Date of report 16 Jul 2024
Reported case interaction between
Efavirenz and RISPERIDONE
Efavirenz and RISPERIDONE
Drugs suspected to be involved in the DDI
Complete list of drugs taken by the patient
Risperidone
Clinical case description
A 27-year-old female with perinatally transmitted HIV had been on antiretroviral therapy (ART) with FTC/TDF/EFV for over 10 years. Her latest laboratory results showed an undetectable HIV viral load and a CD4 T cell count of 588 cells/mL. She was also under psychiatric follow-up for moderate mental retardation and impulsive behaviors. For this reason, treatment with risperidone 3 mg orally daily was initiated in 2020. In 2021, the risperidone dose had to be increased to 4.5 mg daily due to episodes of dysthymia, with a good clinical response up to the present.
Potential drug interactions between these medications were reviewed. This included the potential decrease in risperidone concentrations due to CYP3A4 induction by EFV and the potential risk of QT interval prolongation. Concerning these interactions, the patient initially showed a lack of response to risperidone, prompting an increase in dosage above the recommended dosage in the label (3 mg/day) to control dysthymic episodes. On the other hand, no cardiac events were reported throughout this period. An ECG was performed and showed a normal QT interval value.
Clinical Outcome
Drug Interaction Probability Scale (DIPS)
Editorial Comment
The use of risperidone to treat behavior disorders in patients with intellectual disability is an off-label indication. In two randomized placebo-controlled studies, the mean dose of risperidone was 1.45 mg/day (range, 1 to 4 mg/day) in one [Gagiano C, et al. Psychopharmacology (Berl) 2005; 179(3):629-636], and the other initially used 2 mg twice daily, with increases of 4 mg/day weekly up to a maximum total dose of 12 mg/day [Vanden Borre R, et al. Acta Psychiatr Scand 1993; 87:167-171].
Although in this case it is difficult to confirm whether the risperidone dose needed to be increased due to patient characteristics or the presence of efavirenz, from a pharmacokinetic perspective it is plausible that the dose of risperidone had to be increased due to efavirenz's inducing effect. Risperidone is a major substrate of CYP2D6, CYP3A4, and P-glycoprotein, while efavirenz is a moderate inducer of CYP3A4.
University of Liverpool Recommendation
Potential interaction - may require close monitoring, alteration of drug dosage or timing of administration