US DHHS Guidelines with Australian commentary
Drug-Drug Interactions Overview
Last Updated: October 25, 2018; Last Reviewed: October 25, 2018
Mechanisms of Antiretroviral-Associated Drug Interactions
PK interactions may occur during absorption, metabolism, or elimination of the ARV and/or the interacting drugs. This table does not include a comprehensive list of all possible mechanisms of interactions for individual ARV drugs (e.g., transporters); however, the table lists the most common mechanisms of known interactions and focuses on absorption and CYP- and UGT1A1-mediated interactions.
Note: N/A indicates that there are no clinically relevant interactions by these mechanisms. Identified mechanisms are specific to individual ARV drugs and not combinations of ARV drugs.
|ARV Drugs by Drug Class||Mechanisms That May Affect Oral Absorption of ARV Drugs||Enzymes That Metabolize or are Induced or Inhibited by ARV Drugs||Other Mechanisms of Known Drug Interactions|
|Increasing Gastric pH||Cationic Chelation||P-glyco-protein||CYP Substrate||CYP Inhibitor||CYP Inducer||UGT1A1|
|BIC||N/A||Concentration decreased by products that contain polyvalent cations (e.g., Ca, Mg, Al, Fe, Zn)||Substrate||3A4||N/A||N/A||Substrate||Inhibitor of renal transporters OCT2 and MATE1|
|DTG||N/A||Substrate||3A4 (minor)||N/A||N/A||Substrate||Inhibitor of renal transporters OCT2 and MATE1|
|PK Enhancers (Boosters)|
|RTV||N/A||N/A||Substrate, inhibitor||3A4, 2D6||3A4, 2D6||1A2, 2B6, 2C8, 2C9, 2C19||Inducer||N/A|
Note: When PIs are coadministered with PK enhancers (boosters), the pharmacologic properties of both agents should be considered when assessing potential drug interactions.
|ATV||Concentration decreased||N/A||Substrate, inducer, inhibitor||3A4||3A4||N/A||Inhibitor||OATP inhibitor|
|DRV||N/A||N/A||Substrate, inducer||3A4||3A4||2C9||N/A||OATP inhibitor|
|FPV||Concentration decreased by H2 antagonist||N/A||Substrate, inhibitor||3A4||3A4||N/A||N/A||N/A|
|SQV||N/A||N/A||Substrate, inhibitor||3A4||3A4||N/A||N/A||OATP inhibitor|
|TPV||N/A||N/A||Substrate, inducer||3A4||2D6||3A4, 1A2, 2C19||N/A||OATP inhibitor|
|EFV||N/A||N/A||N/A||2B6 (primary), 2A6, 3A4||3A4||3A4, 2B6, 2C19||N/A||N/A|
|ETR||N/A||N/A||N/A||3A4, 2C9, 2C19||2C9, 2C19||3A4||N/A||N/A|
|NVP||N/A||N/A||N/A||3A4, 2B6||N/A||3A4, 2B6||N/A||N/A|
|ABC||N/A||N/A||N/A||N/A||N/A||N/A||Substrate||Alcohol dehydrogenase substrate|
|TDF||N/A||N/A||Substrate||N/A||N/A||N/A||N/A||Competition of active renal tubular secretion|
|Key to Acronyms: 3TC = lamivudine; ABC = abacavir; Al = aluminum; ARV = antiretroviral; ATV = atazanavir; BIC = bictegravir; Ca = calcium; COBI = cobicistat; CYP = cytochrome P; DOR = doravirine; DRV = darunavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; Fe = iron; FPV = fosamprenavir; FTC = emtricitabine; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; MATE = multidrug and toxin extrusion transporter; Mg = magnesium; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitors; NRTI = nucleoside reverse transcriptase inhibitors; NVP = nevirapine; OCT2 = organic cation transporter 2; OATP = organic anion-transporting polypeptide; PK = pharmacokinetic; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; T-20 = enfuvirtide; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TPV = tipranavir; UGT = uridine diphosphate glucuronosyltransferase; ZDV = zidovudine; Zn = zinc|