Antiepileptic Drug Interactions with HAART

Preferred Antiepileptic Options

Non-enzyme-inducing antiepileptic drugs (NEIAEDs) such as levetiracetam and lamotrigine are the preferred choices for patients on Highly Active Antiretroviral Therapy (HAART) due to minimal drug interactions, as recommended by the American College of Oncology 1, 2
Levetiracetam is the safest option due to its low interaction with cytochromes and minimal effect on antiretroviral drug metabolism, with a strength of evidence level of high 3, 4
Lamotrigine can be safely used with most antiretroviral regimens but may require dose adjustments with certain combinations, with a moderate level of evidence 1, 2

Enzyme-inducing antiepileptic drugs (EIAEDs) such as carbamazepine, phenobarbital, phenytoin, and oxcarbazepine should be avoided as they can significantly decrease antiretroviral drug levels through CYP3A and CYP2C8 induction, with a high level of evidence 5, 4
These interactions can lead to virologic failure and development of HIV drug resistance, with a high level of evidence 5

Avoid carbamazepine, phenytoin, and phenobarbital as they can substantially reduce Protease Inhibitors (PIs) concentrations, with a high level of evidence 5
Valproic acid may increase zidovudine (AZT) levels, potentially increasing toxicity, with a moderate level of evidence 5
Asunaprevir-containing regimens should not be combined with enzyme-inducing antiepileptics, with a high level of evidence 5
Efavirenz, etravirine, and nevirapine can reduce levels of some antiepileptic drugs, with a moderate level of evidence 5
When using daclatasvir with efavirenz or etravirine, the daclatasvir dose should be increased to 90 mg daily, with a moderate level of evidence 5
Avoid didanosine (ddI) with ribavirin due to increased risk of toxicity including lactic acidosis, with a high level of evidence 5
Tenofovir levels may be increased when used with certain antiretrovirals and antiepileptics, requiring monitoring of renal function, with a moderate level of evidence 5

For new-onset seizures in HIV patients, determine if prophylactic treatment is needed (generally not recommended unless seizures have occurred), with a moderate level of evidence 6, 7
Consider the patient's current antiretroviral regimen and potential for interactions, with a high level of evidence 5
Levetiracetam is the safest first choice for patients on any HAART regimen, with a high level of evidence 3, 4
Lamotrigine or valproic acid (with careful monitoring) can be considered for patients with generalized seizures, with a moderate level of evidence 1, 2

Regular monitoring of antiretroviral drug levels when using antiepileptics, with a high level of evidence 5
Monitor for seizure control and antiepileptic drug levels, especially after starting or changing HAART regimens, with a moderate level of evidence 6
Assess for signs of toxicity or treatment failure in both epilepsy and HIV management, with a high level of evidence 5, 6