Patients with chronic kidney disease (CKD) face heightened susceptibility to adverse drug reactions (ADRs) owing to alterations in the pharmacokinetics and pharmacodynamics of medications. Patients with Stage 5 CKD receiving hemodialysis (HD) have numerous medications that are eliminated during the HD process. This study aims to assess the prescribing patterns in stage 5 CKD patients undergoing routine HD and their association with drug-drug interactions (DDIs) and the potential for adverse drug reactions (ADRs) resulting from DDIs. This cross-sectional study encompassed stage 5 CKD patients undergoing routine HD at Dr. Cipto Mangunkusumo General Hospital from 2020 to 2021. Data were obtained from the medical records of the HD Unit. An evaluation was performed utilizing the Lexicomp software to discover DDIs. The study had 147 individuals, with 101 different medications taken, the most prevalent being epoetin alfa (70.4%). Eighty nine percent of patients who underwent treatment associated with a potential DDIs, with the bulk of these interactions classified as moderate (88%). Fifty percent of patients were suspected of experiencing ADRs due to DDIs. Diabetes mellitus exhibited a statistically significant association with suspected ADRs attributable to DDIs (p = 0.04). Hypertension was the most predicted ADR resulting from DDIs, and diabetes mellitus significantly contributed to the incidence of ADRs owing to DDIs in patients with stage 5 CKD on routine HD. In conclusion, DDI in patients undergoing routine HD is sometimes unavoidable considering the many comorbidities. The DDI that occurred was moderate in severity and could be managed well at the Dr. Cipto Mangukusumo General Hospital.