Delavirdine 400 mg three times a day 300 mg once a day HIV infected patients (7) ↑ AUC by 230%, ↑ C max by 128% ↓ AUC by 80%, ↓ C max by 75%, ↓ C min by 17% CONTRAINDICATED Didanosine 167 or 250 mg twice a day for 12 days 300 or 600 mg once a day for 12 days HIV infected patients (11) Dolutegravir 50 mg daily for 14 days 300 mg daily for 14 days Healthy adult subjects ND No significant change in dolutegravir pharmacokinetic s at steady state.
Source: FDA drug label - rifabutin
7.2 Riociguat Coadministration with fixed-dose abacavir/dolutegravir/lamivudine resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions [see Clinical Pharmacology (12.3) ].
Source: FDA drug label - abacavir
Riociguat Coadministration with fixed-dose abacavir/dolutegravir/lamivudine resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions [ see Clinical Pharmacology ( 12.3 ) ].
Source: FDA drug label - abacavir , lamivudine and zidovudine
7.3 Riociguat Coadministration with fixed-dose abacavir/dolutegravir/lamivudine resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - abacavir and lamivudine
7.2 Riociguat Coadministration with fixed-dose abacavir/dolutegravir/lamivudine resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - abacavir sulfate
( 4 , 7 , 12.3 ) 7.1 Effect of Dolutegravir on the Pharmacokinetics of Other Agents In vitro, dolutegravir inhibited the renal organic cation transporters (OCT)2 (IC 50 = 1.93 microM) and multidrug and toxin extrusion transporter (MATE)1 (IC 50 = 6.34 microM). In vivo, dolutegravir inhibits tubular secretion of creatinine by inhibiting OCT2 and potentially MATE1. Dolutegravir may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 (dofetilide, dalfampridine, and metformin) [see Contraindications ( 4 ), Drug Interactions ( 7.3 )] .
Source: FDA drug label - abacavir sulfate, dolutegravir sodium, lamivudine
( 7 ) Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine), may increase the accumulation of metformin. Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine Alcohol Clinical Impact: Alcohol is known to potentiate the effect of metformin on lactate metabolism.
Source: FDA drug label - alogliptin and metformin hydrochloride
Rilpivirine Based on drug interaction study results, the following drugs can be coadministered with rilpivirine (non-antiretrovirals and cabotegravir) or given after discontinuation of rilpivirine (antiretrovirals and non-antiretrovirals): acetaminophen, atorvastatin, cabotegravir, chlorzoxazone, dolutegravir, ethinyl estradiol, norethindrone, raltegravir, ritonavir-boosted atazanavir, ritonavir-boosted darunavir, sildenafil, tenofovir alafenamide, and tenofovir disoproxil fumarate [see Clinical Pharmacology ( 12.3 )] .
Source: FDA drug label - cabotegravir and rilpivirine
Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine Alcohol Clinical Impact: Alcohol is known to potentiate the effect of metformin HCl on lactate metabolism.
Source: FDA drug label - canagliflozin and metformin hydrochloride
Drugs that Reduce Metformin Clearance Clinical Impact Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE] inhibitors, such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology ( 12.3 )].
Source: FDA drug label - dapagliflozin and metformin hydrochloride
7.4 Drugs without Clinically Significant Interactions with Darunavir No dosage adjustments are recommended when darunavir/ritonavir is co-administered with the following medications: atazanavir, dolutegravir, efavirenz, etravirine, nevirapine, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), pitavastatin, raltegravir, ranitidine or rilpivirine.
Source: FDA drug label - darunavir
7.4 Drugs without Clinically Significant Interactions with Darunavir No dosage adjustments are recommended when darunavir/ritonavir is co-administered with the following medications: atazanavir, dolutegravir, efavirenz, etravirine, nevirapine, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), pitavastatin, raltegravir, ranitidine, or rilpivirine.
Source: FDA drug label - darunavir 600 mg
7.4 Drugs without Clinically Significant Interactions with PREZCOBIX Clinically relevant drug-drug interactions have not been observed or are not anticipated with concomitant use of darunavir and cobicistat with rilpivirine, dolutegravir, raltegravir, abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, tenofovir DF, lamivudine, stavudine, zidovudine, or acid modifying medications (antacids, H 2 -receptor antagonists, proton pump inhibitors).
Source: FDA drug label - darunavir ethanolate and cobicistat
( 4 , 7 ) • Drugs that are metabolic inducers may decrease the plasma concentrations of dolutegravir. ( 7.3 ) 7.1 Effect of Dolutegravir on the Pharmacokinetics of Other Agents In vitro, dolutegravir inhibited the renal organic cation transporters, OCT2 (IC 50 = 1.93 microM) and multidrug and toxin extrusion transporter (MATE) 1 (IC 50 = 6.34 microM). In vivo, dolutegravir inhibits tubular secretion of creatinine by inhibiting OCT2 and potentially MATE1.
Source: FDA drug label - dolutegravir sodium
7.2 Potential for DOVATO to Affect Other Drugs Dolutegravir, a component of DOVATO, inhibits the renal organic cation transporters (OCT)2 and multidrug and toxin extrusion transporter (MATE)1; thus, it may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 such as dofetilide, dalfampridine, and metformin [see Contraindications ( 4 ), Drug Interactions ( 7.4 ), Clinical Pharmacology ( 12.3 )]. 7.3 Potential for Other Drugs to Affect the Components of DOVATO Dolutegravir is metabolized by uridine diphosphate (UDP)-glucuronosyl transferase (UGT)1A1 with some contribution from cytochrome P450 (CYP)3A. Dolutegravir is also a substrate of UGT1A3, UGT1A9, breast cancer resistance protein (BCRP), and P-glycoprotein (P-gp) in vitro.
Source: FDA drug label - dolutegravir sodium and lamivudine
7.2 Potential for JULUCA to Affect Other Drugs Dolutegravir, a component of JULUCA, inhibits the renal organic cation transporters (OCT)2 and multidrug and toxin extrusion transporter (MATE)1, thus it may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 such as dofetilide, dalfampridine, and metformin [see Contraindications ( 4 ), Drug Interactions ( 7.4 )] . 7.3 Potential for Other Drugs to Affect the Components of JULUCA Dolutegravir Dolutegravir is metabolized by uridine diphosphate (UDP)-glucuronosyl transferase (UGT)1A1 with some contribution from cytochrome P450 (CYP)3A. Dolutegravir is also a substrate of UGT1A3, UGT1A9, breast cancer resistance protein (BCRP), and P-glycoprotein (P-gp) in vitro.
Source: FDA drug label - dolutegravir sodium and rilpivirine hydrochloride
No clinically significant changes in concentration were observed for doravirine when co-administered with the following agents: dolutegravir, TDF, lamivudine, elbasvir and grazoprevir, ledipasvir and sofosbuvir, ritonavir, ketoconazole, aluminum hydroxide/magnesium hydroxide/simethicone containing antacid, pantoprazole, and methadone [see Clinical Pharmacology (12.3) ]. 7.2 Effect of PIFELTRO on Other Drugs No clinically significant changes in concentration were observed for the following agents when co-administered with doravirine: dolutegravir, lamivudine, TDF, elbasvir and grazoprevir, ledipasvir and sofosbuvir, atorvastatin, an oral contraceptive containing ethinyl estradiol and levonorgestrel, metformin, methadone, and midazolam [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - doravirine
7.3 Drugs without Clinically Significant Interactions with ZEPATIER The interaction between the components of ZEPATIER (elbasvir or grazoprevir) or ZEPATIER and the following drugs were evaluated in clinical studies, and no dose adjustments are needed when ZEPATIER is used with the following drugs individually: acid reducing agents (proton pump inhibitors, H2 blockers, antacids), buprenorphine/naloxone, digoxin, dolutegravir, methadone, mycophenolate mofetil, oral contraceptive pills, phosphate binders, pitavastatin, pravastatin, prednisone, raltegravir, ribavirin, rilpivirine, tenofovir disoproxil fumarate, and sofosbuvir [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - elbasvir and grazoprevir
Drugs that Reduce Metformin Clearance Clinical Impact Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - empagliflozin and metformin hydrochloride
Drugs that Reduce Metformin Clearance Clinical Impact Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - empagliflozin, linagliptin, metformin hydrochloride
Drugs that Reduce Metformin Clearance Clinical Impact Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - empagliflozin, metformin hydrochloride
7.4 Drugs without Clinically Significant Interactions with DESCOVY Based on drug interaction studies conducted with the components of DESCOVY, no clinically significant drug interactions have been either observed or are expected when DESCOVY is combined with the following antiretroviral agents: atazanavir with ritonavir, atazanavir with cobicistat (in those weighing ≥35 kg), darunavir with ritonavir or cobicistat, dolutegravir, efavirenz, ledipasvir, lopinavir/ritonavir, maraviroc, nevirapine, raltegravir, rilpivirine, and sofosbuvir.
Source: FDA drug label - emtricitabine and tenofovir alafenamide
Drugs that Reduce Metformin Clearance Clinical Impact: The risk of lactic acidosis may increase due to concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) which increase systemic exposure to metformin Intervention Consider the benefits and risks of concomitant use.
Source: FDA drug label - ertugliflozin and metformin hydrochloride
Table 4: Significant Drug Interactions Concomitant Drug Class: Drug Name Effect on Concentration of Etravirine or Concomitant Drug Clinical Comment ↑ = increase; ↓ = decrease; ↔ = no change HIV-antiviral agents: integrase strand inhibitors dolutegravir The interaction between INTELENCE and the drug was evaluated in a clinical study. ↓ dolutegravir ↔ etravirine Etravirine significantly reduced plasma concentrations of dolutegravir. Using cross - study comparisons to historical pharmacokinetic data for etravirine, dolutegravir did not appear to affect the pharmacokinetics of etravirine.
Source: FDA drug label - etravirine
Drugs Metabolized by uridine 5'-diphospho--glucuronosyl transferase (UGT) Examples (not fully inclusive): Zidovudine, bictegravir, cabotegravir, dolutegravir, bexagliflozin, canagliflozin, sotagliflozin, deferasirox, lamotrigine, selexipag Clinical Impact Fexinidazole metabolites have the potential to be UGT inducers [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - fexinidazole
HIV integrase inhibitor: Dolutegravir a Fosamprenavir calcium /ritonavir: ↓Dolutegravir The recommended dose of dolutegravir is 50 mg twice daily when coadministered with Fosamprenavircalcium /ritonavir.
Source: FDA drug label - fosamprenavir calcium
7.5 Drugs with No Observed Clinically Significant Interactions with MAVYRET No dose adjustment is required when MAVYRET is coadministered with the following medications: abacavir, amlodipine, caffeine, dextromethorphan, dolutegravir, elvitegravir/ cobicistat, emtricitabine, ethinyl estradiol of 20 mcg or less, felodipine, lamivudine, lamotrigine, losartan, midazolam, norethindrone or other progestin-only contraceptives, omeprazole, raltegravir, rilpivirine, sofosbuvir, tacrolimus, tenofovir alafenamide, tenofovir disoproxil fumarate, tolbutamide, and valsartan.
Source: FDA drug label - glecaprevir and pibrentasvir
Drugs that reduce metformin clearance Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis.
Source: FDA drug label - glipizide and metformin hydrochloride
Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine. (7) • Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin.
Source: FDA drug label - glyburide and metformin hydrochloride
Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine. ( 7 ) • Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin.
Source: FDA drug label - glyburide-metformin hydrochloride
7.3 Drugs without Clinically Significant Interactions with HARVONI Based on drug interaction studies conducted with the components of HARVONI (ledipasvir or sofosbuvir) or HARVONI, no clinically significant drug interactions have been either observed or are expected when HARVONI is used with the following drugs [see Clinical Pharmacology (12.3) ]: abacavir, atazanavir/ritonavir, cyclosporine, darunavir/ritonavir, dolutegravir, efavirenz, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, emtricitabine, lamivudine, methadone, midazolam, oral contraceptives, pravastatin, raltegravir, rilpivirine, tacrolimus, or verapamil.
Source: FDA drug label - ledipasvir and sofosbuvir
Drugs that Reduce Metformin Clearance Clinical Impact Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology (12.3 )].
Source: FDA drug label - linagliptin and metformin hydrochloride
Consider more frequent monitoring ( 7 ) Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin.
Source: FDA drug label - metformin
Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine. Consider more frequent monitoring ( 7 ) • Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin.
Source: FDA drug label - metformin er 500 mg
Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine. Consider more frequent monitoring ( 7 ) Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin.
Source: FDA drug label - metformin hydrochloride
Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine. ( 7 ) Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin.
Source: FDA drug label - metformin hydrochloride extended-release tablets
Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine. Consider more frequent monitoring ( 7 ) Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin.
Source: FDA drug label - metformin hydrochloride tablets
( 7.3 ) Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine), may increase the accumulation of metformin. 7.4 Drugs that Reduce Metformin Clearance Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - pioglitazole and metformin hydrochloride
7.3 Drugs that Reduce Metformin Clearance Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2]/multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [ see Clinical Pharmacology (12.3) ].
Source: FDA drug label - saxagliptin and metformin hydrochloride
Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine. ( 7 ) Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin.
Source: FDA drug label - sitagliptin and metformin hydrochloride
7.4 Drugs without Clinically Significant Interactions with VOSEVI Based on drug interaction studies conducted with the components of VOSEVI (sofosbuvir, velpatasvir, and/or voxilaprevir) or VOSEVI, no clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir: methadone, tacrolimus
Source: FDA drug label - sofosbuvir, velpatasvir, and voxilaprevir
Dolutegravir ↓ Dolutegravir For dosage recommendations, refer to dolutegravir prescribing information.
Source: FDA drug label - tipranavir
7.4 Drugs without Clinically Significant Interactions with EPCLUSA Based on drug interaction studies conducted with the components of EPCLUSA (sofosbuvir or velpatasvir) or EPCLUSA, no clinically significant drug interactions have been observed or are expected with the following drugs [see Clinical Pharmacology (12.3) ]: EPCLUSA: atazanavir/ritonavir, buprenorphine/naloxone, cyclosporine, darunavir/ritonavir, dolutegravir, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, emtricitabine, methadone, naltrexone, raltegravir, or rilpivirine.
Source: FDA drug label - velpatasvir and sofosbuvir