Intensive Adverse Drug Reaction Monitoring Program Improves Detection of Phenytoin-Induced Adverse Drug Reactions

To compare the outcomes of routine versus intensive adverse drug reaction (ADR) monitoring programs among adult in-patients initially treated with phenytoin, and to identify risk factors associated with severe cutaneous adverse reactions (SCARs).

This retrospective cohort study recruited phenytoin-naïve patients treated at a general hospital in Northern Thailand. Potentially eligible admissions were identified through the electronic medical record by extracting all medication orders for phenytoin during October 2018 to May 2021. Patients were consecutively enrolled and divided into routine adverse drug reaction monitoring (n = 500, rADRM) and intensive adverse drug reaction monitoring (n = 500, iADRM) allocated based on ward-based monitoring models. All participants received standard counseling regarding phenytoin dosing and administration. The rADRM group underwent ADR monitoring during routine follow-up visits, while the iADRM group received additional individualized instruction on ADR recognition and access to a direct pharmacist contact for reporting suspected ADRs. Multivariable logistic regression was performed to identify independent risk factors for SCARs.

Patients in the intensive adverse drug reaction monitoring group had a significantly higher detection rate of phenytoin-induced ADRs compared with those in the routine adverse drug reaction monitoring group (OR 2.301, 95% CI 1.091:4.853, p = 0.029), as well as a greater patient-initiated reporting (OR 4.527, 95% CI 2.274:9.010, p < 0.001). Type B ADRs occurred in 3.6% of patients, with the iADRM group documenting more SCARs (36.84% vs. 5.88%, p = 0.044). Discontinuation of phenytoin and prolonged hospitalization were observed in both groups (42.1 vs. 52.9%, p = 0.045). Multivariable logistic regression identified iADRM (OR 13.304, 95% CI 1.183-149.581, p = 0.036), comorbidities (OR 12.935, 95%Cl 1.514:110.48, p =0.019), omeprazole use (OR 57.112, 95%Cl 9.569:340.875, p <0.001), and increased age (OR 0.940, 95%Cl 0.893:0.989, p =0.023) as significant risk factors associated with SCARs.

Intensive ADR monitoring facilitates earlier detection and reporting of phenytoin-associated ADRs including SCARs. Comorbidities, concomitant omeprazole use, and older age were associated with SCARs. Intensive monitoring programs may enhance patient engagement and improve medication safety by enabling timely recognition and management of adverse reactions.