Adult Antiretroviral Guidelines

US DHHS Guidelines with Australian Commentary

INSTI interactions

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Drug Interactions Between Integrase Strand Transfer Inhibitors and Other Drugs

This table provides information on the known or predicted interactions between integrase strand transfer inhibitors (INSTIs) (bictegravir [BIC], dolutegravir [DTG], elvitegravir [EVG], or raltegravir [RAL]) and non-antiretroviral (ARV) drugs. EVG is always coadministered with cobicistat. Cabotegravir (CAB) intramuscular (IM) plus rilpivirine (RPV) IM are co-packaged into a single product and are coadministered as a complete regimen; therefore, the dosing recommendations and clinical comments reflect the combination of CAB IM and RPV IM treatments. Drug interaction studies were not conducted with either CAB IM or RPV IM. Drug interaction studies with oral CAB and RPV were leveraged to make the dosing recommendations for CAB IM and RPV IM. For information regarding interactions between INSTIs and other ARV drugs, including dosing recommendations, refer to Tables 24c24e24f, and 25b.

Recommendations for managing a particular drug interaction may differ, depending on whether a new ARV drug is being initiated in a patient on a stable concomitant medication or whether a new concomitant medication is being initiated in a patient on a stable ARV regimen. The magnitude and significance of drug interactions are difficult to predict when several drugs with competing metabolic pathways are prescribed concomitantly. In cases where an interacting drug needs to be replaced with an alternative, providers should exercise their clinical judgement to select the most appropriate alternative medication to use.

Concomitant Drug
INSTI
Effect on INSTI or Concomitant Drug Concentrations
Dosing Recommendations and Clinical Comments
Acid Reducers
Al, Mg,

+/–

Ca-Containing Antacids

Please refer to the Miscellaneous Drugs section of this table for recommendations on use with other polyvalent cation products (e.g., Fe and Ca supplements, multivitamins).
BICAl/Mg Hydroxide Antacid

  • ↔ BIC AUC if antacid is administered 2 hours after BIC and under fasting conditions
  • BIC AUC ↓ 52% if antacid is administered 2 hours before BIC
  • BIC AUC ↓ 47% to 79% if administered simultaneously with antacid
CaCO3 Antacid

  • ↔ BIC AUC if administered with food
  • BIC AUC ↓ 33% if administered under fasting conditions
With Antacids That Contain Al/Mg

  • Administer antacids that contain Al/Mg at least 2 hours after or 6 hours before BIC.
With Antacids That Contain Ca

  • Administer BIC and antacids that contain Ca together with food.
  • Do not coadminister BIC simultaneously with antacids that contain Ca on an empty stomach.
CAB POCAB PO ↓ expectedWith Antacids That Contain Polyvalent Cations (Al, Mg, or Ca)

  • Administer antacid products at least 2 hours before or 4 hours after taking CAB PO.
CAB IM↔ CAB IM expectedNo dose adjustment needed.
DTGDTG AUC ↓ 74% if administered simultaneously with antacid

DTG AUC ↓ 26% if administered 2 hours before antacid
Administer DTG at least 2 hours before or at least 6 hours after antacids that contain polyvalent cations.
EVG/cEVG AUC ↓ 40% to 50% if administered simultaneously with antacid

EVG AUC ↓ 15% to 20% if administered 2 hours before or after antacid; ↔ with a 4‑hour interval
Separate EVG/c and antacid administration by more than 2 hours.
RALAl/Mg Hydroxide Antacid

  • RAL Cmin ↓ 49% to 63%
CaCO3 Antacid

  • RAL 400 mg twice daily: Cmin ↓ 32%
  • RAL 1,200 mg once daily: Cmin ↓ 48% to 57%
Do not coadminister RAL and Al/Mg hydroxide antacids. Use alternative acid-reducing agent.

With CaCO3 Antacids

  • RAL 1,200 mg once daily: Do not coadminister.
  • RAL 400 mg twice daily: No dose adjustment or separation needed.
H2-Receptor AntagonistsBIC, CAB (PO and IM), DTG, EVG/c↔ INSTINo dose adjustment needed.
RALRAL AUC ↑ 44% and Cmax ↑ 60%No dose adjustment needed.
Proton Pump InhibitorsBIC, CAB (PO and IM), DTG, EVG/c↔ INSTINo dose adjustment needed.
RALRAL AUC ↑ 37% and Cmin ↑ 24%No dose adjustment needed.
Alpha-Adrenergic Antagonists for Benign Prostatic Hyperplasia
AlfuzosinBIC, CAB (PO and IM), DTG, RAL↔ alfuzosin expectedNo dose adjustment needed.
EVG/c↑ alfuzosin expectedContraindicated.
DoxazosinBIC, CAB (PO and IM), DTG, RAL↔ doxazosin expectedNo dose adjustment needed.
EVG/c↑ doxazosin possibleInitiate doxazosin at lowest dose. Titrate based on doxazosin efficacy and adverse events. Doxazosin dose reduction may be needed.
TamsulosinBIC, CAB (PO and IM), DTG, RAL↔ tamsulosin expectedNo dose adjustment needed.
EVG/c↑ tamsulosin expectedDo not coadminister unless the benefits outweigh the risks. If coadministered, monitor for tamsulosin-related adverse events.
TerazosinBIC, CAB (PO and IM), DTG, RAL↔ terazosin expectedNo dose adjustment needed.
EVG/c↑ terazosin possibleInitiate terazosin at lowest dose. Titrate based on terazosin efficacy and adverse events. Terazosin dose reduction may be necessary.
SilodosinBIC, CAB (PO and IM), DTG, RAL↔ silodosin expectedNo dose adjustment needed.
EVG/c↑ silodosin expectedContraindicated.
Antibacterials - Antimycobacterials
RifabutinBICRifabutin 300 mg Once Daily

  • BIC AUC ↓ 38% and Cmin ↓ 56%
Do not coadminister.
CAB POCAB PO AUC ↓ 23% and Cmin ↓ 26%

↔ rifabutin
No dose adjustment needed.
CAB IM↓ CAB IM and RPV expected

↔ rifabutin expected
Contraindicated due to ↓ RPV, which is co-packaged and coadministered with CAB IM.
DTGRifabutin 300 mg Once Daily

  • ↔ DTG AUC and Cmin ↓ 30%
No dose adjustment needed.
EVG/cRifabutin 150 mg Every Other Day With EVG/c Once Daily Compared to Rifabutin 300 mg Once Daily Alone

  • ↔ rifabutin AUC
  • 25-O-desacetyl-rifabutin AUC ↑ 625%
  • EVG AUC ↓ 21% and Cmin ↓ 67%
Do not coadminister.
RALRAL AUC ↑ 19% and Cmin ↓ 20%No dose adjustment needed.
RifampinBICBIC AUC ↓ 75%Contraindicated.
CAB POCAB PO AUC ↓ 59% and Cmin ↓ 50%Contraindicated.
CAB IMCAB IM ↓ expectedContraindicated.
DTGRifampin With DTG 50 mg Twice Daily Compared to DTG 50 mg Twice Daily Alone

  • DTG AUC ↓ 54% and Cmin ↓ 72%
Rifampin With DTG 50 mg Twice Daily Compared to DTG 50 mg Once Daily Alone

  • DTG AUC ↑ 33% and Cmin ↑ 22%
Use DTG 50 mg twice daily (instead of DTG 50 mg once daily) in patients without suspected or documented INSTI-associated resistance mutations.

Consider an alternative to rifampin, such as rifabutin, in patients with certain suspected or documented INSTI-associated resistance mutations.
EVG/cSignificant ↓ EVG and COBI expectedContraindicated.
RALRAL 400 mg

  • RAL AUC ↓ 40% and Cmin ↓ 61%
Rifampin With RAL 800 mg Twice Daily Compared to RAL 400 mg Twice Daily Alone

  • RAL AUC ↑ 27% and Cmin ↓ 53%
Use RAL 800 mg twice daily instead of 400 mg twice daily.

Do not coadminister RAL 1,200 mg once daily with rifampin.

Monitor closely for virologic response or consider using rifabutin as an alternative rifamycin.
RifapentineBIC, EVG/cSignificant ↓ BIC, EVG, and COBI expectedDo not coadminister.
CAB (PO and IM)Significant ↓ CAB (PO and IM) expectedContraindicated.
DTGRifapentine 900 mg Once Weekly

  • DTG AUC ↓ 26% and Cmin ↓ 47%
With once-weekly rifapentine, DTG 50 mg daily may be used in patients with viral suppression on daily DTG. Monitor for virologic efficacy.

Do not coadminister in patients who require twice-daily DTG.

Do not coadminister DTG with once-daily rifapentine.
RALRifapentine 900 mg Once Weekly

  • RAL AUC ↑ 71% and Cmin ↓ 12%
Rifapentine 600 mg Once Daily

  • RAL Cmin ↓ 41%
For once-weekly rifapentine and RAL 400 mg twice daily, no dose adjustment is needed.

Do not coadminister with once-daily rifapentine.
Antibacterials - Macrolides
AzithromycinAll INSTIs↔ azithromycin expectedNo dose adjustment needed.
ClarithromycinBIC↑ BIC possibleNo dose adjustment needed.
CAB (PO and IM), DTG, RAL↔ clarithromycin expectedNo dose adjustment needed.
EVG/c↑ clarithromycin expected

↑ COBI possible
Reduce clarithromycin dose by 50% in patients with CrCl 50 to 60 mL/min.

Do not coadminister in patients with CrCl <50 mL/min. Consider alternative ARV or use azithromycin.
ErythromycinBIC↑ BIC possibleNo dose adjustment needed.
CAB (PO and IM), DTG, RAL↔ INSTI expected

↔ erythromycin expected
No dose adjustment needed.
EVG/c↑ erythromycin expected

↑ COBI possible
No data available for dose recommendation. Consider alternative ARV or use azithromycin.
Anticoagulants
ApixabanBIC, CAB (PO and IM), DTG, RAL↔ apixaban expectedNo dose adjustment needed.
EVG/c↑ apixaban expectedDo not coadminister in patients who require apixaban 2.5 mg twice daily.

Reduce apixaban dose by 50% in patients who require apixaban 5 mg or 10 mg twice daily.
DabigatranBIC, CAB (PO and IM), DTG, RAL↔ dabigatran expectedNo dose adjustment needed.
EVG/c↑ dabigatran expected

With COBI 150 mg Alone

  • Dabigatran AUC ↑ 110% to 127%
Dabigatran dosing recommendation depends on indication and renal function. Refer to dabigatran prescribing information for dosing instructions when using dabigatran concomitantly with P-glycoprotein inhibitors.
EdoxabanBIC, CAB (PO and IM), DTG, RAL↔ edoxaban expectedNo dose adjustment needed.
EVG/c↑ edoxaban expectedStroke Prevention in Nonvalvular Atrial Fibrillation

  • No dose adjustment needed.
Deep Venous Thrombosis and Pulmonary Embolism

  • Administer edoxaban 30 mg once daily.
RivaroxabanBIC, CAB (PO and IM), DTG, RAL↔ rivaroxaban expectedNo dose adjustment needed.
EVG/c↑ rivaroxaban expectedDo not coadminister.
WarfarinBIC, CAB (PO and IM), DTG, RAL↔ warfarin expectedNo dose adjustment needed.
EVG/c↑ or ↓ warfarin possibleMonitor INR and adjust warfarin dose accordingly.
Anticonvulsants
CarbamazepineBIC↓ BIC possibleDo not coadminister.
CAB (PO and IM)↓ CAB expectedContraindicated.
DTGDTG AUC ↓ 49%Increase DTG dose to 50 mg twice daily in ART-naive or ART-experienced (but INSTI-naive) patients.

Do not coadminister in INSTI-experienced patients with known or suspected INSTI resistance.
EVG/cCarbamazepine AUC ↑ 43%

EVG AUC ↓ 69% and Cmin ↓ >99%

↓ COBI expected
Contraindicated.
RAL↓ or ↔ RAL possibleDo not coadminister.
EslicarbazepineAll INSTIs↓ INSTI possible

↓ COBI possible
Consider alternative ARV or anticonvulsant.
EthosuximideBIC, CAB (PO and IM), DTG, RAL↔ ethosuximide expectedNo dose adjustment needed.
EVG/c↑ ethosuximide possibleMonitor for ethosuximide-related adverse events.
LamotrigineBIC, CAB (PO and IM), DTG, RAL↔ lamotrigine expectedNo dose adjustment needed.
EVG/cNo dataMonitor anticonvulsant concentrations and adjust dose accordingly.
Oxcarbazepine BIC, DTG↓ BIC and DTG possibleDo not coadminister.
CAB (PO and IM)↓ CAB expectedContraindicated.
EVG/c, RAL↓ EVG/c and RAL possibleConsider alternative ARV or anticonvulsant.
Phenobarbital, PhenytoinBIC, DTG, RAL↓ BIC and DTG possible

↓ or ↔ RAL possible
Do not coadminister.
CAB (PO and IM), EVG/c↓ CAB and EVG/c expectedContraindicated.
Valproic AcidAll INSTIsNo dataMonitor valproic acid concentration and virologic response.
Antidepressants, Anxiolytics, and Antipsychotics

Also see the Sedative/Hypnotics section below
BupropionBIC, CAB (PO and IM), DTG, RAL↔ bupropion expectedNo dose adjustment needed.
EVG/c↑ bupropion possibleTitrate bupropion dose based on clinical response.
BuspironeBIC, CAB (PO and IM), DTG, RAL↔ buspirone expectedNo dose adjustment needed.
EVG/c↑ buspirone possibleInitiate buspirone at a low dose. Buspirone dose reduction may be needed.
NefazodoneBIC, CAB (PO and IM), DTG, RAL↔ nefazodone expectedNo dose adjustment needed.
EVG/c↑ nefazodone expectedConsider alternative ARV or antidepressant.
TrazodoneBIC, CAB (PO and IM), DTG, RAL↔ trazodone expectedNo dose adjustment needed.
Tricyclic Antidepressants

Amitriptyline, desipramine, doxepin, imipramine, nortriptyline
BIC, CAB (PO and IM), DTG, RAL↔ TCA expectedNo dose adjustment needed.
EVG/cDesipramine AUC ↑ 65%Initiate with lowest dose of TCA and titrate dose carefully.
↑ TCA expectedInitiate with lowest dose of TCA. Titrate dose carefully based on antidepressant response and/or drug concentrations.
Selective Serotonin Reuptake Inhibitors

Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
EVG/c↔ sertralineNo dose adjustment needed.
EVG/c↑ other SSRIs possibleInitiate with lowest dose of SSRI. Titrate dose carefully based on antidepressant response.
BIC, CAB (PO and IM), DTG, RAL↔ SSRI expectedNo dose adjustment needed.
Antipsychotics
AripiprazoleBIC, CAB (PO and IM), DTG, RAL↔ aripiprazole expectedNo dose adjustment needed.
EVG/c↑ aripiprazole expectedAdminister 25% of the usual aripiprazole dose. Titrate based on aripiprazole efficacy and adverse events. Refer to aripiprazole label for dosing recommendations in patients who are known to be CYP2D6 poor metabolizers or who have major depressive disorder.
BrexpiprazoleBIC, CAB (PO and IM), DTG, RAL↔ brexpiprazole expectedNo dose adjustment needed.
EVG/c↑ brexpiprazole expectedAdminister 25% of the usual brexpiprazole dose. Titrate based on brexpiprazole efficacy and adverse events. Refer to brexpiprazole label for dosing recommendations in patients who are known to be CYP2D6 poor metabolizers or who have major depressive disorder.
CariprazineBIC, CAB (PO and IM), DTG, RAL↔ cariprazine expectedNo dose adjustment needed.
EVG/c↑ cariprazine expectedStarting Cariprazine in a Patient Who Is Already Receiving EVG/c

  • Administer cariprazine 1.5 mg on Day 1 and Day 3, with no dose given on Day 2. From Day 4 onward, administer cariprazine 1.5 mg daily. Dose can be increased to a maximum of cariprazine 3 mg daily. If EVG/c is withdrawn, cariprazine dose may need to be increased.
Starting EVG/c in a Patient Who Is Already Receiving Cariprazine

  • For patients receiving cariprazine 3 mg or cariprazine 6 mg daily, reduce the dose by half. For patients receiving cariprazine 4.5 mg daily, reduce dose to cariprazine 1.5 mg or cariprazine 3 mg daily. For patients receiving cariprazine 1.5 mg daily, change to cariprazine 1.5 mg every other day. If EVG/c is withdrawn, cariprazine dose may need to be increased.
IloperidoneBIC, CAB (PO and IM), DTG, RAL↔ iloperidone expectedNo dose adjustment needed.
EVG/c↑ iloperidone expectedDecrease iloperidone dose by 50%.
LumateperoneBIC, CAB (PO and IM), DTG, RAL↔ lumateperone expectedNo dose adjustment needed.
EVG/c↑ lumateperone expectedDo not coadminister.
LurasidoneBIC, CAB (PO and IM), DTG, RAL↔ lurasidone expectedNo dose adjustment needed.
EVG/c↑ lurasidone expectedContraindicated.
OlanzapineAll INSTIs↔ olanzapine expectedNo dose adjustment needed.
Other Antipsychotics

CYP3A4 and/or CYP2D6 substrates (e.g., perphenazine, risperidone, thioridazine)
EVG/c↑ antipsychotic possibleInitiate antipsychotic at a low dose. Antipsychotic dose reduction may be needed.
PimavanserinBIC, CAB (PO and IM), DTG, RAL↔ pimavanserin expectedNo dose adjustment needed.
EVG/c↑ pimavanserin expectedReduce pimavanserin dose to 10 mg.
PimozideBIC, CAB (PO and IM), DTG, RAL↔ pimozide expectedNo dose adjustment needed.
EVG/c↑ pimozide expectedContraindicated.
QuetiapineBIC, CAB (PO and IM), DTG, RAL↔ quetiapine expectedNo dose adjustment needed.
EVG/c↑ quetiapine AUC expectedStarting Quetiapine in a Patient Receiving EVG/c

  • Start quetiapine at the lowest dose and titrate up as needed. Monitor for quetiapine efficacy and adverse events.
Starting EVG/c in a Patient Receiving a Stable Dose of Quetiapine

  • Reduce quetiapine dose to 1/6 of the current dose. Closely monitor for quetiapine efficacy and adverse events.
ZiprasidoneBIC, CAB (PO and IM), DTG, RAL↔ ziprasidone expectedNo dose adjustment needed.
EVG/c↑ ziprasidone possibleMonitor for ziprasidone-related adverse events.
Antifungals
IsavuconazoleBIC, CAB (PO and IM), DTG, RAL↑ INSTI possibleNo dose adjustment needed.
EVG/c↑ isavuconazole expected

↑ or ↓ EVG and COBI possible
If coadministered, consider monitoring isavuconazole concentrations and assessing virologic response.
ItraconazoleBIC↑ BIC expectedNo dose adjustment needed.
CAB (PO and IM), DTG, RAL↔ INSTI expected

↔ itraconazole expected
No dose adjustment needed.
EVG/c↑ itraconazole expected

↑ EVG and COBI possible
Consider monitoring itraconazole concentrations to guide dose adjustments. Do not coadminister with high itraconazole doses (>200 mg/day) unless guided by itraconazole concentrations.
PosaconazoleBIC↑ BIC expectedNo dose adjustment needed.
CAB (PO and IM), DTG, RAL↔ INSTI expected

↔ posaconazole expected
No dose adjustment needed.
EVG/c↑ EVG and COBI possible

↑ posaconazole possible
If coadministered, monitor posaconazole concentrations.
VoriconazoleBIC↑ BIC possibleNo dose adjustment needed.
CAB (PO and IM), DTG, RAL↔ INSTI expected

↔ voriconazole expected
No dose adjustment needed.
EVG/c↑ voriconazole expected

↑ EVG and COBI possible
Do not coadminister voriconazole and COBI, unless the benefit outweighs the risk. If coadministered, consider monitoring voriconazole concentrations and adjust dose accordingly.
Antihyperglycemics
MetforminBICMetformin AUC ↑ 39%Monitor for adverse events of metformin.
DTGDTG 50 mg Once Daily plus Metformin 500 mg Twice Daily

  • Metformin AUC ↑ 79% and Cmax ↑ 66%
DTG 50 mg Twice Daily plus Metformin 500 mg Twice Daily

  • Metformin AUC ↑ 2.4-fold and Cmax ↑ 2-fold
Start metformin at the lowest dose and titrate based on glycemic control. Monitor for adverse events of metformin.

When starting/stopping DTG in patients on metformin, dose adjustment of metformin may be necessary to maintain optimal glycemic control and/or minimize adverse events of metformin.
CAB (PO and IM), RAL↔ metformin expectedNo dose adjustment needed.
SaxagliptinBIC, CAB (PO and IM), DTG, RAL↔ saxagliptin expectedNo dose adjustment needed.
EVG/c↑ saxagliptin expectedLimit saxagliptin dose to 2.5 mg once daily.
Dapagliflozin/

Saxagliptin
BIC, CAB (PO and IM), DTG, RAL↔ dapagliflozin or saxagliptin expectedNo dose adjustment needed.
EVG/c↑ saxagliptin expectedDo not coadminister. Dapagliflozin is available only as a coformulated drug that contains 5 mg of saxagliptin. When coadministered with EVG/c, the dose of saxagliptin should not exceed 2.5 mg once daily; thus, this combination is not recommended.
Antiplatelets
ClopidogrelBIC, CAB (PO and IM), DTG, RAL↔ clopidogrel expectedNo dose adjustment needed.
EVG/c↓ clopidogrel active metabolite, with impaired platelet inhibition expectedDo not coadminister.
PrasugrelBIC, CAB (PO and IM), DTG, RAL↔ prasugrel expectedNo dose adjustment needed.
EVG/c↓ prasugrel active metabolite, with no impairment of platelet inhibition expectedNo dose adjustment needed.
TicagrelorBIC, CAB (PO and IM), DTG, RAL↔ ticagrelor expectedNo dose adjustment needed.
EVG/c↑ ticagrelor expectedDo not coadminister.
VorapaxarBIC, CAB (PO and IM) DTG, RAL↔ vorapaxar expectedNo dose adjustment needed.
EVG/c↑ vorapaxar expectedDo not coadminister.
Antivirals—Orthopoxviruses (Smallpox, Mpox)
BrincidofovirBIC, CAB (PO and IM), DTG, RAL↔ INSTI expectedNo dose adjustment needed.
EVG/c↑ brincidofovir possible

↑ EVG possible
Administer EVG/c dose at least 3 hours after administering brincidofovir and monitor for brincidofovir-related adverse events (i.e., elevations in ALT/AST and bilirubin and GI adverse events).
CidofovirBIC, CAB (PO and IM), DTG, RAL↔ INSTI expected

↔ cidofovir expected
No dose adjustment needed.
TecovirimatCAB (IM)↔ CAB expectedNo dose adjustment needed.

Do not initiate CAB/RPV IM during or within 2 weeks after tecovirimat treatment. (Refer to Table 24b for interaction with RPV.)
BIC, CAB (PO), DTG, EVG/c, RAL↔ INSTI expectedNo dose adjustment needed.
Beta-Agonists, Long-Acting Inhaled
Arformoterol, FormoterolAll INSTIs↔ arformoterol or formoterol expectedNo dose adjustment needed.
IndacaterolBIC, CAB (PO and IM), DTG, RAL↔ indacaterol expectedNo dose adjustment needed.
EVG/c↑ indacaterol expected
OlodaterolBIC, CAB (PO and IM), DTG, RAL↔ olodaterol expectedNo dose adjustment needed.
EVG/c↑ olodaterol expected
SalmeterolBIC, CAB (PO and IM), DTG, RAL↔ salmeterol expectedNo dose adjustment needed.
EVG/c↑ salmeterol possibleDo not coadminister due to the potential for increased risk of salmeterol-associated cardiovascular events.
Cardiac Medications
AmiodaroneBIC, CAB (PO and IM), DTG, RAL↔ INSTI expected

↔ amiodarone expected
No dose adjustment needed.
EVG/c↑ INSTI possible

↑ amiodarone possible
Do not coadminister unless the benefits outweigh the risks. If coadministration is necessary, monitor for amiodarone-related adverse events and consider monitoring ECG and amiodarone concentrations.
Bepridil, Digoxin, Disopyramide, Dronedarone, Flecainide, Systemic Lidocaine, Mexilitine, Propafenone, QuinidineBIC, CAB (PO and IM), DTG↔ expected for the listed antiarrhythmics, except for disopyramide

↑ disopyramide possible
No dose adjustment needed.

Monitor for disopyramide-related adverse events.
RAL↔ expected for the listed antiarrhythmicsNo dose adjustment needed.
EVG/c↑ antiarrhythmics possible

Digoxin Cmax ↑ 41% and ↔ AUC
Therapeutic drug monitoring for antiarrhythmics, if available, is recommended.
Beta Blockers

(e.g., metoprolol, timolol)
BIC, CAB (PO and IM), DTG, RAL↔ beta blocker expectedNo dose adjustment needed.
EVG/c↑ beta blocker possibleBeta blocker dose may need to be decreased; adjust dose based on clinical response.

Consider using an alternative ARV or a beta blocker that is not metabolized by CYP450 enzymes (e.g., atenolol, labetalol, nadolol, sotalol).
BosentanBIC, DTG↓ BIC and DTG possibleNo dose adjustment needed.
CAB (PO and IM)↔ bosentan expectedConsider using alternative ARV or an alternative to bosentan because bosentan may ↓ RPV, which is co-packaged and coadministered with CAB IM. If bosentan is used with RPV, monitor virologic response to ART.
RAL↔ bosentan expectedNo dose adjustment needed.
EVG/c↑ bosentan possibleIn Patients on EVG/c ≥10 Days

  • Start bosentan at 62.5 mg once daily or every other day based on individual tolerability.
In Patients on Bosentan Who Require EVG/c

  • Stop bosentan ≥36 hours before EVG/c initiation. At least 10 days after initiation of EVG/c, resume bosentan at 62.5 mg once daily or every other day based on individual tolerability.
Calcium Channel BlockersBIC↑ BIC possible with diltiazem

↔ expected for all other CCBs
No dose adjustment needed.
CAB (PO and IM), DTG, RAL↔ INSTI expected

↔ CCB expected
No dose adjustment needed.
EVG/c↑ CCB possibleTitrate CCB dose and monitor for CCB efficacy and adverse events.
DofetilideBIC, DTG↑ dofetilide expectedContraindicated.
CAB (PO and IM), RAL↔ dofetilide expectedNo dose adjustment needed.
EVG/c↑ dofetilide possibleDo not coadminister.
EplerenoneBIC, CAB (PO and IM), DTG, RAL↔ eplerenone expectedNo dose adjustment needed.
EVG/c↑ eplerenone expectedContraindicated.
IvabradineBIC, CAB (PO and IM), DTG, RAL↔ ivabradine expectedNo dose adjustment needed.
EVG/c↑ ivabradine expectedContraindicated.
RanolazineBIC, CAB (PO and IM), DTG, RAL↔ ranolazine expectedNo dose adjustment needed.
EVG/c↑ ranolazine expectedContraindicated.
Corticosteroids
Beclomethasone

Inhaled or intranasal
BIC, CAB (PO and IM), DTG, EVG/c, RAL↔ glucocorticoid expectedNo dose adjustment needed.
Budesonide, Ciclesonide, Fluticasone, Mometasone

Inhaled or intranasal
BIC, CAB (PO and IM), DTG, RAL↔ glucocorticoid expectedNo dose adjustment needed.
EVG/c↑ glucocorticoid possibleDo not coadminister unless the potential benefits of inhaled or intranasal corticosteroid outweigh the risks of systemic corticosteroid adverse effects. Coadministration can result in adrenal insufficiency and Cushing’s syndrome. Consider using an alternative corticosteroid (e.g., beclomethasone).
Betamethasone, Budesonide

Systemic
BIC, CAB (PO and IM), DTG, RAL↔ INSTI expected

 ↔ glucocorticoid expected
No dose adjustment needed.
EVG/c↑ glucocorticoid possible

↓ EVG possible
Do not coadminister unless the potential benefits of systemic budesonide outweigh the risks of systemic corticosteroid adverse effects. Coadministration can result in adrenal insufficiency and Cushing’s syndrome.
Dexamethasone

Systemic
BIC↓ BIC possibleConsider alternative corticosteroid for long-term use or alternative ARV. If coadministration is necessary, monitor virologic response to ART.
CAB (PO and IM), DTG, RAL↔ INSTI expectedNo dose adjustment needed.
EVG/c↓ EVG and COBI possibleConsider alternative corticosteroid for long-term use or alternative ARV. If coadministration is necessary, monitor virologic response to ART.
Prednisone, Prednisolone

Systemic
BIC, CAB (PO and IM), DTG, RAL↔ glucocorticoid expectedNo dose adjustment needed.
EVG/c↑ prednisolone possibleCoadministration may be considered if the potential benefits outweigh the risks of systemic corticosteroid adverse effects. If coadministration is necessary, monitor for adrenal insufficiency and Cushing’s syndrome.
Betamethasone, Methylprednisolone,

Prednisolone, Triamcinolone

Local injections, including intra-articular, epidural, or intra-orbital
BIC, CAB (PO and IM), DTG, RAL↔ glucocorticoid expectedNo dose adjustment needed.
EVG/c↑ glucocorticoid expectedDo not coadminister. Coadministration may result in adrenal insufficiency and Cushing’s syndrome.
Hepatitis C Direct-Acting Antiviral Agents
DaclatasvirBIC, CAB (PO and IM), RAL↔ daclatasvir expectedNo dose adjustment needed.
DTG↔ daclatasvirNo dose adjustment needed.
EVG/c↑ daclatasvirDecrease daclatasvir dose to 30 mg once daily.
Dasabuvir plus Ombitasvir/Paritaprevir/ RTVBIC↔ BIC expectedNo dose adjustment needed.
CAB (PO and IM)↔ CAB expected

↑ RPV IM expected
Do not coadminister due to potential for QTc prolongation with higher concentrations of RPV. RPV is co-packaged and coadministered with CAB IM.
DTG↔ DTG, dasabuvir, plus ombitasvir/paritaprevir/RTVNo dose adjustment needed.
EVG/cNo dataDo not coadminister.
RALRAL AUC ↑ 134%No dose adjustment needed.
Elbasvir/GrazoprevirBIC↔ BIC expectedNo dose adjustment needed.
CAB (PO and IM)↔ CAB, elbasvir, and grazoprevir expectedNo dose adjustment needed.
DTG↔ DTG

↔ elbasvir

↔ grazoprevir
No dose adjustment needed.
EVG/c↑ elbasvir expected

↑ grazoprevir expected
Do not coadminister.
RAL↔ RAL with elbasvir

RAL AUC ↑ 43% with grazoprevir

↔ elbasvir

↔ grazoprevir
No dose adjustment needed.
Glecaprevir/PibrentasvirBIC, CAB (PO and IM)↔ BIC or CAB expectedNo dose adjustment needed.
DTG↔ DTG and glecaprevir/ pibrentasvirNo dose adjustment needed.
RALNo significant effect

RAL AUC ↑ 47%
 
EVG/cGlecaprevir AUC ↑ 3-fold

Pibrentasvir AUC ↑ 57%

EVG AUC ↑ 47%
No dose adjustment needed.

If coadministered with TDF, monitor for TDF-related adverse events. Consider monitoring for hepatotoxicity if coadministered with TDF or TAF.
Ledipasvir/SofosbuvirBIC, DTG, RAL↔ BIC, DTG, and RALNo dose adjustment needed.
CAB (PO and IM)↔ CAB expectedNo dose adjustment needed.
EVG/c/TDF/

FTC
↑ TDF expected

↑ ledipasvir expected
Do not coadminister.
EVG/c/TAF/

FTC
↔ EVG/c/TAF/FTC expectedNo dose adjustment needed.
SofosbuvirBIC, CAB (PO and IM), DTG, EVG/C↔ INSTI expected

↔ sofosbuvir expected
No dose adjustment needed.
RAL↔ RAL and sofosbuvirNo dose adjustment needed.
Sofosbuvir/VelpatasvirBIC, DTG, RAL↔ sofosbuvir and velpatasvirNo dose adjustment needed. If coadministered with TDF, monitor for TDF‑related adverse events.
CAB (PO and IM)↔ CAB expected

↔ sofosbuvir and velpatasvir expected
EVG/c↔ EVG/c/TAF/FTC

Velpatasvir AUC ↑ 50%
Sofosbuvir/

Velpatasvir/

Voxilaprevir
BICWhen Administered With Sofosbuvir/

Velpatasvir/

Voxilaprevir (400 mg/100 mg/100 mg) plus Voxilaprevir 100 mg


  • ↔ BIC, sofosbuvir, velpatasvir, voxilaprevir
No dose adjustment needed.
EVG/cWhen Administered With Sofosbuvir/

Velpatasvir/

Voxilaprevir (400 mg/100 mg/100 mg) plus Voxilaprevir 100 mg


  • Sofosbuvir AUC ↑ 22%
  • ↔ velpatasvir
  • Voxilaprevir AUC ↑ 2-fold
No dose adjustment needed. If coadministered with TDF, monitor for TDF-related adverse events. Consider monitoring for hepatotoxicity if coadministered with TDF or TAF.
BIC, CAB (PO and IM), DTG, RAL↔ INSTI expected

↔ sofosbuvir, velpatasvir, and voxilaprevir expected
No dose adjustment needed.
Herbal Products
St. John’s WortBIC, CAB (PO and IM), DTG↓ BIC and DTG possibleDo not coadminister.
EVG/c↓ EVG and COBI expectedContraindicated.
Hormonal Therapies
Contraceptives: Non‑OralBIC, CAB (PO and IM), DTG, RALEtonogestrel (subdermal implant) ↑ 27% with DTG

↔ expected with BIC, CAB, RAL
No dose adjustment needed.
EVG/cNo dataNo data available to make dose recommendation.
Contraceptives: OralBIC, DTG, RAL↔ ethinyl estradiol and norgestimate

↔ INSTI
No dose adjustment needed.
CAB (PO and IM)↔ ethinyl estradiol and levonorgestrel with CAB PONo dose adjustment needed.
EVG/cNorgestimate AUC, Cmax, and Cmin ↑ > 2-fold

Ethinyl estradiol AUC ↓ 25% and Cmin ↓ 44%
The effects of increases in progestin (norgestimate) are not fully known and may include insulin resistance, dyslipidemia, acne, and venous thrombosis. Decreased ethinyl estradiol may lead to more intermenstrual bleeding. Weigh the risks and benefits of using the drug and consider using an alternative ARV or contraceptive method.
↑ drospirenone possibleClinical monitoring is recommended due to the potential for hyperkalemia. Consider using alternative ARV or contraceptive method.
Gender-Affirming TherapyBIC, CAB (PO and IM), DTG, EVG/c, RAL↔ goserelin, leuprolide acetate, and spironolactone expectedNo dose adjustment needed.
BIC, CAB (PO and IM), DTG, RAL↔ estrogen expectedNo dose adjustment needed.
↔ testosterone expectedNo dose adjustment needed.
EVG/c↑ estradiol possible

↑ cyproterone, dutasteride, and finasteride possible
Adjust dutasteride dose as needed based on clinical effects and endogenous hormone concentrations.
↑ testosterone possibleMonitor masculinizing effects of testosterone and monitor for adverse effects. Adjust testosterone dose as necessary.
Menopausal Replacement TherapyBIC, CAB (PO and IM), DTG, RAL↔ estrogen expected with estradiol or conjugated estrogen (equine and synthetic)

↔ drospirenone, medroxyprogesterone, and micronized progesterone expected
No dose adjustment needed.
EVG/c↓ or ↑ estrogen possible

↑ drospirenone possible

↑ oral medroxyprogesterone possible

↑ oral micronized progesterone possible
Adjust estrogen and progestin dose as needed based on clinical effects.
Immunosuppressants
Cyclosporine, Everolimus, Sirolimus, TacrolimusBIC, CAB (PO and IM), DTG, RAL↔ immunosuppressant expectedNo dose adjustment needed.
EVG/c↑ immunosuppressant possibleInitiate with an adjusted dose of immunosuppressant to account for potential increased concentrations of the immunosuppressant. Monitor for immunosuppressant-related adverse events. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with a specialist as necessary.
Lipid-Modifying Agents
Atorvastatin BIC, CAB (PO and IM), DTG, RAL↔ atorvastatin expectedNo dose adjustment needed.
EVG/cAtorvastatin AUC ↑ 2.6-fold and Cmax ↑ 2.3-foldTitrate statin dose carefully. Administer the lowest effective dose while monitoring for adverse events. Do not exceed 20 mg atorvastatin daily.
LomitapideBIC, CAB (PO and IM), DTG, RAL↔ lomitapide expectedNo dose adjustment needed.
EVG/c↑ lomitapide expectedContraindicated.
LovastatinBIC, CAB (PO and IM), DTG, RAL↔ lovastatin expectedNo dose adjustment needed.
EVG/cSignificant ↑ lovastatin expectedContraindicated.
Pitavastatin, PravastatinBIC, CAB (PO and IM), DTG, RAL↔ statin expectedNo dose adjustment needed.
EVG/cNo dataNo data available for dose recommendation.
RosuvastatinBIC, CAB (PO and IM), DTG, RAL↔ rosuvastatin expectedNo dose adjustment needed.
EVG/cRosuvastatin AUC ↑ 38% and Cmax ↑ 89%Titrate statin dose carefully and use the lowest effective dose while monitoring for adverse events.
SimvastatinBIC, CAB (PO and IM), DTG, RAL↔ simvastatin expectedNo dose adjustment needed.
EVG/cSignificant ↑ simvastatin expectedContraindicated.
Narcotics and Treatment for Opioid Dependence
Buprenorphine

Sublingual, buccal, or implant
BIC, CAB (PO and IM), DTG↔ buprenorphine and norbuprenorphine (active metabolite) expectedNo dose adjustment needed.
EVG/cBuprenorphine AUC ↑ 35% and Cmin ↑ 66%

Norbuprenorphine (active metabolite) AUC ↑ 42% and Cmin ↑ 57%
No dose adjustment needed. Monitor for adverse events of buprenorphine. When transferring buprenorphine from transmucosal administration to implantation, monitor to ensure buprenorphine effect is adequate and not excessive.
RAL↔ buprenorphine and norbuprenorphine (active metabolite) (sublingual)

↔ buprenorphine or norbuprenorphine (active metabolite) expected (implant)
No dose adjustment needed.
FentanylBIC, CAB (PO and IM), DTG, RAL↔ fentanyl expectedNo dose adjustment needed.
EVG/c↑ fentanylMonitor for fentanyl efficacy and adverse events, including potentially fatal respiratory depression.
LofexidineBIC, CAB (PO and IM), DTG, RAL↔ lofexidine expectedNo dose adjustment needed.
EVG/c↑ lofexidine possibleMonitor for lofexidine-related adverse events, including symptoms of orthostasis and bradycardia.
MethadoneAll INSTIs↔ methadoneNo dose adjustment needed.
TramadolBIC, CAB (PO and IM), DTG, RAL↔ tramadol and M1 (active metabolite) expectedNo dose adjustment needed.
EVG/c↑ tramadol expected

↓ M1 (active metabolite) possible
Tramadol dose adjustments may be necessary. Monitor for clinical response and tramadol-related adverse events.
PDE5 Inhibitors
AvanafilBIC, CAB (PO and IM), DTG, RAL↔ avanafil expectedNo dose adjustment needed.
EVG/cNo dataDo not coadminister.
SildenafilBIC, CAB (PO and IM), DTG, RAL↔ sildenafil expectedNo dose adjustment needed.
EVG/c↑ sildenafil expectedFor Treatment of Erectile Dysfunction

  • Start with sildenafil 25 mg every 48 hours and monitor for adverse effects of sildenafil.
Contraindicated for treatment of PAH.
TadalafilBIC, CAB (PO and IM), DTG, RAL↔ tadalafil expectedNo dose adjustment needed.
EVG/c↑ tadalafil expectedFor Treatment of Erectile Dysfunction

  • Start with tadalafil 5 mg. Do not exceed a single dose of tadalafil 10 mg every 72 hours. Monitor for adverse effects of tadalafil.
For Treatment of PAH

In Patients on EVG/c >7 Days

  • Start with tadalafil 20 mg once daily. Increase to tadalafil 40 mg once daily based on tolerability.
In Patients on Tadalafil who Require EVG/c

  • Stop tadalafil ≥24 hours before EVG/c initiation. Seven days after EVG/c initiation, restart tadalafil at 20 mg once daily and increase to tadalafil 40 mg once daily based on tolerability.
VardenafilBIC, CAB (PO and IM), DTG, RAL↔ vardenafil expectedNo dose adjustment needed.
EVG/c↑ vardenafil expectedStart with vardenafil 2.5 mg every 72 hours and monitor for adverse effects of vardenafil.
Sedative/Hypnotics
Alprazolam, Clonazepam, Clorazepate, Diazepam, Estazolam, FlurazepamBIC, CAB (PO and IM), DTG, RAL↔ benzodiazepine expectedNo dose adjustment needed.
EVG/c↑ benzodiazepine possibleDose reduction of benzodiazepine may be necessary. Initiate with a low dose and monitor for benzodiazepine-related adverse events.

Consider using an alternative benzodiazepine, such as lorazepam, oxazepam, or temazepam.
Midazolam, TriazolamBIC, CAB (PO and IM), RAL↔ benzodiazepine expectedNo dose adjustment needed.
DTGWith DTG 25 mg

  • ↔ midazolam AUC
No dose adjustment needed.
EVG/c↑ midazolam expected

↑ triazolam expected
Contraindicated.

Do not coadminister triazolam or oral midazolam and EVG/c.

Parenteral midazolam can be administered in a closely monitored setting. Consider dose reduction, especially if >1 dose is administered.
SuvorexantBIC, CAB (PO and IM), DTG, RAL↔ suvorexant expectedNo dose adjustment needed.
EVG/c↑ suvorexant expectedDo not coadminister.
ZolpidemBIC, CAB (PO and IM), DTG, RAL↔ zolpidem expectedNo dose adjustment needed.
EVG/c↑ zolpidem expectedInitiate zolpidem at a low dose. Dose reduction of zolpidem may be necessary.
Miscellaneous Drugs
CalcifediolBIC, CAB (PO and IM), DTG, RAL↔ calcifediol expectedNo dose adjustment needed.
EVG/c↑ calcifediol possibleDose adjustment of calcifediol may be required. Monitor serum 25-hydroxyvitamin D, intact PTH, and serum Ca concentrations.
CisaprideBIC, CAB (PO and IM), DTG, RAL↔ cisapride expectedNo dose adjustment needed.
EVG/c↑ cisapride expectedContraindicated.
ColchicineBIC, CAB (PO and IM), DTG, RAL↔ colchicine expectedNo dose adjustment needed.
EVG/c↑ colchicine expectedDo not coadminister in patients with hepatic or renal impairment.

For Treatment of Gout Flares

  • Administer a single dose of colchicine 0.6 mg, followed by colchicine 0.3 mg 1 hour later. Do not repeat dose for at least 3 days.
For Prophylaxis of Gout Flares

  • If original dose was colchicine 0.6 mg twice daily, decrease to colchicine 0.3 mg once daily. If dose was 0.6 mg once daily, decrease to 0.3 mg every other day.
For Treatment of Familial Mediterranean Fever

  • Do not exceed colchicine 0.6 mg once daily or 0.3 mg twice daily.
DronabinolBIC, CAB (PO and IM), DTG, RAL↔ dronabinol expectedNo dose adjustment needed.
EVG/c↑ dronabinol possibleMonitor for dronabinol-related adverse events.
EluxadolineBIC, CAB (PO and IM), DTG, RAL↔ eluxadoline expectedNo dose adjustment needed.
EVG/c↑ eluxadoline possibleMonitor for eluxadoline-related adverse events.
Ergot DerivativesBIC, CAB (PO and IM), DTG, RAL↔ dihydroergotamine, ergotamine, and methylergonovine expectedNo dose adjustment needed.
EVG/c↑ dihydroergotamine, ergotamine, and methylergonovine expectedContraindicated.
FlibanserinBIC, CAB (PO and IM), DTG, RAL↔ flibanserin expectedNo dose adjustment needed.
EVG/c↑ flibanserin expectedContraindicated.
Polyvalent Cation Supplements

Mg, Al, Fe, Ca, Zn, including multivitamins with minerals

Note: Please refer to the Acid Reducers section in this table for recommendations on use with Al-, Mg-, and Ca-containing antacids.
BIC↔ BIC AUC if administered simultaneously with Fe or Ca and food

BIC AUC ↓ 33% if administered simultaneously with CaCO3 under fasting conditions

BIC AUC ↓ 63% if administered simultaneously with Fe under fasting conditions
With Supplements That Contain Ca or Fe

  • Administer BIC and supplements that contain Ca or Fe together with food.
Do not coadminister BIC under fasting conditions simultaneously with, or 2 hours after, supplements that contain Ca or Fe.
CAB↓ INSTI possibleIf coadministration is necessary, administer INSTI at least 2 hours before or at least 4 hours after supplements that contain polyvalent cations, including but not limited to the following products: cation-containing laxatives; Fe, Ca, or Mg supplements; and sucralfate. Monitor for virologic response.

Many oral multivitamins also contain varying amounts of polyvalent cations; the extent and significance of chelation is unknown.
DTGDTG AUC ↓ 39% if administered simultaneously with CaCO3 under fasting conditions

DTG AUC ↓ 54% if administered simultaneously with Fe under fasting conditions

↔ DTG when administered with Ca or Fe supplement simultaneously with food
With Supplements That Contain Ca or Fe

  • Administer DTG and supplements that contain Ca or Fe together with food, or administer DTG at least 2 hours before or at least 6 hours after supplement.
Do not coadminister DTG under fasting conditions simultaneously with, or 2 hours after, supplements that contain Ca or Fe.
EVG/c, RAL↓ INSTI possibleIf coadministration is necessary, administer INSTI at least 2 hours before or at least 6 hours after supplements that contain polyvalent cations, including but not limited to the following products: cation-containing laxatives; Fe, Ca, or Mg supplements; and sucralfate. Monitor for virologic response.

Many oral multivitamins also contain varying amounts of polyvalent cations; the extent and significance of chelation is unknown.
Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change

Key: Al = aluminum; ALT = alanine aminotransferase; ART = antiretroviral therapy; ARV = antiretroviral; AST = aspartate aminotransferase; AUC = area under the curve; BIC = bictegravir; Ca = calcium; CAB = cabotegravir; CaCO3 = calcium carbonate; CCB = calcium channel blocker; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; COBI = cobicistat; CrCl = creatinine clearance; CYP = cytochrome P; DTG = dolutegravir; ECG = electrocardiogram; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; Fe = iron; FTC = emtricitabine; GI = gastrointestinal; IM = intramuscular; INR= international normalized ratio; INSTI = integrase strand transfer inhibitor; Mg = magnesium; PAH = pulmonary arterial hypertension; PDE5 = phosphodiesterase type 5; PO = orally; PTH = parathyroid hormone; QTc = QT corrected for heart rate; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SSRI = selective serotonin reuptake inhibitors; TAF = tenofovir alafenamide; TCA = tricyclic antidepressants; TDF = tenofovir disoproxil fumarate; Zn = zinc
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