Interactions with Potassium
Angiotensin-Converting Enzyme (ACE) Inhibitors
ACE inhibitors may produce hyperkalemia, particularly when used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs), potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, and in patients with autonomic neuropathy, adrenal insufficiency, renal impairment, and diabetes mellitus (Howes 1995; Shionoiri 1993). For this reason, potassium supplements may not be warranted in patients taking these medications; serum potassium levels should be monitored closely.
Beta-Adrenergic Blockers
Beta-adrenergic blockers may elevate potassium levels by promoting a redistribution of this electrolyte (Preston et al. 1998). Potassium levels should be monitored in patients taking these medications, particularly in patients with compromised renal function.
Cyclosporine
Cyclosporine may induce hyperkalemia by decreasing renal excretion of potassium and interfering with aldosterone production or secretion (Preston et al. 1998). Potassium levels in patients on cyclosporine therapy, particularly those with renal insufficiency, should be monitored carefully.
Digoxin
Hypokalemia increases the risk of cardiac glycoside toxicity (Whang et al. 1985). Normal levels of potassium should be maintained during digoxin treatment.
Heparin
Heparin may contribute to hyperkalemia by impairing renal excretion of potassium as a result of interference with aldosterone production or secretion (Preston et al. 1998). Serum potassium levels should be monitored in patients on heparin therapy, especially if potassium supplements are added to the medication regimen.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
NSAIDs can affect renal function and decrease potassium excretion (Brater 1999). Hyperkalemia can occur in patients with mild renal insufficiency or normal renal function. Ibuprofen may increase the risk for renal insufficiency and cause hyperkalemia in patients that are over 76 years old, on diuretic therapy, or who have cirrhosis and renal vascular disease (Blackshear et al. 1983; Poirier 1984; Whelton, et al. 1990). Individuals taking these medications should avoid potassium supplements.
Trimethoprim; Co-Trimoxazole
Standard doses of trimethoprim monotherapy as well as trimethoprim combined with sulfamethoxazole have been shown to cause hyperkalemia in a significant number of patients treated for various infections (Alappan et al. 1996; Perazella 2000). Patients treated with these medications should be closely monitored for hyperkalemia, especially those with renal insufficiency (Alappan et al. 1996).
Drug Monographs
References
Alappan R, Perazella MA, Buller GK, et al. Hyperkalemia in hospitalized patients treated with trimethoprim-sulfamethoxazole. Ann Intern Med. 1996;124(3):316-320.
Blackshear JL, Davidman M, Stillman MT. Indentification of risk for renal insuffciency from nonsteroidal anti-inflammatory drugs. Arch Intern Med. 1983;143(6):1130-1134.
Brater DC. Effects of nonsteroidal anti-inflammatory drugs on renal function: focus on cyclooxygenase-2-selective inhibition. Am J Med. 1999;107(6A):65S-70S.
Howes LG. Which drugs affect potassium? Drug Saf. 1995 Apr;12(4):240-244.
Perazella MA. Trimethoprim-induced hyperkalemia: clinical data, mechanism, prevention and management. Drug Saf. 2000;22(3):227-236.
Poirier TI. Reversible renal failure associated with ibuprofen: case report and review of the literature. Drug Intell Clin Pharm. 1984;18(1):27-32.
Preston RA, Hirsh MJ MD, Oster, JR MD, et al. University of Miami Division of Clinical Pharmacology therapeutic rounds: drug-induced hyperkalemia. Am J Ther. 1998 Mar; 5(2):125-132.
Shionoiri H. Pharmacokinetic drug interactions with ACE inhibitors. Clin Pharmacokinet. 1993 Jul;25(1):20-58.
Whang R, Oei TO, Watanabe A. Frequency of hypomagnesia in hospitalized patients receiving digitalis. Arch Intern Med. 1985;145(4):655-656.
Whelton, A, Stout RL, Spilman PS, Klassen DK. Renal effects of ibuprofen, piroxicam, and sulindac in patients with asymptomatic renal failure. A prospective, randomized, crossover comparison. Ann Intern Med. 1990;112(8):568-576.