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.