This table provides information on the known or predicted interactions between integrase strand transfer inhibitors (INSTIs) (bictegravir [BIC], dolutegravir [DTG], elvitegravir [EVG], or raltegravir [RAL]) and non-antiretroviral (ARV) drugs. EVG is always coadministered with cobicistat. Cabotegravir (CAB) intramuscular (IM) plus rilpivirine (RPV) IM are co-packaged into a single product and are coadministered as a complete regimen; therefore, the dosing recommendations and clinical comments reflect the combination of CAB IM and RPV IM treatments. Drug interaction studies were not conducted with either CAB IM or RPV IM. Drug interaction studies with oral CAB and RPV were leveraged to make the dosing recommendations for CAB IM and RPV IM. For information regarding interactions between INSTIs and other ARV drugs, including dosing recommendations, refer to Tables 24c, 24e, 24f, and 25b.
Recommendations for managing a particular drug interaction may differ, depending on whether a new ARV drug is being initiated in a patient on a stable concomitant medication or whether a new concomitant medication is being initiated in a patient on a stable ARV regimen. The magnitude and significance of drug interactions are difficult to predict when several drugs with competing metabolic pathways are prescribed concomitantly. In cases where an interacting drug needs to be replaced with an alternative, providers should exercise their clinical judgement to select the most appropriate alternative medication to use.
Concomitant Drug | INSTI | Effect on INSTI or Concomitant Drug Concentrations | Dosing Recommendations and Clinical Comments |
|
---|---|---|---|---|
Acid Reducers | ||||
Al, Mg, +/– Ca-Containing Antacids Please refer to the Miscellaneous Drugs section of this table for recommendations on use with other polyvalent cation products (e.g., Fe and Ca supplements, multivitamins). | BIC | Al/Mg Hydroxide Antacid
| With Antacids That Contain Al/Mg
|
|
CAB PO | CAB PO ↓ expected | With Antacids That Contain Polyvalent Cations (Al, Mg, or Ca)
|
||
CAB IM | ↔ CAB IM expected | No dose adjustment needed. | ||
DTG | DTG AUC ↓ 74% if administered simultaneously with antacid DTG AUC ↓ 26% if administered 2 hours before antacid | Administer DTG at least 2 hours before or at least 6 hours after antacids that contain polyvalent cations. | ||
EVG/c | EVG AUC ↓ 40% to 50% if administered simultaneously with antacid EVG AUC ↓ 15% to 20% if administered 2 hours before or after antacid; ↔ with a 4‑hour interval | Separate EVG/c and antacid administration by more than 2 hours. | ||
RAL | Al/Mg Hydroxide Antacid
| Do not coadminister RAL and Al/Mg hydroxide antacids. Use alternative acid-reducing agent. With CaCO3 Antacids
|
||
H2-Receptor Antagonists | BIC, CAB (PO and IM), DTG, EVG/c | ↔ INSTI | No dose adjustment needed. | |
RAL | RAL AUC ↑ 44% and Cmax ↑ 60% | No dose adjustment needed. | ||
Proton Pump Inhibitors | BIC, CAB (PO and IM), DTG, EVG/c | ↔ INSTI | No dose adjustment needed. | |
RAL | RAL AUC ↑ 37% and Cmin ↑ 24% | No dose adjustment needed. | ||
Alpha-Adrenergic Antagonists for Benign Prostatic Hyperplasia | ||||
Alfuzosin | BIC, CAB (PO and IM), DTG, RAL | ↔ alfuzosin expected | No dose adjustment needed. | |
EVG/c | ↑ alfuzosin expected | Contraindicated. | ||
Doxazosin | BIC, CAB (PO and IM), DTG, RAL | ↔ doxazosin expected | No dose adjustment needed. | |
EVG/c | ↑ doxazosin possible | Initiate doxazosin at lowest dose. Titrate based on doxazosin efficacy and adverse events. Doxazosin dose reduction may be needed. | ||
Tamsulosin | BIC, CAB (PO and IM), DTG, RAL | ↔ tamsulosin expected | No dose adjustment needed. | |
EVG/c | ↑ tamsulosin expected | Do not coadminister unless the benefits outweigh the risks. If coadministered, monitor for tamsulosin-related adverse events. | ||
Terazosin | BIC, CAB (PO and IM), DTG, RAL | ↔ terazosin expected | No dose adjustment needed. | |
EVG/c | ↑ terazosin possible | Initiate terazosin at lowest dose. Titrate based on terazosin efficacy and adverse events. Terazosin dose reduction may be necessary. | ||
Silodosin | BIC, CAB (PO and IM), DTG, RAL | ↔ silodosin expected | No dose adjustment needed. | |
EVG/c | ↑ silodosin expected | Contraindicated. | ||
Antibacterials - Antimycobacterials | ||||
Rifabutin | BIC | Rifabutin 300 mg Once Daily
| Do not coadminister. | |
CAB PO | CAB PO AUC ↓ 23% and Cmin ↓ 26% ↔ rifabutin | No dose adjustment needed. | ||
CAB IM | ↓ CAB IM and RPV expected ↔ rifabutin expected | Contraindicated due to ↓ RPV, which is co-packaged and coadministered with CAB IM. | ||
DTG | Rifabutin 300 mg Once Daily
| No dose adjustment needed. | ||
EVG/c | Rifabutin 150 mg Every Other Day With EVG/c Once Daily Compared to Rifabutin 300 mg Once Daily Alone
| Do not coadminister. | ||
RAL | RAL AUC ↑ 19% and Cmin ↓ 20% | No dose adjustment needed. | ||
Rifampin | BIC | BIC AUC ↓ 75% | Contraindicated. | |
CAB PO | CAB PO AUC ↓ 59% and Cmin ↓ 50% | Contraindicated. | ||
CAB IM | CAB IM ↓ expected | Contraindicated. | ||
DTG | Rifampin With DTG 50 mg Twice Daily Compared to DTG 50 mg Twice Daily Alone
| Use DTG 50 mg twice daily (instead of DTG 50 mg once daily) in patients without suspected or documented INSTI-associated resistance mutations. Consider an alternative to rifampin, such as rifabutin, in patients with certain suspected or documented INSTI-associated resistance mutations. |
||
EVG/c | Significant ↓ EVG and COBI expected | Contraindicated. | ||
RAL | RAL 400 mg
| Use RAL 800 mg twice daily instead of 400 mg twice daily. Do not coadminister RAL 1,200 mg once daily with rifampin. Monitor closely for virologic response or consider using rifabutin as an alternative rifamycin. |
||
Rifapentine | BIC, EVG/c | Significant ↓ BIC, EVG, and COBI expected | Do not coadminister. | |
CAB (PO and IM) | Significant ↓ CAB (PO and IM) expected | Contraindicated. | ||
DTG | Rifapentine 900 mg Once Weekly
| With once-weekly rifapentine, DTG 50 mg daily may be used in patients with viral suppression on daily DTG. Monitor for virologic efficacy. Do not coadminister in patients who require twice-daily DTG. Do not coadminister DTG with once-daily rifapentine. |
||
RAL | Rifapentine 900 mg Once Weekly
| For once-weekly rifapentine and RAL 400 mg twice daily, no dose adjustment is needed. Do not coadminister with once-daily rifapentine. |
||
Antibacterials - Macrolides | ||||
Azithromycin | All INSTIs | ↔ azithromycin expected | No dose adjustment needed. | |
Clarithromycin | BIC | ↑ BIC possible | No dose adjustment needed. | |
CAB (PO and IM), DTG, RAL | ↔ clarithromycin expected | No dose adjustment needed. | ||
EVG/c | ↑ clarithromycin expected ↑ COBI possible | Reduce clarithromycin dose by 50% in patients with CrCl 50 to 60 mL/min. Do not coadminister in patients with CrCl <50 mL/min. Consider alternative ARV or use azithromycin. |
||
Erythromycin | BIC | ↑ BIC possible | No dose adjustment needed. | |
CAB (PO and IM), DTG, RAL | ↔ INSTI expected ↔ erythromycin expected | No dose adjustment needed. | ||
EVG/c | ↑ erythromycin expected ↑ COBI possible | No data available for dose recommendation. Consider alternative ARV or use azithromycin. | ||
Anticoagulants | ||||
Apixaban | BIC, CAB (PO and IM), DTG, RAL | ↔ apixaban expected | No dose adjustment needed. | |
EVG/c | ↑ apixaban expected | Do not coadminister in patients who require apixaban 2.5 mg twice daily. Reduce apixaban dose by 50% in patients who require apixaban 5 mg or 10 mg twice daily. |
||
Dabigatran | BIC, CAB (PO and IM), DTG, RAL | ↔ dabigatran expected | No dose adjustment needed. | |
EVG/c | ↑ dabigatran expected With COBI 150 mg Alone
| Dabigatran dosing recommendation depends on indication and renal function. Refer to dabigatran prescribing information for dosing instructions when using dabigatran concomitantly with P-glycoprotein inhibitors. | ||
Edoxaban | BIC, CAB (PO and IM), DTG, RAL | ↔ edoxaban expected | No dose adjustment needed. | |
EVG/c | ↑ edoxaban expected | Stroke Prevention in Nonvalvular Atrial Fibrillation
|
||
Rivaroxaban | BIC, CAB (PO and IM), DTG, RAL | ↔ rivaroxaban expected | No dose adjustment needed. | |
EVG/c | ↑ rivaroxaban expected | Do not coadminister. | ||
Warfarin | BIC, CAB (PO and IM), DTG, RAL | ↔ warfarin expected | No dose adjustment needed. | |
EVG/c | ↑ or ↓ warfarin possible | Monitor INR and adjust warfarin dose accordingly. | ||
Anticonvulsants | ||||
Carbamazepine | BIC | ↓ BIC possible | Do not coadminister. | |
CAB (PO and IM) | ↓ CAB expected | Contraindicated. | ||
DTG | DTG AUC ↓ 49% | Increase DTG dose to 50 mg twice daily in ART-naive or ART-experienced (but INSTI-naive) patients. Do not coadminister in INSTI-experienced patients with known or suspected INSTI resistance. |
||
EVG/c | Carbamazepine AUC ↑ 43% EVG AUC ↓ 69% and Cmin ↓ >99% ↓ COBI expected | Contraindicated. | ||
RAL | ↓ or ↔ RAL possible | Do not coadminister. | ||
Eslicarbazepine | All INSTIs | ↓ INSTI possible ↓ COBI possible | Consider alternative ARV or anticonvulsant. | |
Ethosuximide | BIC, CAB (PO and IM), DTG, RAL | ↔ ethosuximide expected | No dose adjustment needed. | |
EVG/c | ↑ ethosuximide possible | Monitor for ethosuximide-related adverse events. | ||
Lamotrigine | BIC, CAB (PO and IM), DTG, RAL | ↔ lamotrigine expected | No dose adjustment needed. | |
EVG/c | No data | Monitor anticonvulsant concentrations and adjust dose accordingly. | ||
Oxcarbazepine | BIC, DTG | ↓ BIC and DTG possible | Do not coadminister. | |
CAB (PO and IM) | ↓ CAB expected | Contraindicated. | ||
EVG/c, RAL | ↓ EVG/c and RAL possible | Consider alternative ARV or anticonvulsant. | ||
Phenobarbital, Phenytoin | BIC, DTG, RAL | ↓ BIC and DTG possible ↓ or ↔ RAL possible | Do not coadminister. | |
CAB (PO and IM), EVG/c | ↓ CAB and EVG/c expected | Contraindicated. | ||
Valproic Acid | All INSTIs | No data | Monitor valproic acid concentration and virologic response. | |
Antidepressants, Anxiolytics, and Antipsychotics Also see the Sedative/Hypnotics section below |
||||
Bupropion | BIC, CAB (PO and IM), DTG, RAL | ↔ bupropion expected | No dose adjustment needed. | |
EVG/c | ↑ bupropion possible | Titrate bupropion dose based on clinical response. | ||
Buspirone | BIC, CAB (PO and IM), DTG, RAL | ↔ buspirone expected | No dose adjustment needed. | |
EVG/c | ↑ buspirone possible | Initiate buspirone at a low dose. Buspirone dose reduction may be needed. | ||
Nefazodone | BIC, CAB (PO and IM), DTG, RAL | ↔ nefazodone expected | No dose adjustment needed. | |
EVG/c | ↑ nefazodone expected | Consider alternative ARV or antidepressant. | ||
Trazodone | BIC, CAB (PO and IM), DTG, RAL | ↔ trazodone expected | No dose adjustment needed. | |
Tricyclic Antidepressants Amitriptyline, desipramine, doxepin, imipramine, nortriptyline | BIC, CAB (PO and IM), DTG, RAL | ↔ TCA expected | No dose adjustment needed. | |
EVG/c | Desipramine AUC ↑ 65% | Initiate with lowest dose of TCA and titrate dose carefully. | ||
↑ TCA expected | Initiate with lowest dose of TCA. Titrate dose carefully based on antidepressant response and/or drug concentrations. | |||
Selective Serotonin Reuptake Inhibitors Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline | EVG/c | ↔ sertraline | No dose adjustment needed. | |
EVG/c | ↑ other SSRIs possible | Initiate with lowest dose of SSRI. Titrate dose carefully based on antidepressant response. | ||
BIC, CAB (PO and IM), DTG, RAL | ↔ SSRI expected | No dose adjustment needed. | ||
Antipsychotics | ||||
Aripiprazole | BIC, CAB (PO and IM), DTG, RAL | ↔ aripiprazole expected | No dose adjustment needed. | |
EVG/c | ↑ aripiprazole expected | Administer 25% of the usual aripiprazole dose. Titrate based on aripiprazole efficacy and adverse events. Refer to aripiprazole label for dosing recommendations in patients who are known to be CYP2D6 poor metabolizers or who have major depressive disorder. | ||
Brexpiprazole | BIC, CAB (PO and IM), DTG, RAL | ↔ brexpiprazole expected | No dose adjustment needed. | |
EVG/c | ↑ brexpiprazole expected | Administer 25% of the usual brexpiprazole dose. Titrate based on brexpiprazole efficacy and adverse events. Refer to brexpiprazole label for dosing recommendations in patients who are known to be CYP2D6 poor metabolizers or who have major depressive disorder. | ||
Cariprazine | BIC, CAB (PO and IM), DTG, RAL | ↔ cariprazine expected | No dose adjustment needed. | |
EVG/c | ↑ cariprazine expected | Starting Cariprazine in a Patient Who Is Already Receiving EVG/c
|
||
Iloperidone | BIC, CAB (PO and IM), DTG, RAL | ↔ iloperidone expected | No dose adjustment needed. | |
EVG/c | ↑ iloperidone expected | Decrease iloperidone dose by 50%. | ||
Lumateperone | BIC, CAB (PO and IM), DTG, RAL | ↔ lumateperone expected | No dose adjustment needed. | |
EVG/c | ↑ lumateperone expected | Do not coadminister. | ||
Lurasidone | BIC, CAB (PO and IM), DTG, RAL | ↔ lurasidone expected | No dose adjustment needed. | |
EVG/c | ↑ lurasidone expected | Contraindicated. | ||
Olanzapine | All INSTIs | ↔ olanzapine expected | No dose adjustment needed. | |
Other Antipsychotics CYP3A4 and/or CYP2D6 substrates (e.g., perphenazine, risperidone, thioridazine) | EVG/c | ↑ antipsychotic possible | Initiate antipsychotic at a low dose. Antipsychotic dose reduction may be needed. | |
Pimavanserin | BIC, CAB (PO and IM), DTG, RAL | ↔ pimavanserin expected | No dose adjustment needed. | |
EVG/c | ↑ pimavanserin expected | Reduce pimavanserin dose to 10 mg. | ||
Pimozide | BIC, CAB (PO and IM), DTG, RAL | ↔ pimozide expected | No dose adjustment needed. | |
EVG/c | ↑ pimozide expected | Contraindicated. | ||
Quetiapine | BIC, CAB (PO and IM), DTG, RAL | ↔ quetiapine expected | No dose adjustment needed. | |
EVG/c | ↑ quetiapine AUC expected | Starting Quetiapine in a Patient Receiving EVG/c
|
||
Ziprasidone | BIC, CAB (PO and IM), DTG, RAL | ↔ ziprasidone expected | No dose adjustment needed. | |
EVG/c | ↑ ziprasidone possible | Monitor for ziprasidone-related adverse events. | ||
Antifungals | ||||
Isavuconazole | BIC, CAB (PO and IM), DTG, RAL | ↑ INSTI possible | No dose adjustment needed. | |
EVG/c | ↑ isavuconazole expected ↑ or ↓ EVG and COBI possible | If coadministered, consider monitoring isavuconazole concentrations and assessing virologic response. | ||
Itraconazole | BIC | ↑ BIC expected | No dose adjustment needed. | |
CAB (PO and IM), DTG, RAL | ↔ INSTI expected ↔ itraconazole expected | No dose adjustment needed. | ||
EVG/c | ↑ itraconazole expected ↑ EVG and COBI possible | Consider monitoring itraconazole concentrations to guide dose adjustments. Do not coadminister with high itraconazole doses (>200 mg/day) unless guided by itraconazole concentrations. | ||
Posaconazole | BIC | ↑ BIC expected | No dose adjustment needed. | |
CAB (PO and IM), DTG, RAL | ↔ INSTI expected ↔ posaconazole expected | No dose adjustment needed. | ||
EVG/c | ↑ EVG and COBI possible ↑ posaconazole possible | If coadministered, monitor posaconazole concentrations. | ||
Voriconazole | BIC | ↑ BIC possible | No dose adjustment needed. | |
CAB (PO and IM), DTG, RAL | ↔ INSTI expected ↔ voriconazole expected | No dose adjustment needed. | ||
EVG/c | ↑ voriconazole expected ↑ EVG and COBI possible | Do not coadminister voriconazole and COBI, unless the benefit outweighs the risk. If coadministered, consider monitoring voriconazole concentrations and adjust dose accordingly. | ||
Antihyperglycemics | ||||
Metformin | BIC | Metformin AUC ↑ 39% | Monitor for adverse events of metformin. | |
DTG | DTG 50 mg Once Daily plus Metformin 500 mg Twice Daily
| Start metformin at the lowest dose and titrate based on glycemic control. Monitor for adverse events of metformin. When starting/stopping DTG in patients on metformin, dose adjustment of metformin may be necessary to maintain optimal glycemic control and/or minimize adverse events of metformin. |
||
CAB (PO and IM), RAL | ↔ metformin expected | No dose adjustment needed. | ||
Saxagliptin | BIC, CAB (PO and IM), DTG, RAL | ↔ saxagliptin expected | No dose adjustment needed. | |
EVG/c | ↑ saxagliptin expected | Limit saxagliptin dose to 2.5 mg once daily. | ||
Dapagliflozin/ Saxagliptin | BIC, CAB (PO and IM), DTG, RAL | ↔ dapagliflozin or saxagliptin expected | No dose adjustment needed. | |
EVG/c | ↑ saxagliptin expected | Do not coadminister. Dapagliflozin is available only as a coformulated drug that contains 5 mg of saxagliptin. When coadministered with EVG/c, the dose of saxagliptin should not exceed 2.5 mg once daily; thus, this combination is not recommended. | ||
Antiplatelets | ||||
Clopidogrel | BIC, CAB (PO and IM), DTG, RAL | ↔ clopidogrel expected | No dose adjustment needed. | |
EVG/c | ↓ clopidogrel active metabolite, with impaired platelet inhibition expected | Do not coadminister. | ||
Prasugrel | BIC, CAB (PO and IM), DTG, RAL | ↔ prasugrel expected | No dose adjustment needed. | |
EVG/c | ↓ prasugrel active metabolite, with no impairment of platelet inhibition expected | No dose adjustment needed. | ||
Ticagrelor | BIC, CAB (PO and IM), DTG, RAL | ↔ ticagrelor expected | No dose adjustment needed. | |
EVG/c | ↑ ticagrelor expected | Do not coadminister. | ||
Vorapaxar | BIC, CAB (PO and IM) DTG, RAL | ↔ vorapaxar expected | No dose adjustment needed. | |
EVG/c | ↑ vorapaxar expected | Do not coadminister. | ||
Antivirals—Orthopoxviruses (Smallpox, Mpox) | ||||
Brincidofovir | BIC, CAB (PO and IM), DTG, RAL | ↔ INSTI expected | No dose adjustment needed. | |
EVG/c | ↑ brincidofovir possible ↑ EVG possible | Administer EVG/c dose at least 3 hours after administering brincidofovir and monitor for brincidofovir-related adverse events (i.e., elevations in ALT/AST and bilirubin and GI adverse events). | ||
Cidofovir | BIC, CAB (PO and IM), DTG, RAL | ↔ INSTI expected ↔ cidofovir expected | No dose adjustment needed. | |
Tecovirimat | CAB (IM) | ↔ CAB expected | No dose adjustment needed. Do not initiate CAB/RPV IM during or within 2 weeks after tecovirimat treatment. (Refer to Table 24b for interaction with RPV.) |
|
BIC, CAB (PO), DTG, EVG/c, RAL | ↔ INSTI expected | No dose adjustment needed. | ||
Beta-Agonists, Long-Acting Inhaled | ||||
Arformoterol, Formoterol | All INSTIs | ↔ arformoterol or formoterol expected | No dose adjustment needed. | |
Indacaterol | BIC, CAB (PO and IM), DTG, RAL | ↔ indacaterol expected | No dose adjustment needed. | |
EVG/c | ↑ indacaterol expected | |||
Olodaterol | BIC, CAB (PO and IM), DTG, RAL | ↔ olodaterol expected | No dose adjustment needed. | |
EVG/c | ↑ olodaterol expected | |||
Salmeterol | BIC, CAB (PO and IM), DTG, RAL | ↔ salmeterol expected | No dose adjustment needed. | |
EVG/c | ↑ salmeterol possible | Do not coadminister due to the potential for increased risk of salmeterol-associated cardiovascular events. | ||
Cardiac Medications | ||||
Amiodarone | BIC, CAB (PO and IM), DTG, RAL | ↔ INSTI expected ↔ amiodarone expected | No dose adjustment needed. | |
EVG/c | ↑ INSTI possible ↑ amiodarone possible | Do not coadminister unless the benefits outweigh the risks. If coadministration is necessary, monitor for amiodarone-related adverse events and consider monitoring ECG and amiodarone concentrations. | ||
Bepridil, Digoxin, Disopyramide, Dronedarone, Flecainide, Systemic Lidocaine, Mexilitine, Propafenone, Quinidine | BIC, CAB (PO and IM), DTG | ↔ expected for the listed antiarrhythmics, except for disopyramide ↑ disopyramide possible | No dose adjustment needed. Monitor for disopyramide-related adverse events. |
|
RAL | ↔ expected for the listed antiarrhythmics | No dose adjustment needed. | ||
EVG/c | ↑ antiarrhythmics possible Digoxin Cmax ↑ 41% and ↔ AUC | Therapeutic drug monitoring for antiarrhythmics, if available, is recommended. | ||
Beta Blockers (e.g., metoprolol, timolol) | BIC, CAB (PO and IM), DTG, RAL | ↔ beta blocker expected | No dose adjustment needed. | |
EVG/c | ↑ beta blocker possible | Beta blocker dose may need to be decreased; adjust dose based on clinical response. Consider using an alternative ARV or a beta blocker that is not metabolized by CYP450 enzymes (e.g., atenolol, labetalol, nadolol, sotalol). |
||
Bosentan | BIC, DTG | ↓ BIC and DTG possible | No dose adjustment needed. | |
CAB (PO and IM) | ↔ bosentan expected | Consider using alternative ARV or an alternative to bosentan because bosentan may ↓ RPV, which is co-packaged and coadministered with CAB IM. If bosentan is used with RPV, monitor virologic response to ART. | ||
RAL | ↔ bosentan expected | No dose adjustment needed. | ||
EVG/c | ↑ bosentan possible | In Patients on EVG/c ≥10 Days
|
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Calcium Channel Blockers | BIC | ↑ BIC possible with diltiazem ↔ expected for all other CCBs | No dose adjustment needed. | |
CAB (PO and IM), DTG, RAL | ↔ INSTI expected ↔ CCB expected | No dose adjustment needed. | ||
EVG/c | ↑ CCB possible | Titrate CCB dose and monitor for CCB efficacy and adverse events. | ||
Dofetilide | BIC, DTG | ↑ dofetilide expected | Contraindicated. | |
CAB (PO and IM), RAL | ↔ dofetilide expected | No dose adjustment needed. | ||
EVG/c | ↑ dofetilide possible | Do not coadminister. | ||
Eplerenone | BIC, CAB (PO and IM), DTG, RAL | ↔ eplerenone expected | No dose adjustment needed. | |
EVG/c | ↑ eplerenone expected | Contraindicated. | ||
Ivabradine | BIC, CAB (PO and IM), DTG, RAL | ↔ ivabradine expected | No dose adjustment needed. | |
EVG/c | ↑ ivabradine expected | Contraindicated. | ||
Ranolazine | BIC, CAB (PO and IM), DTG, RAL | ↔ ranolazine expected | No dose adjustment needed. | |
EVG/c | ↑ ranolazine expected | Contraindicated. | ||
Corticosteroids | ||||
Beclomethasone Inhaled or intranasal | BIC, CAB (PO and IM), DTG, EVG/c, RAL | ↔ glucocorticoid expected | No dose adjustment needed. | |
Budesonide, Ciclesonide, Fluticasone, Mometasone Inhaled or intranasal | BIC, CAB (PO and IM), DTG, RAL | ↔ glucocorticoid expected | No dose adjustment needed. | |
EVG/c | ↑ glucocorticoid possible | Do not coadminister unless the potential benefits of inhaled or intranasal corticosteroid outweigh the risks of systemic corticosteroid adverse effects. Coadministration can result in adrenal insufficiency and Cushing’s syndrome. Consider using an alternative corticosteroid (e.g., beclomethasone). | ||
Betamethasone, Budesonide Systemic | BIC, CAB (PO and IM), DTG, RAL | ↔ INSTI expected ↔ glucocorticoid expected | No dose adjustment needed. | |
EVG/c | ↑ glucocorticoid possible ↓ EVG possible | Do not coadminister unless the potential benefits of systemic budesonide outweigh the risks of systemic corticosteroid adverse effects. Coadministration can result in adrenal insufficiency and Cushing’s syndrome. | ||
Dexamethasone Systemic | BIC | ↓ BIC possible | Consider alternative corticosteroid for long-term use or alternative ARV. If coadministration is necessary, monitor virologic response to ART. | |
CAB (PO and IM), DTG, RAL | ↔ INSTI expected | No dose adjustment needed. | ||
EVG/c | ↓ EVG and COBI possible | Consider alternative corticosteroid for long-term use or alternative ARV. If coadministration is necessary, monitor virologic response to ART. | ||
Prednisone, Prednisolone Systemic | BIC, CAB (PO and IM), DTG, RAL | ↔ glucocorticoid expected | No dose adjustment needed. | |
EVG/c | ↑ prednisolone possible | Coadministration may be considered if the potential benefits outweigh the risks of systemic corticosteroid adverse effects. If coadministration is necessary, monitor for adrenal insufficiency and Cushing’s syndrome. | ||
Betamethasone, Methylprednisolone, Prednisolone, Triamcinolone Local injections, including intra-articular, epidural, or intra-orbital | BIC, CAB (PO and IM), DTG, RAL | ↔ glucocorticoid expected | No dose adjustment needed. | |
EVG/c | ↑ glucocorticoid expected | Do not coadminister. Coadministration may result in adrenal insufficiency and Cushing’s syndrome. | ||
Hepatitis C Direct-Acting Antiviral Agents | ||||
Daclatasvir | BIC, CAB (PO and IM), RAL | ↔ daclatasvir expected | No dose adjustment needed. | |
DTG | ↔ daclatasvir | No dose adjustment needed. | ||
EVG/c | ↑ daclatasvir | Decrease daclatasvir dose to 30 mg once daily. | ||
Dasabuvir plus Ombitasvir/Paritaprevir/ RTV | BIC | ↔ BIC expected | No dose adjustment needed. | |
CAB (PO and IM) | ↔ CAB expected ↑ RPV IM expected | Do not coadminister due to potential for QTc prolongation with higher concentrations of RPV. RPV is co-packaged and coadministered with CAB IM. | ||
DTG | ↔ DTG, dasabuvir, plus ombitasvir/paritaprevir/RTV | No dose adjustment needed. | ||
EVG/c | No data | Do not coadminister. | ||
RAL | RAL AUC ↑ 134% | No dose adjustment needed. | ||
Elbasvir/Grazoprevir | BIC | ↔ BIC expected | No dose adjustment needed. | |
CAB (PO and IM) | ↔ CAB, elbasvir, and grazoprevir expected | No dose adjustment needed. | ||
DTG | ↔ DTG ↔ elbasvir ↔ grazoprevir | No dose adjustment needed. | ||
EVG/c | ↑ elbasvir expected ↑ grazoprevir expected | Do not coadminister. | ||
RAL | ↔ RAL with elbasvir RAL AUC ↑ 43% with grazoprevir ↔ elbasvir ↔ grazoprevir | No dose adjustment needed. | ||
Glecaprevir/Pibrentasvir | BIC, CAB (PO and IM) | ↔ BIC or CAB expected | No dose adjustment needed. | |
DTG | ↔ DTG and glecaprevir/ pibrentasvir | No dose adjustment needed. | ||
RAL | No significant effect RAL AUC ↑ 47% | |||
EVG/c | Glecaprevir AUC ↑ 3-fold Pibrentasvir AUC ↑ 57% EVG AUC ↑ 47% | No dose adjustment needed. If coadministered with TDF, monitor for TDF-related adverse events. Consider monitoring for hepatotoxicity if coadministered with TDF or TAF. |
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Ledipasvir/Sofosbuvir | BIC, DTG, RAL | ↔ BIC, DTG, and RAL | No dose adjustment needed. | |
CAB (PO and IM) | ↔ CAB expected | No dose adjustment needed. | ||
EVG/c/TDF/ FTC | ↑ TDF expected ↑ ledipasvir expected | Do not coadminister. | ||
EVG/c/TAF/ FTC | ↔ EVG/c/TAF/FTC expected | No dose adjustment needed. | ||
Sofosbuvir | BIC, CAB (PO and IM), DTG, EVG/C | ↔ INSTI expected ↔ sofosbuvir expected | No dose adjustment needed. | |
RAL | ↔ RAL and sofosbuvir | No dose adjustment needed. | ||
Sofosbuvir/Velpatasvir | BIC, DTG, RAL | ↔ sofosbuvir and velpatasvir | No dose adjustment needed. If coadministered with TDF, monitor for TDF‑related adverse events. | |
CAB (PO and IM) | ↔ CAB expected ↔ sofosbuvir and velpatasvir expected |
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EVG/c | ↔ EVG/c/TAF/FTC Velpatasvir AUC ↑ 50% |
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Sofosbuvir/ Velpatasvir/ Voxilaprevir | BIC | When Administered With Sofosbuvir/ Velpatasvir/ Voxilaprevir (400 mg/100 mg/100 mg) plus Voxilaprevir 100 mg
| No dose adjustment needed. | |
EVG/c | When Administered With Sofosbuvir/ Velpatasvir/ Voxilaprevir (400 mg/100 mg/100 mg) plus Voxilaprevir 100 mg
| No dose adjustment needed. If coadministered with TDF, monitor for TDF-related adverse events. Consider monitoring for hepatotoxicity if coadministered with TDF or TAF. | ||
BIC, CAB (PO and IM), DTG, RAL | ↔ INSTI expected ↔ sofosbuvir, velpatasvir, and voxilaprevir expected | No dose adjustment needed. | ||
Herbal Products | ||||
St. John’s Wort | BIC, CAB (PO and IM), DTG | ↓ BIC and DTG possible | Do not coadminister. | |
EVG/c | ↓ EVG and COBI expected | Contraindicated. | ||
Hormonal Therapies | ||||
Contraceptives: Non‑Oral | BIC, CAB (PO and IM), DTG, RAL | Etonogestrel (subdermal implant) ↑ 27% with DTG ↔ expected with BIC, CAB, RAL | No dose adjustment needed. | |
EVG/c | No data | No data available to make dose recommendation. | ||
Contraceptives: Oral | BIC, DTG, RAL | ↔ ethinyl estradiol and norgestimate ↔ INSTI | No dose adjustment needed. | |
CAB (PO and IM) | ↔ ethinyl estradiol and levonorgestrel with CAB PO | No dose adjustment needed. | ||
EVG/c | Norgestimate AUC, Cmax, and Cmin ↑ > 2-fold Ethinyl estradiol AUC ↓ 25% and Cmin ↓ 44% | The effects of increases in progestin (norgestimate) are not fully known and may include insulin resistance, dyslipidemia, acne, and venous thrombosis. Decreased ethinyl estradiol may lead to more intermenstrual bleeding. Weigh the risks and benefits of using the drug and consider using an alternative ARV or contraceptive method. | ||
↑ drospirenone possible | Clinical monitoring is recommended due to the potential for hyperkalemia. Consider using alternative ARV or contraceptive method. | |||
Gender-Affirming Therapy | BIC, CAB (PO and IM), DTG, EVG/c, RAL | ↔ goserelin, leuprolide acetate, and spironolactone expected | No dose adjustment needed. | |
BIC, CAB (PO and IM), DTG, RAL | ↔ estrogen expected | No dose adjustment needed. | ||
↔ testosterone expected | No dose adjustment needed. | |||
EVG/c | ↑ estradiol possible ↑ cyproterone, dutasteride, and finasteride possible | Adjust dutasteride dose as needed based on clinical effects and endogenous hormone concentrations. | ||
↑ testosterone possible | Monitor masculinizing effects of testosterone and monitor for adverse effects. Adjust testosterone dose as necessary. | |||
Menopausal Replacement Therapy | BIC, CAB (PO and IM), DTG, RAL | ↔ estrogen expected with estradiol or conjugated estrogen (equine and synthetic) ↔ drospirenone, medroxyprogesterone, and micronized progesterone expected | No dose adjustment needed. | |
EVG/c | ↓ or ↑ estrogen possible ↑ drospirenone possible ↑ oral medroxyprogesterone possible ↑ oral micronized progesterone possible | Adjust estrogen and progestin dose as needed based on clinical effects. | ||
Immunosuppressants | ||||
Cyclosporine, Everolimus, Sirolimus, Tacrolimus | BIC, CAB (PO and IM), DTG, RAL | ↔ immunosuppressant expected | No dose adjustment needed. | |
EVG/c | ↑ immunosuppressant possible | Initiate with an adjusted dose of immunosuppressant to account for potential increased concentrations of the immunosuppressant. Monitor for immunosuppressant-related adverse events. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with a specialist as necessary. | ||
Lipid-Modifying Agents | ||||
Atorvastatin | BIC, CAB (PO and IM), DTG, RAL | ↔ atorvastatin expected | No dose adjustment needed. | |
EVG/c | Atorvastatin AUC ↑ 2.6-fold and Cmax ↑ 2.3-fold | Titrate statin dose carefully. Administer the lowest effective dose while monitoring for adverse events. Do not exceed 20 mg atorvastatin daily. | ||
Lomitapide | BIC, CAB (PO and IM), DTG, RAL | ↔ lomitapide expected | No dose adjustment needed. | |
EVG/c | ↑ lomitapide expected | Contraindicated. | ||
Lovastatin | BIC, CAB (PO and IM), DTG, RAL | ↔ lovastatin expected | No dose adjustment needed. | |
EVG/c | Significant ↑ lovastatin expected | Contraindicated. | ||
Pitavastatin, Pravastatin | BIC, CAB (PO and IM), DTG, RAL | ↔ statin expected | No dose adjustment needed. | |
EVG/c | No data | No data available for dose recommendation. | ||
Rosuvastatin | BIC, CAB (PO and IM), DTG, RAL | ↔ rosuvastatin expected | No dose adjustment needed. | |
EVG/c | Rosuvastatin AUC ↑ 38% and Cmax ↑ 89% | Titrate statin dose carefully and use the lowest effective dose while monitoring for adverse events. | ||
Simvastatin | BIC, CAB (PO and IM), DTG, RAL | ↔ simvastatin expected | No dose adjustment needed. | |
EVG/c | Significant ↑ simvastatin expected | Contraindicated. | ||
Narcotics and Treatment for Opioid Dependence | ||||
Buprenorphine Sublingual, buccal, or implant | BIC, CAB (PO and IM), DTG | ↔ buprenorphine and norbuprenorphine (active metabolite) expected | No dose adjustment needed. | |
EVG/c | Buprenorphine AUC ↑ 35% and Cmin ↑ 66% Norbuprenorphine (active metabolite) AUC ↑ 42% and Cmin ↑ 57% | No dose adjustment needed. Monitor for adverse events of buprenorphine. When transferring buprenorphine from transmucosal administration to implantation, monitor to ensure buprenorphine effect is adequate and not excessive. | ||
RAL | ↔ buprenorphine and norbuprenorphine (active metabolite) (sublingual) ↔ buprenorphine or norbuprenorphine (active metabolite) expected (implant) | No dose adjustment needed. | ||
Fentanyl | BIC, CAB (PO and IM), DTG, RAL | ↔ fentanyl expected | No dose adjustment needed. | |
EVG/c | ↑ fentanyl | Monitor for fentanyl efficacy and adverse events, including potentially fatal respiratory depression. | ||
Lofexidine | BIC, CAB (PO and IM), DTG, RAL | ↔ lofexidine expected | No dose adjustment needed. | |
EVG/c | ↑ lofexidine possible | Monitor for lofexidine-related adverse events, including symptoms of orthostasis and bradycardia. | ||
Methadone | All INSTIs | ↔ methadone | No dose adjustment needed. | |
Tramadol | BIC, CAB (PO and IM), DTG, RAL | ↔ tramadol and M1 (active metabolite) expected | No dose adjustment needed. | |
EVG/c | ↑ tramadol expected ↓ M1 (active metabolite) possible | Tramadol dose adjustments may be necessary. Monitor for clinical response and tramadol-related adverse events. | ||
PDE5 Inhibitors | ||||
Avanafil | BIC, CAB (PO and IM), DTG, RAL | ↔ avanafil expected | No dose adjustment needed. | |
EVG/c | No data | Do not coadminister. | ||
Sildenafil | BIC, CAB (PO and IM), DTG, RAL | ↔ sildenafil expected | No dose adjustment needed. | |
EVG/c | ↑ sildenafil expected | For Treatment of Erectile Dysfunction
|
||
Tadalafil | BIC, CAB (PO and IM), DTG, RAL | ↔ tadalafil expected | No dose adjustment needed. | |
EVG/c | ↑ tadalafil expected | For Treatment of Erectile Dysfunction
In Patients on EVG/c >7 Days
|
||
Vardenafil | BIC, CAB (PO and IM), DTG, RAL | ↔ vardenafil expected | No dose adjustment needed. | |
EVG/c | ↑ vardenafil expected | Start with vardenafil 2.5 mg every 72 hours and monitor for adverse effects of vardenafil. | ||
Sedative/Hypnotics | ||||
Alprazolam, Clonazepam, Clorazepate, Diazepam, Estazolam, Flurazepam | BIC, CAB (PO and IM), DTG, RAL | ↔ benzodiazepine expected | No dose adjustment needed. | |
EVG/c | ↑ benzodiazepine possible | Dose reduction of benzodiazepine may be necessary. Initiate with a low dose and monitor for benzodiazepine-related adverse events. Consider using an alternative benzodiazepine, such as lorazepam, oxazepam, or temazepam. |
||
Midazolam, Triazolam | BIC, CAB (PO and IM), RAL | ↔ benzodiazepine expected | No dose adjustment needed. | |
DTG | With DTG 25 mg
| No dose adjustment needed. | ||
EVG/c | ↑ midazolam expected ↑ triazolam expected | Contraindicated. Do not coadminister triazolam or oral midazolam and EVG/c. Parenteral midazolam can be administered in a closely monitored setting. Consider dose reduction, especially if >1 dose is administered. |
||
Suvorexant | BIC, CAB (PO and IM), DTG, RAL | ↔ suvorexant expected | No dose adjustment needed. | |
EVG/c | ↑ suvorexant expected | Do not coadminister. | ||
Zolpidem | BIC, CAB (PO and IM), DTG, RAL | ↔ zolpidem expected | No dose adjustment needed. | |
EVG/c | ↑ zolpidem expected | Initiate zolpidem at a low dose. Dose reduction of zolpidem may be necessary. | ||
Miscellaneous Drugs | ||||
Calcifediol | BIC, CAB (PO and IM), DTG, RAL | ↔ calcifediol expected | No dose adjustment needed. | |
EVG/c | ↑ calcifediol possible | Dose adjustment of calcifediol may be required. Monitor serum 25-hydroxyvitamin D, intact PTH, and serum Ca concentrations. | ||
Cisapride | BIC, CAB (PO and IM), DTG, RAL | ↔ cisapride expected | No dose adjustment needed. | |
EVG/c | ↑ cisapride expected | Contraindicated. | ||
Colchicine | BIC, CAB (PO and IM), DTG, RAL | ↔ colchicine expected | No dose adjustment needed. | |
EVG/c | ↑ colchicine expected | Do not coadminister in patients with hepatic or renal impairment. For Treatment of Gout Flares
|
||
Dronabinol | BIC, CAB (PO and IM), DTG, RAL | ↔ dronabinol expected | No dose adjustment needed. | |
EVG/c | ↑ dronabinol possible | Monitor for dronabinol-related adverse events. | ||
Eluxadoline | BIC, CAB (PO and IM), DTG, RAL | ↔ eluxadoline expected | No dose adjustment needed. | |
EVG/c | ↑ eluxadoline possible | Monitor for eluxadoline-related adverse events. | ||
Ergot Derivatives | BIC, CAB (PO and IM), DTG, RAL | ↔ dihydroergotamine, ergotamine, and methylergonovine expected | No dose adjustment needed. | |
EVG/c | ↑ dihydroergotamine, ergotamine, and methylergonovine expected | Contraindicated. | ||
Flibanserin | BIC, CAB (PO and IM), DTG, RAL | ↔ flibanserin expected | No dose adjustment needed. | |
EVG/c | ↑ flibanserin expected | Contraindicated. | ||
Polyvalent Cation Supplements Mg, Al, Fe, Ca, Zn, including multivitamins with minerals Note: Please refer to the Acid Reducers section in this table for recommendations on use with Al-, Mg-, and Ca-containing antacids. | BIC | ↔ BIC AUC if administered simultaneously with Fe or Ca and food BIC AUC ↓ 33% if administered simultaneously with CaCO3 under fasting conditions BIC AUC ↓ 63% if administered simultaneously with Fe under fasting conditions | With Supplements That Contain Ca or Fe
|
|
CAB | ↓ INSTI possible | If coadministration is necessary, administer INSTI at least 2 hours before or at least 4 hours after supplements that contain polyvalent cations, including but not limited to the following products: cation-containing laxatives; Fe, Ca, or Mg supplements; and sucralfate. Monitor for virologic response. Many oral multivitamins also contain varying amounts of polyvalent cations; the extent and significance of chelation is unknown. |
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DTG | DTG AUC ↓ 39% if administered simultaneously with CaCO3 under fasting conditions DTG AUC ↓ 54% if administered simultaneously with Fe under fasting conditions ↔ DTG when administered with Ca or Fe supplement simultaneously with food | With Supplements That Contain Ca or Fe
|
||
EVG/c, RAL | ↓ INSTI possible | If coadministration is necessary, administer INSTI at least 2 hours before or at least 6 hours after supplements that contain polyvalent cations, including but not limited to the following products: cation-containing laxatives; Fe, Ca, or Mg supplements; and sucralfate. Monitor for virologic response. Many oral multivitamins also contain varying amounts of polyvalent cations; the extent and significance of chelation is unknown. |
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Key to Symbols: ↑ = increase ↓ = decrease ↔ = no change Key: Al = aluminum; ALT = alanine aminotransferase; ART = antiretroviral therapy; ARV = antiretroviral; AST = aspartate aminotransferase; AUC = area under the curve; BIC = bictegravir; Ca = calcium; CAB = cabotegravir; CaCO3 = calcium carbonate; CCB = calcium channel blocker; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; COBI = cobicistat; CrCl = creatinine clearance; CYP = cytochrome P; DTG = dolutegravir; ECG = electrocardiogram; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; Fe = iron; FTC = emtricitabine; GI = gastrointestinal; IM = intramuscular; INR= international normalized ratio; INSTI = integrase strand transfer inhibitor; Mg = magnesium; PAH = pulmonary arterial hypertension; PDE5 = phosphodiesterase type 5; PO = orally; PTH = parathyroid hormone; QTc = QT corrected for heart rate; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SSRI = selective serotonin reuptake inhibitors; TAF = tenofovir alafenamide; TCA = tricyclic antidepressants; TDF = tenofovir disoproxil fumarate; Zn = zinc |