17-27
  3. Drew (2017) J Am Coll Cardiol 55(9): 934-47 +PMID:20185054 [PubMed]
  4. Roden (2004) N Engl J Med 350:1013-22 [PubMed]
  5. Wexler (2011) Am Fam Physician 84(1): 63-9 [PubMed]

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