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John R. Horn, PharmD, FCCP, and Philip D. Hansten, PharmD TrimeThoprim-induced
Tmp plus aceis or arBs
hyperkalemia
The concurrent administration of other may produce an additive risk of hyper- Trimethoprim (TMP)—sulfamethoxa- drugs that can increase serum potassium kalemia. Other risk factors for the devel- can lead to a large increase in potassium opment of hyperkalemia include renal monly used antibiotic combination. concentrations. In a nested, case-control dysfunction, diabetes, advanced age, and study of patients older than 66 years the use of salt substitutes containing potas- tions involve the ability of sulfamethoxa- chrome P450 2C9 substrates, such as tors (ACEIs) or angiotensin warfarin or oral hypoglycemic agents. receptor blockers (ARBs), the component eral of these risk factors and The TMP component has several risk of hospital admission for unique properties that can lead to drug hyperkalemia within 14 days has several For example, a patient with dia- interactions. One of these properties is its of taking TMP, amoxicillin, ability to function like amiloride in the dis- tal portion of the renal tubule. TMP inhib- its the uptake of sodium by the epithelial Patients taking TMP—sul- cell sodium channels in the distal tubule. famethoxazole had nearly a This prevents the reabsorption of sodium 7-fold increase in hospitaliza- lead to drug patient develops a urinary tract from the urine but also alters the electrical tions for hyperkalemia com- interactions. infection, TMP—sulfamethox- balance of the tubular cell. As a result, pared with patients taking the epithelial cell reduces the amount of amoxicillin.4 None of the other antibiotics additive effects of these hyperkalemia risk potassium transported from the cell into studied increased the risk of hyperkale- the tubular lumen and thus into the urine. mia. The use of double-strength TMP tomatic hyperkalemia. The selection of an The result is a reduction in the amount of (160 mg) was associated with a higher risk alternate antibiotic or the lowest effective potassium excreted in the urine and an of hyperkalemia than the single-strength dose of TMP should be considered in this accumulation of serum potassium.1 TMP occurred in patients being treated paTienTs wiTh mulTiple risk
be early signs of hyperkalemia, but moni- for Pneumocystis carinii, for which large FacTors
doses of TMP are typically used.2 Most Potassium-sparing diuretics that can tion is the preferred approach to prevent patients who receive TMP will have a increase serum potassium concentra- serious cardiac events. Early monitoring modest increase in potassium during the tions include spironolactone, eplerenone, becomes more critical in patients with
first 5 to 7 days of treatment.3 Because amiloride, and triamterene. These drugs multiple risk factors, both pharmacologic
there are a number of other drugs that also may interact with TMP and increase the and physiologic, for the development of
may increase serum potassium, the risk risk of patients developing hyperkalemia. hyperkalemia. PT
of TMP-induced hyperkalemia increases It is known that combinations of potas-
with concurrent drug use.
sium-sparing diuretics and ACEIs (eg, enalapril, benazepril, fosinopril, lisinopril) Drs. Horn and Hansten are both professors of pharmacy .com
at the University of Washington School of Pharmacy. For an electronic version of this article, including references, For a list of references, go to www.PharmacyTimes.com/ if any, visit www.hanstenandhorn.com. 46 n 02.11 | Pharmacy Times www.PharmacyTimes.com

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