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

Abstract

Purpose To evaluate the impact of enzyme-inducing antiepileptic drugs (EI-AEDs) on serum antiretroviral (ARV) levels in patients with HIV. Methods Data from the U.S. Military HIV Natural History Study were screened to identify participants taking ARVs with EI-AEDs and controls taking ARVs with non enzyme inducing AEDs (NEI-AEDs). The proportion of serum ARV levels below the recommended minimum concentrations (Cmin) was compared between these groups. Results ARV levels were available for 10 individuals exposed to 16 intervals on combined ARVs/EI-AEDs (phenytoin and carbamazepine) and for 25 controls exposed to 30 overlap intervals on combined ARVs/NEI-AEDs. The percentage of overlap intervals with ≥1 ARV levels below Cmin was higher in the EI-AED group than in controls (37.5% vs. 23.3%; p=0.124). After excluding intervals associated with serum levels of EI-AEDs below the reference range (n=6), the proportion of intervals with ≥1 ARV level below Cmin was significantly greater among EI-AED recipients (60%) compared to controls (23.3%; p=0.008). Conclusions ARV levels below Cmin were more common in participants receiving EI-AEDs, the difference being statistically significant for intervals associated with EI-AED levels within the reference range. These data suggest that, in agreement with current guidelines, EI-AEDs should be avoided in patients receiving ARV therapy.

Pharmacokinetic proofs on interaction between Zolpidem and Phenytoin: a two-treatment, two-period study in healthy male subjects

“…Therefore, these results bring new information referring to the pharmacokinetic interactions previously confirmed for both zolpidem and phenytoin [31][32][33][34].…”

Subacute sclerosing panencephalitis: clinical phenotype, epidemiology, and preventive interventions

“…Levetiracetam is reported to have mild improvement in myoclonus. 48 This situation is largely relevant to sub-Saharan Africa where 83% of children with HIV infection reside and data to support development of recommendations to optimize care in this setting are limited. 9,46 This agent is considered a first-line intervention for the symptomatic treatment of seizures in patients with SSPE in countries such as Turkey and South Africa.…”

“…47 Children coinfected with HIV and SSPE are challenging to manage, as the cross-drug interactions between carbamazepine and antiretroviral agents such as protease inhibitors or non-nucleoside reverse transcriptase inhibitors may result in virological failure, thus requiring careful monitoring of HIV viral titres and carbamazepine levels. 48 This situation is largely relevant to sub-Saharan Africa where 83% of children with HIV infection reside and data to support development of recommendations to optimize care in this setting are limited. 49 CONCLUSIONS SSPE is an avoidable disorder.…”

Neuropsychiatric Aspects of Infectious Diseases

“…64, 65 This must be weighed against the potential disadvantages of other mood stabilizers, such as lithium, which can exacerbate renal disease, or carbamazepine, which can induce bone marrow suppression, hepatotoxicity, and induce the metabolism of ART (particularly protease inhibitors). 64, 66 Lamotrigine has been tested for HIV-associated peripheral neuropathy and may be useful for treating mixed mania or bipolar depression in HIV; however, patients with overt manic symptomatology generally require a traditional mood stabilizer. This anticonvulsant requires careful upward dose titration because of risk of severe hypersensitivity (Stevens-Johnson syndrome).…”