Drug Interactions between Integrase Inhibitors and Other Drugs

Actualizado 01/09/2022 - 12:00

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 C_min↓ 49% to 63% CaCO₃ Antacid RAL 400 mg twice daily: C_min ↓ 32% RAL 1,200 mg once daily: C_min ↓ 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.
H2-Receptor Antagonists	RAL	RAL AUC ↑ 44% and C_max ↑ 60%	No dose adjustment needed.
Proton Pump Inhibitors	BIC, CAB (PO and IM), DTG, EVG/c	↔ INSTI	No dose adjustment needed.
Proton Pump Inhibitors	RAL	RAL AUC ↑ 37% and C_min ↑ 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.
Alfuzosin	EVG/c	↑ alfuzosin expected	Contraindicated.
Doxazosin	BIC, CAB (PO and IM), DTG, RAL	↔ doxazosin expected	No dose adjustment needed.
Doxazosin	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.
Tamsulosin	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.
Terazosin	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.
Silodosin	EVG/c	↑ silodosin expected	Contraindicated.
Antibacterials - Antimycobacterials
Rifabutin	BIC	Rifabutin 300 mg Once Daily BIC AUC ↓ 38% and C_min ↓ 56%		Do not coadminister.
	CAB PO	CAB PO AUC ↓ 23% and C_min ↓ 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 C_min ↓ 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 C_min ↓ 67%		Do not coadminister.
	RAL	RAL AUC ↑ 19% and C_min ↓ 20%		No dose adjustment needed.
Rifampin	BIC	BIC AUC ↓ 75%		Contraindicated.
	CAB PO	CAB PO AUC ↓ 59% and C_min ↓ 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 C_min ↓ 72% Rifampin With DTG 50 mg Twice Daily Compared to DTG 50 mg Once Daily Alone DTG AUC ↑ 33% and C_min ↑ 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 C_min ↓ 61% Rifampin With RAL 800 mg Twice Daily Compared to RAL 400 mg Twice Daily Alone RAL AUC ↑ 27% and C_min ↓ 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 C_min ↓ 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 C_min ↓ 12% Rifapentine 600 mg Once Daily RAL C_min↓ 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.
Apixaban	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.
Dabigatran	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.
Edoxaban	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.
Rivaroxaban	EVG/c	↑ rivaroxaban expected	Do not coadminister.
Warfarin	BIC, CAB (PO and IM), DTG, RAL	↔ warfarin expected	No dose adjustment needed.
Warfarin	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 C_min ↓ >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.
Ethosuximide	EVG/c	↑ ethosuximide possible	Monitor for ethosuximide-related adverse events.
Lamotrigine	BIC, CAB (PO and IM), DTG, RAL	↔ lamotrigine expected	No dose adjustment needed.
Lamotrigine	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.
Phenobarbital, Phenytoin	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.
Bupropion	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.
Buspirone	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.
Nefazodone	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.
	EVG/c	↑ 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.
Aripiprazole	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.
Brexpiprazole	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.
Cariprazine	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.
Iloperidone	EVG/c	↑ iloperidone expected		Decrease iloperidone dose by 50%.
Lumateperone	BIC, CAB (PO and IM), DTG, RAL	↔ lumateperone expected		No dose adjustment needed.
Lumateperone	EVG/c	↑ lumateperone expected		Do not coadminister.
Lurasidone	BIC, CAB (PO and IM), DTG, RAL	↔ lurasidone expected		No dose adjustment needed.
Lurasidone	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.
Pimavanserin	EVG/c	↑ pimavanserin expected		Reduce pimavanserin dose to 10 mg.
Pimozide	BIC, CAB (PO and IM), DTG, RAL	↔ pimozide expected		No dose adjustment needed.
Pimozide	EVG/c	↑ pimozide expected		Contraindicated.
Quetiapine	BIC, CAB (PO and IM), DTG, RAL	↔ quetiapine expected		No dose adjustment needed.
Quetiapine	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.
Ziprasidone	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.
Isavuconazole	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 C_max ↑ 66% DTG 50 mg Twice Daily plus Metformin 500 mg Twice Daily Metformin AUC ↑ 2.4-fold and C_max ↑ 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.
Saxagliptin	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.
Dapagliflozin/ Saxagliptin	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.
Clopidogrel	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.
Prasugrel	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.
Ticagrelor	EVG/c	↑ ticagrelor expected		Do not coadminister.
Vorapaxar	BIC, CAB (PO and IM) DTG, RAL	↔ vorapaxar expected		No dose adjustment needed.
Vorapaxar	EVG/c	↑ vorapaxar expected		Do not coadminister.
Antivirals—Orthopoxviruses (Smallpox, Mpox)
Brincidofovir	BIC, CAB (PO and IM), DTG, RAL	↔ INSTI expected		No dose adjustment needed.
Brincidofovir	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.)
Tecovirimat	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.
Indacaterol	EVG/c	↑ indacaterol expected		No dose adjustment needed.
Olodaterol	BIC, CAB (PO and IM), DTG, RAL	↔ olodaterol expected		No dose adjustment needed.
Olodaterol	EVG/c	↑ olodaterol expected		No dose adjustment needed.
Salmeterol	BIC, CAB (PO and IM), DTG, RAL	↔ salmeterol expected		No dose adjustment needed.
Salmeterol	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.
Amiodarone	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 C_max ↑ 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.
Beta Blockers (e.g., metoprolol, timolol)	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.
Eplerenone	EVG/c	↑ eplerenone expected		Contraindicated.
Ivabradine	BIC, CAB (PO and IM), DTG, RAL	↔ ivabradine expected		No dose adjustment needed.
Ivabradine	EVG/c	↑ ivabradine expected		Contraindicated.
Ranolazine	BIC, CAB (PO and IM), DTG, RAL	↔ ranolazine expected		No dose adjustment needed.
Ranolazine	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.
Betamethasone, Budesonide Systemic	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.
Prednisone, Prednisolone Systemic	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.
Sofosbuvir	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.
St. John’s Wort	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.
Contraceptives: Non‑Oral	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, C_max, and C_min ↑ > 2-fold Ethinyl estradiol AUC ↓ 25% and C_min ↓ 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.
	EVG/c	↑ 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.
	BIC, CAB (PO and IM), DTG, RAL	↔ 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.
	EVG/c	↑ 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.
Menopausal Replacement Therapy	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.
Cyclosporine, Everolimus, Sirolimus, Tacrolimus	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.
Atorvastatin	EVG/c	Atorvastatin AUC ↑ 2.6-fold and C_max ↑ 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.
Lomitapide	EVG/c	↑ lomitapide expected		Contraindicated.
Lovastatin	BIC, CAB (PO and IM), DTG, RAL	↔ lovastatin expected		No dose adjustment needed.
Lovastatin	EVG/c	Significant ↑ lovastatin expected		Contraindicated.
Pitavastatin, Pravastatin	BIC, CAB (PO and IM), DTG, RAL	↔ statin expected		No dose adjustment needed.
Pitavastatin, Pravastatin	EVG/c	No data		No data available for dose recommendation.
Rosuvastatin	BIC, CAB (PO and IM), DTG, RAL	↔ rosuvastatin expected		No dose adjustment needed.
Rosuvastatin	EVG/c	Rosuvastatin AUC ↑ 38% and C_max ↑ 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.
Simvastatin	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 C_min ↑ 66% Norbuprenorphine (active metabolite) AUC ↑ 42% and C_min↑ 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.
Fentanyl	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.
Lofexidine	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.
Tramadol	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.
Avanafil	EVG/c	No data		Do not coadminister.
Sildenafil	BIC, CAB (PO and IM), DTG, RAL	↔ sildenafil expected		No dose adjustment needed.
Sildenafil	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.
Tadalafil	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.
Vardenafil	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.
Suvorexant	EVG/c	↑ suvorexant expected		Do not coadminister.
Zolpidem	BIC, CAB (PO and IM), DTG, RAL	↔ zolpidem expected		No dose adjustment needed.
Zolpidem	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.
Calcifediol	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.
Cisapride	EVG/c	↑ cisapride expected		Contraindicated.
Colchicine	BIC, CAB (PO and IM), DTG, RAL	↔ colchicine expected		No dose adjustment needed.
Colchicine	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.
Dronabinol	EVG/c	↑ dronabinol possible		Monitor for dronabinol-related adverse events.
Eluxadoline	BIC, CAB (PO and IM), DTG, RAL	↔ eluxadoline expected		No dose adjustment needed.
Eluxadoline	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.
Ergot Derivatives	EVG/c	↑ dihydroergotamine, ergotamine, and methylergonovine expected		Contraindicated.
Flibanserin	BIC, CAB (PO and IM), DTG, RAL	↔ flibanserin expected		No dose adjustment needed.
Flibanserin	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 C_min↓ 49% to 63% CaCO₃ Antacid RAL 400 mg twice daily: C_min ↓ 32% RAL 1,200 mg once daily: C_min ↓ 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.
H2-Receptor Antagonists	RAL	RAL AUC ↑ 44% and C_max ↑ 60%	No dose adjustment needed.
Proton Pump Inhibitors	BIC, CAB (PO and IM), DTG, EVG/c	↔ INSTI	No dose adjustment needed.
Proton Pump Inhibitors	RAL	RAL AUC ↑ 37% and C_min ↑ 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.
Alfuzosin	EVG/c	↑ alfuzosin expected	Contraindicated.
Doxazosin	BIC, CAB (PO and IM), DTG, RAL	↔ doxazosin expected	No dose adjustment needed.
Doxazosin	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.
Tamsulosin	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.
Terazosin	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.
Silodosin	EVG/c	↑ silodosin expected	Contraindicated.
Antibacterials - Antimycobacterials
Rifabutin	BIC	Rifabutin 300 mg Once Daily BIC AUC ↓ 38% and C_min ↓ 56%		Do not coadminister.
	CAB PO	CAB PO AUC ↓ 23% and C_min ↓ 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 C_min ↓ 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 C_min ↓ 67%		Do not coadminister.
	RAL	RAL AUC ↑ 19% and C_min ↓ 20%		No dose adjustment needed.
Rifampin	BIC	BIC AUC ↓ 75%		Contraindicated.
	CAB PO	CAB PO AUC ↓ 59% and C_min ↓ 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 C_min ↓ 72% Rifampin With DTG 50 mg Twice Daily Compared to DTG 50 mg Once Daily Alone DTG AUC ↑ 33% and C_min ↑ 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 C_min ↓ 61% Rifampin With RAL 800 mg Twice Daily Compared to RAL 400 mg Twice Daily Alone RAL AUC ↑ 27% and C_min ↓ 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 C_min ↓ 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 C_min ↓ 12% Rifapentine 600 mg Once Daily RAL C_min↓ 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.
Apixaban	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.
Dabigatran	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.
Edoxaban	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.
Rivaroxaban	EVG/c	↑ rivaroxaban expected	Do not coadminister.
Warfarin	BIC, CAB (PO and IM), DTG, RAL	↔ warfarin expected	No dose adjustment needed.
Warfarin	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 C_min ↓ >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.
Ethosuximide	EVG/c	↑ ethosuximide possible	Monitor for ethosuximide-related adverse events.
Lamotrigine	BIC, CAB (PO and IM), DTG, RAL	↔ lamotrigine expected	No dose adjustment needed.
Lamotrigine	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.
Phenobarbital, Phenytoin	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.
Bupropion	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.
Buspirone	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.
Nefazodone	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.
	EVG/c	↑ 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.
Aripiprazole	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.
Brexpiprazole	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.
Cariprazine	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.
Iloperidone	EVG/c	↑ iloperidone expected		Decrease iloperidone dose by 50%.
Lumateperone	BIC, CAB (PO and IM), DTG, RAL	↔ lumateperone expected		No dose adjustment needed.
Lumateperone	EVG/c	↑ lumateperone expected		Do not coadminister.
Lurasidone	BIC, CAB (PO and IM), DTG, RAL	↔ lurasidone expected		No dose adjustment needed.
Lurasidone	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.
Pimavanserin	EVG/c	↑ pimavanserin expected		Reduce pimavanserin dose to 10 mg.
Pimozide	BIC, CAB (PO and IM), DTG, RAL	↔ pimozide expected		No dose adjustment needed.
Pimozide	EVG/c	↑ pimozide expected		Contraindicated.
Quetiapine	BIC, CAB (PO and IM), DTG, RAL	↔ quetiapine expected		No dose adjustment needed.
Quetiapine	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.
Ziprasidone	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.
Isavuconazole	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 C_max ↑ 66% DTG 50 mg Twice Daily plus Metformin 500 mg Twice Daily Metformin AUC ↑ 2.4-fold and C_max ↑ 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.
Saxagliptin	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.
Dapagliflozin/ Saxagliptin	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.
Clopidogrel	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.
Prasugrel	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.
Ticagrelor	EVG/c	↑ ticagrelor expected		Do not coadminister.
Vorapaxar	BIC, CAB (PO and IM) DTG, RAL	↔ vorapaxar expected		No dose adjustment needed.
Vorapaxar	EVG/c	↑ vorapaxar expected		Do not coadminister.
Antivirals—Orthopoxviruses (Smallpox, Mpox)
Brincidofovir	BIC, CAB (PO and IM), DTG, RAL	↔ INSTI expected		No dose adjustment needed.
Brincidofovir	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.)
Tecovirimat	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.
Indacaterol	EVG/c	↑ indacaterol expected		No dose adjustment needed.
Olodaterol	BIC, CAB (PO and IM), DTG, RAL	↔ olodaterol expected		No dose adjustment needed.
Olodaterol	EVG/c	↑ olodaterol expected		No dose adjustment needed.
Salmeterol	BIC, CAB (PO and IM), DTG, RAL	↔ salmeterol expected		No dose adjustment needed.
Salmeterol	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.
Amiodarone	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 C_max ↑ 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.
Beta Blockers (e.g., metoprolol, timolol)	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.
Eplerenone	EVG/c	↑ eplerenone expected		Contraindicated.
Ivabradine	BIC, CAB (PO and IM), DTG, RAL	↔ ivabradine expected		No dose adjustment needed.
Ivabradine	EVG/c	↑ ivabradine expected		Contraindicated.
Ranolazine	BIC, CAB (PO and IM), DTG, RAL	↔ ranolazine expected		No dose adjustment needed.
Ranolazine	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.
Betamethasone, Budesonide Systemic	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.
Prednisone, Prednisolone Systemic	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.
Sofosbuvir	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.
St. John’s Wort	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.
Contraceptives: Non‑Oral	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, C_max, and C_min ↑ > 2-fold Ethinyl estradiol AUC ↓ 25% and C_min ↓ 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.
	EVG/c	↑ 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.
	BIC, CAB (PO and IM), DTG, RAL	↔ 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.
	EVG/c	↑ 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.
Menopausal Replacement Therapy	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.
Cyclosporine, Everolimus, Sirolimus, Tacrolimus	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.
Atorvastatin	EVG/c	Atorvastatin AUC ↑ 2.6-fold and C_max ↑ 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.
Lomitapide	EVG/c	↑ lomitapide expected		Contraindicated.
Lovastatin	BIC, CAB (PO and IM), DTG, RAL	↔ lovastatin expected		No dose adjustment needed.
Lovastatin	EVG/c	Significant ↑ lovastatin expected		Contraindicated.
Pitavastatin, Pravastatin	BIC, CAB (PO and IM), DTG, RAL	↔ statin expected		No dose adjustment needed.
Pitavastatin, Pravastatin	EVG/c	No data		No data available for dose recommendation.
Rosuvastatin	BIC, CAB (PO and IM), DTG, RAL	↔ rosuvastatin expected		No dose adjustment needed.
Rosuvastatin	EVG/c	Rosuvastatin AUC ↑ 38% and C_max ↑ 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.
Simvastatin	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 C_min ↑ 66% Norbuprenorphine (active metabolite) AUC ↑ 42% and C_min↑ 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.
Fentanyl	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.
Lofexidine	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.
Tramadol	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.
Avanafil	EVG/c	No data		Do not coadminister.
Sildenafil	BIC, CAB (PO and IM), DTG, RAL	↔ sildenafil expected		No dose adjustment needed.
Sildenafil	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.
Tadalafil	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.
Vardenafil	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.
Suvorexant	EVG/c	↑ suvorexant expected		Do not coadminister.
Zolpidem	BIC, CAB (PO and IM), DTG, RAL	↔ zolpidem expected		No dose adjustment needed.
Zolpidem	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.
Calcifediol	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.
Cisapride	EVG/c	↑ cisapride expected		Contraindicated.
Colchicine	BIC, CAB (PO and IM), DTG, RAL	↔ colchicine expected		No dose adjustment needed.
Colchicine	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.
Dronabinol	EVG/c	↑ dronabinol possible		Monitor for dronabinol-related adverse events.
Eluxadoline	BIC, CAB (PO and IM), DTG, RAL	↔ eluxadoline expected		No dose adjustment needed.
Eluxadoline	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.
Ergot Derivatives	EVG/c	↑ dihydroergotamine, ergotamine, and methylergonovine expected		Contraindicated.
Flibanserin	BIC, CAB (PO and IM), DTG, RAL	↔ flibanserin expected		No dose adjustment needed.
Flibanserin	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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Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV

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

Drug-Drug Interactions

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

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