Out of total 678 patients, 358 (52.8%) were male and 320 (47.2%) were female. Majority of patients were in the age range of 41-60 years (29.5%) followed by 21-40 years (26.4%). The use of 7-9 drugs (37.3%) and 10-12 drugs (29.4%) were most frequent. Whereas, majority of patients (81.9%) were prescribed ≥2 anti-cancer drugs and ≥4 supportive drugs (87.6%) as presented in Table 1.
Cancer profile and treatment of study subjects
Table 2 illustrates cancer profile and its treatment for study subjects. Solid malignancies were most frequent among the study participants (53.1%) as compared with hematologic malignancies (46.9%). Metastasis was seen in 112 (16.5%) patients whereas 620 (91.4%) patients were receiving curative treatment. Moreover, the use of cytotoxic agents (74.9%) and combination therapy (24%) were common while hormonal or monoclonal agents were rarely prescribed. The most frequent solid malignancies include gastrointestinal cancer (13.1%), breast cancer (9.4%), gynecological cancer (6.9%), musculoskeletal cancer (6.2%) and genitourinary cancer (6%). Likewise, the most frequent hematological malignancies include acute lymphoblastic leukemia (18.7%), non-Hodgkin lymphoma (17.3%), and acute myelogenous leukemia (4.1%).
Prevalence of pDDIs
Figure 1 indicates that 529 patients were exposed to at least one pDDI (overall prevalence = 78%). Majority of patients had 1-2 pDDIs (266), 5-6 pDDIs (100) and 3-4 pDDIs (93).
Levels of pDDIs
Overall 1843 pDDIs were detected, of which, 1240 (67.3%) were of major and 507 (27.5%) were of moderate severity while contraindicated pDDIs were least frequent accounting for 25 (1.4%) pDDIs. The documentary evidence of majority of pDDIs were fair (66.4%) and good (23.8%) (Figure 2).
Predictors of pDDIs
Table 3 demonstrates the results of univariate and multivariate logistic regression analysis for exposure to pDDIs. Results of univariate logistic regression analysis indicates a significant relation of pDDIs with all prescribed drugs, anticancer drugs, supportive care drugs, hospitalization, type of cancer and type of cancer treatment. The odds of pDDIs are 3.6 times with >7 all prescribed drugs (p <0.001), 4.7 times with ≥3 anti-cancer drugs (p<0.001), 1.9 times with >3 supportive care drugs (p = 0.001), 1.8 times with hospitalization (p = 0.004), 2.1 times with combination treatment (p = 0.003) and 0.4 times with solid malignancy (p <0.001). Whereas, the risk is insignificant for gender, age, presence of metastasis and treatment intent.
Likewise, the results of multivariate logistic regression analysis show a significant relation of pDDIs with the presence of >7 all prescribed drugs (p <0.001) and ≥3 anti-cancer drugs (p <0.001). Whereas, the association of pDDIs with supportive care drugs (p = 0.2), hospitalization (p = 0.3), type of cancer (p = 0.2) and type of treatment (p = 0.3) are insignificant.
Abnormal symptoms and laboratory results
Table 4 presents the abnormal biochemical results and symptoms among study subjects. Hematological tests show reduced hemoglobin in majority of patients (58.7%) whereas, 118 (17.4%) patients were reported with reduced red blood cell count. Similarly, leukocytopenia was observed in 96 (14.2%) patients with decreased neutrophil count in 70 (10.3%) patients, decreased lymphocytes in 149 (21.9%) patients and reduced eosinophils and monocytes in 47 (6.9%) and 372 (54.9%) patients, respectively. Abnormal high serum creatinine was reported in 26 (3.8%) patients and 12 (1.8%) patients had elevated bilirubin level. While among the liver function tests, 121 (17.8%) patients had elevated ALT levels and 106 (15.6%) patients had elevated alkaline phosphatase level. Whereas, the most frequently observed symptoms among the study participants include fever (12.1%), generalized body ache (9.3%), nausea & vomiting (4.7%), abdominal pain (4.1%) and cough (3.8%).
Wide spread interacting drug combinations
Most frequently detected pDDIs are enlisted in Table 5 along with their severity, documentation levels and potential adverse outcomes. Reduced therapeutic effectiveness, QT interval prolongation, drug toxicity such as tendon rupture, bone marrow suppression, seizures, serotonin syndrome, neurotoxicity and cardiomyopathy were the potential adverse outcomes of these interactions. Potential drug-drug interactions involving anti-cancer agents are enlisted in additional table 1.