Assessment of Adverse Drug Events, Their Risk Factors, and Management Among Patients Treated for Multidrug-Resistant TB: A Prospective Cohort Study From Pakistan.

Background: Multidrug-resistant tuberculosis (MDR-TB) is a growing public health problem. Treatment regimens used against MDR-TB are costly, prolonged, and associated with more side effects as compared with the drug-susceptible tuberculosis. This study was framed to determine the incidence of adverse drug events, risk factors, and their management in MDR-TB patients. Methods: This prospective follow-up cohort study was conducted at the site of programmatic management of drug-resistant TB located at the Pakistan Institute of Medical Sciences, Islamabad. All patients, irrespective of their age, gender, and ethnicity, were included in the study. Adverse drug events were observed in patients at different time points during the study. Patients enrolled for the treatment from January 2018 were prospectively followed till December 2020 up to their end treatment outcomes. Results: Out of 126 MDR-TB patients enrolled for treatment, 116 met the inclusion criteria and were included in the final analysis. Most patients (50.9%) were between 18 and 45 years of age. A minimum of one adverse event was experienced by (50.9%) patients. Of all the adverse events, gastrointestinal disorders were more frequent (47.4%), followed by arthralgia (28.4%) and psychiatric disturbance (20.6%). Furthermore, multivariate analysis showed a significant association with the incidence of adverse events in patients with age group above 60 years (odds ratio (OR) 4.50; 95% CI 1.05-19.2), active smokers (OR 4.20; 95% CI 1.31-13.4), delayed reporting to the TB center (OR 4.03; 95% CI 1.34-12.1), and treatment without bedaquiline regime (OR 3.54; 95% CI 1.23-10.1). Most of the patients (94.6%), counseled by the pharmacist, were found to be satisfied with the information provided and looked for more pharmacist counseling opportunities in the management of MDR-TB. Conclusion: Current findings recommend that ADEs might be well managed by timely identification and reporting. Bedaquiline coupled with other active medications lowered the chance of ADEs in MDR-TB patients. Elderly patients, active smoking behavior, and those who have a delay in the treatment initiation are more prone to ADEs. Clinical pharmacist's contribution to TB control programs may help caregivers and patients concerning the rational use of medication, early detection, and management of ADEs.

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.

Potential drug-drug interactions associated with adverse clinical outcomes and abnormal laboratory findings in patients with malaria.

BACKGROUND: Hospitalized patients with malaria often present with comorbidities or associated complications for which a variety of drugs are prescribed. Multiple drug therapy often leads to drug-drug interactions (DDIs). Therefore, the current study investigated the prevalence, levels, risk factors, clinical relevance, and monitoring parameters/management guidelines of potential DDIs (pDDIs) among inpatients with malaria. METHODS: A retrospective cohort study was carried out at two tertiary care hospitals. A total of 398 patients' profiles were evaluated for pDDIs using the Micromedex Drug-Reax®. Odds ratios were calculated to identify the strength of association between presence of DDIs and potential risk factors via logistic regression analysis. Further, the clinical relevance of frequent pDDIs was investigated. RESULTS: Of 398 patients, pDDIs were observed in 37.2% patients, while major-pDDIs in 19.3% patients. A total of 325 interactions were found, of which 45.5% were of major- and 34.5% moderate-severity. Patients with the most common pDDIs were found with signs/symptoms and abnormalities in laboratory findings representing nephrotoxicity, hepatotoxicity, QT interval prolongation, and reduced therapeutic efficacy. The following drug pairs reported the highest frequency of adverse events associated with the interactions; calcium containing products-ceftriaxone, isoniazid-rifampin, pyrazinamide-rifampin, isoniazid-acetaminophen, and ciprofloxacin-metronidazole. The adverse events were more common in patients prescribed with the higher doses of interacting drugs. Multivariate regression analysis showed statistically significant association of pDDIs with 5-6 prescribed medicines (p = 0.01), > 6 prescribed medicines (p < 0.001), > 5 days of hospital stay (p = 0.03), and diabetes mellitus (p = 0.04). CONCLUSIONS: PDDIs are commonly observed in patients with malaria. Healthcare professional's knowledge about the most common pDDIs could help in preventing pDDIs and their associated negative effects. Pertinent clinical parameters, such as laboratory findings and signs/symptoms need to be checked, particularly in patients with polypharmacy, longer hospital stay, and diabetes mellitus.

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.

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, 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

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.

Potential drug-drug interactions among pneumonia patients: do these matter in clinical perspectives?

BACKGROUND: Pneumonia patients are usually hospitalized due to severe nature of the disease or for the management of comorbid illnesses or associated symptoms. Such patients are prescribed with multiple medications which increase the likelihood of potential drug-drug interactions (pDDIs). Therefore, in this study the prevalence, levels (severity and documentation), predictors (risk factors), and clinical relevance of pDDIs among inpatients diagnosed with pneumonia have been investigated. METHODS: Clinical records of 431 hospitalized patients with pneumonia were checked for pDDIs using drug interactions screening software (Micromedex-DrugReax). Odds-ratios for predictors were calculated using logistic regression analysis. Clinical relevance of pDDIs was assessed by evaluation of patients' clinical profiles for potential adverse outcomes of the most frequent pDDIs. Abnormal patients' signs/symptoms and laboratory investigations indicating adverse outcomes of interactions were reported. RESULTS: Of total 431 profiles, pDDIs were reported in 73.1%. Almost half of the profiles were having major-pDDIs (53.8%). Total number of pDDIs were 1318, of which 606 were moderate- and 572 were major-pDDIs. Patient's profiles identified with the most frequent interactions were presented with signs, symptoms, and abnormalities in labs indicating decrease therapeutic response, electrolyte abnormalities, hypoglycemia, bleeding, hepatotoxicity, and hypertension. These adverse events were more prevalent in patients taking higher doses of the interacting drugs as compared to lower doses. Logistic regression analysis revealed significant association for major-pDDIs with 6-10 prescribed medicines (OR = 26.1; p = 0.002), > 10 prescribed medicines (OR = 144; p <  0.001), and tuberculosis (OR = 8.2; p = 0.004). CONCLUSIONS: PDDIs are highly prevalent in patients with pneumonia. Most frequent and clinically important pDDIs need particular attention. Polypharmacy and tuberculosis increase the risk of pDDIs. Identifying patients more at risk to pDDIs and careful monitoring of pertinent signs/symptoms and laboratory investigations are important measures to reduce pDDIs and their related adverse consequences.

Potential drug-drug interactions in outpatient department of a tertiary care hospital in Pakistan: a cross-sectional study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Drug-Drug Interactions in Hepatitis Patients: Do these Interactions Matter in Clinical Perspectives?

INTRODUCTION AND AIM: Hepatitis patients usually present with comorbidities and polypharmacy which increases risk of potential drug-drug interactions (pDDIs). We explored frequency, levels, predictors, and clinical relevance of pDDIs in hospitalized hepatitis patients. MATERIAL AND METHODS: Retrospective cohort study was used. Clinical profiles of 413 hepatitis patients were reviewed for pDDIs using Micromedex-DrugReax. Frequency, levels and clinical relevance of pDDIs were reported. Logistic regression analysis was used to calculate odds-ratios for predictors. RESULTS: Of total 413 patients, pDDIs were reported in 55.2%. Major-pDDIs were found in 35% patients. Total 660 pDDIs were identified, of which, 304 (46%) were of major-severity and 299 (45%) of moderateseverity. Patient's profiles of top-10 major-pDDIs were presented with signs/symptoms such as fever, hepatomegaly, anorexia, jaundice, hypertension, tachycardia, bradycardia, & pedal edema; and abnormalities in labs such as electrolytes-level, alanine aminotransferase, blood urea nitrogen, bilirubin-level, & serum creatinine. Significant association was observed for the presence of pDDIs with > 9 prescribed medicines (p < 0.001), hospitalization of > 5 days (p = 0.03), and stroke as comorbidity (p = 0.05). Moreover, odds of exposure to major-pDDIs were significantly higher in patients taking > 9 prescribed medicines (p < 0.001), hospitalization of > 5 days (p = 0.002), and stroke as comorbidity (p = 0.002). CONCLUSION: We observed hepatitis patients presented with a considerable number of clinically relevant pDDIs. Attention should be given to widespread major-pDDIs and their potential adverse outcomes. Clinically relevant parameters, such as labs and signs/symptoms should be monitored particularly in high risk patients having polypharmacy, prolong hospitalization, and stroke as comorbidity.

QT interval prolongation in hospitalized patients on cardiology wards: a prospective observational study.

PURPOSE: Prolonged QT interval may lead to a lethal form of arrhythmia, torsades de pointes (TdP), which is associated with cardiovascular mortality. Therefore, we aimed to identify prevalence of QT interval prolongation, compare clinical characteristics of patients with normal and prolonged QT interval, and identify predictors of QT interval prolongation. METHODS: A prospective observational study was conducted in cardiology wards of two teaching hospitals in Pakistan. Bazett's correction formula was used for the calculation of QTc interval. Prevalence of QT prolongation and pro-QTc scores were calculated. Comparative analysis was performed with respect to various clinical characteristics by applying t test and chi-square test. Odds ratios were calculated using regression analysis. RESULTS: Among 417 patients, 44.6% were found having prolonged QT interval, of which, 17.3% presented with an abnormally high QTc interval (> 500 ms). Significant difference was recorded between the groups (normal vs. prolonged) with respect to age, all prescribed medications, QT drugs, number of risk factors, QT-DDIs (QT-prolonging drug-drug interactions), gender, and diuretics use. Multivariate logistic regression analysis showed significant results for various predictors such as male gender (p = 0.03), various age categories 41-50 years (p = 0.04), 51-60 years (p = 0.01), and > 60 years (p < 0.001), and diuretics (p = 0.008). CONCLUSION: A substantial number of patients in cardiology wards presented with QT prolongation. Proper considerations are needed in order to minimize the associated risk particularly in patients with abnormally high QT prolongation, old age, polypharmacy, one or more QT-prolonging drugs, and high pro-QTc scores.

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.

Potential drug-drug interactions in medical intensive care unit of a tertiary care hospital in Pakistan.

Background Patients admitted to intensive care unit (ICU) present with severe and life-threatening illnesses. Most of them suffer from various comorbidities. They usually receive complex pharmacotherapy with large number of medicines which increase the risk of drug-drug interactions (DDIs). Objective The present report aimed to investigate prevalence and levels of potential DDIs (pDDIs) in medical ICU. Methods Medications profiles of 416 patients were checked for pDDIs using Micromedex Drug-Reax(®). Prevalence, levels of severity and levels of documentation were reported. Results Of total 416 patients, 310 were exposed to pDDIs (overall prevalence = 74.5 %). Likewise, a prevalence rate of 13.9 % was recorded for contraindicated pDDIs, 52.2 % for major pDDI and 58.4 % for moderate pDDI. This study reported 740 interacting drug pairs that were presented in total 1686 pDDIs. Of 1686 pDDIs, 4.3 % were of contraindicated severity, 33.8 % of major severity and 49.6 % of moderate severity, whereas 45.5 % were of fair scientific evidence and 41.4 % of good scientific evidence. Conclusion In this study, pDDIs were found highly prevalent in ICU patients at a rate of 74.5 %. Most of the pDDIs had moderate severity; however, substantial number of interactions (38.1 %) had major and contraindicated severity.