An isolated report describes clonazepam toxicity, which was attributed to concurrent use of amiodarone.
Clinical evidence,mechanism, importance and management
A 78-year-old man with congestive heart failure and coronary artery disease was taking furosemide,potassium, and calcium supplements, a multivitamin preparation, and amiodarone 200mg daily for sustained ventricular tachycardia. Two months after clonazepam 500 micrograms at night was added to treat restless leg syndrome he developed slurred speech,confusion, difficulty in walking, dry mouth and urinary incontinence. This was interpreted as clonazepam toxicity. The problems cleared when clonazepam was stopped. The authors of report suggest that amiodarone may have inhibited oxidative metabolism of clonazepam by liver, thereby allowing it to accumulate. They also point out that this patient may have been more sensitive to these effects because of a degree of hypothyroidism caused by amiodarone. Hypothyroidism is known to decrease metabolism of drugs that undergo oxidative metabolism by liver (See reference number 1).
1. Witt DM,Ellsworth AJ, Leversee JH. Amiodarone–clonazepam interaction. Ann Pharmacother (1993) 27, 1463–4.