Efavirenz

Hepatitis C antiviral agents Boceprevir ↓ boceprevir* Concomitant administration of boceprevir with efavirenz is not recommended because it may result in loss of therapeutic effect of boceprevir Elbasvir/Grazoprevir ↓ elbasvir ↓ grazoprevir Co-administration o efavirenz with elbasvir/grazoprevir is contraindicated [see Contraindications ( 4 )] because it may lead to loss of virologic response to elbasvir/grazoprevir.

Hepatitis C antiviral agents Boceprevir ↓ boceprevir* Concomitant administration of boceprevir with efavirenz is not recommended because it may result in loss of therapeutic effect of boceprevir Elbasvir/Grazoprevir ↓ elbasvir ↓ grazoprevir Co-administration o efavirenz with elbasvir/grazoprevir is contraindicated [see Contraindications ( 4 )] because it may lead to loss of virologic response to elbasvir/grazoprevir.

Co-administration with efavirenz is contraindicated as it is a strong CYP3A inducer that may decrease elbasvir and grazoprevir plasma concentrations, leading to reduced therapeutic effect.

Co-administration may cause significant decrease in plasma concentrations of etravirine and loss of therapeutic effect. Co-administration of etravirine and other NNRTIs is not recommended.

Hepatitis C antiviral agents Boceprevir ↓ boceprevir* Concomitant administration of boceprevir with efavirenz is not recommended because it may result in loss of therapeutic effect of boceprevir Elbasvir/Grazoprevir ↓ elbasvir ↓ grazoprevir Co-administration o efavirenz with elbasvir/grazoprevir is contraindicated [see Contraindications ( 4 )] because it may lead to loss of virologic response to elbasvir/grazoprevir.

Moderate CYP3A inducer that decreases lemborexant exposure, which may reduce DAYVIGO efficacy. Concomitant use should be avoided.

Avoid coadministration of efavirenz with posaconazole unless the benefit outweighs the risks.

CYP450 inducer significantly reduces or slightly decreases voriconazole plasma exposure. Requires dose adjustment if used together.

Efavirenz decreases atazanavir concentrations. Not recommended for treatment-experienced patients; specific dosing with ritonavir required for treatment-naïve patients.

Strong CYP3A inducer may decrease cobimetinib exposure by >80% and reduce efficacy. Avoid concurrent use.

Strong CYP3A4 inducer may reduce deflazacort efficacy. Avoid concomitant use.

Co-administration decreases doravirine plasma concentrations. Use with efavirenz is not recommended.

May significantly decrease plasma concentrations of glecaprevir and pibrentasvir, leading to reduced therapeutic effect. Coadministration is not recommended.

CYP3A4 inducer that significantly decreases guanfacine plasma concentrations and exposure. Guanfacine dose increase up to double the target dosage may be needed.

Efavirenz decreases indinavir concentrations. Optimal dosing not established; dose increase to 1000 mg every 8 hours does not adequately compensate for increased metabolism.

Potent CYP3A4 enzyme inducer that may decrease itraconazole bioavailability and efficacy. Avoid use 2 weeks before and during itraconazole treatment.

Potent CYP3A4 enzyme inducer that may decrease ketoconazole bioavailability and reduce antifungal efficacy. Coadministration not recommended.

Moderate CYP3A4 inducer decreases lurasidone exposure. Lurasidone dose should be increased.

Strong CYP3A4 inducer may reduce plasma macimorelin concentrations and lead to false positive test results. Discontinue prior to use.

Moderate CYP3A inducer may decrease medroxyprogesterone acetate concentrations and reduce contraceptive efficacy. Avoid concomitant use or use backup contraception.

Avoid coadministration unless benefit outweighs risks. Efavirenz may decrease posaconazole plasma concentrations.

Moderate CYP3A4 inducer that decreases pretomanid plasma concentrations. Co-administration should be avoided.

Concomitant use should be avoided. Rifampin decreases efavirenz AUC by 26%.

One HIV-positive patient experienced asymptomatic elevations of ALT, AST, GGT (>5.0 × ULN) and serum bilirubin (>ULN to 1.5 × ULN) at Week 4. Reaction resolved after changing antiretroviral regimen to exclude efavirenz.

Moderate CYP3A4/5 inducer may reduce axitinib plasma exposure and should be avoided if possible.

CYP2B6 inducer that decreases bupropion exposure; dose increase may be necessary but should not exceed maximum recommended dose.

Dose increase may be necessary as concomitant treatment decreases bupropion and hydroxybupropion exposure.

CYP2B6 inducer that decreases bupropion and hydroxybupropion exposure. Dosage increase of bupropion may be necessary but should not exceed maximum recommended dose.

CYP2B6 inducer that can decrease bupropion and hydroxybupropion exposure. Dose increase of bupropion may be necessary but should not exceed maximum recommended dose.

CYP2B6 inducer that may decrease bupropion and hydroxybupropion exposure. Dose increase may be necessary but should not exceed maximum recommended dose.

Efavirenz is a hepatic CYP enzyme inducer expected to reduce caspofungin acetate plasma concentrations. Increased caspofungin dosing should be considered.

May decrease systemic concentrations of hormonal contraceptives and diminish effectiveness or increase breakthrough bleeding.

CYP3A4 inducer that may reduce plasma concentrations of estrogens, possibly decreasing therapeutic effects and altering uterine bleeding profile.

May decrease plasma concentrations of etonogestrel and diminish contraceptive effectiveness or increase breakthrough bleeding.

Fexinidazole induces CYP2B6, decreasing efavirenz plasma concentrations and efficacy.

Efavirenz decreases amprenavir concentrations. Appropriate doses of unboosted combination not established; additional ritonavir required with fosamprenavir/ritonavir once daily.

Moderate CYP3A4 inducer that significantly decreases guanfacine plasma concentrations. Consider dose increase.

CYP3A4 inducer may decrease serum hydrocortisone concentrations and increase risk of adrenal crisis; may require dose increase.

Efavirenz, a non-nucleoside reverse transcriptase inhibitor, may significantly decrease plasma concentrations of estrogen and/or progestin.

Non-nucleoside reverse transcriptase inhibitor that may decrease plasma concentrations of estrogen and/or progestin.

Metabolic enzyme inducer that may decrease plasma concentrations of levonorgestrel and ethinyl estradiol, potentially diminishing contraceptive effectiveness or increasing breakthrough bleeding.

Efavirenz decreases lopinavir concentrations. Once daily dosing not recommended when coadministered.

CYP3A inducer that may decrease maraviroc concentration; dosage adjustment may be required.

Mifepristone should be used with caution with efavirenz; metabolized by CYP2B6.

CYP2B6 inducer that may reduce CONTRAVE efficacy by reducing bupropion exposure. Avoid concomitant use.

May decrease systemic concentrations of norethindrone and potentially diminish contraceptive effectiveness or increase breakthrough bleeding.

Induces CYP3A activity, increasing efavirenz clearance and lowering plasma concentrations.

Moderate CYP 3A inducer that decreases praziquantel AUC and Cmax. Should be avoided unless benefit outweighs risks.

Induces CYP3A activity, increasing efavirenz clearance and lowering plasma concentrations.

Additional ritonavir dosing may be required when coadministered with efavirenz and certain protease inhibitors.

Metabolic enzyme inducer that may decrease systemic concentrations of estrogen and/or progestin, potentially diminishing contraceptive effectiveness.

Velpatasvir/ Sofosbuvir ↓ velpatasvir Coadministration of efavirenz and sofosbuvir/velpatasvir is not recommended because it may result in loss of therapeutic effect of sofosbuvir/velpatasvir. Velpatasvir /Sofosbuvir/ Voxilaprevir ↓ velpatasvir ↓ voxilaprevir Coadministration of efavirenz and sofosbuvir/velpatasvir/voxilaprevir is not recommended because it may result in loss of therapeutic effect of sofosbuvir/velpatasvir/voxilaprevir Other agents Anticoagulant:Warfarin ↑ or ↓ warfarin Monitor international normalised ratio (INR) and adjust warfarin dosage if necessary.

Telotristat ethyl may decrease the efficacy of efavirenz by decreasing its systemic exposure. Monitor patient response and consider increasing efavirenz dosage if necessary.

Velpatasvir/ Sofosbuvir ↓ velpatasvir Coadministration of efavirenz and sofosbuvir/velpatasvir is not recommended because it may result in loss of therapeutic effect of sofosbuvir/velpatasvir. Velpatasvir /Sofosbuvir/ Voxilaprevir ↓ velpatasvir ↓ voxilaprevir Coadministration of efavirenz and sofosbuvir/velpatasvir/voxilaprevir is not recommended because it may result in loss of therapeutic effect of sofosbuvir/velpatasvir/voxilaprevir Other agents Anticoagulant:Warfarin ↑ or ↓ warfarin Monitor international normalised ratio (INR) and adjust warfarin dosage if necessary.

Velpatasvir /Sofosbuvir/ Voxilaprevir ↓ velpatasvir ↓ voxilaprevir Coadministration of efavirenz and sofosbuvir/velpatasvir/voxilaprevir is not recommended because it may result in loss of therapeutic effect of sofosbuvir/velpatasvir/voxilaprevir Other agents Anticoagulant:Warfarin ↑ or ↓ warfarin Monitor international normalised ratio (INR) and adjust warfarin dosage if necessary.

Azithromycin had a modest effect on efavirenz pharmacokinetics; efavirenz had modest effect on azithromycin. No dosage adjustment recommended.

7.5 Drugs Without Clinically Significant Interactions with Efavirenz No dosage adjustment is recommended when efavirenz is given with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, lorazepam, nelfinavir, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), paroxetine, and raltegravir.

This table includes potentially significant interactions, but is not all inclusive Table 5: Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction Concomitant Drug Class: Drug Name Effect Clinical Comment HIV antiviral agents Protease inhibitor: Fosamprenavir calcium ↓ amprenavir Fosamprenavir (unboosted): Appropriate doses of the combinations with respect to safety and efficacy have not been established. Fosamprenavir/ritonavir: An additional 100 mg/day (300 mg total) of ritonavir is recommended when efavirenz tablets are administered with fosamprenavir/ritonavir once daily. No change in the ritonavir dose is required when efavirenz tablets are administered with fosamprenavir plus ritonavir twice daily.

HMG-CoA reductase inhibitors: Atorvastatin Pravastatin Simvastatin ↓ atorvastatin * ↓ pravastatin * ↓ simvastatin * Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased.

Anti-infective: Clarithromycin ↓ clarithromycin * ↑ 14-OH metabolite * Consider alternatives to macrolide antibiotics because of the risk of QT interval prolongation.

Others (e.g., felodipine, nicardipine, nifedipine, verapamil) ↓ calcium channel blocker When co-administered with efavirenz, dosage adjustment of calcium channels blocker may be needed and should be guided by clinical response (refer to the full prescribing information for the calcium channel blocker).

7.5 Drugs Without Clinically Significant Interactions with Efavirenz No dosage adjustment is recommended when efavirenz is given with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, lorazepam, nelfinavir, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), paroxetine, and raltegravir.

This table includes potentially significant interactions, but is not all inclusive Table 5: Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction Concomitant Drug Class: Drug Name Effect Clinical Comment HIV antiviral agents Protease inhibitor: Fosamprenavir calcium ↓ amprenavir Fosamprenavir (unboosted): Appropriate doses of the combinations with respect to safety and efficacy have not been established. Fosamprenavir/ritonavir: An additional 100 mg/day (300 mg total) of ritonavir is recommended when efavirenz tablets are administered with fosamprenavir/ritonavir once daily. No change in the ritonavir dose is required when efavirenz tablets are administered with fosamprenavir plus ritonavir twice daily.

Pibrentasvir/Glecaprevir ↓ pibrentasvir Co-administration of efavirenz is not recommended because it may lead to reduced therapeutic effect of pibrentasvir/glecaprevir Simeprevir ↓simeprevir* ↔efavirenz* Concomitant administration of simeprevir with efavirenz is not recommended because it may result in loss oftherapeutic effect of simeprevir.

Protease inhibitor: Lopinavir/ritonavir ↓ lopinavir * Lopinavir/ritonavir once daily dosing is not recommended when co-administered with efavirenz. The dose of lopinavir/ritonavir must be increased when co-administered with efavirenz. See the lopinavir/ritonavir prescribing information for dose adjustments of lopinavir/ritonavir when co-administered with efavirenz in adult and pediatric patients.

7.5 Drugs Without Clinically Significant Interactions with Efavirenz No dosage adjustment is recommended when efavirenz is given with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, lorazepam, nelfinavir, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), paroxetine, and raltegravir.

7.5 Drugs Without Clinically Significant Interactions with Efavirenz No dosage adjustment is recommended when efavirenz is given with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, lorazepam, nelfinavir, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), paroxetine, and raltegravir.

Nevirapine decreases efavirenz concentrations. No appropriate doses established for safe and effective use of this combination.

Others (e.g., felodipine, nicardipine, nifedipine, verapamil) ↓ calcium channel blocker When co-administered with efavirenz, dosage adjustment of calcium channels blocker may be needed and should be guided by clinical response (refer to the full prescribing information for the calcium channel blocker).

Others (e.g., felodipine, nicardipine, nifedipine, verapamil) ↓ calcium channel blocker When co-administered with efavirenz, dosage adjustment of calcium channels blocker may be needed and should be guided by clinical response (refer to the full prescribing information for the calcium channel blocker).

Pibrentasvir/Glecaprevir ↓ pibrentasvir Co-administration of efavirenz is not recommended because it may lead to reduced therapeutic effect of pibrentasvir/glecaprevir Simeprevir ↓simeprevir* ↔efavirenz* Concomitant administration of simeprevir with efavirenz is not recommended because it may result in loss oftherapeutic effect of simeprevir.

HMG-CoA reductase inhibitors: Atorvastatin Pravastatin Simvastatin ↓ atorvastatin * ↓ pravastatin * ↓ simvastatin * Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased.

7.5 Drugs Without Clinically Significant Interactions with Efavirenz No dosage adjustment is recommended when efavirenz is given with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, lorazepam, nelfinavir, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), paroxetine, and raltegravir.

Protease inhibitor: Saquinavir ↓ saquinavir * Appropriate doses of the combination of efavirenz and saquinavir/ritonavir with respect to safety and efficacy have not been established.

Pibrentasvir/Glecaprevir ↓ pibrentasvir Co-administration of efavirenz is not recommended because it may lead to reduced therapeutic effect of pibrentasvir/glecaprevir Simeprevir ↓simeprevir* ↔efavirenz* Concomitant administration of simeprevir with efavirenz is not recommended because it may result in loss oftherapeutic effect of simeprevir.

HMG-CoA reductase inhibitors: Atorvastatin Pravastatin Simvastatin ↓ atorvastatin * ↓ pravastatin * ↓ simvastatin * Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased.

7.5 Drugs Without Clinically Significant Interactions with Efavirenz No dosage adjustment is recommended when efavirenz is given with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, lorazepam, nelfinavir, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), paroxetine, and raltegravir.