INSTI interactions

Guidelines > Drug-Drug Interactions > INSTI interactions

Drug Interactions Between Integrase Strand Transfer Inhibitors and Other Drugs

DHHS Last Updated: September 2024Australian Commentary Last Updated: December 2024

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. Monitor blood pressure. 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 blood pressure.
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. Monitor blood pressure. 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
Bedaquiline	BIC, CAB (PO and IM), DTG, RAL	↔ bedaquiline	No dosage adjustment needed
Bedaquiline	EVG/c	↑ bedaquiline possible	Do not coadminister. unless benefits outweigh risks. If coadministered, consider therapeutic drug monitoring and monitor for bedaquiline-related adverse effects, including hepatotoxicity and QTc prolongation.
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% Rifapentine 6 00 mg Once Daily With DTG 50 mg Twice Daily vs DTG 50 mg Once Daily Alone ↔ DTG AUC and C_min	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. With once-daily rifapentine for 4 weeks (1HP), use DTG 50 mg twice daily. See Tuberculosis/HIV Coinfection for more on rifapentine and DTG use.
	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%	Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation in Adult Patients CrCl >30mL/min: no dose adjustments needed CrCl <30mL/min do not coadminister. Treatment and Reduction in the Risk of Recurrence of DVT and PE or Prophylaxis of DVT and PE Following Hip Replacement Surgery in Adult Patients CrCl >50mL/min: no dose adjustments needed CrCl <50mL/min do not coadminister.
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.
Antiseizure
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, Primidone	BIC, DTG, RAL	↓ BIC and DTG possible ↓ or ↔ RAL possible	Do not coadminister.
Phenobarbital, Phenytoin, Primidone	CAB (PO and IM), EVG/c	↓ CAB and EVG/c expected	Contraindicated.
Valproic Acid	DTG	DTG ↓ possible	No dose adjustment needed. Take with food and monitor virologic response.
Valproic Acid	BIC, CAB (PO and IM), RAL	No data	No dose adjustment needed. Monitor virologic response.
Antidepressants, Anxiolytics, and Antipsychotics Also see the Sedative/Hypnotics section below
*Antidepressants, Anxiolytics*
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.
Desvenlafaxine	All INSTIs	↔ desvenlafaxine expected	No dose adjustment needed
Duloxetine	BIC, CAB (PO and IM), DTG, RAL	↔ duloxetine expected	No dose adjustment needed
Duloxetine	EVG/c	↔ duloxetine possible	No dose adjustment needed
Mirtazapine	BIC, CAB (PO and IM), DTG, RAL	↔ mirtazapine expected	No dose adjustment needed
Mirtazapine	EVG/c	↔ mirtazapine possible	Monitor for mirtazapine-related adverse events. Mirtazapine dose reduction may be necessary.
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.
Trazodone	EVG/c	↔ trazodone possible	Titrate dose based on antidepressant response and monitor for trazodone-related adverse events.
Tricyclic Antidepressants (e.g., 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 (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine)	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.
Venlafaxine	BIC, CAB (PO and IM), DTG, RAL	↔ venlafaxine expected	No dose adjustment needed.
Venlafaxine	EVG/c	↑ venlafaxine possible	Monitor for venlafaxine-related adverse events.
*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 effectiveness 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 effectiveness 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, Olanzapine/Samidorphan	All INSTIs	↔ olanzapine expected	No dose adjustment needed.
Olanzapine, Olanzapine/Samidorphan	EVG/c	↔ olanzapine expected ↑ samidorphan possible	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.
Antimigraine
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
*Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonists*
Atogepant	BIC, CAB (PO and IM), DTG, RAL	↔ atogepant expected ↑ atogepant expected	No dose adjustment needed
Atogepant	EVG/c	↑ atogepant expected	Chronic migraine: Do not coadminister. Episodic migraine: Administer atogepant at a dose of 10 mg once daily.
Rimegepant	BIC, CAB (PO and IM), DTG, RAL	↔ rimegepant expected	No dose adjustment needed
Rimegepant	EVG/c	↑ rimegepantexpected	Do not coadminister.
Ubrogepant	BIC, CAB (PO and IM), DTG, RAL	↔ ubrogepantexpected	No dose adjustment needed
Ubrogepant	EVG/c	↑ ubrogepant expected	Contraindicated
Zavegepant	BIC, CAB (PO and IM), DTG, RAL	↔ zavegepant expected	No dose adjustment needed
Zavegepant	EVG/c	↑ zavegepant expected	Do not coadminister.
*Serotonin 5-HT1B, 1D Receptor Agonist*
Almotriptan	BIC, CAB (PO and IM), DTG, RAL	↔ almotriptan expected	No dose adjustment needed
Almotriptan	EVG/c	↑ almotriptan expected	Administer single dose of almotriptan 6.25 mg. Maximum dose shoul not exceed 12.5 mg in a 24-hour period
Eletriptan	BIC, CAB (PO and IM), DTG, RAL	↔ eletriptan expected	No dose adjustment needed
Eletriptan	EVG/c	↑ eletriptan expected	Contraindicated
Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan	All INSTIs	↔ triptan expected	No dose adjustment needed
Antifungals
Ibrexafungerp	BIC, CAB (PO and IM), DTG, RAL	↔ ibrexafungerp expected	No dose adjustment needed
Ibrexafungerp	EVG/c	↑ ibrexafungerp expected	Reduce Ibrexafungerp does up to 150 mg twice daily
Isavuconazole	BIC, CAB (PO and IM), DTG, RAL	↑ INSTI possible	No dose adjustment needed.
Isavuconazole	EVG/c	↑ isavuconazole expected ↑ or ↓ EVG and COBI possible	Contraindicated
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.
Antimalarials
Artemether/ Lumefantrine	BIC	↔ antimalarial expected	No dose adjustment needed.
	CAB (PO and IM), DTG, RAL	↔ antimalarial expected	No dose adjustment needed.
	EVG/c	↑ artemether and lumefantrine possible	Monitor for artemether and lumefantrine-related adverse events, including QTc prolongation.
Artesunate	All INSTIs	↔ dihydroartemisinin expected	No dose adjustment needed
Atovaquone/Proguanil	All INSTIs	↔ atovaquone/proguanil expected	No dose adjustment needed
Mefloquine	CAB (PO and IM), DTG, RAL	↔ mefloquine expected	No dose adjustment needed
Mefloquine	EVG/c	↑ mefloquine possible	Monitor for mefloquine-related adverse events, including psychiatric symptoms and QTc prolongation.
Glucose-Lowering
Metformin	BIC	Metformin AUC ↑ 39%	Monitor for adverse events of metformin.
	CAB (PO and IM), RAL	↔ metformin expected	No dose adjustment needed.
	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.
	EVG/c	↑ 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.
Antipneumocystis and Antitoxoplasmosis
Atovaquone	All INSTIs	↔ atovaquone expected	No dose adjustment needed.
Antivirals—Hepatitis C
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 No significant effect RAL AUC grazoprevir expected	Do not coadminister.
	RAL	↔ RAL with elbasvir AUC ↑ 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 ↑ 46%	No dose adjustment needed
	EVG/c	Glecaprevir AUC ↑ 3-fold Pibrentasvir AUC ↑ 57% EVG AUC ↑ 47%	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
Antivirals—Miscellaneous (e.g., for CMV, 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.
Antivirals—SARS-CoV-2
Molnupiravir	BIC, CAB (PO and IM), DTG, EVG/c, RAL	↔ INSTI and molnupiravir expected	No dose adjustment needed
Ritonavir-boosted Nirmatrelvi	BIC, CAB (PO and IM), DTG, EVG/c, RAL	↔ INSTI and ritonavir- boosted nirmatrelvir expected	No dose adjustment needed
Ritonavir-boosted Nirmatrelvi	EVG/c/FTC/ TAF	↑ TAF possible ↔ ritonavir-boosted nirmatrelvir expected	No dose adjustment needed
Remdesivir	BIC, CAB (PO and IM), DTG, RAL	↔ INSTI and remdesivir 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
Olodaterol	BIC, CAB (PO and IM), DTG, RAL	↔ olodaterol expected	No dose adjustment needed.
Olodaterol	EVG/c	↑ olodaterol expected
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
*Antiarrhythmics*
Amiodarone	BIC, CAB (PO and IM), DTG, RAL	↔ INSTI expected ↔ amiodarone expected	No dose adjustment needed.
Amiodarone	EVG/c	↑ 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.
Digoxin	BIC, CAB (PO and IM), DTG	↔ digoxin expected	No dose adjustment needed.
Digoxin	EVG/c	Digoxin C_max ↑ 41% and ↔ AUC	Therapeutic drug monitoring for digoxin is recommended if available.
Dofetilide	CAB (PO and IM)	↔ dofetilide expected	No dose adjustment needed.
	BIC, DTG	↑ dofetilide possible	Contraindicated
	EVG/c	↑ dofetilide possible	Do not coadminister
Disopyramide	BIC, CAB (PO and IM), RAL	↔ disopyramide expected	No dose adjustment needed
	DTG	↑ disopyramide possible	Consider alternative ARV or antiarrhythmics. If coadministered, monitor disopyramide concentrations and for antiarrhythmic-related adverse events.
	EVG/c	↑ disopyramide expected	Do not coadminister
Dronedarone	BIC, CAB (PO and IM), DTG, RAL	↔ dronedarone expected	No dose adjustment needed
Dronedarone	EVG/c	↑ dronedarone expected	Contraindicated
Flecainide	BIC, CAB(PO and IM), DTG, RAL	↔ flecainide expected	No dose adjustment needed
Flecainide	EVG/c	↑ flecainide possible	Consider alternative ARV or antiarrhythmics. If coadministered, monitor flecainide concentrations and for antiarrhythmic-related adverse events.
Propafenone	BIC, CAB(PO and IM), DTG, RAL	↔ propafenone expected	No dose adjustment needed
Propafenone	EVG/c	↑ propafenone possible	Consider alternative ARV or antiarrhythmics. If coadministered, monitor propafenone concentrations and for antiarrhythmic-related adverse events.
Mexiletine	BIC, CAB(PO and IM), DTG, RAL	↔ mexiletine expected	No dose adjustment needed
Mexiletine	EVG/c	↑ mexiletine possible	Consider alternative ARV or antiarrhythmics. If coadministered, monitor mexiletine concentrations and for antiarrhythmic-related adverse events.
Systemic Lidocaine	BIC, CAB(PO and IM), DTG, RAL	↔ lidocaine expected	No dose adjustment needed
Systemic Lidocaine	EVG/c	↑ lidocaine possible	Consider alternative ARV or antiarrhythmics. If coadministered, monitor lidocaine concentrations and for antiarrhythmic-related adverse events.
Quinidine	BIC, CAB(PO and IM), DTG, RAL	↔ quinidine expected	No dose adjustment needed
Quinidine	EVG/c	↑ quinidine possible	Consider alternative ARV or antiarrhythmics. If coadministered, monitor quinidine concentrations and for antiarrhythmic-related adverse events.
*Beta Blockers*
A tenolol, Bisoprolol, Carvedilol, Metoprolol, Nadolol, Nebivolol, Sotalol	CAB (PO and IM), RAL	↔ beta blocker expected	No dose adjustment needed.
	BIC, DTG, EVG/c	↑ beta blocker possible	Beta-blocker dose may need to be decreased; adjust dose based on clinical response.
*Calcium Channel Blockers*
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.
*Cardiac—Other*
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.
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.
Mavacamten	BIC, CAB (PO and IM), DTG, RAL	↔ mavacamten expected	No dose adjustment needed.
Mavacamten	EVG/c	↑ mavacamten 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.
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	Do not coadminister.
Hormonal Therapies
Injectable Contraceptives Depot MPA	BIC, CAB (PO and IM), DTG, RAL	↔ INSTI and injectable contraceptive expected	No dose adjustment needed.
Injectable Contraceptives Depot MPA	EVG/c	↑ MPA possible	No dose adjustment needed.
Oral Contraceptives (e.g., desogestrel, drospirenone, ethinyl estradiol, levonorgestrel, norethindrone, norgestimate)	BIC, CAB (PO, IM), DTG, RAL	↔ ethinyl estradiol and norgestimate with DTG ↔ ethinyl estradiol and levonorgestrel with CAB PO ↔ ethinyl estradiol and norgestimate expected with BIC, RAL ↔ norgestimate expected with CAB PO and IM ↔ levonorgestrel expected ↔ drospirenone expected ↔ norethindrone expected	No dose adjustment needed.
	EVG/c	Norgestimate AUC, C_max, and C_min ↑ > 2-fold Ethinyl estradiol AUC ↓ 25% and C_min ↓ 44% ↑ drospirenone possible	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	↑ levonorgestrel possible ↑ norethindrone expected	No dose adjustment needed.
Subdermal Implant Contraceptives (e.g., etonogestrel, levonorgestrel)	BIC, CAB (PO and IM), DTG, RAL	Etonogestrel ↑ 27% with DTG ↔ etonogestrel or levonorgestrel expected with BIC, CAB, RAL	No dose adjustment needed.
	EVG/c	↑ etonogestrel expected ↑ levonorgestrel expected	No dose adjustment needed.
Transdermal Contraceptives (e.g., ethinyl estradiol/norelgestromin, ethinyl estradiol/levonorgestrel)	BIC, CAB (PO and IM), DTG, RAL	↔ contraceptive expected	No dose adjustment needed.
	EVG/c	↑ progestin possible ↓ ethinyl estradiol possible	No dose adjustment needed.
Vaginal Ring Contraceptives (e.g., etonogestrel/ethinyl estradiol, segesterone/ethinyl estradiol)	BIC, CAB (PO and IM), DTG, RAL	↔ contraceptive expected	No dose adjustment needed.
	EVG/c	↑ progestin possible ↓ ethinyl estradiol possible	For segesterone/ethinyl estradiol vaginal rings, use alternative ARV or contraceptive methods.
Emergency Contraceptives Levonorgestrel (PO)	BIC, CAB (PO and IM), DTG, RAL	↔ levonorgestrel expected	No dose adjustment needed.
Emergency Contraceptives Levonorgestrel (PO)	EVG/c	↑ levonorgestrel possible	No dose adjustment needed.
Hormonal Therapies—Gender-Affirming and Menopause
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	↓ or ↑ estrogen 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.
Fluvastatin	BIC, CAB (PO and IM), DTG, RAL	↔ fluvastatin expected	No dose adjustment needed.
Fluvastatin	EVG/c	↑ fluvastatin possible	Administer the lowest effective fluvastatin dose while monitoring for adverse events.
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 dose adjustment needed. Monitor for adverse events.
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
*Benzodiazepines*
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.
*Orexin Receptor Antagonists*
Daridorexant, Lemborexant, Suvorexant	BIC, CAB (PO and IM), DTG, RAL	↔ daridorexant, lemborexant, suvorexant expected	No dose adjustment needed.
Daridorexant, Lemborexant, Suvorexant	EVG/c	↑ daridorexant, lemborexant, suvorexant expected	Do not coadminister.
*Other Sedatives*
Eszopiclone	BIC, CAB (PO and IM), DTG, RAL	↔ eszopiclone expected	No dose adjustment needed.
Eszopiclone	EVG/c	↑ eszopiclone expected	Start with lowest dose and increase to a max of 2 mg daily. Monitor for eszopiclone-related adverse events
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.
Finerenone	BIC, CAB (PO and IM), DTG, RAL	↔ finerenone expected	No dose adjustment needed.
Finerenone	BIC, CAB (PO and IM), DTG, RAL	↑ finerenone expected	Contraindicated.
Flibanserin	BIC, CAB (PO and IM), DTG, RAL	↔ flibanserin expected	No dose adjustment needed.
Flibanserin	EVG/c	↑ flibanserin expected	Contraindicated.
Naloxegol	BIC, CAB (PO and IM), DTG, RAL	↔ naloxegol expected	No dose adjustment needed.
Naloxegol	EVG/c	↑ naloxegol 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.
Praziquantel	BIC, CAB (PO and IM), DTG, RAL	↔ praziquantel and INSTI expected	No dose adjustment needed.
Praziquantel	EVG/c	↑ praziquantel expected	Consider alternative ARV. If coadministration is necessary, monitor for praziquantel-related adverse events.
Key to Symbols: ↑ = increase ↓ = decrease ↔ = less than 20% change in AUC 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; CMV = cytomegalovirus; COBI = cobicistat; CrCl = creatinine clearance; CYP = cytochrome P450; DTG = dolutegravir; DVT = deep vein thrombosis; 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; MPA = medroxyprogesterone acetate; PAH = pulmonary arterial hypertension; PDE5 = phosphodiesterase type 5; PE = pulmonary embolism; PO = orally; PTH = parathyroid hormone; QTc = QT corrected for heart rate; RAL = raltegravir; RPV = rilpivirine; SSRI = selective serotonin reuptake inhibitors; TAF = tenofovir alafenamide; TCA = tricyclic antidepressants; TDF = tenofovir disoproxil fumarate; Zn = zinc

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While the Australian Department of Health provides financial support for the ARV Guidelines, the material contained in this resource should not be taken to represent the views of the Australian Department of Health.

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Adult Antiretroviral Guidelines

US DHHS Guidelines with Australian Commentary