Review of Drug-Drug Interactions between Antiretroviral and Atypical Antipsychotic Medications

Review of Drug-Drug Interactions between Antiretroviral and Atypical Antipsychotic Medications

Authors: Cristi Sarmiento, PharmD Candidate¹, Erika Rodriguez, PharmD Candidate¹, Andrew Karas, PharmD¹, Elizabeth Sherman, PharmD, AAHIVP^1,2,

1. College of Pharmacy, Nova Southeastern University
2. South Florida, Southeast AIDS Education and Training Center

Drug-drug interactions occur frequently in the treatment of HIV due to the hepatic metabolism of antiretrovirals through the cytochrome P (CYP) 450 oxidase system. Complicating things further, antiretrovirals (ARVs) are one of the few instances in pharmacotherapy where pharmacokinetic boosters are used to augment therapy.  Another class of frequently utilized drugs with a narrow therapeutic index that are heavily hepatically metabolized are atypical antipsychotics. Although named to indicate treatment of psychotic disorders, atypical antipsychotics are frequently used to treat many other psychiatric conditions such as bipolar disorder, major depression, behavioral and psychological symptoms of dementia, autism and other developmental disorders, and Tourette’s disorder among many others.¹ These widespread indications are pertinent to HIV clinicians since up to 23% of patients with HIV in the outpatient setting are diagnosed with a psychiatric illness compared to only 0.4% in the general U.S. population.  Additionally, patients diagnosed with HIV have an increased risk for both schizophrenia and acute psychosis.²   As such, psychotropic medications are frequently co-prescribed with antiretroviral therapy.

It is vital for clinicians to maintain a working knowledge of all commercially available ARV agents and atypical antipsychotics as there may be clinically significant drug-drug interactions influencing their use. Overlooking drug-drug interactions can result in harmful adverse events since, as previously mentioned, both classes encounter pharmacokinetic profiles involving hepatic metabolism via CYP P450 enzyme systems, in particular CYP3A4 and CYP2D6. The clinical impact of these interactions between ARVs and atypical antipsychotics may range from insignificant effects on plasma concentrations to clinical decompensation of psychiatric condition, life-threatening arrhythmias such as torsades de pointes, seizures, orthostatic hypotension and syncope, and paralytic ileus.²

The table below, adapted from the DHHS Adult HIV Guidelines and the University of Liverpool HIV drug interactions website, outlines important drug-drug interactions that should be taken into consideration when prescribing atypical antipsychotics in patients receiving ARVs.  Of note, this table only covers oral therapy and not long-acting injectable formulations of atypical antipsychotics. The table is organized by atypical antipsychotic and ARV classes, identifying the effect on drug concentrations, the dosing recommendations, and clinical comments. Importantly, boosted protease inhibitors and unboosted atazanavir are contraindicated with lurasidone and are expected to increase other atypical antipsychotic levels, requiring dose reductions of the antipsychotic. Non-nucleoside reverse transcriptase inhibitors, as a class, can either increase, decrease, or have no interaction when co-administered with atypical antipsychotics (refer to the table for guidance). The integrase strand transfer inhibitors bictegravir, dolutegravir, and raltegravir have no interactions when co-administered with atypical antipsychotics, requiring no dose adjustments, and may be an optimal choice for patients receiving both classes of medications. However, the boosted integrase inhibitor elvitegravir/cobicistat may increase atypical antipsychotic levels, requiring dose reductions of the antipsychotic. No interactions were identified between atypical antipsychotics and nucleoside reverse transcriptase inhibitors or entry inhibitors. Due to the often complex pharmacokinetic interactions of these two classes of medications, serum concentration monitoring of atypical antipsychotics is warranted if starting antiretroviral therapy.⁴

Table 1: Drug-drug interactions between antiretroviral and atypical antipsychotic medications

References:

1. McDonagh M, Peterson K, Carson S, Fu R, Thakurta S. Drug Class Review: Atypical Antipsychotic Drugs: Final Update 3 Report [Internet]. Drug Class Reviews. 2010. Portland (OR): Oregon Health & Science University.
2. Goodlet KJ, Zmarlicka MT, Peckham AM. Drug–drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs. CNS Spectrums.2018:1-26. doi:10.1017/S109285291800113X
3. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. Available at www.aidsinfo.nih.gov. Accessed January 18, 2019.
4. Hiemke C, Bergemann N, Clement H, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry. 2018;51:9-62
5. Nuplazid (pimavanserin) [prescribing information]. San Diego, CA: Acadia Pharmaceuticals Inc; June 2018.
6. Drug Interaction Checker Lite. Liverpool HIV Interactions. Available at https://www.hiv-druginteractions.org/checker. Accessed January 18, 2019.