The patient seemed well otherwise and was able to tolerate food and fluids.

Since the patient was taking TMP-SMX and was on lisinopril, there was a possibility that hyperkalemia could be responsible for the patient’s symptoms. STAT labs including a CBC and CMP were drawn and sent to the lab. The patient was discharged from Urgent Care and advised that she would be called with the lab results in a few hours.

The results were received 2 hours later with unremarkable CBC. Potassium levels were noted to be 9.5 mmol/L (normal: 3.5 to 5.2 mmol/L), creatinine was within normal limits.

The patient was advised to go to the nearest emergency department for emergent treatment of hyperkalemia. Repeat potassium was 9.8mmol/L. Nephrology was consulted and diagnosed hyperkalemia induced by TMP-SMX with concomitant use of lisinopril.

At 3 day follow up the patient reported that the rash was subsiding, and she was feeling better overall.

 Among older patients treated with ACEIs or ARBs, the use of TMP-SMX is associated with a major increase in the risk of hyperkalemia-associated hospitalization relative to other antibiotics. Alternate antibiotic therapy should be considered in these patients when clinically appropriate.

 Trimethoprim-sulfamethoxazole can interact with a variety of drugs that may require adjustment of therapy and more frequent monitoring. Interacting drugs include oral anticoagulants such as warfarin, cyclosporine, oral hypoglycemics, rifampin, dapsone, phenytoin, methenamine, and possibly angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).

Trimethoprim may enhance the hyperkalemic effect of angiotensin-converting enzyme (ACE) inhibitors. Serum potassium should be monitored closely if this combination is used. Consider using an alternative to TMP-SMZ when possible, particularly in patients with other risk factors for hyperkalemia (e.g., renal dysfunction, older age, use of other drugs or supplements that can increase potassium, use of higher-dose TMP-SMZ, etc.). Hyperkalemia is an established, though often unrecognized, side effect of trimethoprim.

Trimethoprim appears to reduce renal potassium excretion, acting similarly to the structurally similar potassium-sparing diuretic amiloride. Patients at high risk of developing trimethoprim-induced hyperkalemia appear to include the higher dose trimethoprim, older age, renal insufficiency, use of prednisone, and concurrent use of drugs that can cause or exacerbate hyperkalemia (such as ACEIs, ARBs, aldosterone antagonists, etc.).

Hyperkalemia is a medical emergency that can result in life-threatening arrhythmia. Identification is imperative and treatment should be swift. If suspected or identified an EKG should be performed immediately to determine if arrhythmia and cardiac arrest is impending. Treatment may include calcium, insulin, glucose, cation exchange resins, diuretics, and in severe cases, hemodialysis. See table below. Any inciting medications or combinations of medications should be discontinued.