Prescribed medications are a primary cause of hyperkalemia in 35-75% of hospitalized patients.High-risk patients are those with underlying renal impairment, hypoaldosteronism, and taking combination of drugs that can increase potassium level. Several classes of medications can induce hyperkalemia by different mechanisms.Recognition and close monitoring of those medications is necessary to reduce morbidity and mortality related to hyperkalemia.

Drug-induced hyperkalemia may range from asymptomatic to life threatening.Symptoms are mainly related to cardiac and muscular functions. The most serious manifestations include muscle weakness or paralysis, respiratory failure, cardiac conduction abnormalities, and cardiac arrhythmias.

There are 3 major mechanisms of drug-induced hyperkalemia:
  • Impaired renal excretion of potassium
  • Extracellular potassium shift
  • Excessive potassium intake.
Drug classes that are known to cause hyperkalemia are listed below (table 1).

Table 1. Drugs known to cause hyperkalemia and their mechanism of action1,2
Impaired renal excretion
Extracellular potassium shift Excessive potassium intake
ACE inhibitors, ARBs
Direct renin inhibitors
Aldosterone agonists
Potassium-sparing diuretics
Trimethoprim, pentamidine
Cyclosporine, tacrolimus
Heparin, LMWH
β blockers
Digoxin intoxication
Intravenous cationic amino acids (lysine, arginine)
Salt substitutes
Penicillin G
Stored blood products
Drug-induced hyperkalemia can be prevented by slow dose titration and close monitoring of serum potassium within the first week of therapy and after each dose adjustment. NSAIDs, especially chronic use, should be avoided in the elderly, dehydrated patients, patients with renal insufficiency, and those taking other drugs known to increase potassium. Alternative therapies with non-NSAID analgesics or topical agents should be recommended.

Management of acute hyperkalemia should be guided by the serum potassium level and severity of symptoms.4,5

Treatment Mechanism Onset/
40-80 mg IV
Increases renal excretion of potassium 15 min./
4 hours
Monitor volume status
Sodium polystyrene sulfonate (SPS)
50 mg PO or rectal
Removes potassium from the gut in exchange of sodium 1-2 hours/ 4-6 hours May lead to sodium retention
Regular insulin
5-10 units IV with 50 ml of 50% dextrose
Shifts potassium from the vascular space into the cells 30 min./
4-6 hours

Lower dose recommended in renal insufficiency
Monitor for hypoglycemia
Albuterol 0.5 mg IV
or 10-20 mg via nebulizer over 10 minutes
Shifts potassium intracellularly 30 min./
2-4 hours

Monitor for tachycardia
Potentially ineffective in patients receiving beta-blockers
Sodium bicarbonate
50-100 mEq IV bolus over 5 minutes
Shifts potassium intracellularly 5-10 min./
2 hours
Used in patients with metabolic acidosis
Calcium gluconate
15-30 mL of 10% solution
Membrane potential stabilizer 1-3 min./
30 min.

Goal: normalization of ECG changes
No effect on potassium level
Hemodialysis Removes potassium from the body Immediate Used in refractory hyperkalemia and
renal failure

  1. Perazella MA. Drug-induced hyperkalemia: old culprits and new offenders. Am J Med. 2000; 109(4):307–14.
  2. Ben Salem CB, Badreddine A, Fathallah N,et al. Drud-induced hyperkalemia. Drug Saf. 2014; 37:677-692.
  3. Noize P, Bagheri H, Durrieu G, et al. Life-threatening drug-associated hyperkalemia: a retrospective study from laboratory signals. Pharmacoepidemiol Drug Saf. 2011; 20(7):747–53.
  4. Rossignol P, Legrand M, Kosiborod M, et al. Emergency management of severe hyperkalemia guidelines for best practice and opportunities for the future. Pharmacol Res. 2016; 113(ptA):585-591.
  5. Weisberg LS. Management of severe hyperkalemia. Crit Care Med. 2008; 36(12):3246-3251.