Prevalence of Co-Trimoxazole Induced Hyperkalemia in Chronic and Acute Users in a Tertiary Teaching Hospital
Authors: Al-Adawi Rana Moustafa , Jassim Zainab Malik 
Published: July 2019

Septrin

Objective

The primary purpose of this research is to evaluate the risk of hyperkalemia in patients receiving co-trimoxazole. The secondary purpose is to detect the changes of potassium levels from baseline to 7, 14, 21, and 30 days, determine the association between co-trimoxazole dose and potassium level and examine the relationship between renal function and hyperkalemia.

Methods

The approach was through retrospective observation of all patients treated with co-trimoxazole during Jan 2012 till Jan 2013.

Key finding

There was no significant correlation between co-trimoxazole doses and hyperkalemia (29% in 480 mg, 31.6% in 960 and 19.4% in 1920 mg; p = 0.129) within each dose group, however, around 62% of hyperkalemia cases were associated with significant increase in serum creatinine (p = 0.00). The highest mean change of potassium level in once daily dosing was at “baseline–7 days” interval, while it was highest at “baseline-30 days” interval in every other day dosing. However; none of the changes from baseline to 7, 14, 21 and 30 days was found to be significant. 40.9% of the studied patients were female and 59.1% were male and the mean age 54 ±  15 was significant higher in hyperkalemia group compare to 42.6 ±  20 in non hyperkalemia group (p = 0.001).

Conclusion

Although many patients taking co-trimoxazoledeveloped Hyperkalemia, the effect of age, dose, renal function and the use of other concomitant medications can't be ignored.

Keywords

co-trimoxazole, hyperkalemia, side effect

Objective

The primary purpose of this research is to evaluate the risk of hyperkalemia in patients receiving co-trimoxazole. The secondary purpose is to detect the changes of potassium levels from baseline to 7, 14, 21, and 30 days, determine the association between co-trimoxazole dose and potassium level and examine the relationship between renal function and hyperkalemia.

Methods

The approach was through retrospective observation of all patients treated with co-trimoxazole during Jan 2012 till Jan 2013.

Key finding

There was no significant correlation between co-trimoxazole doses and hyperkalemia (29% in 480 mg, 31.6% in 960 and 19.4% in 1920 mg; p = 0.129) within each dose group, however, around 62% of hyperkalemia cases were associated with significant increase in serum creatinine (p = 0.00). The highest mean change of potassium level in once daily dosing was at “baseline-7 days” interval, while it was highest at “baseline-30 days” interval in every other day dosing. However; none of the changes from baseline to 7, 14, 21 and 30 days was found to be significant. 40.9% of the studied patients were female and 59.1% were male and the mean age 54 ±  15 was significant higher in hyperkalemia group compare to 42.6 ±  20 in non hyperkalemia group (p = 0.001).

Conclusion

Although many patients taking co-trimoxazoledeveloped Hyperkalemia, the effect of age, dose, renal function and the use of other concomitant medications can't be ignored.

Keywords

co-trimoxazole, hyperkalemia, side effect Co-trimoxazole is an antibacterial drug that consists of two active ingredients, sulphamethoxazole and trimethoprime.

Sulphamethoxazole acts by inhibition of synthesis of dihydrofolateby bacterial cell through inhibition of Bara- amino-benzoic acid result in inhibition of bacterial growth, while the trimethoprimeact by blocking of tetrahydrofolate production by reversible inhibition the bacterial dihydrofolate reductase (DHR), resulting in inhibition of bacterial folic acid production which is necessary for biosynthesis of purine which is essential component of many bacterial nucleic acid production, [1][2].

Co-trimoxazole used with wide range of infections like: Chronic bronchitis, Cyclosporiasis (unlabeled use), Granuloma inguinale(donovanosis) (unlabeled use), Isosporiasis (Isospora belliinfection) in HIV-positive patients (unlabeled use; CDC, 2009), Meningitis (bacterial), Nocardia, Osteomyelitis due to MRSA (unlabeled use), Pneumocystis jirovecii pneumonia (PCP), Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment in HIV-positive patients (CDC, 2009), Prosthetic joint infection (unlabeled use), Q fever (unlabeled use), Septic arthritis due to MRSA (unlabeled use), Shigellosis, Skin/soft tissue infection due to community-acquired MRSA (unlabeled use), Stenotrophomonas maltophilia (ventilator-associated pneumonia), Toxoplasma gondii encephalitis (unlabeled use; CDC, 2009), Travelers’ diarrhea AND Urinary tract infection [1]. Co-trimoxazole has many adverse drug reactions including Nausea, vomiting, anorexia, skin rash, urticaria, photosensitivity, SJS and hypokalemia. Each ADR has different mechanism some are due to allergic reaction while others are due to toxic metabolite, where the expected mechanism of hyperkalemia is the capability of trimethoprime to block the renal tubule secretion of potassium, due it's structural similarity to the potassium sparing diuretics, resulting in increase in serum potassium level, (ref: AnIm 124:316, 1996). Co-administration of ACE-I or ARBs was found to be associated with 7 fold increment of hyperkalemiainduced hospitalization. The same ADR has reported with potassium sparing diuretics, however the mechanism of hyperkalemia is due to decreasing the serum concentration of Aldosterone which reabsorb potassium at distal renal tubule [7].

Hyperkalemia is defined as serum potassium level above the normal range which 3.5–5.5 mEq/L, The symptoms usually is asymptomatic or associated with non-specific symptoms, like nausea, vomiting, weakness, fatigue or palpitation, unless the potassium level reaches 7 mEq/L, where some neurological and hemodynamic disturbance may occur, while increasing the potassium level to 8 mEq/L can be fatal as it may cause respiratory paralysis and cardiac arrest [3][4]. Hyperkalemia is a serious side effect of co-trimoxazole and some times evidence it is fatal. Therefore, we are going to retrospectively investigate potassium level in patients receiving co-trimoxazole for acute and chronic periods for all indications either as a treatment or prophylaxis, giving the focus on the rate of this under estimated side effect, in order to clearly identify the high risk patients and recommend the proper monitoring.

Conclusion

Around quarter of patients taking co-trimoxazole developed hyperkalemia; the effect of renal function, advanced age and the use of other concomitant medications that affect the potassium level put patients at higher risk of developing hyperkalemia. Incidence of hyperkalemia was more in daily rather than every other day dosing as well more in 960 mg daily dose comparing with other doses (480 mg and 1920 mg). We identified patients with high risk factor like renal impaired patients, advance aged, or patients who are receiving ACE-I, ABRs during the co-trimoxazole course are essential to minimize the incidence of such a severe adverse drug reaction of one of the broad spectrum antibiotic with various indications.