Prevalence and significance of potential drug-drug interactions among cancer patients receiving chemotherapy.

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.

Prevalence of QTc interval prolongation and its associated risk factors among psychiatric patients: a prospective observational study.

BACKGROUND: QT interval prolongation is a growing concern worldwide, posing psychiatric patients to life-threatening fatal arrhythmias i.e., torsade de pointes. This study aimed to identify the prevalence of QT interval prolongation, its associated risk factors and prescribing patterns of QT prolonging drugs among psychiatric patients. METHOD: A prospective observational study was conducted that included psychiatric patients from a tertiary care hospital and a psychiatry clinic in Peshawar, Khyber Pakhtunkhwa, Pakistan. Electrocardiogram was recorded of those patients who were using psychotropic medications for ≥7 days, aged 18 years or more, and of either gender, male or female. The Fredericia correction formula was used for measuring QTc values (corrected QT). Chi-square test was applied to estimate differences between patients with or without prolonged QTc interval whereas, logistic regression analysis was performed to identify various predictors of QT interval prolongation. RESULTS: Out of 405 patients, the QTc interval was prolonged in 23 (5.7%) patients including 1 (0.2%) patient with highly abnormal prolonged QTc interval (> 500 ms). QT drugs (91.6%), female sex (38.7%) and hypertension (10.6%) were the most common QT prolonging risk factors. Prolonged QTc interval was significantly higher among male patients (p = 0.007). CONCLUSION: In the present study, QT interval prolongation was observed in a considerable number of psychiatric patients. While, the high prevalence of QT prolonging risk factors among these patients warrants the increased risk of fatal arrhythmias. Therefore, risk assessment and electrocardiographic monitoring, and prescription of safer alternatives are highly recommended.

Aflatoxin B1 in compound feed and feed ingredients from Khyber Pakhtunkhwa.

A large-scale study was conducted to explore AFB1 contamination in feed samples using Thin Layer Chromatography, following an AOAC protocol. Samples were identified which were not compliant with the maximum limits for AFB1 as regulated in the United States and Pakistan. Of a total of 923 samples, 51 samples (5.5%) were not compliant according to Pakistan and 267 (28.9%) were not compliant with US-FDA standards. The overall prevalence of non-compliant samples of compound feed was 26.2% (n = 117) according to US-FDA standards, while none of the samples were non-compliant according to Pakistan standards. Among feed ingredients, the overall prevalence of non-compliant samples was 10.7% (n = 51) and 31.4% (n = 150) according to Pakistan and USFDA standards, respectively. Non-compliant feed with respect to AFB1 contamination was highly prevalent in Khyber Pakhtunkhwa, posing a serious threat to production performance and animals health.

Drug safety in hospitalized patients with tuberculosis: Drug interactions and adverse drug effects.

BACKGROUND: Hospitalized patients with tuberculosis (TB) are prescribed with drugs having high risk of potential drug-drug interactions (pDDIs) and adverse drug effects (ADEs). OBJECTIVES: To explore the adverse effects of anti-tuberculosis (anti-TB) drugs and the prevalence and predictors of pDDIs in hospitalized patients with TB. METHODS: Clinical profiles of 436 TB patients were reviewed for adverse effects induced by anti-TB drugs and screened for pDDIs using Micromedex-DrugReax. Prevalence and severity levels of pDDIs were reported. Odds ratios for predictors were calculated using logistic regression analysis. RESULTS: Of total 436 patients, adverse effects of anti-TB drugs were found in 36%. ADEs were highly prevalent in patients with high doses of anti-TB drugs. Hepatotoxicity, neuropathy, insomnia, arthralgia, psychosis, hematological alterations, skin rashes, red color stool, diplopia, and photophobia were the identified ADEs. All drugs types- and anti-TB drugs-pDDIs were reported in 78.2% and 55.7%, respectively. Major-pDDIs of anti-TB drugs were identified in 55.5%. Total 1090 anti-TB drugs pDDIs were found, among them, 55.6% were of major- and 40.5% were of moderate-severity. Significant association was observed for the pDDIs with ≥7 prescribed medicines (P < 0.001). Potential adverse outcomes of the most frequent interactions were hepatotoxicity, decreased drug's effectiveness, QT-interval prolongation, nephrotoxicity, and gastrointestinal ulceration. CONCLUSIONS: Patients with TB present with a considerable number of clinically important pDDIs and ADEs (particularly hepatotoxicity). TB patients should be monitored for adverse effects of anti-TB drugs. Attention should be given to major-pDDIs. Patients more at risk to interactions should be identified and monitored for related adverse outcomes.

Association of H1-antihistamines with torsade de pointes: a pharmacovigilance study of the food and drug administration adverse event reporting system.

Background: This study aimed to measure the association of various H1-antihistamines (H1A) with Torsade de Pointes (TdP), and present a comprehensive overview of H1A-induced TdP cases reported to the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: All H1A-induced TdP cases (n = 406) were retrieved from the FAERS database using the preferred term 'Torsade de Pointes' of MedDRA version-22 from 1990 to 2019. Four data-mining algorithms were used for disproportionality analysis: Reporting Odds Ratio (ROR); Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Information Content (IC). H1A with >3 TdP cases were included. Results: A total of 12 signals (Astemizole, cetirizine, chlorpheniramine, clemastine, desloratadine, diphenhydramine, hydroxyzine, loratadine, meclizine, promethazine, terfenadine, and trimeprazine) were identified including six new signals (cetirizine, chlorpheniramine, clemastine, desloratadine, loratadine, and meclizine). The number of risk factors (p = 0.031) and concomitant QT-prolonging drugs (p = <0.001) were significantly lower among new signals vs old signals. Moreover, new signals were strongly associated with QT-prolongation, cardiac reactions, and electrolyte abnormalities as compared with old signals. Conclusions: Our study found the increased torsadogenic potential of new signals compared with previously known old signals, hence necessitating clinical studies to determine the actual torsadogenic potential of newly identified signals.

Potential Drug-Drug Interactions in Patients With Urinary Tract Infections: A Contributing Factor in Patient and Medication Safety.

Introduction: Hospitalized patients with urinary tract infections (UTIs) often present with comorbid illnesses and are subsequently prescribed multiple medications, which increases the likelihood of drug-drug interactions. Therefore, this study aimed to explore the prevalence, levels, risk factors, and clinical relevance of potential drug-drug interactions (pDDIs) in hospitalized patients with UTIs. Secondly, we aimed to develop management guidelines and identify monitoring parameters for the most frequent interactions. Methods: A retrospective cross-sectional study was conducted in internal medicine wards of two tertiary care hospitals in Peshawar, Khyber Pakhtunkhwa, Pakistan. The clinical profiles of 422 patients with UTIs were reviewed for pDDIs using the Micromedex Drug-Reax®. Logistic regression was applied to assess the association of pDDIs with various risk factors. The clinical relevance of frequent pDDIs was identified by assessing the potential adverse outcomes of pDDIs including patients' signs, symptoms, and abnormal laboratory findings. Results: Of 422 patients, at least one pDDI was identified in 62.3% patients, while 40% patients had at least one major pDDI. A total of 1,086 pDDIs were identified, of which 53.4% and 39.3% were of moderate and major severity, respectively. Patients with most frequent pDDIs were presented with hypoglycemia, hepatotoxicity, nephrotoxicity, hypertension, and decreased therapeutic response. These adverse events were more prevalent in patients taking higher doses of interacting drugs. Multivariate regression analysis revealed significant association of pDDIs with six or more medicines (p < 0.001), diabetes mellitus (p < 0.001), ischemic heart disease (p = 0.02), and congestive cardiac failure (p = 0.04). Conclusions: Patients with UTIs present with a considerable number of clinically important pDDIs. Polypharmacy, diabetes mellitus, ischemic heart disease, and congestive cardiac failure increase the risk of pDDIs. Knowledge about the most frequent pDDIs will enable healthcare professionals to implement optimized monitoring and management strategies regarding associated adverse consequences in order to ensure patient safety. Most of the interactions can be managed by considering alternative therapy and dose reduction.

Moxifloxacin-induced QT interval prolongation and torsades de pointes: a narrative review.

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 OPINION: 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.

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

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.

Potential drug-drug interactions in pediatric patients admitted to intensive care unit of Khyber Teaching Hospital, Peshawar, Pakistan: A cross-sectional study.

PURPOSE: To investigate frequencies, levels, clinical relevance and predictors of potential drug-drug interactions (pDDIs) in pediatric intensive care unit (PICU). METHODS: Case notes of 411 patients were reviewed for pDDIs through Micromedex. Frequencies, levels and clinical relevance of pDDIs were reported. Logistic regression was applied to calculate the odds-ratios for predictors of pDDIs. RESULTS: We recorded pDDIs in 59.4% patients. Major-pDDIs were found in 34.5% patients. Total 990 pDDIs were identified, of which, 37.8% were of moderate-severity and 30.6% of major-severity. Patient's case notes of top-ten pDDIs showed presence of signs/symptoms such as fever, jaundice, vomiting, anorexia, tachycardia, drowsiness, & lethargy; and abnormalities in labs such as total leukocytes count, blood urea nitrogen, alanine aminotransferase, & potassium-level. Odds of exposure to major-pDDIs were significantly higher in patients aged 6-12years (p=0.008); hospital stay of ≥7days (p=0.05); and ≥11 prescribed medicines (p<0.001). CONCLUSION: Substantial numbers of patients in PICU are exposed to pDDIs. Major-pDDIs are of particular concern. Timely identification of pDDIs, preferably with computerized source, is crucial point for their management. Monitoring of clinically relevant parameters and identification of various predictors are needed to minimize or prevent the associated negative consequences of pDDIs.

Prevalence, predictors and outcomes of potential drug-drug interactions in left ventricular failure: considerable factors for quality use of medicines

Hospitalized patients with left ventricular failure (LVF) are at high risk for potential drug-drug interactions (pDDIs) and its related adverse effects owing to multiple risk factors such as old age, comorbidities and polypharmacy. This cross-sectional study conducted in two tertiary care hospitals aim to identify frequency, levels and predictors of pDDIs in LVF patients. Data about patients' demographic, hospital stay, medication therapy, sign/symptoms and laboratory test results were collected for 385 patients with LVF. Micromedex Drug-Reax® was used to screen patients' medication profiles for pDDIs. Overall prevalence and severity-wise prevalence of pDDIs were identified. Chi-square test was performed for comparative analysis of various variables. Logistic regression was applied to determine the odds-ratios (OR) for predictors of pDDIs. The prevalence of pDDIs was 96.4% (n=371). Overall 335 drug-interacting pairs were detected, which were presented in a total of 2870 pDDIs. Majority of pDDIs were of major- (48.9%) and moderate-severity (47.5%). Logistic regression analysis shows significant association of >6 all types of pDDIs with >12 drugs as compared with <8 drugs (OR=16.5; p=<0.001). Likewise, there was a significant association of >4 major-pDDIs with men as compared with female (OR=1.9; p=0.007) and >12 drugs as compared with <8 drugs (OR=10.9; p=<0.001). Hypotension (n=57), impaired renal function (23) and increased blood pressure (22) were the most frequent adverse outcomes associated with pDDIs. This study shows high prevalence of pDDIs in LVF patients. Majority of pDDIs were of major- and moderate-severity. Male patients and those prescribed greater number of medicines were more exposed to major-pDDIs

Non-Hodgkin's lymphoma of the breast presenting as breast abscess during pregnancy.

Primary non-Hodgkin's lymphoma of the breast is an uncommon disease. In all patients with breast lump, primary lymphoma of breast should be considered as it is one of the most easily missed pathology. We report a case of a 22 years old lactating mother who presented with the complaint of a painful swelling in the right breast, noticed during the last trimester of her pregnancy, mimicking breast abscess.