Discussion

Almost one-third of patients developed hyperkalemia, with age >60 years was identified as high-risk. However, dosing frequency did not significantly influence hyperkalemia incidence. All patients with co-trimoxazole induced hyperkalemia were managed with the medical treatment including (stop the offending agents, shifting extracellular potassium into the cells and excreting the potassium out of the body) 2. No cardiac arrests or hemodialysis was required secondary to the refractory hyperkalemia.
A previous study by Fralick et al. affirmed that co-trimoxazole use with an ACE-I or ARB was associated with increased risk of sudden death due to severe hyperkalemia [OR 1.38: 95%CI (1.09 to 1.76)] when compared with amoxicillin 3. Noteworthy, the patient population of this study was older adults (>66 years); hence, the incidence of hyperkalemia was more pronounced. Additionally, a nested case-control study of a cohort of older patients (>66 years) concluded that the potential for hyperkalemia-associated hospitalization was increased seven-fold among older patients receiving ACE-Is or ARBs (adjusted OR, 6.7; 95% CI, 4.5-10.0) 5. Furthermore, among the β-blocker users, Weir et al. found that the rate of hospitalization among co-trimoxazole users was considerably higher when compared to amoxicillin (OR 5.1; 95% CI 2.8 to 9.4) 6. Studies have also demonstrated that older people receiving co-trimoxazole in combination with other medication known to contribute to hyperkalemia are at higher risk of hyperkalemia, 3,5 which is consistent with our findings.
The co-administration of immunosuppressants was significantly associated with increased incidence of hyperkalemia, either alone or in combination with β-blockers. Several studies and case reports found that tacrolimus and cyclosporine cause elevation in plasma potassium concentration, which can be further augmented by co-administration of ACE-I or ARBs4,7.
A review by Perazella et al. reported that co-trimoxazole can cause hyperkalemia regardless of dose 2. However, a retrospective study showed that hyperkalemia incidence was more frequent with the higher doses of co-trimoxazole 8. In this study, the results failed to confirm a correlation between hyperkalemia incidence and the total daily doses (once daily or twice daily of the DS 800/160 mg) of co-trimoxazole.
There is some evidence that pharmacists have a crucial role in monitoring drug therapy to detect and prevent ADRs 9. Hence, pharmacists can contribute to active monitoring of potassium levels and additionally educating patients on the potential for interactions with other medication, conditions and food.
This study has the inherent limitations of a retrospective study design in that only the specific data collected and recorded during routine clinical practice could be captured. While we excluded those with renal impairment, hyperkalemia could be a result of other factors such as excess dietary potassium intake, electrolyte imbalance, and other factors. The limited sample size may have meant that the study was underpowered for the comparison made hence the results should be interpreted with caution. There may also be issues with generalizability to other populations and settings. Furthermore, the study was completed several years earlier, although clinical practice is relatively unchanged hence the data and findings remain valid. There is a need for prospective studies with more frequent monitoring of potassium and serum creatinine levels.