Adult Antiretroviral Guidelines

US DHHS Guidelines with Australian Commentary

PI Drug interactions

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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 24c25a, 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
AntacidsATV (unboosted), ATV/c, ATV/rWhen Given Simultaneously
  • ↓ ATV expected
Administer ATV at least 2 hours before or 2 hours after antacids or buffered medications.
H2 Receptor AntagonistsATV (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 expectedH2RA 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/rWith Ranitidine
  • ↔ DRV/r

↔ PI expected
No dose adjustment needed.
Proton Pump InhibitorsATV (unboosted)With Omeprazole 40 mg
  • ATV AUC ↓ 94%
Do not coadminister.
ATV/c, ATV/rWith 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 expectedNo 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
AlfuzosinAll PIs↑ alfuzosin expectedContraindicated.
DoxazosinAll PIs↑ doxazosin possibleInitiate doxazosin at lowest dose and titrate while monitoring for clinical response/adverse events. Dose reduction may be necessary.
TamsulosinAll PIs↑ tamsulosin expectedDo not coadminister, unless benefits outweigh risks. If coadministered, monitor for tamsulosin-related adverse events.
TerazosinAll PIs↔ or ↑ terazosin possibleInitiate terazosin at lowest dose and titrate while monitoring for clinical response/adverse events. Dose reduction may be necessary.
SilodosinAll PIs↑ silodosin expectedContraindicated.
Antibacterials—Antimycobacterials
BedaquilineAll PIsWith 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.
RifabutinATV (unboosted)↑ rifabutin AUC expectedRecommended 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/rCompared With Rifabutin (300 mg Once Daily) Alone, Rifabutin (150 mg Once Daily) Plus ATV/r
  • Rifabutin AUC ↑ 110% and metabolite AUC ↑ 2,101%
DRV/rCompared With Rifabutin (300 mg Once Daily) Alone, Rifabutin (150 mg Every Other Day) Plus DRV/r
  • ↔ rifabutin AUC and metabolite AUC ↑ 881%
LPV/rCompared 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.
RifampinAll 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.
RifapentineAll PIs↓ PI expectedDo not coadminister.
Antibacterials—Macrolides
AzithromycinATV (unboosted), ATV/c, ATV/r↑ azithromycin possibleNo dose adjustment needed.
DRV/c, DRV/r↔ azithromycin expectedNo dose adjustment needed.
ClarithromycinATV (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/rDRV/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.
ErythromycinAll PIs↑ erythromycin expected
↑ PIs expected
Consider alternative ARV or use azithromycin.
Anticoagulants
ApixabanATV (unboosted)↑ apixaban possibleNo data available for dose recommendation. Consider alternative ARV or anticoagulant.
PI/c, PI/r↑ apixaban expectedDo 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%.

DabigatranATV (unboosted), DRV/c, DRV/r, LPV/rNo dataNo data available for dose recommendation. Consider alternative ARV or anticoagulant.
ATV/c, ATV/rWith 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.
EdoxabanATV (unboosted), DRV/c, DRV/r, LPV/rNo dataNo data available for dose recommendation. Consider alternative ARV or anticoagulant.
ATV/r, ATV/c↑ edoxaban expectedStroke Prevention in Nonvalvular Atrial Fibrillation Indication
  • No dose adjustment needed.

Deep Venous Thrombosis and Pulmonary Embolism Indication
  • Administer edoxaban 30 mg once daily.

RivaroxabanATV (unboosted)↑ rivaroxaban possibleNo data available for dose recommendation. Consider alternative ARV or anticoagulant.
PI/c, PI/r↑ rivaroxaban expectedDo not coadminister.
WarfarinPI/cNo dataMonitor 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.
PI/r↓ warfarin possible
Anticonvulsants
CarbamazepineATV (unboosted)May ↓ PI concentrations substantiallyDo 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/rCarbamazepine AUC ↑ 45%
↔ DRV
Monitor anticonvulsant concentration and adjust dose accordingly.
PI/c↑ carbamazepine possible
↓ COBI expected
↓ PI expected
Contraindicated.
EslicarbazepineAll PIs↓ PI possibleConsider alternative ARV or anticonvulsant. If coadministration is necessary, monitor for virologic response. Consider monitoring anticonvulsant and PI concentrations.
EthosuximideAll PIs↑ ethosuximide possibleMonitor for ethosuximide-related adverse events.
LamotrigineATV (unboosted)↔ lamotrigineNo dose adjustment needed.
ATV/rLamotrigine AUC ↓ 32%A dose increase of lamotrigine may be needed; monitor lamotrigine concentration or consider alternative ARV or anticonvulsant.
LPV/rLamotrigine AUC ↓ 50%
↔ LPV
DRV/r↓ lamotrigine possible
PI/cNo dataMonitor anticonvulsant concentration and adjust dose accordingly.
OxcarbazepineAll PIs↓ PI possibleConsider alternative ARV or anticonvulsant. If coadministration necessary, monitor for virologic response. Consider monitoring anticonvulsant and PI concentrations.
PhenobarbitalATV (unboosted)↓ ATV expectedDo 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.
PhenytoinATV (unboosted)↓ ATV expectedDo 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/rPhenytoin 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 AcidAll 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
BupropionATV (unboosted)↔ bupropion expectedNo dose adjustment needed.
ATV/r, DRV/r↓ bupropion possibleTitrate bupropion dose based on clinical response.
LPV/rBupropion AUC ↓ 57%
PI/c↔ bupropion expectedNo dose adjustment needed.
BuspironeAll PIs↑ buspirone expectedAdminister 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.
NefazodoneAll PIs↑ nefazodone expected
↑ PI possible
Monitor for nefazodone-related adverse events and PI tolerability.
TrazodoneAll PIsRTV 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 expectedAdminister 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/rParoxetine AUC ↓ 39%
Sertraline AUC ↓ 49%
Titrate SSRI dose based on clinical response.
All PIs except DRV/rNo dataTitrate SSRI dose using the lowest available initial or maintenance dose.
Antipsychotics
AripiprazoleATV (unboosted)↑ aripiprazole expectedAdminister 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.
PI/c, PI/r↑ aripiprazole expectedAdminister 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.
BrexpiprazoleATV (unboosted)↑ brexpiprazole expectedAdminister 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.
PI/c, PI/r↑ brexpiprazole expectedAdminister 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.
CariprazineAll PIs↑ cariprazine expectedStarting 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.
IloperidoneAll PIs↑ iloperidone expectedDecrease iloperidone dose by 50%.
LumateperoneAll PIs↑ lumateperone expectedDo not coadminister.
LurasidoneATV (unboosted)↑ lurasidone expectedConsider 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.
PI/c, PI/r↑ lurasidone expectedContraindicated.
OlanzapineATV (unboosted), PI/c↔ olanzapine expectedNo dose adjustment needed.
PI/r↓ olanzapine possibleMonitor for therapeutic effectiveness of olanzapine.
Other Antipsychotics
CYP3A4 and/or CYP2D6 substrates (e.g., clozapine, perphenazine, risperidone, thioridazine)
PI/c, PI/r↑ antipsychotic possibleTitrate the antipsychotic dose using the lowest initial dose or adjust the maintenance dose accordingly. Monitor for adverse events, including QTc prolongation.
PimavanserinATV (unboosted)No dataNo data available for dose recommendation. Consider alternative ARV or antipsychotic.
LPV/r↑ pimavanserin expectedDo not coadminister, due to risk for QTc prolongation.
All other PIs↑ pimavanserin expectedReduce pimavanserin dose to 10 mg once daily.
PimozideAll PIs↑ pimozide expectedContraindicated.
QuetiapineAll PIs↑ quetiapine expectedStarting 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.
    ZiprasidoneLPV/r↑ ziprasidone expectedDo not coadminister, due to risk for QTc prolongation
    ↑ ziprasidone expectedMonitor for ziprasidone-related adverse events, including QTc prolongation.
    Antifungals
    FluconazoleAll PIs↔ PI expected
    ↔ fluconazole expected
    No dose adjustment needed.
    IsavuconazoleLPV/rIsavuconazole AUC ↑ 96%
    LPV AUC ↓ 27%
    RTV AUC ↓ 31%
    If coadministered, monitor isavuconazole concentrations and adverse events. Monitor for virologic response.
    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.
    ItraconazoleATV (unboosted)↑ itraconazole expectedDose based on itraconazole concentrations and monitor for itraconazole-related adverse events.
    PI/r, PI/c↑ itraconazole expected
    ↑ PI expected
    Itraconazole doses >200 mg/day are not recommended unless dosing is guided by itraconazole concentrations.
    PosaconazoleATV (unboosted)ATV AUC ↑ 268%
    ↑ or ↓ posaconazole possible
    If coadministered, monitor posaconazole concentrations and monitor for posaconazole-related or PI-related adverse events.
    ATV/rATV AUC ↑ 146%
    ↑ posaconazole possible
    All other PIs↑ PI expected
    ↑ posaconazole possible
    VoriconazoleATV (unboosted)↑ or ↓ PI possible
    ↑ or ↓ voriconazole possible
    If coadministered, monitor voriconazole concentrations and monitor for voriconazole-related or PI-related adverse events.
    PI/cNo dataDo not coadminister voriconazole and RTV or COBI unless benefits outweigh risks. If coadministered, monitor voriconazole concentration and adjust dose accordingly.
    PI/rRTV 100 mg twice daily ↓ voriconazole AUC 39%
    Antimalarials
    Artemether/LumefantrineATV (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/rArtemether AUC ↓ 16%
    DHAa AUC ↓ 18%
    Lumefantrine AUC ↑ 175%
    ↔ DRV
    LPV/rArtemether AUC ↓ 40%
    DHA AUC ↓ 45%
    Lumefantrine AUC ↑ 4.8-fold
    ↔ LPV
    Atovaquone/ProguanilATV/r, LPV/rWith 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.
    MefloquineAll PIsWith RTV 200 mg Twice Daily
    • RTV AUC ↓ 31% and Cmin ↓ 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
    ClopidogrelAll boosted PIsClopidogrel 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.
    PrasugrelAll boosted PIsPrasugrel 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.
    TicagrelorAll PIs↑ ticagrelor expectedDo not coadminister.
    VorapaxarAll PIs↑ vorapaxar expectedDo not coadminister.
    Antipneumocystis and Antitoxoplasmosis Drug
    Atovaquone
    Oral suspension
    ATV/r↔ atovaquoneNo dose adjustment needed.
    All other PIs↔ atovaquone expectedNo dose adjustment needed.
    Antivirals—Orthopoxviruses (Mpox, Smallpox)
    BrincidofovirAll PIs↑ brincidofovir possibleGive 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).
    CidofovirAll PIs↔ cidofovirNo dose adjustment needed.
    TecovirimatAll PIs↔ tecovirimatNo dose adjustment needed.
    Beta-Agonists, Long-Acting Inhaled
    Arformoterol, FormoterolATV (unboosted), ATV/c, ATV/r↑ arformoterol possibleNo dose adjustment needed.
    DRV/c, DRV/r, LPV/r↔ arformoterol expectedNo dose adjustment needed.
    IndacaterolAll PIsWith RTV 300 mg Twice Daily
    • Indacaterol AUC ↑ 1.7-fold
    No dose adjustment needed in patients receiving indacaterol 75 mcg daily.
    OlodaterolAll PIs↑ olodaterol expectedNo dose adjustment needed.
    SalmeterolAll PIs↑ salmeterol possibleDo not coadminister, due to potential increased risk of salmeterol-related CV events.
    Cardiac Medications
    AmiodaroneATV/r↑ amiodarone possible
    ↑ PI possible
    Contraindicated.
    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 possibleConsider alternative ARV or antiarrhythmics. If coadministered, monitor for antiarrhythmic-related adverse events.
    PI/c, PI/r↑ antiarrhythmic possibleDo not coadminister.
    DronedaroneATV (unboosted)↑ dronedarone possibleDo not coadminister.
    PI/c, PI/r↑ dronedarone expectedContraindicated.
    FlecainideAll PIs↑ flecainide possibleDo not coadminister.
    PropafenoneAll PIs↑ propafenone possibleDo not coadminister.
    QuinidineATV/r↑ quinidine expectedContraindicated.
    All other PIs↑ quinidine possibleDo not coadminister.
    Beta-Blockers
    (e.g., carvedilol, metoprolol, timolol)
    All PIs↑ beta-blockers possibleMay 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).
    BosentanAll PIsWith 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 DiltiazemAll PIs↑ dihydropyridine possible
    ↑ verapamil possible
    Titrate CCB dose and monitor closely. ECG monitoring is recommended when CCB is used with ATV.
    DigoxinPI/c, PI/rRTV 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.
    DiltiazemATV (unboosted), ATV/c, ATV/rUnboosted 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.
    DRV/c, DRV/r, LPV/r↑ diltiazem possibleTitrate diltiazem dose according to clinical response and adverse events.
    EplerenonePI/c, PI/r↑ eplerenone expectedContraindicated.
    RanolazineATV (unboosted)↑ ranolazine possibleDo not coadminister..
    PI/c, PI/r↑ ranolazine expectedContraindicated.
    IvabradineAll PIs↑ ranolazine expectedContraindicated.
    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.
    All PIs except DRV/r↔ 17-BMP expectedNo 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.
    All PIs↑ prednisolone possible
    Betamethasone, Methylprednisolone, Triamcinolone
    Local injections, including intra-articular, epidural, or intra-orbital
    All PIs↑ glucocorticoids expectedDo not coadminister. Coadministration can result in adrenal insufficiency and Cushing’s syndrome.
    Glucose-Lowering Medications
    CanagliflozinATV (unboosted), PI/c↔ canagliflozinNo dose adjustment needed.
    PI/r↓ canagliflozin expectedIf 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.
    SaxagliptinAll PIs↑ saxagliptin expectedLimit saxagliptin dose to 2.5 mg once daily.
    Dapagliflozin/SaxagliptinAll PIs↑ saxagliptin expectedDo 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
    DaclatasvirATV/c, ATV/rATV/c, ATV/rDecrease daclatasvir dose to 30 mg once daily.
    ATV (unboosted), DRV/c, DRV/r, LPV/r↔ daclatasvirNo dose adjustment needed.
    Dasabuvir plus Paritaprevir/Ombitasvir/ RTVATV (unboosted)↔ ATVATV 300 mg alone, without COBI or additional RTV, should be given in the morning with dasabuvir plus paritaprevir/ombitasvir/RTV.
    ATV/c, ATV/rNo dataThis 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.
    DRVDRV Cmin ↓ 43% to 48%Do not coadminister.
    LPV/rParitaprevir AUC ↑ 117%Do not coadminister.
    DRV/cNo dataDo not coadminister.
    Elbasvir/GrazoprevirATV/rElbasvir 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/rElbasvir AUC ↑ 66%
    Grazoprevir AUC ↑ 7.5-fold
    ↔ DRV
    LPV/rElbasvir AUC ↑ 3.7-fold
    Grazoprevir AUC ↑ 12.9-fold
    ↔ LPV
    ATV (unboosted), ATV/c, DRV/c↑ grazoprevir expected
    Glecaprevir/PibrentasvirATV (unboosted), ATV/c, ATV/rWith (ATV 300 mg plus RTV 100 mg) Once Daily
    • Glecaprevir AUC ↑ 6.5-fold
    • Pibrentasvir AUC ↑ 64%
    Contraindicated.
    DRV/c, DRV/rWith (DRV 800 mg plus RTV 100 mg) Once Daily
    • Glecaprevir AUC ↑ 5-fold
    • ↔ pibrentasvir
    Do not coadminister..
    LPV/rGlecaprevir AUC ↑ 4-fold
    Pibrentasvir ↑ 2.5-fold
    Do not coadminister..
    Ledipasvir/SofosbuvirATV/rATV 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.
    ATV (unboosted), ATV/c, DRV/c, DRV/r, LPV/rATV (unboosted), ATV/c, DRV/c, DRV/r, LPV/r
    Sofosbuvir/VelpatasvirATV/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 expectedNo dose adjustment needed.
    Sofosbuvir/Velpatasvir/VoxilaprevirATV (unboosted), ATV/c, ATV/rWith ATV/r
    • Voxilaprevir AUC ↑ 4.3-fold
    • Velpatasvir AUC ↑ 93%
    • Sofosbuvir AUC ↑ 40%
    Do not coadminister.
    LPV/r↑ voxilaprevir expectedDo not coadminister.
    DRV/c, DRV/rWith DRV/r
    • Voxilaprevir AUC ↑ 2.4-fold
    • ↔ DRV/r, velpatasvir, and sofosbuvir
    No dose adjustment needed.
    Herbal Products
    St. John’s WortAll PIs↓ PI expectedContraindicated.
    Hormonal Therapies
    Contraceptives–Injectable
    Depot MPA
    LPV/rMPA AUC ↑ 46%No dose adjustment needed.
    All other PIsNo dataNo dose adjustment needed.
    Contraceptives–OralATV (unboosted)Ethinyl estradiol AUC ↑ 48%

    Norethindrone AUC ↑ 110%
    Prescribe an oral contraceptive that contains no more than 30 mcg of ethinyl estradiolb 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/cDrosperinone AUC ↑ 130%
    Ethinyl estradiol AUC ↓ 22%
    Contraindicated with drospirenone-containing hormonal contraceptive due to potential for hyperkalemia. Use alternative ARV or contraceptive methods.
    ↔ ethinyl estradiol AUC and Cmin ↓ 25%
    ↔ levonorgestrel
    No dose adjustment needed.
    ATV/rEthinyl estradiol AUC ↓ 19% and Cmin ↓ 37%
    Norgestimate AUC ↑ 85%
    Norethindrone AUC ↑ 51% and Cmin ↑ 67%
    Oral contraceptive should contain at least 35 mcg of ethinyl estradiol.c
    DRV/cDrospirenone AUC ↑ 58%
    Ethinyl estradiol AUC ↓ 30%
    Clinical monitoring is recommended due to the potential for hyperkalemia. Use alternative ARV or contraceptive methods.
    DRV/rEthinyl estradiol AUC ↓ 44% and Cmin ↓ 62%
    Norethindrone AUC ↓ 14% and Cmin ↓ 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/rEthinyl estradiol AUC ↓ 42% and Cmin ↓ 32% to 58%
    Norethindrone AUC ↓ 17% and Cmin ↓ 32%
    ↔ Cminmin Etonogestrel (metabolite of oral desogestrel)
    Consider using an oral contraceptive with at least 35 mcg of ethinyl estradiol.
    Contraceptives–Subdermal Implant
    Etonogestrel
    LPV/rEtonogestrel AUC ↑ 52% and Cmin ↑ 34%No dose adjustment needed.
    All other PIs↑ etonogestrel expectedNo dose adjustment needed.
    Contraceptives–Subdermal Implant
    Levonorgestrel
    All PIs↑ levonorgestrel expectedNo dose adjustment needed.
    Contraceptives–Transdermal
    Ethinyl Estradiol/Norelgestromin
    LPV/r↔ LPV
    Ethinyl estradiol AUC ↓ 45%
    Norelgestromin AUC ↑ 83%
    No dose adjustment needed.
    All other PIsNo data
    Contraceptives–Vaginal Ring
    Etonogestrel/Ethinyl Estradiol
    ATV/rEthinyl estradiol AUC ↓ 26%
    Etonogestrel AUC ↑ 79%
    No dose adjustment needed.
    All other PIsNo data
    Contraceptives–Vaginal Ring
    Segesterone/Ethinyl Estradiol
    All PIsNo dataUse alternative ARV or contraceptive methods.
    Emergency Contraceptives
    Levonorgestrel (oral)
    All PIs↑ levonorgestrel expectedNo dose adjustment needed.
    Gender-Affirming TherapyPI/c↑ estradiol possibleAdjust estradiol dose as needed based on clinical effects and endogenous hormone concentrations.
    PI/r↓ or ↑ estradiol possible
    All PIs↔ goserelin, leuprolide acetate, and spironolactone expectedNo 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 possibleAdjust testosterone dose as needed based on clinical effects and endogenous hormone concentrations.
    Menopausal Replacement TherapyAll PIs↓ or ↑ estrogen possible with estradiol or conjugated estrogen (equine and synthetic)Adjust estrogen dose as needed based on clinical effects.
    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, TacrolimusAll PIs↑ immunosuppressant expectedInitiate 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.
    EverolimusDRV/c, DRV/rDRV/c, DRV/rDo not coadminister.
    All other PIs↑ immunosuppressant expectedInitiate 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
    AtorvastatinATV (unboosted), ATV/r↑ atorvastatin possibleAdminister the lowest effective atorvastatin dose while monitoring for adverse events.
    ATV/cAtorvastatin AUC ↑ 9.2-fold and Cmax ↑ 18.9-foldDo not coadminister.
    DRV/cAtorvastatin AUC ↑ 3.9-fold and Cmax ↑ 4.2-foldAdminister the lowest effective atorvastatin dose while monitoring for adverse events. Do not exceed 20 mg atorvastatin daily.
    DRV/rDRV/r plus atorvastatin 10 mg similar to atorvastatin 40 mg administered aloneAdminister the lowest effective atorvastatin dose while monitoring for adverse events. Do not exceed 20 mg atorvastatin daily.
    LPV/rAtorvastatin AUC ↑ 5.9-fold and Cmax ↑ 4.7-foldAdminister the lowest effective atorvastatin dose while monitoring for adverse events. Do not exceed 20 mg atorvastatin daily.
    LomitapideAll PIs↑ lomitapide expectedContraindicated.
    LovastatinAll PIsSignificant ↑ lovastatin expectedContraindicated.
    PitavastatinAll PIsWith Unboosted ATV
    • ↑ pitavastatin AUC 31% and Cmax ↑ 60%
    • ↔ ATV

    With DRV/r
    • ↓ pitavastatin AUC 26%
    • ↔ DRV/r

    With LPV/r
    • ↓ pitavastatin AUC 20%
    • ↔ LPV
    No dose adjustment needed.
    PravastatinATV (unboosted), ATV/c, ATV/rNo dataAdminister the lowest effective pravastatin dose while monitoring for adverse events.
    DRV/c, DRV/rWith 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/rLPV/rNo dose adjustment needed.
    RosuvastatinATV (unboosted)↑ rosuvastatin expectedAdminister the lowest effective rosuvastatin dose while monitoring for adverse events. Do not exceed rosuvastatin 10 mg daily.
    ATV/rRosuvastatin AUC ↑ 3-fold and Cmax ↑ 7-fold
    ATV/cRosuvastatin AUC ↑ 3.4-fold and Cmax ↑ 10.6-fold
    DRV/cRosuvastatin AUC ↑ 1.9-fold and Cmax ↑ 3.8-fold
    DRV/rRosuvastatin AUC ↑ 48% and Cmax ↑ 2.4-foldAdminister the lowest effective rosuvastatin dose while monitoring for adverse events.
    LPV/rRosuvastatin AUC ↑ 2.1-fold and Cmax ↑ 4.7-foldAdminister the lowest effective rosuvastatin dose while monitoring for adverse events. Do not exceed rosuvastatin 10 mg daily.
    SimvastatinAll PIsSignificant ↑ simvastatin expectedContraindicated.
    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/rBuprenorphine 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 Cmin ↑ 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/rNo dataTitrate 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.
    FentanylAll PIs↑ fentanyl possibleMonitor for fentanyl-related adverse events, including potentially fatal respiratory depression
    LofexidineATV (unboosted)↔ lofexidine expectedNo dose adjustment needed.
    PI/c, PI/r↑ lofexidine possibleMonitor for lofexidine-related adverse events, including symptoms of orthostasis and bradycardia.
    MethadoneATV (unboosted)↔ ATVNo dose adjustment needed.
    PI/cNo dataTitrate methadone dose using the lowest feasible initial dose. Dose adjustment of methadone may be needed. Monitor for methadone-related adverse events.
    All PI/rATV/r and DRV/r ↓ R-methadoned 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.
    OxycodoneAll PIsLPV/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.
    TramadolAll PIs↑ tramadol expected
    ↓ M1 (active metabolite) possible
    Tramadol dose adjustments may be necessary. Monitor for clinical response and tramadol-related adverse events.
    PDE5 Inhibitors
    AvanafilATV (unboosted)No dataAvanafil dose should not exceed 50 mg once every 24 hours.
    PI/c, PI/rRTV 600 mg twice daily (for 5 days) ↑ avanafil AUC 13-fold and ↑ Cmax 2.4-foldDo not coadminister.
    SildenafilAll PIsDRV/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.
    TadalafilAll PIsRTV 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.
    VardenafilAll PIsRTV 600 mg twice daily ↑ vardenafil AUC 49-foldStart with vardenafil 2.5 mg every 72 hours and monitor for adverse events of vardenafil.
    Sedative/Hypnotics
    Alprazolam, Clonazepam, DiazepamAll 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, TemazepamAll PIsNo dataThese benzodiazepines are metabolized via non-CYP450 pathways and therefore have less interaction potential than other benzodiazepines.
    MidazolamAll PIs↑ midazolam expectedOral 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.
    SuvorexantAll PIs↑ suvorexant expected↑ suvorexant expected
    TriazolamAll PIs↑ triazolam expected
    RTV 200 mg twice daily ↑ triazolam half-life 1,200% and ↑ AUC 2,000%
    Contraindicated.
    ZolpidemPI/c, PI/r↑ zolpidem possibleInitiate zolpidem at a low dose and monitor for zolpidem-related adverse events. Dose reduction may be necessary.
    Miscellaneous Drugs
    CalcifediolAll PIs↑ calcifediol possibleDose adjustment of calcifediol may be required, and serum 25-hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored.
    CisaprideAll PIs↑ cisapride expectedContraindicated.
    ColchicineAll PIsRTV 100 mg twice daily ↑ colchicine AUC 296% and Cmax ↑ 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).
    DronabinolAll PIs↑ dronabinol possibleMonitor for dronabinol-related adverse events.
    EluxadolineAll PIs↑ eluxadoline expectedAdminister eluxadoline at a dose of 75 mg twice daily and monitor for eluxadoline-related adverse events.
    Ergot DerivativesAll PIs↑ dihydroergotamine, ergotamine, and methylergonovine expectedContraindicated.
    FlibanserinAll PIs↑ flibanserin expectedContraindicated.
    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
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