What antiepileptic drugs are safe to use with Highly Active Antiretroviral Therapy (HAART)?

Antiepileptic Drugs Safe with HAART

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. 1

Preferred Antiepileptic Options with HAART

First-line options:

• Levetiracetam is the safest option due to its low interaction with cytochromes and minimal effect on antiretroviral drug metabolism 1
• Lamotrigine can be safely used with most antiretroviral regimens but may require dose adjustments with certain combinations 1

Antiepileptic Drugs to Avoid:

• 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 1
• These interactions can lead to virologic failure and development of HIV drug resistance 1

Specific Interactions with Antiretroviral Classes

Protease Inhibitors (PIs):

• Avoid carbamazepine, phenytoin, and phenobarbital as they can substantially reduce PI concentrations 1
• Valproic acid may increase zidovudine (AZT) levels, potentially increasing toxicity 1
• Asunaprevir-containing regimens should not be combined with enzyme-inducing antiepileptics 1

Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs):

• Efavirenz, etravirine, and nevirapine can reduce levels of some antiepileptic drugs 1
• When using daclatasvir with efavirenz or etravirine, the daclatasvir dose should be increased to 90 mg daily 1

Nucleoside Reverse Transcriptase Inhibitors (NRTIs):

• Avoid didanosine (ddI) with ribavirin due to increased risk of toxicity including lactic acidosis 1
• Tenofovir levels may be increased when used with certain antiretrovirals and antiepileptics, requiring monitoring of renal function 1

Clinical Decision-Making Algorithm

1. First assess seizure type and HIV treatment status:

   • For new-onset seizures in HIV patients, determine if prophylactic treatment is needed (generally not recommended unless seizures have occurred) 1
   • Consider the patient's current antiretroviral regimen and potential for interactions 1

2. Select appropriate antiepileptic based on interaction potential:

   • For patients on any HAART regimen: Levetiracetam is the safest first choice 1
   • For patients with partial seizures: Gabapentin or lamotrigine can be considered 2, 3
   • For patients with generalized seizures: Lamotrigine or valproic acid (with careful monitoring) 1

3. Monitoring recommendations:

   • Regular monitoring of antiretroviral drug levels when using antiepileptics 1
   • Monitor for seizure control and antiepileptic drug levels, especially after starting or changing HAART regimens 1
   • Assess for signs of toxicity or treatment failure in both epilepsy and HIV management 1

Important Considerations and Pitfalls

• Enzyme-inducing antiepileptics can accelerate metabolism of many antiretrovirals, leading to subtherapeutic levels and treatment failure 1
• Some newer antiepileptic drugs (gabapentin, levetiracetam) have minimal effect on hepatic enzymes, making them safer options 2, 3
• Valproic acid may inhibit metabolism of some antiretrovirals, potentially increasing toxicity 1
• When treating HIV/epilepsy comorbidity, prioritize antiepileptic drugs with minimal drug-drug interactions to maintain HIV viral suppression 1
• Consider therapeutic drug monitoring when using combinations of antiepileptics and antiretrovirals with known interaction potential 1