Potential drug-drug interactions in prescriptions for highly prevalent infectious disease at tertiary care hospitals of Peshawar, Pakistan

Abstract

Infectious diseases impose the greatest health burden, both in the form of morbidity and mortality. Some infectious diseases such as hepatitis, urinary tract infections (UTIs), pneumonia, malaria, and tuberculosis (TB) are among the frequent causes of hospitalization. Various antimicrobial agents (AMAs) are commonly prescribed for the treatment of such diseases. Besides that, large number of other medicines are also prescribed in order to treat the associated symptoms/complications and various comorbidities. Concomitant intake of such a large number of medicines increases the likelihood of potential drug-drug interactions (pDDIs) in these patients. However, this issue remains poorly addressed. Therefore, this research aimed to explore the prevalence, levels, and predictors of pDDIs in selected infectious diseases (hepatitis, UTIs, pneumonia, malaria, and TB) at hospital settings; and to develop management guidelines. Five different cross-sectional studies were conducted at two major tertiary care hospitals in Peshawar, Pakistan. Patients’ medication list was screened for pDDIs by the drug interactions tool available on IBM-Micromedex® database. Prevalence as well as levels of pDDIs were identified. The strength of association between various predictors and pDDIs was assessed using logistic regression analysis. Furthermore, monitoring/management guidelines were developed for the widespread pDDIs. Overall prevalence of pDDIs was 55.2% in hepatitis, 62.3% in UTIs, 73.1% in pneumonia, 37.2% in malaria, and 78.2% in TB. The prevalence of major-pDDIs was 35% in hepatitis, 40% in UTIs, 53.8% in pneumonia, 19.3% in malaria, and 70.8% in TB. Total 660 pDDIs were identified in hepatitis, 1086 in UTIs, 1318 in pneumonia, 325 in malaria, and 1716 in TB. Of the total identified pDDIs, major-pDDIs were 46% in hepatitis, 43.4% in pneumonia, 39.3% in UTIs, 45.5% in malaria, and 52.8% in TB. Overall, polypharmacy and longer hospital stay were the most common predictors of pDDIs in infectious diseases. Moreover, a significant association of pDDIs was also found with a variety of comorbidities such as stroke, diabetes mellitus (DM), ischemic heart disease (IHD), and congestive cardiac failure (CCF). Specifically, following were the significant predictors in each disease i.e., hepatitis: >9 prescribed medicines (p < 0.001), >5 days hospitalization (p = 0.03), and stroke (p = 0.05); UTIs: >6 prescribed medicines (p < 0.001), DM (p < 0.001), CCF (p = 0.03), and IHD (p = 0.02); pneumonia: >6 prescribed medicines (p < 0.001) and TB (p = 0.004); malaria: with >5 prescribed medicines (p = 0.01), >5 days hospitalization (p = 0.03), and DM (p = 0.04); and TB: >7 prescribed medicines (p < 0.001). Signs/symptoms of hepatotoxicity were observed in patients with the following interacting pairs, isoniazid + rifampin, pyrazinamide + rifampin, and isoniazid + acetaminophen. Hyperkalemia was found in patients in case of ramipril + spironolactone. Clinical manifestations suggesting poor therapeutic response and electrolytes abnormalities were detected in patients with the interactions of aspirin with furosemide, calcium containing products with ceftriaxone, and diclofenac with spironolactone. Increased bleeding risk was found with the interaction of clopidogrel and aspirin. Patients with the following interacting pairs, metronidazole + sodium phosphate/biphosphate, metronidazole + norfloxacin, metronidazole + octreotide, prochlorperazine + quinine, metronidazole + quinine, domperidone + ranitidine, and ciprofloxacin + metronidazole were presented with the clinical features suggesting QT interval prolongation. Higher doses of the interacting combinations most frequently resulted in adverse outcomes. It is concluded that pDDIs are highly prevalent among patients with hepatitis, UTIs, pneumonia, and TB. A substantial number of major-pDDIs are present in most of the infectious diseases. Polypharmacy, longer hospitalization, stroke, DM, IHD, and CCF increase the risk of pDDIs. Hepatotoxicity, reduced therapeutic effects, hypoglycemia, hyperkalemia/electrolytes abnormalities, QT interval prolongation, and increased risk of bleeding were the common adverse outcomes of theses interactions. Adverse outcomes more frequently occur with higher doses of the interacting drugs. Software based screening of DDIs will help in identification and prevention of DDIs. Careful monitoring for adverse effects associated with pDDIs will contribute to patient safety.