Prevalence of QT interval prolonging drug–drug interactions (QT-DDIs) in psychiatry wards of tertiary care hospitals in Pakistan: a multicenter cross-sectional study

Abstract

Background QT prolongation and associated arrhythmias, torsades de pointes (TdP), are considerable negative outcomes of many antipsychotic and antidepressant agents frequently used by psychiatric patients. Objective To identify the prevalence, levels, and predictors of QT prolonging drug-drug interactions (QT-DDIs), and AZCERT (Arizona Center for Education and Research on Therapeutics) classification of drugs involved in QT-DDIs. Setting Psychiatry wards of three major tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan. Method This was a multicenter cross-sectional study. Micromedex DrugReax was used for identification of QT-DDIs. TdP risks were identified by the AZCERT classification. Multivariate logistic regression analysis was performed to identify predictors of QT-DDIs. Main outcome measure Prevalence of QT-DDIs (overall, age-wise and gender-wise) and their levels of severity and documentation; AZCERT classes of drugs involved in QT-DDIs; and odds ratios for predictors of QT-DDIs. Results Of 600 patients, 58.5% were female. Median age was 25 years (IQR = 20-35). Overall 51.7% patients had QT-DDIs. Of total 698 identified QT-DDIs, most were of major-severity (98.4%) and fair-documentation (93.7%). According to the AZCERT classification, 36.4% of the interacting drugs were included in list-1 (known risk of TdP), 26.9% in list-2 (possible risk of TdP) and 27.5% in list-3 (conditional risk of TdP). Drugs commonly involved in QT-DDI were olanzapine (n = 146), haloperidol (138), escitalopram (122), risperidone (91), zuclopenthixol (87), quetiapine (n80) and fluoxetine (74). In multivariate logistic regression analysis, QT-DDIs were significantly associated with 6-7 prescribed medications (p = 0.04) and >7 medications (p = 0.03). Similarly, there was significant association of occurrence of QT-DDIs with 2-3 QT drugs (p < 0.001) and >3 QT drugs (p < 0.001). Conclusion A considerable number of patients are exposed to QT-DDIs in psychiatry. There is a need to implement protocol for monitoring the outcomes of QT-DDIs.

Evaluation of Potential Drug-Drug Interactions among Patients of the Nephrology and Kidney Transplant Wards of a Major Teaching Hospital in Iran

“…The reliability rating for more than half of the pDDIs (55.9%) was fair; this was similar to Khan et al in which the majority of the pDDIs were fair in reliability [19] Our findings show about half of pDDIs have a theoretical basis for inferring the possibility of an ADE, but these interactions have not been substantiated in clinical practice. However, the importance of pDDIs with fair or poor documentation should not be ignored and should be evaluated by a specialist because they may result in severe consequences in the case of potentiation by similar interactions or predisposing risk factors.…”

Content Validation of an Algorithm for the Assessment, Management and Monitoring of Drug-Induced QTc Prolongation in the Psychiatric Population

“…7 Studies have shown that people diagnosed with a SMI are often on polypharmacy making them more vulnerable to QTc-prolonging drug-drug interactions. [8][9][10] Furthermore, because of an ever-increasing number of medications available, clinicians may face difficulties on how to assess, manage, monitor and refer patients at risk of QTc prolongation. Poor access to health care facilities may also increase the risk of adverse outcomes derived from the use of QT prolonging drug combinations, further contributing to the high premature mortality observed in the SMI population.…”

Coprescription of QT interval-prolonging antipsychotics with potentially interacting medications in Thailand

“…17 A recent study from Pakistan reported that 51.7% of patients in the psychiatric wards of three hospitals in 2015–2016 were exposed to potential QT-prolonging drug interactions. 18…”

“…A limited number of studies have focused on QT prolongation associated with drugs interacting with antipsychotics. 16–18 An analysis of Medicaid data during 2000–2003 in patients with schizophrenia in the US showed that 23% of the patients were exposed to potentially harmful drug interactions. 16 The majority of the interactions occurred with prescriptions from the same physician or pharmacies.…”