Table 2 Summary of drug-drug interactions between INSTIs with selected coadministered drugs

Al, Mg, ± Ca-containing Antacids & Polyvalent Cation Supplements (Al, Ca, Fe, Mg, Zn, including multivitamins with minerals)

BIC

↓ BIC ⟷ BIC with food & Ca/Fe

CAB

↓ CAB

DTG

↓ DTG ⟷ DTG with food & Ca/Fe

EVG/c

↓ EVG/c

RAL

↓ RAL

Alpha Adrenergic Inhibitors (for Benign Prostatic Hyperplasia)

Alfuzosin

EVG/c

↑ alfuzosin

Tamsulosin

EVG/c

↑ tamsulosin

Silodosin

EVG/c

↑ silodosin

Anticoagulants & antiplatelets

Apixaban

EVG/c

↑ apixaban

Clopidogrel

EVG/c

↓ clopidogrel active metabolite, with impaired platelet inhibition expected

Dabigatran

EVG/c

↑ dabigatran

Edoxaban

EVG/c

↑ edoxaban

Prasugrel

EVG/c

↓ prasugrel active metabolite, with no impairement of platelet inhibition expected

Rivaroxaban

EVG/c

↑ rivaroxaban

Ticagrelor

EVG/c

↑ ticagrelor

Vorapaxar

EVG/c

↑ vorapaxar

Warfarin

EVG/c

↑ or ↓ warfarin

Anticonvulsants

Carbamazepine

BIC

↓ BIC

CAB

↓ CAB

DTG

↓ DTG

EVG/c

↑ carbamazepine, ↓ EVG & COBI

RAL

↓ or ⟷ RAL

Eslicarbazepine

All INSTIs

↓ INSTI, ↓ COBI

Ethosuximide

EVG/c

↑ ethosuximide

Lamotrigine

EVG/c

No data

Oxcarbazepine

BIC, DTG

↓ BIC, DTG

CAB

↓ CAB

EVG/c, RAL

↓ EVG/c, RAL

Phenobarbital, phenytoin

BIC

↓ BIC

CAB

↓ CAB

DTG

↓ DTG

EVG/c

↓ EVG/c

RAL

↓ OR ⟷ RAL

Valproic Acid

All INSTIs

No data

Antidepressants/ anxiolytics/ antipsychotics

Aripiprazole

EVG/c

↑ aripiprazole

Brexpiprazole

EVG/c

↑ brexpiprazole

Cariprazine

EVG/c

↑ cariprazine

Bupropion

EVG/c

↑ or ↓ bupropion

Buspirone

EVG/c

↑ buspirone

Fluvoxamine

EVG/c

↑ or ↓ EVG

Iloperidone

EVG/c

↑ iloperidone

Lumateperone

EVG/c

↑ lumateperone

Lurasidone

EVG/c

↑ lurasidone

Nefazodone

EVG/c

↑ nefazodone

Olanzapine

All INSTIs

⟷ olanzapine

Other antipsychotics (CYP3A4 and/or CYP2D6 substrates (e.g., perphenazine, risperidone, thioridazine)

EVG/c

↑ antipsychotic

Pimavanserin

EVG/c

↑ pimavanserin

Pimozide

EVG/c

↑ pimozide

Quetiapine

EVG/c

↑ quetiapine

SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)

BIC, CAB, DTG, RAL

⟷ SSRI

EVG/c

⟷ sertraline, ↑ other SSRI

TCAs (amitriptyline, desipramine, doxepin, imipramine, nortriptyline)

EVG/c

↑ TCAs

Trazodone

EVG/c

↑ trazodone

Ziprasidone

EVG/c

↑ ziprasidone

Antifungals

Isavuconazole

EVG/c

↑ isavuconazole ↑ or ↓ EVG & COBI

Itraconazole, Posaconazole, Voriconazole

EVG/c

↑ antifungal ↑ EVG & COBI

Antihyperglycemic drugs

Metformin

BIC

↑ metformin

DTG

↑ metformin

CAB PO and IM, RAL

⟷ metformin

Saxagliptan

EVG/c

↑ saxagliptan

Antibacterials

Azithromycin

All INSTIs

⟷ azithromycin

Clarithromycin

EVG/c

↑ clarithromycin, COBI

Erythromycin

EVG/c

↑ erythromycin, COBI

Rifabutin

BIC

↓ BIC

CAB

↓ CAB IM

DTG

⟷ DTG

EVG/c

↑ rifabutin active metabolites, ↓ EVG

RAL

↑ RAL

Rifampin

BIC

↓ BIC

CAB

↓ CAB

DTG

↓ DTG

EVG/c

↓ EVG & COBI

RAL

↓ RAL

Rifapentine

BIC

↓ BIC

CAB

↓ CAB

DTG

↓ DTG

EVG/c

↓ EVG & COBI

RAL

↑ or ↓ RAL

Cardiac medications

Amiodarone

EVG/c

↑ amiodarone

Beta-blockers (i.e., metoprolol, timolol, etc.)

EVG/c

↑ beta-blockers

Calcium channel blockers (CCBs)

EVG/c

↑ CCB

Dofetilide

BIC, DTG

↑ dofetilide

EVG/c

↑ dofetilide

Eplerenone

EVG/c

↑ eplerenone

Herbal products

St. John’s Wort

BIC, CAB, DTG

↓ BIC & DTG

EVG/c

↓ EVG & COBI

Hormonal therapies

Contraceptives: non-oral

BIC, CAB, DTG, RAL

Etonogestrel (subdermal implant) ↑ with DTG ⟷ BIC, CAB, RAL

Contraceptives: oral

BIC, CAB, DTG, RAL

⟷ ethinyl estradiol, norgestimate, ⟷ levonorgestrel with PO CAB

EVG/c

↑ norgestimate, drospirenone

↓ ethinyl estradiol

Gender-Affiriming Therapy

EVG/c

↑ estradiol, cyproterone, dutasteride, & finasteride ↑ testosterone

Menopausal Hormone Replacement Therapy

BIC, CAB, DTG, RAL

↓ estrogen from conjugated estrogen (equine or synthetic) or estradiol ⟷ drospirenone, medroxyprogesterone, or micronized progesterone

BIC, CAB, EVG/c

↓ or ↑ estrogen, ↑ drospirenone, PO medroxyprogesterone, PO micronized progesterone

Immunosuppressive drugs

Cyclosporine, everolimus, sirolimus, tacrolimus

EVG/c

↑ immunosuppressive therapy

Lipid-modifying agents

Atorvastatin

EVG/c

↑ atorvastatin

Lomitapide

EVG/c

↑ lomitapide

Lovastatin

EVG/c

↑ lovastatin

Pitavastatin, pravastatin

EVG/c

No data

Rosuvastatin

EVG/c

↑ rosuvastatin

Simvastatin

EVG/c

↑ simvastatin

Narcotics/ opioid dependence treatment

Buprenorphine (Sublingual, buccal, or implant)

EVG/c

↑ buprenorphine, norbuprenorphine

RAL

⟷ sublingual, implant

Fentanyl

EVG/c

↑ fentanyl

Lofexidine

EVG/c

↑ lofexidine

Methadone

BIC, CAB, DTG, EVG/c, RAL

No significant effect

Tramadol

EVG/c

↑ tramadol, ↓ M1 (active metabolite)

PDE-5 inhibitors

Avanafil

EVG/c

No data

Sildenafil

EVG/c

↑ sildenafil

Tadalafil

EVG/c

↑ tadalafil

Vardenafil

EVG/c

↑ vardenafil

Sedatives/hypnotics

Alprazolam, clonazepam, clorazepate, diazepam, estazolam, flurazepam

EVG/c

↑ benzodiazepines

Midazolam, triazolam

DTG

⟷ midazolam

EVG/c

↑ midazolam, triazolam

Suvorexant

EVG/c

↑ suvorexant

Zolpidem

EVG/c

↑ zolpidem