Updated
Reviewed
Sep. 01, 2022

Drug-Drug Interactions

Table 24d. 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 24c, 24e, 24f, 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).

BIC

Al/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 PO

CAB PO ↓ expected

With 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 expected

No dose adjustment needed.

DTG

DTG 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/c

EVG 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.

RAL

Al/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 Antagonists

BIC, CAB (PO and IM), DTG, EVG/c

↔ INSTI

No dose adjustment needed.

RAL

RAL AUC ↑ 44% and Cmax ↑ 60%

No dose adjustment needed.

Proton Pump Inhibitors

BIC, CAB (PO and IM), DTG, EVG/c

↔ INSTI

No dose adjustment needed.

RAL

RAL AUC ↑ 37% and Cmin ↑ 24%

No dose adjustment needed.

Alpha-Adrenergic Antagonists for Benign Prostatic Hyperplasia

Alfuzosin

BIC, CAB (PO and IM), DTG, RAL

↔ alfuzosin expected

No dose adjustment needed.

EVG/c

↑ alfuzosin expected

Contraindicated.

Doxazosin

BIC, CAB (PO and IM), DTG, RAL

↔ doxazosin expected

No dose adjustment needed.

EVG/c

↑ doxazosin possible

Initiate doxazosin at lowest dose. Titrate based on doxazosin efficacy and adverse events. Doxazosin dose reduction may be needed.

Tamsulosin

BIC, CAB (PO and IM), DTG, RAL

↔ tamsulosin expected

No dose adjustment needed.

EVG/c

↑ tamsulosin expected

Do not coadminister unless the benefits outweigh the risks. If coadministered, monitor for tamsulosin-related adverse events.

Terazosin

BIC, CAB (PO and IM), DTG, RAL

↔ terazosin expected

No dose adjustment needed.

EVG/c

↑ terazosin possible

Initiate terazosin at lowest dose. Titrate based on terazosin efficacy and adverse events. Terazosin dose reduction may be necessary.

Silodosin

BIC, CAB (PO and IM), DTG, RAL

↔ silodosin expected

No dose adjustment needed.

EVG/c

↑ silodosin expected

Contraindicated.

Antibacterials - Antimycobacterials

Rifabutin

BIC

Rifabutin 300 mg Once Daily

  • BIC AUC ↓ 38% and Cmin ↓ 56%

Do not coadminister.

CAB PO

CAB 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.

DTG

Rifabutin 300 mg Once Daily

  • ↔ DTG AUC and Cmin ↓ 30%

No dose adjustment needed.

EVG/c

Rifabutin 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.

RAL

RAL AUC ↑ 19% and Cmin ↓ 20%

No dose adjustment needed.

Rifampin

BIC

BIC AUC ↓ 75%

Contraindicated.

CAB PO

CAB PO AUC ↓ 59% and Cmin ↓ 50%

Contraindicated.

CAB IM

CAB IM ↓ expected

Contraindicated.

DTG

Rifampin 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/c

Significant ↓ EVG and COBI expected

Contraindicated.

RAL

RAL 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.

Rifapentine

BIC, EVG/c

Significant ↓ BIC, EVG, and COBI expected

Do not coadminister.

CAB (PO and IM)

Significant ↓ CAB (PO and IM) expected

Contraindicated.

DTG

Rifapentine 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.

RAL

Rifapentine 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

Azithromycin

All INSTIs

↔ azithromycin expected

No dose adjustment needed.

Clarithromycin

BIC

↑ BIC possible

No dose adjustment needed.

CAB (PO and IM), DTG, RAL

↔ clarithromycin expected

No 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.

Erythromycin

BIC

↑ BIC possible

No 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

Apixaban

BIC, CAB (PO and IM), DTG, RAL

↔ apixaban expected

No dose adjustment needed.

EVG/c

↑ apixaban expected

Do 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.

Dabigatran

BIC, CAB (PO and IM), DTG, RAL

↔ dabigatran expected

No 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.

Edoxaban

BIC, CAB (PO and IM), DTG, RAL

↔ edoxaban expected

No dose adjustment needed.

EVG/c

↑ edoxaban expected

Stroke Prevention in Nonvalvular Atrial Fibrillation

  • No dose adjustment needed.

Deep Venous Thrombosis and Pulmonary Embolism

  • Administer edoxaban 30 mg once daily.

Rivaroxaban

BIC, CAB (PO and IM), DTG, RAL

↔ rivaroxaban expected

No dose adjustment needed.

EVG/c

↑ rivaroxaban expected

Do not coadminister.

Warfarin

BIC, CAB (PO and IM), DTG, RAL

↔ warfarin expected

No dose adjustment needed.

EVG/c

↑ or ↓ warfarin possible

Monitor INR and adjust warfarin dose accordingly.

Anticonvulsants

Carbamazepine

BIC

↓ BIC possible

Do not coadminister.

CAB (PO and IM)

↓ CAB expected

Contraindicated.

DTG

DTG 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/c

Carbamazepine AUC ↑ 43%

EVG AUC ↓ 69% and Cmin ↓ >99%

↓ COBI expected

Contraindicated.

RAL

↓ or ↔ RAL possible

Do not coadminister.

Eslicarbazepine

All INSTIs

↓ INSTI possible

↓ COBI possible

Consider alternative ARV or anticonvulsant.

Ethosuximide

BIC, CAB (PO and IM), DTG, RAL

↔ ethosuximide expected

No dose adjustment needed.

EVG/c

↑ ethosuximide possible

Monitor for ethosuximide-related adverse events.

Lamotrigine

BIC, CAB (PO and IM), DTG, RAL

↔ lamotrigine expected

No dose adjustment needed.

EVG/c

No data

Monitor anticonvulsant concentrations and adjust dose accordingly.

Oxcarbazepine

BIC, DTG

↓ BIC and DTG possible

Do not coadminister.

CAB (PO and IM)

↓ CAB expected

Contraindicated.

EVG/c, RAL

↓ EVG/c and RAL possible

Consider alternative ARV or anticonvulsant.

Phenobarbital, Phenytoin

BIC, DTG, RAL

↓ BIC and DTG possible

↓ or ↔ RAL possible

Do not coadminister.

CAB (PO and IM), EVG/c

↓ CAB and EVG/c expected

Contraindicated.

Valproic Acid

All INSTIs

No data

Monitor valproic acid concentration and virologic response.

Antidepressants, Anxiolytics, and Antipsychotics
Also see the Sedative/Hypnotics section below

Bupropion

BIC, CAB (PO and IM), DTG, RAL

↔ bupropion expected

No dose adjustment needed.

EVG/c

↑ bupropion possible

Titrate bupropion dose based on clinical response.

Buspirone

BIC, CAB (PO and IM), DTG, RAL

↔ buspirone expected

No dose adjustment needed.

EVG/c

↑ buspirone possible

Initiate buspirone at a low dose. Buspirone dose reduction may be needed.

Nefazodone

BIC, CAB (PO and IM), DTG, RAL

↔ nefazodone expected

No dose adjustment needed.

EVG/c

↑ nefazodone expected

Consider alternative ARV or antidepressant.

Trazodone

BIC, CAB (PO and IM), DTG, RAL

↔ trazodone expected

No dose adjustment needed.

Tricyclic Antidepressants

Amitriptyline, desipramine, doxepin, imipramine, nortriptyline

BIC, CAB (PO and IM), DTG, RAL

↔ TCA expected

No dose adjustment needed.

EVG/c

Desipramine AUC ↑ 65%

Initiate with lowest dose of TCA and titrate dose carefully.

↑ TCA expected

Initiate 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

↔ sertraline

No dose adjustment needed.

EVG/c

↑ other SSRIs possible

Initiate with lowest dose of SSRI. Titrate dose carefully based on antidepressant response.

BIC, CAB (PO and IM), DTG, RAL

↔ SSRI expected

No dose adjustment needed.

Antipsychotics

Aripiprazole

BIC, CAB (PO and IM), DTG, RAL

↔ aripiprazole expected

No dose adjustment needed.

EVG/c

↑ aripiprazole expected

Administer 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.

Brexpiprazole

BIC, CAB (PO and IM), DTG, RAL

↔ brexpiprazole expected

No dose adjustment needed.

EVG/c

↑ brexpiprazole expected

Administer 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.

Cariprazine

BIC, CAB (PO and IM), DTG, RAL

↔ cariprazine expected

No dose adjustment needed.

EVG/c

↑ cariprazine expected

Starting 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.

Iloperidone

BIC, CAB (PO and IM), DTG, RAL

↔ iloperidone expected

No dose adjustment needed.

EVG/c

↑ iloperidone expected

Decrease iloperidone dose by 50%.

Lumateperone

BIC, CAB (PO and IM), DTG, RAL

↔ lumateperone expected

No dose adjustment needed.

EVG/c

↑ lumateperone expected

Do not coadminister.

Lurasidone

BIC, CAB (PO and IM), DTG, RAL

↔ lurasidone expected

No dose adjustment needed.

EVG/c

↑ lurasidone expected

Contraindicated.

Olanzapine

All INSTIs

↔ olanzapine expected

No dose adjustment needed.

Other Antipsychotics

CYP3A4 and/or CYP2D6 substrates (e.g., perphenazine, risperidone, thioridazine)

EVG/c

↑ antipsychotic possible

Initiate antipsychotic at a low dose. Antipsychotic dose reduction may be needed.

Pimavanserin

BIC, CAB (PO and IM), DTG, RAL

↔ pimavanserin expected

No dose adjustment needed.

EVG/c

↑ pimavanserin expected

Reduce pimavanserin dose to 10 mg.

Pimozide

BIC, CAB (PO and IM), DTG, RAL

↔ pimozide expected

No dose adjustment needed.

EVG/c

↑ pimozide expected

Contraindicated.

Quetiapine

BIC, CAB (PO and IM), DTG, RAL

↔ quetiapine expected

No dose adjustment needed.

EVG/c

↑ quetiapine AUC expected

Starting 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.

Ziprasidone

BIC, CAB (PO and IM), DTG, RAL

↔ ziprasidone expected

No dose adjustment needed.

EVG/c

↑ ziprasidone possible

Monitor for ziprasidone-related adverse events.

Antifungals

Isavuconazole

BIC, CAB (PO and IM), DTG, RAL

↑ INSTI possible

No dose adjustment needed.

EVG/c

↑ isavuconazole expected

↑ or ↓ EVG and COBI possible

If coadministered, consider monitoring isavuconazole concentrations and assessing virologic response.

Itraconazole

BIC

↑ BIC expected

No 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.

Posaconazole

BIC

↑ BIC expected

No 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.

Voriconazole

BIC

↑ BIC possible

No 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

Metformin

BIC

Metformin AUC ↑ 39%

Monitor for adverse events of metformin.

DTG

DTG 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 expected

No dose adjustment needed.

Saxagliptin

BIC, CAB (PO and IM), DTG, RAL

↔ saxagliptin expected

No dose adjustment needed.

EVG/c

↑ saxagliptin expected

Limit saxagliptin dose to 2.5 mg once daily.

Dapagliflozin/

Saxagliptin

BIC, CAB (PO and IM), DTG, RAL

↔ dapagliflozin or saxagliptin expected

No dose adjustment needed.

EVG/c

↑ saxagliptin expected

Do 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

Clopidogrel

BIC, CAB (PO and IM), DTG, RAL

↔ clopidogrel expected

No dose adjustment needed.

EVG/c

↓ clopidogrel active metabolite, with impaired platelet inhibition expected

Do not coadminister.

Prasugrel

BIC, CAB (PO and IM), DTG, RAL

↔ prasugrel expected

No dose adjustment needed.

EVG/c

↓ prasugrel active metabolite, with no impairment of platelet inhibition expected

No dose adjustment needed.

Ticagrelor

BIC, CAB (PO and IM), DTG, RAL

↔ ticagrelor expected

No dose adjustment needed.

EVG/c

↑ ticagrelor expected

Do not coadminister.

Vorapaxar

BIC, CAB (PO and IM) DTG, RAL

↔ vorapaxar expected

No dose adjustment needed.

EVG/c

↑ vorapaxar expected

Do not coadminister.

Antivirals—Orthopoxviruses (Smallpox, Monkeypox)

Brincidofovir

BIC, CAB (PO and IM), DTG, RAL

↔ INSTI expected

No 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).

Cidofovir

BIC, CAB (PO and IM), DTG, RAL

↔ INSTI expected

↔ cidofovir expected

No dose adjustment needed.

Tecovirimat

CAB (IM)

↔ CAB expected

No 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 expected

No dose adjustment needed.

Beta-Agonists, Long-Acting Inhaled

Arformoterol, Formoterol

All INSTIs

↔ arformoterol or formoterol expected

No dose adjustment needed.

Indacaterol

BIC, CAB (PO and IM), DTG, RAL

↔ indacaterol expected

No dose adjustment needed.

EVG/c

↑ indacaterol expected

Olodaterol

BIC, CAB (PO and IM), DTG, RAL

↔ olodaterol expected

No dose adjustment needed.

EVG/c

↑ olodaterol expected

Salmeterol

BIC, CAB (PO and IM), DTG, RAL

↔ salmeterol expected

No dose adjustment needed.

EVG/c

↑ salmeterol possible

Do not coadminister due to the potential for increased risk of salmeterol-associated cardiovascular events.

Cardiac Medications

Amiodarone

BIC, 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, Quinidine

BIC, 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 antiarrhythmics

No 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 expected

No dose adjustment needed.

EVG/c

↑ beta blocker possible

Beta 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).

Bosentan

BIC, DTG

↓ BIC and DTG possible

No dose adjustment needed.

CAB (PO and IM)

↔ bosentan expected

Consider 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 expected

No dose adjustment needed.

EVG/c

↑ bosentan possible

In 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 Blockers

BIC

↑ 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 possible

Titrate CCB dose and monitor for CCB efficacy and adverse events.

Dofetilide

BIC, DTG

↑ dofetilide expected

Contraindicated.

CAB (PO and IM), RAL

↔ dofetilide expected

No dose adjustment needed.

EVG/c

↑ dofetilide possible

Do not coadminister.

Eplerenone

BIC, CAB (PO and IM), DTG, RAL

↔ eplerenone expected

No dose adjustment needed.

EVG/c

↑ eplerenone expected

Contraindicated.

Ivabradine

BIC, CAB (PO and IM), DTG, RAL

↔ ivabradine expected

No dose adjustment needed.

EVG/c

↑ ivabradine expected

Contraindicated.

Ranolazine

BIC, CAB (PO and IM), DTG, RAL

↔ ranolazine expected

No dose adjustment needed.

EVG/c

↑ ranolazine expected

Contraindicated.

Corticosteroids

Beclomethasone

Inhaled or intranasal

BIC, CAB (PO and IM), DTG, EVG/c, RAL

↔ glucocorticoid expected

No dose adjustment needed.

Budesonide, Ciclesonide, Fluticasone, Mometasone

Inhaled or intranasal

BIC, CAB (PO and IM), DTG, RAL

↔ glucocorticoid expected

No dose adjustment needed.

EVG/c

↑ glucocorticoid possible

Do 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 possible

Consider 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 expected

No dose adjustment needed.

EVG/c

↓ EVG and COBI possible

Consider 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 expected

No dose adjustment needed.

EVG/c

↑ prednisolone possible

Coadministration 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 expected

No dose adjustment needed.

EVG/c

↑ glucocorticoid expected

Do not coadminister. Coadministration may result in adrenal insufficiency and Cushing’s syndrome.

Hepatitis C Direct-Acting Antiviral Agents

Daclatasvir

BIC, CAB (PO and IM), RAL

↔ daclatasvir expected

No dose adjustment needed.

DTG

↔ daclatasvir

No dose adjustment needed.

EVG/c

↑ daclatasvir

Decrease daclatasvir dose to 30 mg once daily.

Dasabuvir plus Ombitasvir/Paritaprevir/ RTV

BIC

↔ BIC expected

No 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/RTV

No dose adjustment needed.

EVG/c

No data

Do not coadminister.

RAL

RAL AUC ↑ 134%

No dose adjustment needed.

Elbasvir/Grazoprevir

BIC

↔ BIC expected

No dose adjustment needed.

CAB (PO and IM)

↔ CAB, elbasvir, and grazoprevir expected

No 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/Pibrentasvir

BIC, CAB (PO and IM)

↔ BIC or CAB expected

No dose adjustment needed.

DTG

↔ DTG and glecaprevir/ pibrentasvir

No dose adjustment needed.

RAL

No significant effect

RAL AUC ↑ 47%

 

EVG/c

Glecaprevir 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/Sofosbuvir

BIC, DTG, RAL

↔ BIC, DTG, and RAL

No dose adjustment needed.

CAB (PO and IM)

↔ CAB expected

No dose adjustment needed.

EVG/c/TDF/
FTC

↑ TDF expected

↑ ledipasvir expected

Do not coadminister.

EVG/c/TAF/
FTC

↔ EVG/c/TAF/FTC expected

No dose adjustment needed.

Sofosbuvir

BIC, CAB (PO and IM), DTG, EVG/C

↔ INSTI expected

↔ sofosbuvir expected

No dose adjustment needed.

RAL

↔ RAL and sofosbuvir

No dose adjustment needed.

Sofosbuvir/Velpatasvir

BIC, DTG, RAL

↔ sofosbuvir and velpatasvir

No 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

BIC

When Administered With Sofosbuvir/
Velpatasvir/
Voxilaprevir (400 mg/100 mg/100 mg) plus Voxilaprevir 100 mg

  • ↔ BIC, sofosbuvir, velpatasvir, voxilaprevir

No dose adjustment needed.

EVG/c

When 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 Wort

BIC, CAB (PO and IM), DTG

↓ BIC and DTG possible

Do not coadminister.

EVG/c

↓ EVG and COBI expected

Contraindicated.

Hormonal Therapies

Contraceptives: Non‑Oral

BIC, CAB (PO and IM), DTG, RAL

Etonogestrel (subdermal implant) ↑ 27% with DTG

↔ expected with BIC, CAB, RAL

No dose adjustment needed.

EVG/c

No data

No data available to make dose recommendation.

Contraceptives: Oral

BIC, DTG, RAL

↔ ethinyl estradiol and norgestimate

↔ INSTI

No dose adjustment needed.

CAB (PO and IM)

↔ ethinyl estradiol and levonorgestrel with CAB PO

No dose adjustment needed.

EVG/c

Norgestimate 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 possible

Clinical monitoring is recommended due to the potential for hyperkalemia. Consider using alternative ARV or contraceptive method.

Gender-Affirming Therapy

BIC, CAB (PO and IM), DTG, EVG/c, RAL

↔ goserelin, leuprolide acetate, and spironolactone expected

No dose adjustment needed.

BIC, CAB (PO and IM), DTG, RAL

↔ estrogen expected

No dose adjustment needed.

↔ testosterone expected

No 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 possible

Monitor masculinizing effects of testosterone and monitor for adverse effects. Adjust testosterone dose as necessary.

Menopausal Replacement Therapy

BIC, 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, Tacrolimus

BIC, CAB (PO and IM), DTG, RAL

↔ immunosuppressant expected

No dose adjustment needed.

EVG/c

↑ immunosuppressant possible

Initiate 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 expected

No dose adjustment needed.

EVG/c

Atorvastatin AUC ↑ 2.6-fold and Cmax ↑ 2.3-fold

Titrate statin dose carefully. Administer the lowest effective dose while monitoring for adverse events. Do not exceed 20 mg atorvastatin daily.

Lomitapide

BIC, CAB (PO and IM), DTG, RAL

↔ lomitapide expected

No dose adjustment needed.

EVG/c

↑ lomitapide expected

Contraindicated.

Lovastatin

BIC, CAB (PO and IM), DTG, RAL

↔ lovastatin expected

No dose adjustment needed.

EVG/c

Significant ↑ lovastatin expected

Contraindicated.

Pitavastatin, Pravastatin

BIC, CAB (PO and IM), DTG, RAL

↔ statin expected

No dose adjustment needed.

EVG/c

No data

No data available for dose recommendation.

Rosuvastatin

BIC, CAB (PO and IM), DTG, RAL

↔ rosuvastatin expected

No dose adjustment needed.

EVG/c

Rosuvastatin AUC ↑ 38% and Cmax ↑ 89%

Titrate statin dose carefully and use the lowest effective dose while monitoring for adverse events.

Simvastatin

BIC, CAB (PO and IM), DTG, RAL

↔ simvastatin expected

No dose adjustment needed.

EVG/c

Significant ↑ simvastatin expected

Contraindicated.

Narcotics and Treatment for Opioid Dependence

Buprenorphine

Sublingual, buccal, or implant

BIC, CAB (PO and IM), DTG

↔ buprenorphine and norbuprenorphine (active metabolite) expected

No dose adjustment needed.

EVG/c

Buprenorphine 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.

Fentanyl

BIC, CAB (PO and IM), DTG, RAL

↔ fentanyl expected

No dose adjustment needed.

EVG/c

↑ fentanyl

Monitor for fentanyl efficacy and adverse events, including potentially fatal respiratory depression.

Lofexidine

BIC, CAB (PO and IM), DTG, RAL

↔ lofexidine expected

No dose adjustment needed.

EVG/c

↑ lofexidine possible

Monitor for lofexidine-related adverse events, including symptoms of orthostasis and bradycardia.

Methadone

All INSTIs

↔ methadone

No dose adjustment needed.

Tramadol

BIC, CAB (PO and IM), DTG, RAL

↔ tramadol and M1 (active metabolite) expected

No 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

Avanafil

BIC, CAB (PO and IM), DTG, RAL

↔ avanafil expected

No dose adjustment needed.

EVG/c

No data

Do not coadminister.

Sildenafil

BIC, CAB (PO and IM), DTG, RAL

↔ sildenafil expected

No dose adjustment needed.

EVG/c

↑ sildenafil expected

For Treatment of Erectile Dysfunction

  • Start with sildenafil 25 mg every 48 hours and monitor for adverse effects of sildenafil.

Contraindicated for treatment of PAH.

Tadalafil

BIC, CAB (PO and IM), DTG, RAL

↔ tadalafil expected

No dose adjustment needed.

EVG/c

↑ tadalafil expected

For 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.

Vardenafil

BIC, CAB (PO and IM), DTG, RAL

↔ vardenafil expected

No dose adjustment needed.

EVG/c

↑ vardenafil expected

Start with vardenafil 2.5 mg every 72 hours and monitor for adverse effects of vardenafil.

Sedative/Hypnotics

Alprazolam, Clonazepam, Clorazepate, Diazepam, Estazolam, Flurazepam

BIC, CAB (PO and IM), DTG, RAL

↔ benzodiazepine expected

No dose adjustment needed.

EVG/c

↑ benzodiazepine possible

Dose 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, Triazolam

BIC, CAB (PO and IM), RAL

↔ benzodiazepine expected

No dose adjustment needed.

DTG

With 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.

Suvorexant

BIC, CAB (PO and IM), DTG, RAL

↔ suvorexant expected

No dose adjustment needed.

EVG/c

↑ suvorexant expected

Do not coadminister.

Zolpidem

BIC, CAB (PO and IM), DTG, RAL

↔ zolpidem expected

No dose adjustment needed.

EVG/c

↑ zolpidem expected

Initiate zolpidem at a low dose. Dose reduction of zolpidem may be necessary.

Miscellaneous Drugs

Calcifediol

BIC, CAB (PO and IM), DTG, RAL

↔ calcifediol expected

No dose adjustment needed.

EVG/c

↑ calcifediol possible

Dose adjustment of calcifediol may be required. Monitor serum 25-hydroxyvitamin D, intact PTH, and serum Ca concentrations.

Cisapride

BIC, CAB (PO and IM), DTG, RAL

↔ cisapride expected

No dose adjustment needed.

EVG/c

↑ cisapride expected

Contraindicated.

Colchicine

BIC, CAB (PO and IM), DTG, RAL

↔ colchicine expected

No dose adjustment needed.

EVG/c

↑ colchicine expected

Do 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.

Dronabinol

BIC, CAB (PO and IM), DTG, RAL

↔ dronabinol expected

No dose adjustment needed.

EVG/c

↑ dronabinol possible

Monitor for dronabinol-related adverse events.

Eluxadoline

BIC, CAB (PO and IM), DTG, RAL

↔ eluxadoline expected

No dose adjustment needed.

EVG/c

↑ eluxadoline possible

Monitor for eluxadoline-related adverse events.

Ergot Derivatives

BIC, CAB (PO and IM), DTG, RAL

↔ dihydroergotamine, ergotamine, and methylergonovine expected

No dose adjustment needed.

EVG/c

↑ dihydroergotamine, ergotamine, and methylergonovine expected

Contraindicated.

Flibanserin

BIC, CAB (PO and IM), DTG, RAL

↔ flibanserin expected

No dose adjustment needed.

EVG/c

↑ flibanserin expected

Contraindicated.

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 possible

If 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.

DTG

DTG 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 possible

If 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

Drug-Drug Interactions

Table 24d. Drug Interactions Between Integrase Strand Transfer Inhibitors and Other Drugs

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).

BIC

Al/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 PO

CAB PO ↓ expected

With 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 expected

No dose adjustment needed.

DTG

DTG 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/c

EVG 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.

RAL

Al/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 Antagonists

BIC, CAB (PO and IM), DTG, EVG/c

↔ INSTI

No dose adjustment needed.

RAL

RAL AUC ↑ 44% and Cmax ↑ 60%

No dose adjustment needed.

Proton Pump Inhibitors

BIC, CAB (PO and IM), DTG, EVG/c

↔ INSTI

No dose adjustment needed.

RAL

RAL AUC ↑ 37% and Cmin ↑ 24%

No dose adjustment needed.

Alpha-Adrenergic Antagonists for Benign Prostatic Hyperplasia

Alfuzosin

BIC, CAB (PO and IM), DTG, RAL

↔ alfuzosin expected

No dose adjustment needed.

EVG/c

↑ alfuzosin expected

Contraindicated.

Doxazosin

BIC, CAB (PO and IM), DTG, RAL

↔ doxazosin expected

No dose adjustment needed.

EVG/c

↑ doxazosin possible

Initiate doxazosin at lowest dose. Titrate based on doxazosin efficacy and adverse events. Doxazosin dose reduction may be needed.

Tamsulosin

BIC, CAB (PO and IM), DTG, RAL

↔ tamsulosin expected

No dose adjustment needed.

EVG/c

↑ tamsulosin expected

Do not coadminister unless the benefits outweigh the risks. If coadministered, monitor for tamsulosin-related adverse events.

Terazosin

BIC, CAB (PO and IM), DTG, RAL

↔ terazosin expected

No dose adjustment needed.

EVG/c

↑ terazosin possible

Initiate terazosin at lowest dose. Titrate based on terazosin efficacy and adverse events. Terazosin dose reduction may be necessary.

Silodosin

BIC, CAB (PO and IM), DTG, RAL

↔ silodosin expected

No dose adjustment needed.

EVG/c

↑ silodosin expected

Contraindicated.

Antibacterials - Antimycobacterials

Rifabutin

BIC

Rifabutin 300 mg Once Daily

  • BIC AUC ↓ 38% and Cmin ↓ 56%

Do not coadminister.

CAB PO

CAB 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.

DTG

Rifabutin 300 mg Once Daily

  • ↔ DTG AUC and Cmin ↓ 30%

No dose adjustment needed.

EVG/c

Rifabutin 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.

RAL

RAL AUC ↑ 19% and Cmin ↓ 20%

No dose adjustment needed.

Rifampin

BIC

BIC AUC ↓ 75%

Contraindicated.

CAB PO

CAB PO AUC ↓ 59% and Cmin ↓ 50%

Contraindicated.

CAB IM

CAB IM ↓ expected

Contraindicated.

DTG

Rifampin 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/c

Significant ↓ EVG and COBI expected

Contraindicated.

RAL

RAL 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.

Rifapentine

BIC, EVG/c

Significant ↓ BIC, EVG, and COBI expected

Do not coadminister.

CAB (PO and IM)

Significant ↓ CAB (PO and IM) expected

Contraindicated.

DTG

Rifapentine 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.

RAL

Rifapentine 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

Azithromycin

All INSTIs

↔ azithromycin expected

No dose adjustment needed.

Clarithromycin

BIC

↑ BIC possible

No dose adjustment needed.

CAB (PO and IM), DTG, RAL

↔ clarithromycin expected

No 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.

Erythromycin

BIC

↑ BIC possible

No 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

Apixaban

BIC, CAB (PO and IM), DTG, RAL

↔ apixaban expected

No dose adjustment needed.

EVG/c

↑ apixaban expected

Do 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.

Dabigatran

BIC, CAB (PO and IM), DTG, RAL

↔ dabigatran expected

No 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.

Edoxaban

BIC, CAB (PO and IM), DTG, RAL

↔ edoxaban expected

No dose adjustment needed.

EVG/c

↑ edoxaban expected

Stroke Prevention in Nonvalvular Atrial Fibrillation

  • No dose adjustment needed.

Deep Venous Thrombosis and Pulmonary Embolism

  • Administer edoxaban 30 mg once daily.

Rivaroxaban

BIC, CAB (PO and IM), DTG, RAL

↔ rivaroxaban expected

No dose adjustment needed.

EVG/c

↑ rivaroxaban expected

Do not coadminister.

Warfarin

BIC, CAB (PO and IM), DTG, RAL

↔ warfarin expected

No dose adjustment needed.

EVG/c

↑ or ↓ warfarin possible

Monitor INR and adjust warfarin dose accordingly.

Anticonvulsants

Carbamazepine

BIC

↓ BIC possible

Do not coadminister.

CAB (PO and IM)

↓ CAB expected

Contraindicated.

DTG

DTG 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/c

Carbamazepine AUC ↑ 43%

EVG AUC ↓ 69% and Cmin ↓ >99%

↓ COBI expected

Contraindicated.

RAL

↓ or ↔ RAL possible

Do not coadminister.

Eslicarbazepine

All INSTIs

↓ INSTI possible

↓ COBI possible

Consider alternative ARV or anticonvulsant.

Ethosuximide

BIC, CAB (PO and IM), DTG, RAL

↔ ethosuximide expected

No dose adjustment needed.

EVG/c

↑ ethosuximide possible

Monitor for ethosuximide-related adverse events.

Lamotrigine

BIC, CAB (PO and IM), DTG, RAL

↔ lamotrigine expected

No dose adjustment needed.

EVG/c

No data

Monitor anticonvulsant concentrations and adjust dose accordingly.

Oxcarbazepine

BIC, DTG

↓ BIC and DTG possible

Do not coadminister.

CAB (PO and IM)

↓ CAB expected

Contraindicated.

EVG/c, RAL

↓ EVG/c and RAL possible

Consider alternative ARV or anticonvulsant.

Phenobarbital, Phenytoin

BIC, DTG, RAL

↓ BIC and DTG possible

↓ or ↔ RAL possible

Do not coadminister.

CAB (PO and IM), EVG/c

↓ CAB and EVG/c expected

Contraindicated.

Valproic Acid

All INSTIs

No data

Monitor valproic acid concentration and virologic response.

Antidepressants, Anxiolytics, and Antipsychotics
Also see the Sedative/Hypnotics section below

Bupropion

BIC, CAB (PO and IM), DTG, RAL

↔ bupropion expected

No dose adjustment needed.

EVG/c

↑ bupropion possible

Titrate bupropion dose based on clinical response.

Buspirone

BIC, CAB (PO and IM), DTG, RAL

↔ buspirone expected

No dose adjustment needed.

EVG/c

↑ buspirone possible

Initiate buspirone at a low dose. Buspirone dose reduction may be needed.

Nefazodone

BIC, CAB (PO and IM), DTG, RAL

↔ nefazodone expected

No dose adjustment needed.

EVG/c

↑ nefazodone expected

Consider alternative ARV or antidepressant.

Trazodone

BIC, CAB (PO and IM), DTG, RAL

↔ trazodone expected

No dose adjustment needed.

Tricyclic Antidepressants

Amitriptyline, desipramine, doxepin, imipramine, nortriptyline

BIC, CAB (PO and IM), DTG, RAL

↔ TCA expected

No dose adjustment needed.

EVG/c

Desipramine AUC ↑ 65%

Initiate with lowest dose of TCA and titrate dose carefully.

↑ TCA expected

Initiate 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

↔ sertraline

No dose adjustment needed.

EVG/c

↑ other SSRIs possible

Initiate with lowest dose of SSRI. Titrate dose carefully based on antidepressant response.

BIC, CAB (PO and IM), DTG, RAL

↔ SSRI expected

No dose adjustment needed.

Antipsychotics

Aripiprazole

BIC, CAB (PO and IM), DTG, RAL

↔ aripiprazole expected

No dose adjustment needed.

EVG/c

↑ aripiprazole expected

Administer 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.

Brexpiprazole

BIC, CAB (PO and IM), DTG, RAL

↔ brexpiprazole expected

No dose adjustment needed.

EVG/c

↑ brexpiprazole expected

Administer 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.

Cariprazine

BIC, CAB (PO and IM), DTG, RAL

↔ cariprazine expected

No dose adjustment needed.

EVG/c

↑ cariprazine expected

Starting 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.

Iloperidone

BIC, CAB (PO and IM), DTG, RAL

↔ iloperidone expected

No dose adjustment needed.

EVG/c

↑ iloperidone expected

Decrease iloperidone dose by 50%.

Lumateperone

BIC, CAB (PO and IM), DTG, RAL

↔ lumateperone expected

No dose adjustment needed.

EVG/c

↑ lumateperone expected

Do not coadminister.

Lurasidone

BIC, CAB (PO and IM), DTG, RAL

↔ lurasidone expected

No dose adjustment needed.

EVG/c

↑ lurasidone expected

Contraindicated.

Olanzapine

All INSTIs

↔ olanzapine expected

No dose adjustment needed.

Other Antipsychotics

CYP3A4 and/or CYP2D6 substrates (e.g., perphenazine, risperidone, thioridazine)

EVG/c

↑ antipsychotic possible

Initiate antipsychotic at a low dose. Antipsychotic dose reduction may be needed.

Pimavanserin

BIC, CAB (PO and IM), DTG, RAL

↔ pimavanserin expected

No dose adjustment needed.

EVG/c

↑ pimavanserin expected

Reduce pimavanserin dose to 10 mg.

Pimozide

BIC, CAB (PO and IM), DTG, RAL

↔ pimozide expected

No dose adjustment needed.

EVG/c

↑ pimozide expected

Contraindicated.

Quetiapine

BIC, CAB (PO and IM), DTG, RAL

↔ quetiapine expected

No dose adjustment needed.

EVG/c

↑ quetiapine AUC expected

Starting 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.

Ziprasidone

BIC, CAB (PO and IM), DTG, RAL

↔ ziprasidone expected

No dose adjustment needed.

EVG/c

↑ ziprasidone possible

Monitor for ziprasidone-related adverse events.

Antifungals

Isavuconazole

BIC, CAB (PO and IM), DTG, RAL

↑ INSTI possible

No dose adjustment needed.

EVG/c

↑ isavuconazole expected

↑ or ↓ EVG and COBI possible

If coadministered, consider monitoring isavuconazole concentrations and assessing virologic response.

Itraconazole

BIC

↑ BIC expected

No 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.

Posaconazole

BIC

↑ BIC expected

No 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.

Voriconazole

BIC

↑ BIC possible

No 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

Metformin

BIC

Metformin AUC ↑ 39%

Monitor for adverse events of metformin.

DTG

DTG 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 expected

No dose adjustment needed.

Saxagliptin

BIC, CAB (PO and IM), DTG, RAL

↔ saxagliptin expected

No dose adjustment needed.

EVG/c

↑ saxagliptin expected

Limit saxagliptin dose to 2.5 mg once daily.

Dapagliflozin/

Saxagliptin

BIC, CAB (PO and IM), DTG, RAL

↔ dapagliflozin or saxagliptin expected

No dose adjustment needed.

EVG/c

↑ saxagliptin expected

Do 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

Clopidogrel

BIC, CAB (PO and IM), DTG, RAL

↔ clopidogrel expected

No dose adjustment needed.

EVG/c

↓ clopidogrel active metabolite, with impaired platelet inhibition expected

Do not coadminister.

Prasugrel

BIC, CAB (PO and IM), DTG, RAL

↔ prasugrel expected

No dose adjustment needed.

EVG/c

↓ prasugrel active metabolite, with no impairment of platelet inhibition expected

No dose adjustment needed.

Ticagrelor

BIC, CAB (PO and IM), DTG, RAL

↔ ticagrelor expected

No dose adjustment needed.

EVG/c

↑ ticagrelor expected

Do not coadminister.

Vorapaxar

BIC, CAB (PO and IM) DTG, RAL

↔ vorapaxar expected

No dose adjustment needed.

EVG/c

↑ vorapaxar expected

Do not coadminister.

Antivirals—Orthopoxviruses (Smallpox, Monkeypox)

Brincidofovir

BIC, CAB (PO and IM), DTG, RAL

↔ INSTI expected

No 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).

Cidofovir

BIC, CAB (PO and IM), DTG, RAL

↔ INSTI expected

↔ cidofovir expected

No dose adjustment needed.

Tecovirimat

CAB (IM)

↔ CAB expected

No 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 expected

No dose adjustment needed.

Beta-Agonists, Long-Acting Inhaled

Arformoterol, Formoterol

All INSTIs

↔ arformoterol or formoterol expected

No dose adjustment needed.

Indacaterol

BIC, CAB (PO and IM), DTG, RAL

↔ indacaterol expected

No dose adjustment needed.

EVG/c

↑ indacaterol expected

Olodaterol

BIC, CAB (PO and IM), DTG, RAL

↔ olodaterol expected

No dose adjustment needed.

EVG/c

↑ olodaterol expected

Salmeterol

BIC, CAB (PO and IM), DTG, RAL

↔ salmeterol expected

No dose adjustment needed.

EVG/c

↑ salmeterol possible

Do not coadminister due to the potential for increased risk of salmeterol-associated cardiovascular events.

Cardiac Medications

Amiodarone

BIC, 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, Quinidine

BIC, 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 antiarrhythmics

No 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 expected

No dose adjustment needed.

EVG/c

↑ beta blocker possible

Beta 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).

Bosentan

BIC, DTG

↓ BIC and DTG possible

No dose adjustment needed.

CAB (PO and IM)

↔ bosentan expected

Consider 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 expected

No dose adjustment needed.

EVG/c

↑ bosentan possible

In 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 Blockers

BIC

↑ 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 possible

Titrate CCB dose and monitor for CCB efficacy and adverse events.

Dofetilide

BIC, DTG

↑ dofetilide expected

Contraindicated.

CAB (PO and IM), RAL

↔ dofetilide expected

No dose adjustment needed.

EVG/c

↑ dofetilide possible

Do not coadminister.

Eplerenone

BIC, CAB (PO and IM), DTG, RAL

↔ eplerenone expected

No dose adjustment needed.

EVG/c

↑ eplerenone expected

Contraindicated.

Ivabradine

BIC, CAB (PO and IM), DTG, RAL

↔ ivabradine expected

No dose adjustment needed.

EVG/c

↑ ivabradine expected

Contraindicated.

Ranolazine

BIC, CAB (PO and IM), DTG, RAL

↔ ranolazine expected

No dose adjustment needed.

EVG/c

↑ ranolazine expected

Contraindicated.

Corticosteroids

Beclomethasone

Inhaled or intranasal

BIC, CAB (PO and IM), DTG, EVG/c, RAL

↔ glucocorticoid expected

No dose adjustment needed.

Budesonide, Ciclesonide, Fluticasone, Mometasone

Inhaled or intranasal

BIC, CAB (PO and IM), DTG, RAL

↔ glucocorticoid expected

No dose adjustment needed.

EVG/c

↑ glucocorticoid possible

Do 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 possible

Consider 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 expected

No dose adjustment needed.

EVG/c

↓ EVG and COBI possible

Consider 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 expected

No dose adjustment needed.

EVG/c

↑ prednisolone possible

Coadministration 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 expected

No dose adjustment needed.

EVG/c

↑ glucocorticoid expected

Do not coadminister. Coadministration may result in adrenal insufficiency and Cushing’s syndrome.

Hepatitis C Direct-Acting Antiviral Agents

Daclatasvir

BIC, CAB (PO and IM), RAL

↔ daclatasvir expected

No dose adjustment needed.

DTG

↔ daclatasvir

No dose adjustment needed.

EVG/c

↑ daclatasvir

Decrease daclatasvir dose to 30 mg once daily.

Dasabuvir plus Ombitasvir/Paritaprevir/ RTV

BIC

↔ BIC expected

No 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/RTV

No dose adjustment needed.

EVG/c

No data

Do not coadminister.

RAL

RAL AUC ↑ 134%

No dose adjustment needed.

Elbasvir/Grazoprevir

BIC

↔ BIC expected

No dose adjustment needed.

CAB (PO and IM)

↔ CAB, elbasvir, and grazoprevir expected

No 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/Pibrentasvir

BIC, CAB (PO and IM)

↔ BIC or CAB expected

No dose adjustment needed.

DTG

↔ DTG and glecaprevir/ pibrentasvir

No dose adjustment needed.

RAL

No significant effect

RAL AUC ↑ 47%

 

EVG/c

Glecaprevir 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/Sofosbuvir

BIC, DTG, RAL

↔ BIC, DTG, and RAL

No dose adjustment needed.

CAB (PO and IM)

↔ CAB expected

No dose adjustment needed.

EVG/c/TDF/
FTC

↑ TDF expected

↑ ledipasvir expected

Do not coadminister.

EVG/c/TAF/
FTC

↔ EVG/c/TAF/FTC expected

No dose adjustment needed.

Sofosbuvir

BIC, CAB (PO and IM), DTG, EVG/C

↔ INSTI expected

↔ sofosbuvir expected

No dose adjustment needed.

RAL

↔ RAL and sofosbuvir

No dose adjustment needed.

Sofosbuvir/Velpatasvir

BIC, DTG, RAL

↔ sofosbuvir and velpatasvir

No 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

BIC

When Administered With Sofosbuvir/
Velpatasvir/
Voxilaprevir (400 mg/100 mg/100 mg) plus Voxilaprevir 100 mg

  • ↔ BIC, sofosbuvir, velpatasvir, voxilaprevir

No dose adjustment needed.

EVG/c

When 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 Wort

BIC, CAB (PO and IM), DTG

↓ BIC and DTG possible

Do not coadminister.

EVG/c

↓ EVG and COBI expected

Contraindicated.

Hormonal Therapies

Contraceptives: Non‑Oral

BIC, CAB (PO and IM), DTG, RAL

Etonogestrel (subdermal implant) ↑ 27% with DTG

↔ expected with BIC, CAB, RAL

No dose adjustment needed.

EVG/c

No data

No data available to make dose recommendation.

Contraceptives: Oral

BIC, DTG, RAL

↔ ethinyl estradiol and norgestimate

↔ INSTI

No dose adjustment needed.

CAB (PO and IM)

↔ ethinyl estradiol and levonorgestrel with CAB PO

No dose adjustment needed.

EVG/c

Norgestimate 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 possible

Clinical monitoring is recommended due to the potential for hyperkalemia. Consider using alternative ARV or contraceptive method.

Gender-Affirming Therapy

BIC, CAB (PO and IM), DTG, EVG/c, RAL

↔ goserelin, leuprolide acetate, and spironolactone expected

No dose adjustment needed.

BIC, CAB (PO and IM), DTG, RAL

↔ estrogen expected

No dose adjustment needed.

↔ testosterone expected

No 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 possible

Monitor masculinizing effects of testosterone and monitor for adverse effects. Adjust testosterone dose as necessary.

Menopausal Replacement Therapy

BIC, 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, Tacrolimus

BIC, CAB (PO and IM), DTG, RAL

↔ immunosuppressant expected

No dose adjustment needed.

EVG/c

↑ immunosuppressant possible

Initiate 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 expected

No dose adjustment needed.

EVG/c

Atorvastatin AUC ↑ 2.6-fold and Cmax ↑ 2.3-fold

Titrate statin dose carefully. Administer the lowest effective dose while monitoring for adverse events. Do not exceed 20 mg atorvastatin daily.

Lomitapide

BIC, CAB (PO and IM), DTG, RAL

↔ lomitapide expected

No dose adjustment needed.

EVG/c

↑ lomitapide expected

Contraindicated.

Lovastatin

BIC, CAB (PO and IM), DTG, RAL

↔ lovastatin expected

No dose adjustment needed.

EVG/c

Significant ↑ lovastatin expected

Contraindicated.

Pitavastatin, Pravastatin

BIC, CAB (PO and IM), DTG, RAL

↔ statin expected

No dose adjustment needed.

EVG/c

No data

No data available for dose recommendation.

Rosuvastatin

BIC, CAB (PO and IM), DTG, RAL

↔ rosuvastatin expected

No dose adjustment needed.

EVG/c

Rosuvastatin AUC ↑ 38% and Cmax ↑ 89%

Titrate statin dose carefully and use the lowest effective dose while monitoring for adverse events.

Simvastatin

BIC, CAB (PO and IM), DTG, RAL

↔ simvastatin expected

No dose adjustment needed.

EVG/c

Significant ↑ simvastatin expected

Contraindicated.

Narcotics and Treatment for Opioid Dependence

Buprenorphine

Sublingual, buccal, or implant

BIC, CAB (PO and IM), DTG

↔ buprenorphine and norbuprenorphine (active metabolite) expected

No dose adjustment needed.

EVG/c

Buprenorphine 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.

Fentanyl

BIC, CAB (PO and IM), DTG, RAL

↔ fentanyl expected

No dose adjustment needed.

EVG/c

↑ fentanyl

Monitor for fentanyl efficacy and adverse events, including potentially fatal respiratory depression.

Lofexidine

BIC, CAB (PO and IM), DTG, RAL

↔ lofexidine expected

No dose adjustment needed.

EVG/c

↑ lofexidine possible

Monitor for lofexidine-related adverse events, including symptoms of orthostasis and bradycardia.

Methadone

All INSTIs

↔ methadone

No dose adjustment needed.

Tramadol

BIC, CAB (PO and IM), DTG, RAL

↔ tramadol and M1 (active metabolite) expected

No 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

Avanafil

BIC, CAB (PO and IM), DTG, RAL

↔ avanafil expected

No dose adjustment needed.

EVG/c

No data

Do not coadminister.

Sildenafil

BIC, CAB (PO and IM), DTG, RAL

↔ sildenafil expected

No dose adjustment needed.

EVG/c

↑ sildenafil expected

For Treatment of Erectile Dysfunction

  • Start with sildenafil 25 mg every 48 hours and monitor for adverse effects of sildenafil.

Contraindicated for treatment of PAH.

Tadalafil

BIC, CAB (PO and IM), DTG, RAL

↔ tadalafil expected

No dose adjustment needed.

EVG/c

↑ tadalafil expected

For 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.

Vardenafil

BIC, CAB (PO and IM), DTG, RAL

↔ vardenafil expected

No dose adjustment needed.

EVG/c

↑ vardenafil expected

Start with vardenafil 2.5 mg every 72 hours and monitor for adverse effects of vardenafil.

Sedative/Hypnotics

Alprazolam, Clonazepam, Clorazepate, Diazepam, Estazolam, Flurazepam

BIC, CAB (PO and IM), DTG, RAL

↔ benzodiazepine expected

No dose adjustment needed.

EVG/c

↑ benzodiazepine possible

Dose 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, Triazolam

BIC, CAB (PO and IM), RAL

↔ benzodiazepine expected

No dose adjustment needed.

DTG

With 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.

Suvorexant

BIC, CAB (PO and IM), DTG, RAL

↔ suvorexant expected

No dose adjustment needed.

EVG/c

↑ suvorexant expected

Do not coadminister.

Zolpidem

BIC, CAB (PO and IM), DTG, RAL

↔ zolpidem expected

No dose adjustment needed.

EVG/c

↑ zolpidem expected

Initiate zolpidem at a low dose. Dose reduction of zolpidem may be necessary.

Miscellaneous Drugs

Calcifediol

BIC, CAB (PO and IM), DTG, RAL

↔ calcifediol expected

No dose adjustment needed.

EVG/c

↑ calcifediol possible

Dose adjustment of calcifediol may be required. Monitor serum 25-hydroxyvitamin D, intact PTH, and serum Ca concentrations.

Cisapride

BIC, CAB (PO and IM), DTG, RAL

↔ cisapride expected

No dose adjustment needed.

EVG/c

↑ cisapride expected

Contraindicated.

Colchicine

BIC, CAB (PO and IM), DTG, RAL

↔ colchicine expected

No dose adjustment needed.

EVG/c

↑ colchicine expected

Do 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.

Dronabinol

BIC, CAB (PO and IM), DTG, RAL

↔ dronabinol expected

No dose adjustment needed.

EVG/c

↑ dronabinol possible

Monitor for dronabinol-related adverse events.

Eluxadoline

BIC, CAB (PO and IM), DTG, RAL

↔ eluxadoline expected

No dose adjustment needed.

EVG/c

↑ eluxadoline possible

Monitor for eluxadoline-related adverse events.

Ergot Derivatives

BIC, CAB (PO and IM), DTG, RAL

↔ dihydroergotamine, ergotamine, and methylergonovine expected

No dose adjustment needed.

EVG/c

↑ dihydroergotamine, ergotamine, and methylergonovine expected

Contraindicated.

Flibanserin

BIC, CAB (PO and IM), DTG, RAL

↔ flibanserin expected

No dose adjustment needed.

EVG/c

↑ flibanserin expected

Contraindicated.

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 possible

If 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.

DTG

DTG 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 possible

If 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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