An isolated report describes acute hyperkalaemia and cardiovascular collapse when dantrolene was given to a patient taking verapamil,but not when he was subsequently given nifedipine. Animal studies have found similar effects with combination of dantrolene and verapamil or diltiazem, but not with nifedipine oramlodipine.
Clinical evidence,mechanism, importance and management
A case report describes a 60-year-old man with insulin-dependent diabetes undergoing a right hemicolectomy. Due to inoperable coronary artery disease,which was causing angina pain he was taking verapamil 80mg three times daily. On morning of surgery he was given verapamil 80mg with his pre-operative sedation and then, 2 hrs later at start of surgery, he was given intravenous dantrolene 220mg over 30 minutes, because he was known to have previously had malignant hypertension. After surgery,when he was on ITU, it was found that his potassium had risen from 4.6 mmol/L before surgery to 6.1 mmol/L at end of surgery (about 90 minutes after dantrolene infusion). He was given 10 units of insulin,but an hour later his potassium was 7.1 mmol/L. He was given more insulin,but then developed metabolic acidosis and some cardiac depression, which resolved when he was given bicarbonate and hetastarch 5%. He received three further doses of dantrolene without incident (See reference number 1).
The authors of report attributed effects seen to an interaction between verapamil and dantrolene. They note that hyperkalaemia has been seen following dantrolene infusions, but case they cite was in response to suxamethonium, and UK and US manufacturers of dantrolene do not include hyperkalaemia as an adverse effect (See reference number 2,3). Nevertheless, overall picture is that hyperkalaemia, of whatever cause, can apparently increase myocardial depression caused by verapamil (See reference number 4,5). This case seems to be only report of an interaction between verapamil, and several factors do not make this a clear-cut case of an interaction. However,hyperkalaemia and cardiovascular collapse have been seen in pigs and dogs given dantrolene and verapamil,(See reference number 6-8) and so an interaction cannot be completely ruled out. The manufacturers of dantrolene contraindicate its use in patients taking verapamil (See reference number 2,3). One animal study suggests that diltiazem may interact similarly,(See reference number 9) and combination of diltiazem and dantrolene may also cause ventricular arrhythmias (See reference number 10). The manufacturers of diltiazem similarly contraindicate concurrent use (See reference number 10). Studies suggest that amlodipine(See reference number 4) and nifedipine(See reference number 9) do not interact and they may therefore be safer alternatives. In case above(See reference number 1) patient later underwent further surgery while taking nifedipine, without any significant adverse effect (although potassium was moderately raised to 5.4 mmol/L).
Rubin AS,Zablocki AD. Hyperkalemia, verapamil, and dantrolene. Anesthesiology (1987)66, 246–9.
Dantrium Intravenous (Dantrolene sodium). Procter & Gamble Pharmaceuticals UK Ltd. UKSummary of product characteristics,April 2005.
Dantrium Intravenous (Dantrolene sodium). Procter & Gamble Pharmaceuticals. US Prescribing information,May 2001.
Freysz M,Timour Q, Bernaud C, Bertrix L, Faucon G. Cardiac implications of amlodipinedantrolene combinations. Can J Anaesth (1996) 43, 50–5.
Jolly SR,Keaton N, Movahed A, Rose GC, Reeves WC. Effect of hyperkalemia on experimental myocardial depression by verapamil. Am Heart J (1991) 121, 517–23.
Lynch C,Durbin CG, Fisher NA, Veselis RA, Althaus JS. Effects of dantrolene and verapamil on atrioventricular conduction and cardiovascular performance in dogs. Anesth Analg (1986) 65, 252–8.3954091
San Juan AC,Port JD, Wong KC. Hyperkalemia after dantrolene administration in dogs. Anesth Analg (1986) 65, S131.
Saltzman LS,Kates RA, Corke BC, Norfleet EA, Heath KR. Hyperkalemia and cardiovascular collapse after verapamil and dantrolene administration in swine. Anesth Analg (1984) 63, 473–8.
Saltzman LS,Kates RA, Norfleet EA, Corke BC, Heath KS. Hemodynamic interactions ofdiltiazem-dantrolene and nifedipine and nifedipine-dantrolene. Anesthesiology (1984) 61, A11.
Tildiem Retard (Diltiazem hydrochloride). Sanofi-Aventis. UK Summary of product characteristics,April 2004.