Can Amiodarone Cause Diarrhea?
Yes, diarrhea is a recognized adverse effect of amiodarone, though it occurs less frequently than other gastrointestinal side effects and is not typically a reason for drug discontinuation.
Evidence from Guidelines and Drug Labels
The 2017 AHA/ACC/HRS guidelines do not list diarrhea among the common adverse effects of amiodarone in their comprehensive antiarrhythmic medication table, which notably omits gastrointestinal effects for amiodarone while documenting them for other agents like propranolol, quinidine, and sotalol 1. This suggests diarrhea is not among the most clinically significant adverse effects of amiodarone compared to other antiarrhythmics.
The FDA drug label for amiodarone lists diarrhea as a treatment-emergent adverse event that occurred in less than 2% of patients receiving intravenous amiodarone in controlled and uncontrolled studies 2. The label also notes that vomiting (sometimes fatal) has been reported, and emphasizes the importance of correcting electrolyte disturbances in patients experiencing severe or prolonged diarrhea, particularly when receiving concomitant diuretics 2.
Clinical Context and Frequency
In clinical practice, gastrointestinal side effects with amiodarone are common overall, but diarrhea is not the predominant manifestation 3. One early study found that 56 of 70 patients (80%) experienced gastrointestinal side effects, with constipation being the most common—not diarrhea 3. This pattern suggests that while diarrhea can occur, constipation is actually the more typical gastrointestinal complaint with amiodarone therapy.
Clinical Significance and Management
Diarrhea from amiodarone rarely necessitates drug discontinuation, as it is not listed among the adverse effects that commonly lead to stopping therapy 2. The most common reasons for discontinuing amiodarone are hypotension (1.6%), cardiac arrest (1.2%), ventricular tachycardia (1.1%), and cardiogenic shock (1%), not gastrointestinal effects 2.
Important Caveats:
If severe or prolonged diarrhea develops, electrolyte monitoring becomes critical 2. Hypokalemia and hypomagnesemia can exaggerate QTc prolongation and increase the risk of torsades de pointes, which is particularly relevant given the patient's potential hypocalcemia mentioned in the context 2.
Diarrhea should not be automatically attributed to amiodarone without considering drug interactions 2. Many medications can cause gastrointestinal disturbances, and amiodarone interacts with numerous drugs that might independently cause diarrhea 4.
The timing of symptom onset matters 5. Most amiodarone side effects develop after weeks to months of therapy due to the drug's unique pharmacokinetics, with a half-life averaging 58 days 1, 5. Diarrhea occurring immediately after starting amiodarone is less likely to be drug-related than symptoms developing after prolonged exposure.
Monitoring Recommendations
While diarrhea itself does not require specific monitoring beyond standard amiodarone surveillance, the American Academy of Family Physicians recommends baseline and every-six-month monitoring of liver function tests, thyroid function, and a directed history and physical examination 6. If diarrhea is severe or persistent, additional attention to electrolyte balance (particularly potassium, magnesium, and calcium given the patient's history) is warranted 2.