Antiepileptic drug selection for people with HIV/AIDS: Evidence‐based guidelines from the ILAE and AAN

Abstract

Summary A joint panel of the American Academy of Neurology (AAN) and the International League Against Epilepsy (ILAE) convened to develop guidelines for selection of antiepileptic drugs (AEDs) among people with HIV/AIDS. The literature was systematically reviewed to assess the global burden of relevant comorbid entities, to determine the number of patients who potentially utilize AEDs and antiretroviral agents (ARVs), and to address AED–ARV interactions. Key findings from this literature search included the following: AED–ARV administration may be indicated in up to 55% of people taking ARVs. Patients receiving phenytoin may require a lopinavir/ritonavir dosage increase of approximately 50% to maintain unchanged serum concentrations (Level C). Patients receiving valproic acid may require a zidovudine dosage reduction to maintain unchanged serum zidovudine concentrations (Level C). Coadministration of valproic acid and efavirenz may not require efavirenz dosage adjustment (Level C). Patients receiving ritonavir/atazanavir may require a lamotrigine dosage increase of approximately 50% to maintain unchanged lamotrigine serum concentrations (Level C). Coadministration of raltegravir/atazanavir and lamotrigine may not require lamotrigine dosage adjustment (Level C). Coadministration of raltegravir and midazolam may not require midazolam dosage adjustment (Level C). Patients may be counseled that it is unclear whether dosage adjustment is necessary when other AEDs and ARVs are combined (Level U). It may be important to avoid enzyme‐inducing AEDs in people on ARV regimens that include protease inhibitors or nonnucleoside reverse transcriptase inhibitors because pharmacokinetic interactions may result in virologic failure, which has clinical implications for disease progression and development of ARV resistance. If such regimens are required for seizure control, patients may be monitored through pharmacokinetic assessments to ensure efficacy of the ARV regimen (Level C).

The impact of enzyme-inducing antiepileptic drugs on antiretroviral drug levels: A case-control study

“…Evidence-based guidelines for AED selection for people with HIV/AIDS(Birbeck et al, 2012b, Birbeck et al, 2012c) indicate that clinically significant drug interactions can occur when antiretroviral (ARV) agents are combined with enzyme-inducing AEDs (EI-AEDs), including carbamazepine, phenytoin, and phenobarbital. These interactions can have bi-directional effects, resulting in altered serum levels of both EI-AEDs and ARVs.…”

Neurologic Complications of HIV-1 Infection and Its Treatment in the Era of Antiretroviral Therapy

“…36 The early data regarding the 38 Given the high comorbidity of these conditions as well as the greater availability worldwide of antiepileptics that are enzyme inducers, these guidelines help neurologists in making appropriate adjustments to maximize therapeutic efficacy of antiepileptic drugYART regimens.…”

Careers in Global Neurology

“…In the past 3 years, a Global Health Section has been founded within the American Academy of Neurology (AAN) 6, 7 , the American Neurological Association (ANA) has initiated an International Outreach Committee 8 , the American Epilepsy Society (AES) has joined forces with the International League against Epilepsy (ILAE) to draft shared clinical care guidelines 9, 10 , and the American Brain Foundation/AAN has awarded at least one clinical research training fellowship annually to a candidate conducting research outside of the US. Change agents within academic neurology pushing for greater global engagements have primarily been younger academics seeking to carve a more defined niche for their interests and to work within the existing framework of US academic neurology.…”