Risk factors of early adverse drug reactions with phenytoin: A prospective inpatient cohort

• Published in: Epilepsy & behavior Vol. 76; pp. 139 - 144
• Main Authors: Uribe-San-Martín, Reinaldo, Ciampi, Ethel, Uslar, Wilhelm, Villagra, Silvana, Plaza, Jose, Godoy, Jaime, Mellado, Patricio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2017
• Subjects: Adult; Adverse drug reaction; Aged; Aged, 80 and over; Anticonvulsants - administration & dosage; Anticonvulsants - adverse effects; Anticonvulsants - blood; Antiepileptic drug; Drug monitoring; Drug-Related Side Effects and Adverse Reactions; Female; Hospitalization - statistics & numerical data; Humans; Inpatients - statistics & numerical data; Male; Middle Aged; Pharmacovigilance; Phenytoin; Phenytoin - administration & dosage; Phenytoin - adverse effects; Phenytoin - blood; Polypharmacy; Prospective Studies; Risk Factors; Antiepileptic drug; Drug monitoring; Adverse drug reaction; Pharmacovigilance; Phenytoin
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2017.08.032

Phenytoin (PHT) is an effective and inexpensive antiepileptic drug (AED). However, its use has been limited for fear of adverse drug reactions (ADRs) and is being replaced by newer AED, increasing the costs and causing major budget problems, particularly for developing countries. The objective of this study was to determine ADR frequency, explore, and establish related risk factors. Prospective data were collected from a cohort of inpatients using PHT for the first time. Pharmacovigilance was performed during hospitalization and after one month from the discharge. Clinical variables, plasma levels, and concomitant medications were collected and their association with the occurrence of different ADRs was explored. One hundred patients were included: 59 were women, and mean age was 59±21years. Thirty-three patients presented ADR, all moderate and idiosyncratic. The most frequent were rash (17%), fever (10%), and elevated transaminases (10%). Female gender (85% vs 52%, p=0.029), younger age (mean age: 49 vs 62years, p=0.032), and higher PHT plasmatic levels after IV-PO load (mean plasmatic levels: 18.6 vs 13.9μg/mL, p=0.040) were found to be associated with rash. A higher number of concomitant medications were also found to be associated with the risk for developing any ADR. The multivariate analysis revealed an association between rash and younger age (cut-off: 35years old; relative risk (RR)=11.7; p=0.026), and higher PHT plasmatic levels (cut-off: 16μg/mL; RR=12.5; p=0.021); and increased risk of elevated transaminases with use of PHT inductors (RR=18; p=0.006). A longer hospital stay was found in patients who developed fever (mean: 43days, p<0.0001) and elevated transaminases (mean: 26days, p=0.041) compared with patients without ADR (mean: 17days). Phenytoin is a widely used AED associated with easily detectable ADR through structured pharmacovigilance. The development of ADR is associated with longer hospital stays. Recognition of local risk factors may lead to ADR prevention in a near future. Larger studies are needed to better define PHT-related ADR risk profile and to individualize treatment regimens. •Phenytoin (PHT) use has been limited for fear of adverse drug reactions (ADR).•Recognizing the potential risk factors for developing ADR could avoid or reduce their severity through pharmacovigilance.•In this cohort, thirty three percent of patients treated with PHT presented ADR, all moderate and idiosyncratic.•Female gender, younger age and higher PHT plasmatic levels were risk factors for developing rash.•A higher number of concomitant medications also increased risk of any ADR (rash, fever or elevated transaminases).•Recognition of local risk factors and individualized treatment may lead to ADR prevention.