(065) Potential Pharmacodynamic and Pharmacokinetic Drug-Drug Interactions(DDIs) of QT Prolonging Drugs in a cohort of Psychiatry Patients

Publication Number: 1061

Background: At least 170 approved drugs including psychotropics are linked to QT prolongation, which can lead to serious adverse drug reactions (ADRs), such as Torsade de Pointes (TdP).

Objectives: The aim of this study was to analyze the prevalence and type of potential pharmacokinetic, and pharmacodynamic drug-drug interactions (DDIs) between QT-prolonging drugs in psychiatry.

Methods: This prospective cross-sectional study was carried out in the psychiatry OPD at All India Institute of Medical Sciences (AIIMS), Rishikesh, Uttarakhand, India from October 1, 2017 to September 30, 2018 using the relevant prescriptions (i.e., the OPD case record forms and treatment sheets).
Patients were screened for intake of QT-prolonging drugs. For each patient, the entire medication list was analyzed for the potential interactions, with particular attention on the high-risk QT-prolonging ones. Arizona Center for Education and Research on Therapeutics (AzCERT) QT drug lists were used to classify TdP risks of psychotropic and other medications.
Statistical analyses provided measures of central tendencies and dispersion for continuous data and number of observations and proportions for categorical variables.

Results: One thousand three hundred twenty-six (1326) patients attending the psychiatry OPD during the study period were scrutinized. Seven hundred fifty-one (751) patients (56.6%) were males whereas 575 (43.4%) were females in our study. Of the 1326 patients, 636 patients (47.9%) were identified as receiving interacting medications with the potential ability to induce TdP. Nine hundred seventeen (917) interacting medication pairs with potential torsadogenic risk were encountered. Most of the identified drug-drug interactions associated with potential TdP risk could interact pharmacodynamically rather than pharmacokinetically. The most frequent drug-drug interacting pairs with a pharmacodynamic basis were escitalopram-olanzapine (68), risperidone-domperidone (46), fluoxetine-olanzapine (36), haloperidol-risperidone (35), and olanzapine-pantoprazole (34). A few potential torsadogenic interacting pairs with a pharmacokinetic basis were also identified, viz., omeprazole-amitriptyline (5), omeprazole-sertraline (3), ciprofloxacin-amitriptyline (2), ketoconazole-imipramine (2), and cimetidine-amitriptyline (1).

Conclusions: Physicians should be aware of the cardiac risk potential of different drugs and also about individual risk factors which could increase the tolerability of psychopharmacological treatment. For the prevention of cardiac ADRs, the physician should evaluate the risk for potential QT prolongation and TdP for each drug and patient-specific risk factors before prescribing these drugs or drug combinations.