Amiodarone: at low dose can cause tremor, numbness, bradycardia and thyroid disease.

Clinical bottom line (level 1a)

  1. Patients on low-dose amiodarone are at increased risk of the following adverse events compared with placebo:
    • discontinuing the drug (NNH = 14 at 12 months)
    • neurological disturbance (NNH = 55 at 12 months)
    • bradycardia (NNH = 62 at 12 months)
    • thyroid disease (NNH = 79 at 12 months)
    • skin rash (NNH = 100 at 12 months)
    • visual complaints (NNH = 400 at 12 months)
Vorperian et al: Journal of the American College of Cardiology 1997; 30 (3): 791-798
Expires November 2003

The study

Systematic review of double-blinded controlled trials of
  • Patients: any patient
  • Intervention: on low-dose oral amiodarone (400 mg/day or less) compared with placebo
  • Outcome: adverse event


    • Articles found in all using MEDLINE, 1966 to 1996 (search terms: not given ) and references and review articles were also searched.

    Selection criteria: detailed in text
    Appraisal criteria: detailed in text
    Articles excluded if:
    • cross-over design
    • follow-up <12 months


    Four trials found on 1465 patients (738 on amiodarone, 727 on placebo)

    The evidence

    Outcome Time to outcome CER OR
    (95% CI)    		 NNT
    (95% CI)
    thyroid disease 12 months /
    (0.4%)    		 4.23
    (2.04 to 8.75)     		79
    (33 to 240)
    neurological (tremor, gait disturbance, numbness) 12 months /
    (1.9%)    		 2.00
    (1.09 to 3.70)     		55
    (21 to 600)
    skin rash 12 months /
    (0.7%)    		 2.48
    (1.05 to 6.17)     		100
    (29 to 2900)
    visual complaints 12 months /
    (0.1%)    		 3.43
    (1.22 to 9.64)     		400
    (120 to 4500)
    bradycardia 12 months /
    (1.4%)    		 2.18
    (1.11 to 4.27)     		62
    (23 to 660)
    drug discontinued 12 months /
    (15.4%)    		 1.60
    (1.22 to 2.09)     		14
    (8 to 36)

    • There was no clear increase in hepatic, GI or pulmonary adverse outcomes on low-dose amiodarone compared with placebo.

    Comments

    1. How do these rates of adverse events compare with other antiarrhythmics?

    Citation

    1. Vorperian VR, Havighurst TC, Miller S, et al: Adverse effects of low-dose amiodarone: a meta-analysis. Journal of the American College of Cardiology 1997; 30 (3): 791-798
    Contributor: Chris Ball and Clare Wotton, November 2000
    Reviewer:

    Clinical Question.
    Patient any
    Intervention or Exposure amiodarone
    Comparison placebo
    Outcome adverse effects