Background: Cancer patients often receive multiple drugs to maximize their therapeutic benefit, treat co-morbidities and counter the adverse effects of chemotherapy. Concomitant administration of multiple drugs increases the risk of drug interactions leading to compromised therapeutic efficacy or safety of therapy. The purpose of this study was to identify the prevalence, levels and predictors of potential drug-drug interactions (pDDIs) among cancer patients. Methods: Six hundred and 78 patients receiving chemotherapy from two tertiary care hospitals were included in this cross-sectional study. Patient medication profiles were screened for pDDIs using the Micromedex® database. Logistic regression analysis was performed to identify the predictors of pDDIs. Results: The overall prevalence of pDDIs was 78%, majority of patients had 1–2 pDDIs (39.2%). A total of 1843 pDDIs were detected. Major-pDDIs were most frequent (67.3%) whereas, a significant association of pDDIs was found between > 7 all prescribed drugs (p < 0.001) and ≥ 3 anti-cancer drugs (p < 0.001). Potential adverse outcomes of these interactions include reduced therapeutic effectiveness, QT interval prolongation, tendon rupture, bone marrow suppression and neurotoxicity. Conclusions: Major finding of this study is the high prevalence of pDDIs signifying the need of strict patient monitoring for pDDIs among cancer patients. Patients at higher risk to pDDIs include those prescribed with > 7 any types of drugs or ≥ 3 anticancer drugs. Moreover, list of most frequently identified major and moderate interactions will aid health care professional in timely identification and prevention of pDDIs.

Introduction: Moxifloxacin is widely used for the treatment of a number of infectious diseases because of its favorable pharmacological profile and high clinical success rate. However, it is often criticized for its higher risk of QTc interval prolongation (QTIP) and torsades de pointes (TdP). Areas covered: A review of published literature on moxifloxacin-related QTIP and TdP. Readers will be provided with a comprehensive overview of the prevalence, cellular mechanism, risk factors, and magnitude of QTIP of moxifloxacin. Expert commentary: In healthy subjects, moxifloxacin prolongs the QTc interval by 11.5–19.5 ms, it binds at the Tyr652 residue in the S6 pore domain of the human ether a-go-go gene related potassium channel. Considerable QTIP (30–60 ms) have also been reported in some patients, for instance the incidence of QTIP (30–60 ms) in elderly pneumonia patients was 15.5%. Moxifloxacin-induced QTIP may be of little clinical importance in healthy individuals. However, marked QTIP (>60 ms) and TdP have been reported in high-risk patients (patients who have multiple QT prolonging risk factors). Patients must be thoroughly assessed prior to the use of moxifloxacin and high-risk patients must be identified using risk assessment tools to ensure safe use of moxifloxacin and to safeguard patients’ health.

Potential drug–drug interactions (pDDIs) are one of the preventable drug related problems having the risk of serious adverse events or therapeutic failure. In developing countries like Pakistan, this issue remains poorly addressed. The objective of this study was to explore prevalence of pDDIs in the Outpatient Department (OPD) of a tertiary care hospital in Pakistan. The secondary aim was to describe the levels of reported pDDIs and develop a list of widespread clinically relevant interactions. Prescriptions of 2400 OPD patients were analyzed for pDDIs through Micromedex Drug-Reax®. Prevalence, severity- and documentation-levels and widespread clinically relevant interactions were reported. Of total 2400 prescriptions, pDDIs were present in 22.3%. Whereas, moderate- and major-pDDIs were found in 377 (15.7%) and 225 (9.4%), respectively. PDDIs were more prevalent in Medicine (9.2%) and Cardiology (2.6%) as compared with other OPD specialties. Total 942 pDDIs were identified, of which, the majority were either moderate- (61.9%) or major-pDDIs (32.1%). Some of the most common interactions were ibuprofen + levofloxacin (n = 50), ciprofloxacin + diclofenac (32), aspirin + atenolol (24), and diclofenac + levofloxacin (19). The potential adverse outcomes of widespread interactions were seizures, bleeding, QT-interval prolongation, arrhythmias, tendon rupture, hypoglycemia/hyperglycemia, serotonin syndrome, drug toxicity, and decreased therapeutic response. OPD patients were at risk to pDDIs, particularly to major- and moderate-pDDIs. Screening of prescriptions for pDDIs and monitoring of pharmacotherapy in terms of response and associated adverse drug events will contribute to patient safety.

Medical inpatients are at increased risk of QT interval prolongation due to multiple risk actors and QT prolonging drugs. This study aimed to identify the prevalence of risk factors for QT prolongation; QT prolonging medications; associated drug-drug interactions (QT-DDIs); their predictors; and TdP (torsades de pointes) risks of drugs. This cohort study was carried out in medical wards of two tertiary hospitals in Khyber Pakhtunkhwa, Pakistan. The QT-DDIs were identified using Micromedex DrugReax® and AZCERT (Arizona Center for Education and Research on Therapeutics) QT drugs lists. AZCERT QT drugs lists were used to identify TdP risks. Logistic regression analysis was performed to identify predictors of QT-DDIs. Total 400 patients were included in this study. The most frequent QT prolonging risk factors included use of ≥1 QT prolonging drugs (74.5%), female gender (55%) and diabetes mellitus (36.3%). Total 487 QT prolonging drugs were identified. According to AZCERT classification, 33.8% of the interacting drugs were included in list-1 (known risk of TdP), 0.9% in list-2 (possible risk of TdP) and 58.8% in list-3 (conditional risk of TdP). The occurrence of QT-DDIs was significantly associated with ≥10 prescribed medications (p = 0.01), chronic liver disease (p = 0.05), chronic obstructive pulmonary disease (p = 0.03), gastroenteritis (p = 0.02), antimicrobials (p < 0.001), antiemetics (p < 0.001) and antinausea (p < 0.001). A substantial number of patients were exposed to risk factors for QT prolongation; and QT prolonging drugs such as proton pump inhibitors, antimicrobials and diuretics which may lead to serious outcomes.