Table 2.
Summary of drug-drug interactions between INSTIs with selected coadministered drugs
| Coadminstered Drug | INSTI | Effect on INSTI or Coadministered Drug Concentrations |
|---|---|---|
| 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 |