Australian Commentary to the US DHHS Guidelines for the use of Antiretroviral Agents in Adults and Adolescents with HIV

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ARV Guidelines > Adult Guidelines > Drug-Drug Interactions > PI Drug interactions

Drug Interactions Between Protease Inhibitors and Other Drugs

DHHS Last Updated: September 2022

Table 24a. Drug Interactions Between Protease Inhibitors and Other Drugs

This table provides information on the known or predicted interactions between protease inhibitors (PIs) and non-antiretroviral (ARV) drugs. When information is available, interactions for boosted atazanavir (ATV) (with either ritonavir [RTV] or cobicistat [COBI]) and unboosted ATV are listed separately. The term “all PIs” refers to both unboosted ATV and ATV, darunavir (DRV), and lopinavir (LPV) boosted with either RTV or COBI. This table does not include interactions for fosamprenavir (FPV), nelfinavir (NFV), or tipranavir (TPV). For information regarding interactions between PIs and other ARV drugs, including dosing recommendations, refer to Tables 24c, 25a, 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.

Note: FPV, NFV, and TPV are no longer commonly used in clinical practice and are not included in this table. Please refer to the U.S. Food and Drug Administration product labels for information regarding drug interactions between these PIs and concomitant medications.

Concomitant Drug	PI	Effect on PI and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Acid Reducers
Antacids	ATV (unboosted), ATV/c, ATV/r	When Given Simultaneously ↓ ATV expected	Administer ATV at least 2 hours before or 2 hours after antacids or buffered medications.
H2 Receptor Antagonists	ATV (unboosted)	When Given Simultaneously With Famotidine ATV AUC ↓ 41% When Given 2 Hours Before and ≥10 Hours After H2RA ↔ ATV	A single dose of H2RA should not exceed a dose equivalent to famotidine 20 mg, and the total daily dose should not exceed a dose equivalent to famotidine 20 mg twice daily in PI-naive patients. Give an ATV with food at least 2 hours before and at least 10 hours after the H2RA. Do not coadminister unboosted ATV plus H2RA in PI-experienced patients.
	ATV/c, ATV/r	↓ ATV expected	H2RA dose should not exceed a dose equivalent to famotidine 40 mg twice daily in ART-naive patients or famotidine 20 mg twice daily in ART-experienced patients. Give ATV 300 mg (plus COBI 150 mg or RTV 100 mg) with food simultaneously with and/or ≥10 hours after the dose of H2RA. If using TDF and H2RA in ART-experienced patients, administer ATV 400 mg plus RTV 100 mg with food simultaneously with and/or ≥10 hours after the dose of H2RA. Do not coadminister ATV/c with TDF and H2RA in ART-experienced patients.
	DRV/c, DRV/r, LPV/r	With Ranitidine ↔ DRV/r ↔ PI expected	No dose adjustment needed.
Proton Pump Inhibitors	ATV (unboosted)	With Omeprazole 40 mg ATV AUC ↓ 94%	Do not coadminister.
	ATV/c, ATV/r	With Omeprazole 40 mg ATV AUC ↓ 76% When Omeprazole 20 mg Is Given 12 Hours before ATV/c or ATV/r ATV AUC ↓ 42%	PPI dose should not exceed a dose equivalent to omeprazole 20 mg daily in PI-naive patients. PPIs should be administered at least 12 hours before ATV/c or ATV/r. Do not coadminister in PI-experienced patients.
	DRV/c, LPV/r	↔ PI expected	No dose adjustment needed.
	DRV/r	↔ DRV/r Omeprazole AUC ↓ 42%	Consider alternative ARV or acid reducer. If coadministered, monitor for omeprazole efficacy. If the patient does not experience symptomatic relief, increase the dose to no more than omeprazole 40 mg daily.
Alpha-Adrenergic Antagonists for Benign Prostatic Hyperplasia
Alfuzosin	All PIs	↑ alfuzosin expected	Contraindicated.
Doxazosin	All PIs	↑ doxazosin possible	Initiate doxazosin at lowest dose and titrate while monitoring for clinical response/adverse events. Dose reduction may be necessary.
Tamsulosin	All PIs	↑ tamsulosin expected	Do not coadminister, unless benefits outweigh risks. If coadministered, monitor for tamsulosin-related adverse events.
Terazosin	All PIs	↔ or ↑ terazosin possible	Initiate terazosin at lowest dose and titrate while monitoring for clinical response/adverse events. Dose reduction may be necessary.
Silodosin	All PIs	↑ silodosin expected	Contraindicated.
Antibacterials—Antimycobacterials
Bedaquiline	All PIs	With LPV/r Bedaquiline AUC ↑ 1.9-fold With Other PI/r, ATV/c, or DRV/c ↑ bedaquiline possible	Do not coadminister unless benefits outweigh risks. Monitor liver function and ECG for QTc prolongation.
Rifabutin	ATV (unboosted)	↑ rifabutin AUC expected	Recommended dose is rifabutin 150 mg once daily. Monitor for antimycobacterial activity and consider therapeutic drug monitoring. Monitor for rifabutin-related adverse events, including neutropenia and uveitis. PK data in this table are results from healthy volunteer studies. Lower rifabutin exposure has been reported in patients with HIV than in healthy study participants.
	ATV/r	Compared With Rifabutin (300 mg Once Daily) Alone, Rifabutin (150 mg Once Daily) Plus ATV/r Rifabutin AUC ↑ 110% and metabolite AUC ↑ 2,101%
	DRV/r	Compared With Rifabutin (300 mg Once Daily) Alone, Rifabutin (150 mg Every Other Day) Plus DRV/r ↔ rifabutin AUC and metabolite AUC ↑ 881%
	LPV/r	Compared With Rifabutin (300 mg Daily) Alone, Rifabutin (150 mg Once Daily) Plus LPV/r Rifabutin AUC ↑ 203% and metabolite AUC ↑ 375%
	PI/c	↑ rifabutin expected ↓ COBI expected	Do not coadminister.
Rifampin	All PIs	↓ PI concentration by >75%	Contraindicated. Increasing the dose of RTV does not overcome this interaction and may increase hepatotoxicity. Increasing the COBI dose is not recommended. Consider rifabutin if a rifamycin is indicated.
Rifapentine	All PIs	↓ PI expected	Do not coadminister.
Antibacterials—Macrolides
Azithromycin	ATV (unboosted), ATV/c, ATV/r	↑ azithromycin possible	No dose adjustment needed.
Azithromycin	DRV/c, DRV/r	↔ azithromycin expected	No dose adjustment needed.
Clarithromycin	ATV (unboosted)	Clarithromycin AUC ↑ 94% ATV ↑ 28%	Reduce clarithromycin dose by 50% or consider alternative ARV or azithromycin. Monitor for clarithromycin-related adverse events, including QTc prolongation.
	ATV/r, PI/c	↑ clarithromycin expected ↑ ATV/r and PI/c expected	Consider alternative ARV or azithromycin.
	DRV/r, LPV/r	DRV/r ↑ clarithromycin AUC 57% LPV/r ↑ clarithromycin expected RTV 500 mg twice daily ↑ clarithromycin 77%	Consider alternative ARV or azithromycin. If use of clarithromycin is necessary in a patient with impaired renal function, reduce clarithromycin dose by 50% in patients with CrCl 30 to 60 mL/min. In patients with CrCl <30 mL/min, reduce clarithromycin dose by 75%. Monitor for clarithromycin-related adverse events, including QTc prolongation.
Erythromycin	All PIs	↑ erythromycin expected ↑ PIs expected	Consider alternative ARV or use azithromycin.
Anticoagulants
Apixaban	ATV (unboosted)	↑ apixaban possible	No data available for dose recommendation. Consider alternative ARV or anticoagulant.
Apixaban	PI/c, PI/r	↑ apixaban expected	Do not coadminister in patients who require apixaban 2.5 mg twice daily. In Patients Requiring Apixaban 5 mg or 10 mg Twice Daily Reduce apixaban dose by 50%.
Dabigatran	ATV (unboosted), DRV/c, DRV/r, LPV/r	No data	No data available for dose recommendation. Consider alternative ARV or anticoagulant.
Dabigatran	ATV/c, ATV/r	With COBI 150 mg Alone Dabigatran AUC ↑ 110% to 127% With ATV/r ↑ dabigatran expected	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	ATV (unboosted), DRV/c, DRV/r, LPV/r	No data	No data available for dose recommendation. Consider alternative ARV or anticoagulant.
Edoxaban	ATV/r, ATV/c	↑ edoxaban expected	Stroke Prevention in Nonvalvular Atrial Fibrillation Indication No dose adjustment needed. Deep Venous Thrombosis and Pulmonary Embolism Indication Administer edoxaban 30 mg once daily.
Rivaroxaban	ATV (unboosted)	↑ rivaroxaban possible	No data available for dose recommendation. Consider alternative ARV or anticoagulant.
Rivaroxaban	PI/c, PI/r	↑ rivaroxaban expected	Do not coadminister.
Warfarin	PI/c	No data	Monitor INR closely when stopping or starting PI/c or PI/r and adjust warfarin dose accordingly. If switching between RTV and COBI, the effect of COBI on warfarin is not expected to be equivalent to RTV’s effect on warfarin.
Warfarin	PI/r	↓ warfarin possible
Anticonvulsants
Carbamazepine	ATV (unboosted)	May ↓ PI concentrations substantially	Do not coadminister.
	ATV/r, LPV/r	↑ carbamazepine possible May ↓ PI concentrations substantially	Consider alternative ARV or anticonvulsant. If coadministration is necessary, consider monitoring concentrations of both drugs and assess virologic response. Carbamazepine dose reduction may be necessary. Do not coadminister with LPV/r once daily.
	DRV/r	Carbamazepine AUC ↑ 45% ↔ DRV	Monitor anticonvulsant concentration and adjust dose accordingly.
	PI/c	↑ carbamazepine possible ↓ COBI expected ↓ PI expected	Contraindicated.
Eslicarbazepine	All PIs	↓ PI possible	Consider alternative ARV or anticonvulsant. If coadministration is necessary, monitor for virologic response. Consider monitoring anticonvulsant and PI concentrations.
Ethosuximide	All PIs	↑ ethosuximide possible	Monitor for ethosuximide-related adverse events.
Lamotrigine	ATV (unboosted)	↔ lamotrigine	No dose adjustment needed.
	ATV/r	Lamotrigine AUC ↓ 32%	A dose increase of lamotrigine may be needed; monitor lamotrigine concentration or consider alternative ARV or anticonvulsant.
	LPV/r	Lamotrigine AUC ↓ 50% ↔ LPV
	DRV/r	↓ lamotrigine possible
	PI/c	No data	Monitor anticonvulsant concentration and adjust dose accordingly.
Oxcarbazepine	All PIs	↓ PI possible	Consider alternative ARV or anticonvulsant. If coadministration necessary, monitor for virologic response. Consider monitoring anticonvulsant and PI concentrations.
Phenobarbital	ATV (unboosted)	↓ ATV expected	Do not coadminister.
	ATV/r, DRV/r	↓ phenobarbital possible ↓ PI possible	Consider alternative anticonvulsant. If coadministration is necessary, consider monitoring concentrations of both drugs and assessing virologic response.
	LPV/r	↓ phenobarbital possible ↓ LPV/r possible	Do not coadminister with LPV/r once daily. Consider alternative anticonvulsant. If coadministration necessary, consider monitoring concentrations of both drugs and assessing virologic response.
	PI/c	↓ COBI expected ↓ PI expected	Contraindicated.
Phenytoin	ATV (unboosted)	↓ ATV expected	Do not coadminister.
	ATV/r, DRV/r	↓ phenytoin possible ↓ PI possible	Consider alternative anticonvulsant. If coadministration is necessary, consider monitoring concentrations of both drugs and assessing virologic response.
	LPV/r	Phenytoin AUC ↓ 31% LPV/r AUC ↓ 33%	Do not coadminister with LPV/r once daily. Consider alternative anticonvulsant or monitor concentrations of both drugs and assess virologic response.
	PI/c	↓ COBI expected ↓ PI expected	Contraindicated.
Valproic Acid	All PIs	↓ or ↔ VPA possible LPV AUC ↑ 38% No data for other PIs	Monitor VPA concentrations and monitor for PI tolerability.
Antidepressants, Anxiolytics, and Antipsychotics Also see the Sedative/Hypnotics section below
Bupropion	ATV (unboosted)	↔ bupropion expected	No dose adjustment needed.
	ATV/r, DRV/r	↓ bupropion possible	Titrate bupropion dose based on clinical response.
	LPV/r	Bupropion AUC ↓ 57%	Titrate bupropion dose based on clinical response.
	PI/c	↔ bupropion expected	No dose adjustment needed.
Buspirone	All PIs	↑ buspirone expected	Administer lowest dose of buspirone with caution and titrate buspirone dose based on clinical response. Dose reduction may be necessary. Monitor for buspirone-related adverse events.
Nefazodone	All PIs	↑ nefazodone expected ↑ PI possible	Monitor for nefazodone-related adverse events and PI tolerability.
Trazodone	All PIs	RTV 200 mg twice daily (for 2 days) Trazodone ↑ AUC 240%	Administer lowest dose of trazodone and monitor for CNS and CV adverse events.
Tricyclic Antidepressants Amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, trimipramine	All PIs	↑ TCA expected	Administer lowest possible TCA dose and titrate based on clinical assessment and/or drug concentrations. Monitor for TCA-related adverse events.
Selective Serotonin Reuptake Inhibitors (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)	DRV/r	Paroxetine AUC ↓ 39% Sertraline AUC ↓ 49%	Titrate SSRI dose based on clinical response.
	All PIs except DRV/r	No data	Titrate SSRI dose using the lowest available initial or maintenance dose.
*Antipsychotics*
Aripiprazole	ATV (unboosted)	↑ aripiprazole expected	Administer 50% of the usual aripiprazole dose. Titrate dose based on clinical monitoring for efficacy/adverse events. Refer to aripiprazole label for doses to use in patients who have major depressive disorder or who are known to be CYP2D6 poor metabolizers.
Aripiprazole	PI/c, PI/r	↑ aripiprazole expected	Administer 25% of the usual aripiprazole dose. Titrate dose based on clinical monitoring for efficacy/adverse events. Refer to aripiprazole label for doses to use in patients who have major depressive disorder or who are known to be CYP2D6 poor metabolizers.
Brexpiprazole	ATV (unboosted)	↑ brexpiprazole expected	Administer 50% of the usual brexpiprazole dose. Titrate dose based on clinical monitoring for efficacy/adverse events. Refer to brexpiprazole label for doses to use in patients who have major depressive disorder or who are known to be CYP2D6 poor metabolizers.
Brexpiprazole	PI/c, PI/r	↑ brexpiprazole expected	Administer 25% of the usual brexpiprazole dose. Titrate the dose based on clinical monitoring for efficacy/adverse events. Refer to brexpiprazole label for doses to use in patients who have major depressive disorder or who are known to be CYP2D6 poor metabolizers.
Cariprazine	All PIs	↑ cariprazine expected	Starting Cariprazine in a Patient Who Is Already Receiving a PI 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 the PI is withdrawn, cariprazine dose may need to be increased. Starting a PI 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 taking cariprazine 4.5 mg daily, the dose should be reduced to cariprazine 1.5 mg or cariprazine 3 mg daily. For patients taking cariprazine 1.5 mg daily, change to cariprazine 1.5 mg every other day. If PI is withdrawn, the cariprazine dose may need to be increased.
Iloperidone	All PIs	↑ iloperidone expected	Decrease iloperidone dose by 50%.
Lumateperone	All PIs	↑ lumateperone expected	Do not coadminister.
Lurasidone	ATV (unboosted)	↑ lurasidone expected	Consider alternative ARV or antipsychotic. If coadministration is necessary and atazanavir is added to lurasidone therapy, reduce lurasidone dose by 50%. If coadministration is necessary and lurasidone is added to ATV therapy, the recommended starting dose of lurasidone is 20 mg daily and the maximum recommended dose is 80 mg daily.
Lurasidone	PI/c, PI/r	↑ lurasidone expected	Contraindicated.
Olanzapine	ATV (unboosted), PI/c	↔ olanzapine expected	No dose adjustment needed.
Olanzapine	PI/r	↓ olanzapine possible	Monitor for therapeutic effectiveness of olanzapine.
Other Antipsychotics CYP3A4 and/or CYP2D6 substrates (e.g., clozapine, perphenazine, risperidone, thioridazine)	PI/c, PI/r	↑ antipsychotic possible	Titrate the antipsychotic dose using the lowest initial dose or adjust the maintenance dose accordingly. Monitor for adverse events, including QTc prolongation.
Pimavanserin	ATV (unboosted)	No data	No data available for dose recommendation. Consider alternative ARV or antipsychotic.
	LPV/r	↑ pimavanserin expected	Do not coadminister, due to risk for QTc prolongation.
	All other PIs	↑ pimavanserin expected	Reduce pimavanserin dose to 10 mg once daily.
Pimozide	All PIs	↑ pimozide expected	Contraindicated.
Quetiapine	All PIs	↑ quetiapine expected	Starting Quetiapine in a Patient Receiving a PI Initiate quetiapine at the lowest dose and titrate up as needed. Monitor for quetiapine effectiveness and adverse events, including QTc prolongation. Starting a PI in a Patient Receiving a Stable Dose of Quetiapine Consider alternative ARV. If coadministered, reduce quetiapine dose to 1/6 of the current dose. Closely monitor for quetiapine effectiveness and adverse events, including QTc prolongation.
Ziprasidone	LPV/r	↑ ziprasidone expected	Do not coadminister, due to risk for QTc prolongation
Ziprasidone		↑ ziprasidone expected	Monitor for ziprasidone-related adverse events, including QTc prolongation.
Antifungals
Fluconazole	All PIs	↔ PI expected ↔ fluconazole expected	No dose adjustment needed.
Isavuconazole	LPV/r	Isavuconazole AUC ↑ 96% LPV AUC ↓ 27% RTV AUC ↓ 31%	If coadministered, monitor isavuconazole concentrations and adverse events. Monitor for virologic response.
Isavuconazole	All PIs except LPV/r	↑ isavuconazole expected ↑ PI possible	If coadministered, monitor isavuconazole concentrations and monitor for isavuconazole-related adverse events. Monitor for PI tolerability.
Itraconazole	ATV (unboosted)	↑ itraconazole expected	Dose based on itraconazole concentrations and monitor for itraconazole-related adverse events.
Itraconazole	PI/r, PI/c	↑ itraconazole expected ↑ PI expected	Itraconazole doses >200 mg/day are not recommended unless dosing is guided by itraconazole concentrations.
Posaconazole	ATV (unboosted)	ATV AUC ↑ 268% ↑ or ↓ posaconazole possible	If coadministered, monitor posaconazole concentrations and monitor for posaconazole-related or PI-related adverse events.
	ATV/r	ATV AUC ↑ 146% ↑ posaconazole possible
	All other PIs	↑ PI expected ↑ posaconazole possible
Voriconazole	ATV (unboosted)	↑ or ↓ PI possible ↑ or ↓ voriconazole possible	If coadministered, monitor voriconazole concentrations and monitor for voriconazole-related or PI-related adverse events.
	PI/c	No data	Do not coadminister voriconazole and RTV or COBI unless benefits outweigh risks. If coadministered, monitor voriconazole concentration and adjust dose accordingly.
	PI/r	RTV 100 mg twice daily ↓ voriconazole AUC 39%
Antimalarials
Artemether/Lumefantrine	ATV (unboosted), PI/c	↑ lumefantrine expected No data for artemether	Clinical significance is unknown. If coadministered, monitor closely for antimalarial efficacy and lumefantrine-related adverse events, including QTc prolongation.
	DRV/r	Artemether AUC ↓ 16% DHAa AUC ↓ 18% Lumefantrine AUC ↑ 175% ↔ DRV
	LPV/r	Artemether AUC ↓ 40% DHA AUC ↓ 45% Lumefantrine AUC ↑ 4.8-fold ↔ LPV
Atovaquone/Proguanil	ATV/r, LPV/r	With ATV/r Atovaquone AUC ↓ 46% Proguanil AUC ↓ 41% With LPV/r Atovaquone AUC ↓ 74% Proguanil AUC ↓ 38%	Clinical significance is unknown. Consider alternative ARV or malaria prophylaxis.
Mefloquine	All PIs	With RTV 200 mg Twice Daily RTV AUC ↓ 31% and C_min ↓ 43% ↔ mefloquine With ATV (Unboosted), PI/c, or PI/r No data ↑ mefloquine possible	Clinical significance is unknown. Consider alternative ARV or antimalarial drug. If coadministered, monitor for mefloquine-related adverse events, including psychiatric symptoms and QTc prolongation. Monitor virologic response.
Antiplatelets
Clopidogrel	All boosted PIs	Clopidogrel active metabolite AUC ↓ 69% in people with HIV compared to healthy volunteers without HIV. Impaired platelet inhibition observed in people with HIV.	Do not coadminister.
Prasugrel	All boosted PIs	Prasugrel active metabolite AUC ↓ 52% in people with HIV compared to healthy volunteers without HIV. Adequate platelet inhibition observed in people with HIV.	No dose adjustment needed.
Ticagrelor	All PIs	↑ ticagrelor expected	Do not coadminister.
Vorapaxar	All PIs	↑ vorapaxar expected	Do not coadminister.
Antipneumocystis and Antitoxoplasmosis Drug
Atovaquone Oral suspension	ATV/r	↔ atovaquone	No dose adjustment needed.
Atovaquone Oral suspension	All other PIs	↔ atovaquone expected	No dose adjustment needed.
Antivirals—Orthopoxviruses (Mpox, Smallpox)
Brincidofovir	All PIs	↑ brincidofovir possible	Give PI 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	All PIs	↔ cidofovir	No dose adjustment needed.
Tecovirimat	All PIs	↔ tecovirimat	No dose adjustment needed.
Beta-Agonists, Long-Acting Inhaled
Arformoterol, Formoterol	ATV (unboosted), ATV/c, ATV/r	↑ arformoterol possible	No dose adjustment needed.
Arformoterol, Formoterol	DRV/c, DRV/r, LPV/r	↔ arformoterol expected	No dose adjustment needed.
Indacaterol	All PIs	With RTV 300 mg Twice Daily Indacaterol AUC ↑ 1.7-fold	No dose adjustment needed in patients receiving indacaterol 75 mcg daily.
Olodaterol	All PIs	↑ olodaterol expected	No dose adjustment needed.
Salmeterol	All PIs	↑ salmeterol possible	Do not coadminister, due to potential increased risk of salmeterol-related CV events.
Cardiac Medications
Amiodarone	ATV/r	↑ amiodarone possible ↑ PI possible	Contraindicated.
Amiodarone	All other PIs	↑ amiodarone possible ↑ PI possible	Do not coadminister unless the benefits outweigh the risks. If coadministered, monitor for amiodarone-related adverse events and consider monitoring ECG and amiodarone drug concentration.
Antiarrhythmics (e.g., disopyramide, dofetilide, lidocaine, mexiletine, propafenone)	ATV (unboosted)	↑ antiarrhythmic possible	Consider alternative ARV or antiarrhythmics. If coadministered, monitor for antiarrhythmic-related adverse events.
	PI/c, PI/r	↑ antiarrhythmic possible	Do not coadminister.
Dronedarone	ATV (unboosted)	↑ dronedarone possible	Do not coadminister.
Dronedarone	PI/c, PI/r	↑ dronedarone expected	Contraindicated.
Flecainide	All PIs	↑ flecainide possible	Do not coadminister.
Propafenone	All PIs	↑ propafenone possible	Do not coadminister.
Quinidine	ATV/r	↑ quinidine expected	Contraindicated.
Quinidine	All other PIs	↑ quinidine possible	Do not coadminister.
Beta-Blockers (e.g., carvedilol, metoprolol, timolol)	All PIs	↑ beta-blockers possible	May need to decrease beta-blocker dose; adjust dose based on clinical response. Consider using beta-blockers that are not metabolized by CYP2D6 enzymes (e.g., atenolol, labetalol, nadolol, sotalol).
Bosentan	All PIs	With LPV/r ↑ bosentan 48-fold (Day 4) and ↑ 5-fold (Day 10) With other PI ↑ bosentan expected With ATV (unboosted) ↓ ATV expected	Do not coadminister bosentan and unboosted ATV. In Patients on a PI (Other than Unboosted ATV) >10 Days Start bosentan at 62.5 mg once daily or every other day In Patients on Bosentan Who Require a PI (Other Than Unboosted ATV) Stop bosentan ≥36 hours before PI initiation and restart bosentan 10 days after PI initiation at 62.5 mg once daily or every other day. When Switching Between COBI and RTV Maintain the same bosentan dose.
Calcium Channel Blockers, Except Diltiazem	All PIs	↑ dihydropyridine possible ↑ verapamil possible	Titrate CCB dose and monitor closely. ECG monitoring is recommended when CCB is used with ATV.
Digoxin	PI/c, PI/r	RTV 200 mg twice daily ↑ digoxin AUC 29% and ↑ half-life 43% DRV/r ↑ digoxin AUC 36% COBI ↑ digoxin Cmax 41% and ↔ AUC	Monitor digoxin concentrations. Digoxin dose may need to be decreased. Titrate initial digoxin dose.
Diltiazem	ATV (unboosted), ATV/c, ATV/r	Unboosted ATV ↑ diltiazem AUC 125% Greater ↑ of diltiazem AUC is likely with ATV/c or ATV/r	Decrease diltiazem dose by at least 50%. If starting diltiazem, start with the lowest dose and titrate according to clinical response and adverse events. ECG monitoring is recommended.
Diltiazem	DRV/c, DRV/r, LPV/r	↑ diltiazem possible	Titrate diltiazem dose according to clinical response and adverse events.
Eplerenone	PI/c, PI/r	↑ eplerenone expected	Contraindicated.
Ranolazine	ATV (unboosted)	↑ ranolazine possible	Do not coadminister..
Ranolazine	PI/c, PI/r	↑ ranolazine expected	Contraindicated.
Ivabradine	All PIs	↑ ranolazine expected	Contraindicated.
Corticosteroids
Beclomethasone Inhaled or intranasal	DRV/r	↔ 17-BMP (active metabolite) AUC RTV 100 mg twice daily ↑ 17-BMP AUC 2-fold	No dose adjustment needed.
Beclomethasone Inhaled or intranasal	All PIs except DRV/r	↔ 17-BMP expected	No dose adjustment needed.
Budesonide, Ciclesonide, Fluticasone, Mometasone Inhaled or intranasal	All PIs	↑ glucocorticoids possible RTV 100 mg twice daily ↑ fluticasone AUC 350-fold	Do not coadminister unless the potential benefits of inhaled or intranasal corticosteroid outweigh the risks of adverse events associated with corticosteroids. Coadministration can result in adrenal insufficiency and Cushing’s syndrome. Consider alternative inhaled/intranasal corticosteroid (e.g., beclomethasone).
Betamethasone, Budesonide Systemic	All PIs	↑ glucocorticoids possible ↓ PI possible	Do not coadminister unless the potential benefits of systemic corticosteroid outweigh the risks of adverse events associated with systemic corticosteroids. Coadministration can result in adrenal insufficiency and Cushing’s syndrome.
Dexamethasone Systemic	All PIs	↑ glucocorticoids possible ↓ PI possible	Consider alternative corticosteroid for long-term use. If coadministration is necessary, monitor virologic response to ART.
Prednisone, Prednisolone Systemic	LPV/r	↑ prednisolone AUC 31%	Coadministration may be considered if the potential benefits outweigh the risks of adverse events associated with systemic corticosteroids. If coadministered, monitor for adrenal insufficiency, Cushing’s syndrome, and other corticosteroid-related adverse events.
Prednisone, Prednisolone Systemic	All PIs	↑ prednisolone possible
Betamethasone, Methylprednisolone, Triamcinolone Local injections, including intra-articular, epidural, or intra-orbital	All PIs	↑ glucocorticoids expected	Do not coadminister. Coadministration can result in adrenal insufficiency and Cushing’s syndrome.
Glucose-Lowering Medications
Canagliflozin	ATV (unboosted), PI/c	↔ canagliflozin	No dose adjustment needed.
Canagliflozin	PI/r	↓ canagliflozin expected	If a patient is already tolerating canagliflozin 100 mg daily, increase canagliflozin dose to 200 mg daily. If a patient is already tolerating canagliflozin 200 mg daily and requires additional glycemic control, management strategy is based on renal function. In Patients with eGFR ≥60 mL/min/1.73 m² Canagliflozin dose may be increased to 300 mg daily. In Patients with eGFR <60 mL/min/1.73 m² Consider adding another antihyperglycemic agent.
Saxagliptin	All PIs	↑ saxagliptin expected	Limit saxagliptin dose to 2.5 mg once daily.
Dapagliflozin/Saxagliptin	All PIs	↑ saxagliptin expected	Do not coadminister. Dapagliflozin is only available 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.
Hepatitis C Direct-Acting Antiviral Agents
Daclatasvir	ATV/c, ATV/r	ATV/c, ATV/r	Decrease daclatasvir dose to 30 mg once daily.
Daclatasvir	ATV (unboosted), DRV/c, DRV/r, LPV/r	↔ daclatasvir	No dose adjustment needed.
Dasabuvir plus Paritaprevir/Ombitasvir/ RTV	ATV (unboosted)	↔ ATV	ATV 300 mg alone, without COBI or additional RTV, should be given in the morning with dasabuvir plus paritaprevir/ombitasvir/RTV.
	ATV/c, ATV/r	No data	This HCV regimen contains RTV. If ATV is part of the ARV regimen, prescribe ATV 300 mg daily without COBI or RTV. ATV should be administered in the morning, at the same time as ombitasvir/paritaprevir/RTV plus dasabuvir. Resume RTV or COBI regimen when HCV therapy is completed.
	DRV	DRV C_min ↓ 43% to 48%	Do not coadminister.
	LPV/r	Paritaprevir AUC ↑ 117%	Do not coadminister.
	DRV/c	No data	Do not coadminister.
Elbasvir/Grazoprevir	ATV/r	Elbasvir AUC ↑ 4.8-fold Grazoprevir AUC ↑ 10.6-fold Elbasvir ↔ ATV Grazoprevir ↑ ATV AUC 43%	Contraindicated. May increase the risk of ALT elevations due to a significant increase in grazoprevir plasma concentrations caused by OATP1B1/3 inhibition.
	DRV/r	Elbasvir AUC ↑ 66% Grazoprevir AUC ↑ 7.5-fold ↔ DRV
	LPV/r	Elbasvir AUC ↑ 3.7-fold Grazoprevir AUC ↑ 12.9-fold ↔ LPV
	ATV (unboosted), ATV/c, DRV/c	↑ grazoprevir expected
Glecaprevir/Pibrentasvir	ATV (unboosted), ATV/c, ATV/r	With (ATV 300 mg plus RTV 100 mg) Once Daily Glecaprevir AUC ↑ 6.5-fold Pibrentasvir AUC ↑ 64%	Contraindicated.
	DRV/c, DRV/r	With (DRV 800 mg plus RTV 100 mg) Once Daily Glecaprevir AUC ↑ 5-fold ↔ pibrentasvir	Do not coadminister..
	LPV/r	Glecaprevir AUC ↑ 4-fold Pibrentasvir ↑ 2.5-fold	Do not coadminister..
Ledipasvir/Sofosbuvir	ATV/r	ATV AUC ↑ 33% Ledipasvir AUC ↑ 113% ↔ sofosbuvir	No dose adjustment needed. Coadministration of ledipasvir/sofosbuvir with TDF and a PI/r results in increased exposure to TDF. The safety of the increased TDF exposure has not been established. Consider alternative HCV or ARV drugs to avoid increased risk of TDF toxicities. If coadministration is necessary, monitor for TDF-related adverse events.
Ledipasvir/Sofosbuvir	ATV (unboosted), ATV/c, DRV/c, DRV/r, LPV/r	ATV (unboosted), ATV/c, DRV/c, DRV/r, LPV/r
Sofosbuvir/Velpatasvir	ATV/r	↔ ATV/r ↔ sofosbuvir Velpatasvir AUC ↑ 2.4-fold	No dose adjustment needed.
	DRV/r	↔ DRV/r Sofosbuvir AUC ↓ 28% ↔ velpatasvir	No dose adjustment needed.
	ATV (unboosted), ATV/c, DRV/c, LPV/r	↔ sofosbuvir and velpatasvir expected	No dose adjustment needed.
Sofosbuvir/Velpatasvir/Voxilaprevir	ATV (unboosted), ATV/c, ATV/r	With ATV/r Voxilaprevir AUC ↑ 4.3-fold Velpatasvir AUC ↑ 93% Sofosbuvir AUC ↑ 40%	Do not coadminister.
	LPV/r	↑ voxilaprevir expected	Do not coadminister.
	DRV/c, DRV/r	With DRV/r Voxilaprevir AUC ↑ 2.4-fold ↔ DRV/r, velpatasvir, and sofosbuvir	No dose adjustment needed.
Herbal Products
St. John’s Wort	All PIs	↓ PI expected	Contraindicated.
Hormonal Therapies
Contraceptives–Injectable Depot MPA	LPV/r	MPA AUC ↑ 46%	No dose adjustment needed.
Contraceptives–Injectable Depot MPA	All other PIs	No data	No dose adjustment needed.
Contraceptives–Oral	ATV (unboosted)	Ethinyl estradiol AUC ↑ 48% Norethindrone AUC ↑ 110%	Prescribe an oral contraceptive that contains no more than 30 mcg of ethinyl estradiol^b or use alternative ARV or contraceptive methods. Oral contraceptives that contain less than 25 mcg of ethinyl estradiol or progestins other than norethindrone or norgestimate have not been studied.
	ATV/c	Drosperinone AUC ↑ 130% Ethinyl estradiol AUC ↓ 22%	Contraindicated with drospirenone-containing hormonal contraceptive due to potential for hyperkalemia. Use alternative ARV or contraceptive methods.
	ATV/c	↔ ethinyl estradiol AUC and C_min ↓ 25% ↔ levonorgestrel	No dose adjustment needed.
	ATV/r	Ethinyl estradiol AUC ↓ 19% and C_min ↓ 37% Norgestimate AUC ↑ 85% Norethindrone AUC ↑ 51% and C_min ↑ 67%	Oral contraceptive should contain at least 35 mcg of ethinyl estradiol.^c
	DRV/c	Drospirenone AUC ↑ 58% Ethinyl estradiol AUC ↓ 30%	Clinical monitoring is recommended due to the potential for hyperkalemia. Use alternative ARV or contraceptive methods.
	DRV/r	Ethinyl estradiol AUC ↓ 44% and C_min ↓ 62% Norethindrone AUC ↓ 14% and C_min ↓ 30%	When Used for Contraception Consider alternative ARV or contraceptive methods. If combined, consider using an oral contraceptive with at least 35 mcg of ethinyl estradiol. When Used for Other Clinical Indications (e.g., Acne, Menstrual Cycle Regulation) Monitor for clinical effectiveness of hormonal therapy.
	LPV/r	Ethinyl estradiol AUC ↓ 42% and C_min ↓ 32% to 58% Norethindrone AUC ↓ 17% and C_min ↓ 32% ↔ C_minmin Etonogestrel (metabolite of oral desogestrel)	Consider using an oral contraceptive with at least 35 mcg of ethinyl estradiol.
Contraceptives–Subdermal Implant Etonogestrel	LPV/r	Etonogestrel AUC ↑ 52% and C_min ↑ 34%	No dose adjustment needed.
Contraceptives–Subdermal Implant Etonogestrel	All other PIs	↑ etonogestrel expected	No dose adjustment needed.
Contraceptives–Subdermal Implant Levonorgestrel	All PIs	↑ levonorgestrel expected	No dose adjustment needed.
Contraceptives–Transdermal Ethinyl Estradiol/Norelgestromin	LPV/r	↔ LPV Ethinyl estradiol AUC ↓ 45% Norelgestromin AUC ↑ 83%	No dose adjustment needed.
	All other PIs	No data	No dose adjustment needed.
Contraceptives–Vaginal Ring Etonogestrel/Ethinyl Estradiol	ATV/r	Ethinyl estradiol AUC ↓ 26% Etonogestrel AUC ↑ 79%	No dose adjustment needed.
	All other PIs	No data	No dose adjustment needed.
Contraceptives–Vaginal Ring Segesterone/Ethinyl Estradiol	All PIs	No data	Use alternative ARV or contraceptive methods.
Emergency Contraceptives Levonorgestrel (oral)	All PIs	↑ levonorgestrel expected	No dose adjustment needed.
Gender-Affirming Therapy	PI/c	↑ estradiol possible	Adjust estradiol dose as needed based on clinical effects and endogenous hormone concentrations.
	PI/r	↓ or ↑ estradiol possible
	All PIs	↔ goserelin, leuprolide acetate, and spironolactone expected	No dose adjustment needed.
	All PIs	↑ dutasteride possible ↑ finasteride possible	Adjust dutasteride dose as needed based on clinical effects and endogenous hormone concentrations. No dose adjustment needed for finasteride.
	All PIs	↑ testosterone possible	Adjust testosterone dose as needed based on clinical effects and endogenous hormone concentrations.
Menopausal Replacement Therapy	All PIs	↓ or ↑ estrogen possible with estradiol or conjugated estrogen (equine and synthetic)	Adjust estrogen dose as needed based on clinical effects.
Menopausal Replacement Therapy	All PIs	↑ drospirenone possible ↑ medroxyprogesterone ↑ micronized progesterone See the different Contraceptives entries for other progestin-PI interactions	Adjust progestin/progesterone dose as needed based on clinical effects. Drospirenone is not contraindicated with ATV/c products because it is prescribed at a lower dose for menopausal HRT than products used for hormonal contraceptives.
Immunosuppressants
Cyclosporine, Sirolimus, Tacrolimus	All PIs	↑ immunosuppressant expected	Initiate with an adjusted dose of immunosuppressant to account for potential increased concentrations of the immunosuppressant and monitor for immunosuppressant-related adverse events. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with a specialist as necessary.
Everolimus	DRV/c, DRV/r	DRV/c, DRV/r	Do not coadminister.
Everolimus	All other PIs	↑ immunosuppressant expected	Initiate with an adjusted dose of immunosuppressant to account for potential increased concentrations of the immunosuppressant and monitor for immunosuppressant-related adverse events. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with a specialist as necessary.
Lipid-Modifying Agents
Atorvastatin	ATV (unboosted), ATV/r	↑ atorvastatin possible	Administer the lowest effective atorvastatin dose while monitoring for adverse events.
	ATV/c	Atorvastatin AUC ↑ 9.2-fold and C_max ↑ 18.9-fold	Do not coadminister.
	DRV/c	Atorvastatin AUC ↑ 3.9-fold and C_max ↑ 4.2-fold	Administer the lowest effective atorvastatin dose while monitoring for adverse events. Do not exceed 20 mg atorvastatin daily.
	DRV/r	DRV/r plus atorvastatin 10 mg similar to atorvastatin 40 mg administered alone	Administer the lowest effective atorvastatin dose while monitoring for adverse events. Do not exceed 20 mg atorvastatin daily.
	LPV/r	Atorvastatin AUC ↑ 5.9-fold and C_max ↑ 4.7-fold	Administer the lowest effective atorvastatin dose while monitoring for adverse events. Do not exceed 20 mg atorvastatin daily.
Lomitapide	All PIs	↑ lomitapide expected	Contraindicated.
Lovastatin	All PIs	Significant ↑ lovastatin expected	Contraindicated.
Pitavastatin	All PIs	With Unboosted ATV ↑ pitavastatin AUC 31% and C_max ↑ 60% ↔ ATV With DRV/r ↓ pitavastatin AUC 26% ↔ DRV/r With LPV/r ↓ pitavastatin AUC 20% ↔ LPV	No dose adjustment needed.
Pravastatin	ATV (unboosted), ATV/c, ATV/r	No data	Administer the lowest effective pravastatin dose while monitoring for adverse events.
	DRV/c, DRV/r	With DRV/r Pravastatin AUC ↑ 81% following single dose of pravastatin Pravastatin AUC ↑ 23% at steady state	Administer the lowest effective pravastatin dose while monitoring for adverse events.
	LPV/r	LPV/r	No dose adjustment needed.
Rosuvastatin	ATV (unboosted)	↑ rosuvastatin expected	Administer the lowest effective rosuvastatin dose while monitoring for adverse events. Do not exceed rosuvastatin 10 mg daily.
	ATV/r	Rosuvastatin AUC ↑ 3-fold and C_max ↑ 7-fold
	ATV/c	Rosuvastatin AUC ↑ 3.4-fold and C_max ↑ 10.6-fold
	DRV/c	Rosuvastatin AUC ↑ 1.9-fold and C_max ↑ 3.8-fold
	DRV/r	Rosuvastatin AUC ↑ 48% and C_max ↑ 2.4-fold	Administer the lowest effective rosuvastatin dose while monitoring for adverse events.
	LPV/r	Rosuvastatin AUC ↑ 2.1-fold and C_max ↑ 4.7-fold	Administer the lowest effective rosuvastatin dose while monitoring for adverse events. Do not exceed rosuvastatin 10 mg daily.
Simvastatin	All PIs	Significant ↑ simvastatin expected	Contraindicated.
Narcotics and Treatment for Opioid Dependence
Buprenorphine Sublingual, buccal, or implant	ATV (unboosted)	Buprenorphine AUC ↑ 93% Norbuprenorphine (active metabolite) AUC ↑ 76% ↓ ATV possible	Do not coadminister.
	ATV/r	Buprenorphine AUC ↑ 66% Norbuprenorphine (active metabolite) AUC ↑ 105%	Monitor for sedation and other signs or symptoms of overmedication. Buprenorphine dose reduction may be necessary. It may be necessary to remove the implant and treat with a formulation that permits dose adjustments.
	DRV/r	↔ buprenorphine Norbuprenorphine (active metabolite) AUC ↑ 46% and C_min ↑ 71%	No dose adjustment needed. Monitor for buprenorphine-related adverse events. When transferring buprenorphine from transmucosal delivery to implantation, monitor to ensure buprenorphine effect is adequate and not excessive
	LPV/r	↔ LPV/r
	↔ LPV/r	No data	Titrate buprenorphine dose using the lowest initial dose. Dose adjustment of buprenorphine may be needed. It may be necessary to remove implant and treat with a formulation that permits dose adjustments. Monitor for buprenorphine-related adverse events.
Fentanyl	All PIs	↑ fentanyl possible	Monitor for fentanyl-related adverse events, including potentially fatal respiratory depression
Lofexidine	ATV (unboosted)	↔ lofexidine expected	No dose adjustment needed.
Lofexidine	PI/c, PI/r	↑ lofexidine possible	Monitor for lofexidine-related adverse events, including symptoms of orthostasis and bradycardia.
Methadone	ATV (unboosted)	↔ ATV	No dose adjustment needed.
	PI/c	No data	Titrate methadone dose using the lowest feasible initial dose. Dose adjustment of methadone may be needed. Monitor for methadone-related adverse events.
	All PI/r	ATV/r and DRV/r ↓ R-methadone^d AUC 16% to 18% LPV/r ↓ methadone AUC 26% to 53%	Opioid withdrawal is unlikely, but may occur. Monitor for opioid withdrawal and increase methadone dose as clinically indicated.
Oxycodone	All PIs	LPV/r ↑ oxycodone AUC 2.6-fold Other PIs: ↑ oxycodone expected	Monitor for opioid-related adverse events, including potentially fatal respiratory depression. Oxycodone dose reduction may be necessary.
Tramadol	All PIs	↑ tramadol expected ↓ M1 (active metabolite) possible	Tramadol dose adjustments may be necessary. Monitor for clinical response and tramadol-related adverse events.
PDE5 Inhibitors
Avanafil	ATV (unboosted)	No data	Avanafil dose should not exceed 50 mg once every 24 hours.
Avanafil	PI/c, PI/r	RTV 600 mg twice daily (for 5 days) ↑ avanafil AUC 13-fold and ↑ C_max 2.4-fold	Do not coadminister.
Sildenafil	All PIs	DRV/r plus sildenafil 25 mg similar to sildenafil 100 mg alone RTV 500 mg twice daily ↑ sildenafil AUC 1,000%	For Treatment of Erectile Dysfunction Start with sildenafil 25 mg every 48 hours and monitor for adverse events of sildenafil. Contraindicated for treatment of PAH.
Tadalafil	All PIs	RTV 200 mg twice daily ↑ tadalafil AUC 124%	RTV 200 mg twice daily ↑ tadalafil AUC 124% Start with tadalafil 5 mg and do not exceed a single dose of tadalafil 10 mg every 72 hours. Monitor for adverse events of tadalafil. For Treatment of PAH In Patients on a PI >7 Days Start with tadalafil 20 mg once daily and increase to tadalafil 40 mg once daily based on tolerability. In Patients on Tadalafil who Require a PI Stop tadalafil ≥24 hours before PI initiation. Seven days after PI initiation, restart tadalafil at 20 mg once daily and increase to tadalafil 40 mg once daily based on tolerability. In Patients Switching between COBI and RTV Maintain tadalafil dose. For Treatment of Benign Prostatic Hyperplasia Maximum recommended daily dose is tadalafil 2.5 mg per day.
Vardenafil	All PIs	RTV 600 mg twice daily ↑ vardenafil AUC 49-fold	Start with vardenafil 2.5 mg every 72 hours and monitor for adverse events of vardenafil.
Sedative/Hypnotics
Alprazolam, Clonazepam, Diazepam	All PIs	↑ benzodiazepine possible RTV 200 mg twice daily (for 2 days) ↑ alprazolam half-life 222% and ↑ AUC 248%	Consider alternative benzodiazepines, such as lorazepam, oxazepam, or temazepam.
Lorazepam, Oxazepam, Temazepam	All PIs	No data	These benzodiazepines are metabolized via non-CYP450 pathways and therefore have less interaction potential than other benzodiazepines.
Midazolam	All PIs	↑ midazolam expected	Oral midazolam is contraindicated with PIs. Parenteral midazolam can be used with caution when given in a monitored situation with appropriate medical management available in case of respiratory sedation and/or prolonged sedation. Consider dose reduction, especially if more than a single dose of midazolam is administered.
Suvorexant	All PIs	↑ suvorexant expected	↑ suvorexant expected
Triazolam	All PIs	↑ triazolam expected RTV 200 mg twice daily ↑ triazolam half-life 1,200% and ↑ AUC 2,000%	Contraindicated.
Zolpidem	PI/c, PI/r	↑ zolpidem possible	Initiate zolpidem at a low dose and monitor for zolpidem-related adverse events. Dose reduction may be necessary.
Miscellaneous Drugs
Calcifediol	All PIs	↑ calcifediol possible	Dose adjustment of calcifediol may be required, and serum 25-hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored.
Cisapride	All PIs	↑ cisapride expected	Contraindicated.
Colchicine	All PIs	RTV 100 mg twice daily ↑ colchicine AUC 296% and C_max ↑ 184% Significant ↑ colchicine expected with all PIs, with or without COBI or RTV	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 colchicine 0.3 mg twice daily. Contraindicated in patients with hepatic (Child-Pugh Score A, B or C) or renal impairment (CrCl <60 mL/min).
Dronabinol	All PIs	↑ dronabinol possible	Monitor for dronabinol-related adverse events.
Eluxadoline	All PIs	↑ eluxadoline expected	Administer eluxadoline at a dose of 75 mg twice daily and monitor for eluxadoline-related adverse events.
Ergot Derivatives	All PIs	↑ dihydroergotamine, ergotamine, and methylergonovine expected	Contraindicated.
Flibanserin	All PIs	↑ flibanserin expected	Contraindicated.
^a DHA is an active metabolite of artemether. ^b The following products contain no more than 30 mcg of ethinyl estradiol combined with norethindrone or norgestimate: Lo Minastrin Fe; Lo Loestrin Fe; Loestrin 1/20, 1.5/30; Loestrin Fe 1/20, 1.5/30; Loestrin 24 Fe; Minastrin 24 Fe; Ortho Tri-Cyclen Lo. Generic formulations also may be available. ^c The following products contain at least 35 mcg of ethinyl estradiol combined with norethindrone or norgestimate: Brevicon; Femcon Fe; Modicon; Norinyl 1/35; Ortho-Cyclen; Ortho-Novum 1/35, 7/7/7; Ortho Tri-Cyclen; Ovcon 35; Tri-Norinyl. Generic formulations also may be available. ^d R-methadone is the active form of methadone. Key to Symbols ↑ = increase ↓ = decrease ↔ = no change Key: 17-BMP = beclomethasone 17-monopropionate; ALT = alanine aminotransferase; ART = antiretroviral therapy; ARV = antiretroviral; AST = aspartate aminotransferase; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; CCB = calcium channel blocker; CNS = central nervous system; COBI = cobicistat; CrCl = creatinine clearance; CV = cardiovascular; CYP = cytochrome P; DHA = dihydroartemisinin; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; EVG/c = elvitegravir/cobicistat; GI = gastrointestinal; H2RA = H2 receptor antagonist; HCV = hepatitis C virus; HRT = hormone replacement therapy; INR = international normalized ratio; LPV = lopinavir; LPV/r = lopinavir/ritonavir; MPA = medroxyprogesterone acetate; OATP = organic anion-transporting polypeptide; PAH = pulmonary arterial hypertension; PDE5 = phosphodiesterase type 5; PI = protease inhibitor; PI/c = protease inhibitor/cobicistat; PI/r = protease inhibitor/ritonavir; PK = pharmacokinetic; PPI = proton pump inhibitor; PTH = parathyroid hormone; QTc = QT corrected for heart rate; RTV = ritonavir; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant; TDF = tenofovir disoproxil fumarate; VPA = valproic acid