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Efavirenz, emtricitabine, and tenofovir disoproxil fumarate: Drug information

Efavirenz, emtricitabine, and tenofovir disoproxil fumarate: Drug information
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ALERT: US Boxed Warning
Posttreatment acute exacerbation of hepatitis B:

Severe, acute exacerbations of hepatitis B virus (HBV) have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued products containing emtricitabine and/or tenofovir disoproxil fumarate. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue efavirenz/emtricitabine/tenofovir disoproxil fumarate. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Brand Names: Canada
  • APO-Efavir-Emtricitab-Tenofo;
  • Atripla [DSC];
  • AURO-Efav-Emtri-Tenof;
  • JAMP-Efavirenz/Emtricit/Tenofo;
  • MYLAN-Efavir/Emtricitab/Tenofo;
  • PMS-Efav-Emtri-Tenofovir;
  • RIVA-Efavirenz/Emtricit/Tenofo;
  • SANDOZ Efavirenz/Emtri/Tenofov [DSC];
  • TEVA-Efavir/Emtricitab/Tenofov
Pharmacologic Category
  • Antiretroviral, Reverse Transcriptase Inhibitor, Non-nucleoside (Anti-HIV);
  • Antiretroviral, Reverse Transcriptase Inhibitor, Nucleoside (Anti-HIV);
  • Antiretroviral, Reverse Transcriptase Inhibitor, Nucleotide (Anti-HIV)
Dosing: Adult
HIV-1 infection, treatment

HIV-1 infection, treatment: Oral: One tablet (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥ 50 mL/minute: No dosage adjustment necessary.

CrCl <50 mL/minute: Not recommended.

Dosing: Liver Impairment: Adult

Mild hepatic impairment (Child-Pugh class A): No dosage adjustment necessary; use with caution.

Moderate or severe hepatic impairment (Child-Pugh class B, C): Not recommended.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Efavirenz, emtricitabine, and tenofovir disoproxil fumarate: Pediatric drug information")

Note: International Considerations: Doses are expressed as tenofovir disoproxil fumarate salt, consistent with US and Canadian labeling; in some other countries, dosing may be expressed as tenofovir disoproxil base. Tenofovir disoproxil fumarate 300 mg is equivalent to tenofovir disoproxil base 245 mg.

HIV-1 infection, treatment

HIV-1 infection, treatment:

Note: The use of efavirenz is not recommended in patients 3 months to <3 years (Ref). May be used alone or in combination with other antiretroviral (ARV) agents; gene mutation and ARV resistance patterns should be evaluated (refer to https://www.iasusa.org for more information) when necessary.

Children and Adolescents weighing ≥40 kg: Oral: One tablet (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg per tablet) once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Children and Adolescents weighing ≥40 kg:

CrCl ≥50 mL/minute: No dosage adjustment necessary.

CrCl <50 mL/minute: Use not recommended.

Dosing: Liver Impairment: Pediatric

Children and Adolescents weighing ≥40 kg:

Baseline hepatic impairment:

Mild hepatic impairment: No dosage adjustment is necessary; monitor closely.

Moderate to severe hepatic impairment: Not recommended.

Hepatotoxicity during therapy:

Serum transaminases >5 times ULN: Consider discontinuing therapy.

Serum transaminase elevation AND clinical signs or symptoms of hepatitis or hepatic decompensation: Discontinue therapy.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults administered efavirenz plus emtricitabine in combination with tenofovir disoproxil fumarate. Also see individual agents.

>10%: Endocrine & metabolic: Hypercholesterolemia (22%)

1% to 10%:

Cardiovascular: Increased serum creatine kinase (9%)

Dermatologic: Skin rash (7%)

Endocrine & metabolic: Hyperglycemia (2%), increased serum triglycerides (4%)

Gastrointestinal: Diarrhea (9%), increased serum amylase (8%), nausea (9%), vomiting (2%)

Genitourinary: Hematuria (3%)

Hematologic & oncologic: Decreased neutrophils (3%)

Hepatic: Increased serum alanine aminotransferase (2%), increased serum alkaline phosphatase (1%), increased serum aspartate aminotransferase (3%)

Nervous system: Anxiety (5%), depression (9%), dizziness (8%), fatigue (9%), headache (6%), insomnia (5%)

Respiratory: Nasopharyngitis (5%), sinusitis (8%), upper respiratory tract infection (8%)

<1%: Genitourinary: Glycosuria

Frequency not defined: Nervous system: Abnormal dreams

Postmarketing: Renal: Membranous glomerulonephritis (Rawala 2019)

Contraindications

Clinically significant hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, toxic skin reactions) to efavirenz, emtricitabine, tenofovir disoproxil fumarate or any component of the formulation; coadministration with voriconazole or elbasvir/grazoprevir.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with astemizole (not marketed in Canada), bepridil (not marketed in Canada), cisapride (not marketed in Canada), ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), midazolam, pimozide, St. John's wort, terfenadine (not marketed in Canada), or triazolam.

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: CNS symptoms (eg, insomnia, abnormal dreams, hallucinations) have been reported with efavirenz; symptoms usually start during first 1 to 2 days of treatment and generally resolve after 2 to 4 weeks; administration at bedtime may improve tolerability of CNS symptoms. May also cause CNS depression (eg, impaired concentration, dizziness, drowsiness); avoid potentially hazardous tasks such as driving or operating machinery. Late-onset neurotoxicity, including ataxia and encephalopathy, may occur months to years after initiation of efavirenz therapy. Some of these events have been reported in patients with CYP2B6 genetic polymorphisms (associated with increase efavirenz levels at standard doses). Promptly assess patients with signs and symptoms of serious neurologic adverse effects and consider discontinuation of therapy.

• Decreased bone mineral density: In clinical trials, tenofovir disoproxil fumarate has been associated with decreases in bone mineral density in adults with HIV and increases in bone metabolism markers. Serum parathyroid hormone and 1,25 vitamin D levels were also higher. Decreases in bone mineral density have also been observed in clinical trials of pediatric patients with HIV. Observations in chronic hepatitis B infected pediatric patients (12 to <18 years of age) were similar. In all pediatric clinical trials, skeletal growth (height) appears unaffected. Consider monitoring of bone density in adult and pediatric patients with a history of pathologic fractures or with other risk factors for bone loss or osteoporosis. Consider calcium and vitamin D supplementation for all patients; effect of supplementation has not been studied but may be beneficial. Long-term bone health and fracture risk unknown. If abnormalities are suspected, expert assessment is recommended.

• Fat redistribution: May cause redistribution/accumulation of body fat (eg, central obesity, dorsocervical fat enlargement [buffalo hump], peripheral wasting, facial wasting, breast enlargement, cushingoid appearance).

• Hepatotoxicity: Hepatitis, including fulminant hepatitis sometimes fatal or progressing to hepatic failure requiring transplantation, has been reported, including patients with no preexisting hepatic disease or other identifiable risk factors. Monitor liver function tests at baseline and during treatment in all patients. Consider discontinuation in patients who have persistent elevations of serum transaminases >5 times ULN; discontinue if signs or symptoms of hepatitis or hepatic decompensation occur with serum transaminase elevation.

• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) later in therapy; further evaluation and treatment may be required.

• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with use of nucleoside analogs, alone or in combination with other antiretrovirals. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (marked transaminase elevation may/may not accompany hepatomegaly and steatosis).

• Osteomalacia and renal dysfunction: Tenofovir disoproxil fumarate may cause osteomalacia with proximal renal tubulopathy. Bone pain, extremity pain, fractures, arthralgias, weakness, and muscle pain have been reported. In patients at risk for renal dysfunction, persistent or worsening bone or muscle symptoms should be evaluated for hypophosphatemia and osteomalacia.

• Psychiatric effects: Serious psychiatric symptoms have been associated with efavirenz, including severe depression, suicide attempts and ideation, paranoia, aggression, and mania. Use with caution in patients with a history of mental illness/drug abuse.

• QT prolongation: QT prolongation has been reported with efavirenz; consider alternative therapy in patients at risk of torsades de pointes or when coadministered with medications with known risk of torsades de pointes.

• Rash: Rash, ranging from mild to moderate maculopapular skin eruptions to life-threatening cutaneous reactions (eg, Stevens-Johnson syndrome), may occur with efavirenz. Mild to moderate rashes occur within 2 weeks (median onset: 11 days) and resolve within 1 month in patients continuing treatment. Treatment may be reinitiated in patients interrupting therapy for mild to moderate rashes; discontinue use and consider alternative therapy if severe rash associated with blistering, desquamation, mucosal involvement, or fever develops. Pediatric patients are more susceptible to development of rash (median time to onset: 28 days); prophylactic antihistamines should be considered.

• Renal toxicity: Tenofovir disoproxil fumarate may cause renal toxicity (acute renal failure and/or Fanconi syndrome); avoid use with concurrent or recent nephrotoxic therapy (including high-dose or multiple nonsteroidal anti-inflammatory drug [NSAID] use). Acute renal failure has occurred in HIV-infected patients with risk factors for renal impairment who were on a stable tenofovir disoproxil fumarate regimen to which a high dose or multiple NSAID therapy was added. Consider alternatives to NSAIDs in patients taking tenofovir and at risk for renal impairment. Prior to initiation of therapy and as clinically appropriate during therapy, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. IDSA guidelines recommend discontinuing tenofovir disoproxil fumarate (and substituting with alternative antiretroviral therapy) in patients with HIV who develop a decline in GFR (a >25% decrease in GFR from baseline and to a level of <60 mL/minute/1.73 m2) during use, particularly in presence of proximal tubular dysfunction (eg, euglycemic glycosuria, increased urinary phosphorus excretion and hypophosphatemia, proteinuria [new onset or worsening]) (IDSA [Lucas 2014]). Discontinue if evidence of Fanconi syndrome occurs.

Disease-related concerns:

• Hepatic impairment: Not recommended in patients with moderate or severe hepatic impairment (Child-Pugh class B, C). Use caution in patients with mild hepatic impairment (Child-Pugh class A). Monitor liver function tests before and during treatment.

• HIV-associated dementia: Avoid efavirenz based regimens if possible in patients with HIV-associated dementia; neuropsychiatric side effects of efavirenz may hinder assessment of the effects of antiretrovirals on the improvement of symptoms associated with HIV-associated dementia (HHS [adult] 2023).

• Renal impairment: Use is not recommended in patients with CrCl <50 mL/minute.

• Seizure disorder: Use efavirenz with caution in patients with a history of seizure disorder; seizures have been associated with use.

Warnings: Additional Pediatric Considerations

Efavirenz may cause a rash, which usually presents as mild to moderate pruritic maculopapular skin eruptions but typically does not require discontinuation. Rash is reported more frequently in pediatric patients compared to adults, and may be more severe (incidence: Adults 26% to 27%, pediatric patients 32% to 40%; grade 3 or 4: Adults 0.9%, pediatric patients 3%) and take longer to appear (median onset: Adults: 11 days; pediatric patients: 28 days [range: 3 to 1,642 days]). Rash may be treated with antihistamines and corticosteroids and usually resolves within 1 month while continuing therapy. Discontinue if severe rash (involving blistering, desquamation, mucosal involvement, or fever) occurs. Consider prophylaxis with antihistamines in children due to frequency and severity of rash reported in children.

Neuropsychiatric effects due to efavirenz may also occur in pediatric patients. The overall reported incidence of CNS adverse effects was 53% (all patients) versus 25% in controls; incidence of neuropsychiatric symptoms in children receiving efavirenz was reported to be 14% in clinical studies and increased to 30% with efavirenz serum concentrations >4 mcg/mL (Puthanakit 2009; Shubber 2013). CNS adverse effects may be more difficult to detect in children because of the challenges assessing neurologic symptoms, such as impaired concentration, sleep disturbances, or behavior disorders, in these patients. Consider evaluation of efavirenz serum concentrations if CNS/neuropsychiatric adverse effects are persistent or severe; may require drug substitution if a suitable alternative exists. Alternatively, consider dose reduction with monitoring of trough concentration and dose adjustment. One study reported an 11% incidence of new-onset seizures in children <36 months of age (HHS [pediatric] 2022).

Emtricitabine-associated hyperpigmentation may occur at a higher frequency in pediatric patients (32%) compared to adults.

Tenofovir disoproxil fumarate (TDF) disrupts vitamin D metabolism and has been associated with decreased bone mineral density (BMD) in adults and children. Plasma concentrations of the TDF metabolite tenofovir (TFV) have been associated with endocrine disruption and low BMD; tenofovir alafenamide (TAF) is associated with lower TFV concentrations and less decline in BMD than TDF. Data suggest the impact of treatment with TDF on BMD may be greater in children who are less mature (eg, sexual maturity ratings [SMRs] 1 to 2 [previously Tanner stages]) than in those with more advanced pubertal development (SMR ≥3). The potential for BMD loss during the important period of rapid bone accrual in childhood and early adolescence is concerning and favors use of abacavir or TAF in children with SMRs 1 to 3 (children with perinatally acquired HIV are already at risk for low peak bone mass). Prior to initiation of therapy, assessment of benefits versus potential risk should be assessed; with TDF therapy, monitor plasma vitamin D concentrations; supplement with vitamin D as needed; calcium carbonate supplementation may also be considered. Monitoring of BMD may be considered in patients with additional risk factors for decreased bone density (HHS [pediatric] 2022).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Efavirenz-Emtricitab-Tenofo DF Oral)

600-200-300 mg (per each): $10.08 - $113.80

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Atripla: efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg [DSC]

Generic: efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg

Administration: Adult

Administer on an empty stomach; dosing at bedtime may improve tolerability of CNS symptoms.

Administration: Pediatric

Oral: Administer at bedtime to improve tolerability of CNS adverse effects. Administer with water on an empty stomach; administration with food (particularly with high fat content) increases absorption and is associated with increased neuropsychiatric adverse effects (Ref).

Use: Labeled Indications

HIV-1 infection, treatment: Treatment of HIV-1 infection in adults and pediatric patients weighing ≥40 kg; may be used alone or in combination with other antiretroviral agents.

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Abemaciclib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Abemaciclib. Risk X: Avoid

Abiraterone Acetate: CYP3A4 Inducers (Moderate) may decrease serum concentration of Abiraterone Acetate. Risk C: Monitor

Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Acalabrutinib. Risk C: Monitor

Acoramidis: UGT1A1 Inducers may decrease serum concentration of Acoramidis. Risk X: Avoid

Acyclovir-Valacyclovir: May increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Acyclovir-Valacyclovir. Risk C: Monitor

Adefovir: May decrease therapeutic effects of Tenofovir Products. Adefovir may increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Adefovir. Risk X: Avoid

Alcohol (Ethyl): Efavirenz may increase adverse/toxic effects of Alcohol (Ethyl). Specifically, the risk for central nervous system toxicities and hepatotoxicity may be increased. Efavirenz may decrease serum concentration of Alcohol (Ethyl). Risk C: Monitor

ALfentanil: CYP3A4 Inducers (Moderate) may decrease serum concentration of ALfentanil. Management: If concomitant use of alfentanil and moderate CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider Therapy Modification

Alpelisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Alpelisib. Risk C: Monitor

ALPRAZolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of ALPRAZolam. Risk C: Monitor

Aminoglycosides: May increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Aminoglycosides. Risk C: Monitor

Aminosalicylic Acid: May decrease serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor

AmLODIPine: CYP3A4 Inducers (Moderate) may decrease serum concentration of AmLODIPine. Risk C: Monitor

Amodiaquine: Efavirenz may increase hepatotoxic effects of Amodiaquine. Efavirenz may increase serum concentration of Amodiaquine. Management: Avoid concurrent use of amodiaquine and efavirenz if possible. If such combination is unavoidable in the pursuit of prompt therapy, monitor closely for patient response and hepatotoxicity. Risk D: Consider Therapy Modification

Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease serum concentration of Antihepaciviral Combination Products. Risk X: Avoid

Apremilast: CYP3A4 Inducers (Moderate) may decrease serum concentration of Apremilast. Risk C: Monitor

Aprepitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Aprepitant. Risk C: Monitor

ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor

ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of ARIPiprazole. Risk C: Monitor

Artemether and Lumefantrine: Efavirenz may decrease serum concentration of Artemether and Lumefantrine. Efavirenz may decrease active metabolite exposure of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. Risk C: Monitor

Asciminib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Atazanavir: Efavirenz may decrease serum concentration of Atazanavir. Management: Only use boosted atazanavir (400 mg daily) with efavirenz in treatment-naive patients. Do not use lower doses of atazanavir, un-boosted atazanavir, or use in treatment-experienced patients. Risk D: Consider Therapy Modification

Atazanavir: Tenofovir Disoproxil Fumarate may decrease serum concentration of Atazanavir. Atazanavir may increase serum concentration of Tenofovir Disoproxil Fumarate. Management: Use boosted atazanavir in adults; give combo (atazanavir/ritonavir or atazanavir/cobicistat with tenofovir) as a single daily dose with food. Pediatric patients, pregnant patients, and use of H2-blockers require dose changes. See Lexi Interact monograph. Risk D: Consider Therapy Modification

Atidarsagene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Atidarsagene Autotemcel. Risk X: Avoid

Atogepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider Therapy Modification

Atorvastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atorvastatin. Risk C: Monitor

Atovaquone: Efavirenz may decrease serum concentration of Atovaquone. Management: Consider alternatives to the use of atovaquone with efavirenz when possible. If this combination must be used, monitor for evidence of reduced atovaquone clinical effectiveness. Risk D: Consider Therapy Modification

Atrasentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atrasentan. Risk X: Avoid

Avacopan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avacopan. Risk X: Avoid

Avanafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avanafil. Risk X: Avoid

Avapritinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avapritinib. Risk X: Avoid

Axitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Axitinib. Management: Concurrent use of axitinib with a moderate CYP3A4 inducer should be avoided when possible. If any such combination is necessary, monitor for reduced axitinib efficacy. Risk D: Consider Therapy Modification

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bedaquiline. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Bedaquiline. Risk X: Avoid

Belumosudil: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid coadministration of belumosudil with these substrates of BCRP for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the BCRP substrate may be required. Risk D: Consider Therapy Modification

Benzhydrocodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor

Betibeglogene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Betibeglogene Autotemcel. Risk X: Avoid

Bictegravir: UGT1A1 Inducers may decrease serum concentration of Bictegravir. Risk C: Monitor

Bortezomib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bortezomib. Risk C: Monitor

Bosutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bosutinib. Risk C: Monitor

Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of Brexpiprazole. Risk C: Monitor

Brigatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inducers when possible. If combined, increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose, up to maximum of twice the dose. Risk D: Consider Therapy Modification

Buprenorphine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Buprenorphine. Risk C: Monitor

BuPROPion: CYP2B6 Inducers (Moderate) may decrease serum concentration of BuPROPion. Risk C: Monitor

BusPIRone: CYP3A4 Inducers (Moderate) may decrease serum concentration of BusPIRone. Risk C: Monitor

Cabotegravir: UGT1A1 Inducers may decrease serum concentration of Cabotegravir. Risk X: Avoid

Cabozantinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cabozantinib. Management: For cabozantinib tablets (Cabometyx), avoid combined use if possible. If combined, increase cabozantinib by 20 mg from previous dose, max 80 mg daily. For cabozantinib capsules (Cometriq), monitor for reduced cabozantinib efficacy if combined. Risk D: Consider Therapy Modification

Calcifediol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Calcifediol. Risk C: Monitor

Calcitriol (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Calcitriol (Systemic). Risk C: Monitor

Cannabis: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor

Capivasertib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Capivasertib. Risk X: Avoid

Capmatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Capmatinib. Risk X: Avoid

CarBAMazepine: May decrease serum concentration of Efavirenz. Efavirenz may decrease serum concentration of CarBAMazepine. Risk X: Avoid

Cariprazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cariprazine. Risk X: Avoid

Caspofungin: Inducers of Drug Clearance may decrease serum concentration of Caspofungin. Management: Consider using an increased caspofungin dose of 70 mg daily in adults (or 70 mg/m2, up to a maximum of 70 mg, daily in pediatric patients) when coadministered with known inducers of drug clearance. Risk D: Consider Therapy Modification

Ceritinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ceritinib. Risk C: Monitor

Cidofovir: May increase serum concentration of Tenofovir Products. Tenofovir Products may increase serum concentration of Cidofovir. Risk C: Monitor

Cladribine: Agents that Undergo Intracellular Phosphorylation may decrease therapeutic effects of Cladribine. Risk X: Avoid

Clarithromycin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Clarithromycin. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A4 inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and impair its efficacy. Risk D: Consider Therapy Modification

Clindamycin (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Clindamycin (Systemic). Risk C: Monitor

CloZAPine: CYP3A4 Inducers (Moderate) may decrease serum concentration of CloZAPine. Risk C: Monitor

Cobicistat: Tenofovir Disoproxil Fumarate may increase adverse/toxic effects of Cobicistat. More specifically, cobicistat may impair proper tenofovir disoproxil fumarate monitoring and dosing. Risk C: Monitor

Cobimetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cobimetinib. Risk X: Avoid

Codeine: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Codeine. Risk C: Monitor

Copanlisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Copanlisib. Risk C: Monitor

Crinecerfont: CYP3A4 Inducers (Moderate) may decrease serum concentration of Crinecerfont. Management: Double the evening dose of crinecerfont and continue the morning dose unchanged during coadministration with moderate CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification

Crizotinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Crizotinib. Risk C: Monitor

CycloPHOSphamide: CYP2B6 Inducers (Moderate) may increase active metabolite exposure of CycloPHOSphamide. Risk C: Monitor

CycloSPORINE (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of CycloSPORINE (Systemic). Risk C: Monitor

CYP3A4 Inducers (Moderate): May decrease serum concentration of Efavirenz. Risk C: Monitor

CYP3A4 Inducers (Strong): May decrease serum concentration of Efavirenz. Risk C: Monitor

Daclatasvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Risk D: Consider Therapy Modification

Dapsone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Dapsone (Systemic). Risk C: Monitor

Daridorexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Daridorexant. Risk X: Avoid

Darolutamide: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Darunavir: May increase serum concentration of Efavirenz. Efavirenz may decrease serum concentration of Darunavir. Management: Monitor for decreased concentrations and effects of darunavir and/or increased concentrations and effects of efavirenz when darunavir/ritonavir is combined with efavirenz. The use of darunavir/cobicistat in combination with efavirenz is not recommended. Risk D: Consider Therapy Modification

Dasabuvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dasabuvir. Risk X: Avoid

Dasatinib: CYP3A4 Inducers (Moderate) may increase serum concentration of Dasatinib. Risk C: Monitor

Deferasirox: UGT1A1 Inducers may decrease serum concentration of Deferasirox. Management: Avoid concomitant use of deferasirox and UGT1A1 inducers when possible. If combined, consider a 50% increase in the initial deferasirox dose, with monitoring of serum ferritin concentrations and clinical response to guide further dosing. Risk D: Consider Therapy Modification

Deflazacort: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Deflazacort. Risk X: Avoid

DexAMETHasone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of DexAMETHasone (Systemic). Risk C: Monitor

DiazePAM: CYP3A4 Inducers (Moderate) may decrease serum concentration of DiazePAM. Risk C: Monitor

Didanosine: Tenofovir Disoproxil Fumarate may decrease therapeutic effects of Didanosine. Tenofovir Disoproxil Fumarate may increase serum concentration of Didanosine. Management: When combined in adults with CrCL greater than 60 mL/min, decrease didanosine to 250 mg daily if 60 kg or more, or to 200 mg if less than 60 kg. Avoid if CrCL is less than 60 mL/min. Risk D: Consider Therapy Modification

Dienogest: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dienogest. Risk C: Monitor

DilTIAZem: CYP3A4 Inducers (Moderate) may decrease serum concentration of DilTIAZem. Risk C: Monitor

Disopyramide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Disopyramide. Risk C: Monitor

Dolutegravir: Efavirenz may decrease serum concentration of Dolutegravir. Management: Increase dolutegravir to 50 mg twice/day in adults. Increase weight-based dose to twice daily in pediatric patients. Recommendations vary for combo products; see interaction monograph for details. Not recommended with Dovato or Juluca brand combos. Risk D: Consider Therapy Modification

DOXOrubicin (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of DOXOrubicin (Conventional). Risk X: Avoid

DroNABinol: CYP3A4 Inducers (Moderate) may decrease serum concentration of DroNABinol. Risk C: Monitor

Dronedarone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dronedarone. Risk C: Monitor

Duvelisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Duvelisib. Management: Avoid if possible. If used, on day 12 of combination increase duvelisib from 25 mg twice daily to 40 mg twice daily or from 15 mg twice daily to 25 mg twice daily. Resume prior duvelisib dose 14 days after stopping moderate CYP3A4 inducer. Risk D: Consider Therapy Modification

Dydrogesterone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dydrogesterone. Risk C: Monitor

Elacestrant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elacestrant. Risk X: Avoid

Elbasvir and Grazoprevir: Efavirenz may decrease serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor

Eliglustat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Eliglustat. Risk C: Monitor

Elivaldogene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid

Eltrombopag: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Encorafenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Encorafenib. Risk C: Monitor

Encorafenib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Ensartinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ensartinib. Risk X: Avoid

Entrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Entrectinib. Risk X: Avoid

Enzalutamide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Enzalutamide. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Enzalutamide. Risk C: Monitor

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Erdafitinib. Management: If a moderate CYP3A4 inducer must be used at the start of erdafitinib, administer erdafitinib at a dose of 9 mg daily. If a moderate CYP3A4 inducer is discontinued, continue erdafitinib at the same dose unless there is evidence of drug toxicity. Risk D: Consider Therapy Modification

Ergonovine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase serum concentration of Ergonovine. Specifically, this would be most likely with delavrdine, while other Non-Nucleoside Reverse Transcriptase Inhibitors may be more likely to decrease the concentration of Ergonovine. Risk X: Avoid

Erlotinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and strong CYP3A4 inducers whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider Therapy Modification

Estrogen Derivatives: CYP3A4 Inducers (Moderate) may decrease serum concentration of Estrogen Derivatives. Risk C: Monitor

Etoposide Phosphate: CYP3A4 Inducers (Moderate) may decrease serum concentration of Etoposide Phosphate. Risk C: Monitor

Etoposide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Etoposide. Risk C: Monitor

Everolimus: CYP3A4 Inducers (Moderate) may decrease serum concentration of Everolimus. Risk C: Monitor

Exemestane: CYP3A4 Inducers (Moderate) may decrease serum concentration of Exemestane. Risk C: Monitor

Fedratinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fedratinib. Risk X: Avoid

Felodipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Felodipine. Risk C: Monitor

FentaNYL: CYP3A4 Inducers (Moderate) may decrease serum concentration of FentaNYL. Risk C: Monitor

Fexinidazole: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Fexinidazole. Risk X: Avoid

Finerenone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Finerenone. Risk X: Avoid

Flibanserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Flibanserin. Risk X: Avoid

Fosamprenavir: Efavirenz may decrease active metabolite exposure of Fosamprenavir. Management: For once-daily fosamprenavir/ritonavir with efavirenz, increase ritonavir dose to 300 mg/day in adult patients. No ritonavir dose adjustment is required if using twice-daily fosamprenavir/ritonavir. Risk D: Consider Therapy Modification

Fosaprepitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Risk C: Monitor

Fosnetupitant: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Fosnetupitant. Risk C: Monitor

Fosphenytoin-Phenytoin: May decrease serum concentration of Efavirenz. Efavirenz may decrease serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor

Fostamatinib: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Fostamatinib. Risk C: Monitor

Fruquintinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fruquintinib. Management: Avoid this combination when possible. If combined, continue the same fruquintinib dose, but monitor for reduced fruquintinib efficacy. Risk D: Consider Therapy Modification

Futibatinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Ganaxolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and moderate CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider Therapy Modification

Ganciclovir-Valganciclovir: Tenofovir Products may increase serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase serum concentration of Tenofovir Products. Risk C: Monitor

Gefitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gefitinib. Risk C: Monitor

Gemigliptin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gemigliptin. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Gemigliptin. Risk C: Monitor

Gepirone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gepirone. Risk C: Monitor

Gepotidacin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gepotidacin. Risk C: Monitor

Gilteritinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Ginkgo Biloba: May decrease serum concentration of Efavirenz. Risk C: Monitor

Glasdegib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Glasdegib. Management: Avoid use of glasdegib and moderate CYP3A4 inducers whenever possible. If combined, increase glasdegib dose from 100 mg daily to 200 mg daily or from 50 mg daily to 100 mg daily. Resume previous glasdegib dose 7 days after discontinuation of the inducer. Risk D: Consider Therapy Modification

Glecaprevir and Pibrentasvir: Efavirenz may decrease serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid

GuanFACINE: CYP3A4 Inducers (Moderate) may decrease serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider Therapy Modification

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor

Hormonal Contraceptives: Efavirenz may decrease serum concentration of Hormonal Contraceptives. Management: Use a back-up method during coadministration, and to continue back-up contraception for 12 weeks after stopping efavirenz to ensure contraceptive reliability. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Risk D: Consider Therapy Modification

Horsetail: May decrease therapeutic effects of Efavirenz. Risk C: Monitor

HYDROcodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of HYDROcodone. Risk C: Monitor

Hydrocortisone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Hydrocortisone (Systemic). Risk C: Monitor

Ibrexafungerp: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ibrexafungerp. Risk X: Avoid

Ibrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ibrutinib. Risk C: Monitor

Idelalisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Idelalisib. Risk C: Monitor

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Ifosfamide. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Ifosfamide. Risk C: Monitor

Imatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Imatinib. Risk C: Monitor

Indinavir: Efavirenz may decrease serum concentration of Indinavir. Management: The appropriate dose adjustments for indinavir when used together with efavirenz are unknown. The use of higher unboosted indinavir doses is not likely an adequate approach. Use of a ritonavir-boosted indinavir regimen could be considered. Risk D: Consider Therapy Modification

Irinotecan Products: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. Risk C: Monitor

Isavuconazonium Sulfate: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Moderate) may decrease isavuconazole serum concentrations. Risk C: Monitor

Isradipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Isradipine. Risk C: Monitor

Istradefylline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Istradefylline. Risk C: Monitor

Itraconazole: Efavirenz may decrease serum concentration of Itraconazole. Efavirenz may decrease active metabolite exposure of Itraconazole. Risk X: Avoid

Ivabradine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ivabradine. Risk X: Avoid

Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ivacaftor. Risk C: Monitor

Ixabepilone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ixabepilone. Risk C: Monitor

Ixazomib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ixazomib. Risk C: Monitor

Ketamine: CYP2B6 Inducers (Moderate) may decrease serum concentration of Ketamine. Risk C: Monitor

Ketoconazole (Systemic): Efavirenz may decrease serum concentration of Ketoconazole (Systemic). Management: The use of ketoconazole concurrently with or within 2 weeks of efavirenz is not recommended. If such a combination cannot be avoided, monitor patients closely for evidence of diminished clinical response to ketoconazole. Risk D: Consider Therapy Modification

Lapatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lapatinib. Risk C: Monitor

Larotrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Larotrectinib. Management: Double the larotrectinib dose if used together with a moderate CYP3A4 inducer. Following discontinuation of the moderate CYP3A4 inducer, resume the previous dose of larotrectinib after a period of 3 to 5 times the inducer's half-life. Risk D: Consider Therapy Modification

Lazertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lazertinib. Risk X: Avoid

Ledipasvir: May increase serum concentration of Tenofovir Disoproxil Fumarate. Management: Avoid this combination if TDF is used as part of the elvitegravir/cobicistat/emtricitabine/TDF product. Consider alternatives when TDF is used with a ritonavir or cobicistat boosted protease inhibitor. Monitor for increased TDF toxicities if combined. Risk D: Consider Therapy Modification

Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification

Lefamulin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification

Leflunomide: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Lemborexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lemborexant. Risk X: Avoid

Lenacapavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lenacapavir. Risk X: Avoid

Leniolisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Leniolisib. Risk X: Avoid

Leniolisib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid

Lercanidipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lercanidipine. Risk C: Monitor

Letermovir: UGT1A1 Inducers may decrease serum concentration of Letermovir. Risk X: Avoid

Levamlodipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Levamlodipine. Risk C: Monitor

Levoketoconazole: Efavirenz may decrease serum concentration of Levoketoconazole. Risk X: Avoid

Levomethadone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Levomethadone. Risk C: Monitor

Levomethadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease serum concentration of Levomethadone. Management: Levomethadone dosage adjustments will likely be required with efavirenz and nevirapine, and may be necessary with rilpivirine as well. Risk C: Monitor

LinaGLIPtin: CYP3A4 Inducers (Moderate) may decrease serum concentration of LinaGLIPtin. Risk C: Monitor

Lonafarnib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lonafarnib. Risk X: Avoid

Lopinavir: Efavirenz may decrease serum concentration of Lopinavir. Management: Avoid once daily use of lopinavir/ritonavir with efavirenz. Avoid use of this combination in patients less than 6 months of age. Lopinavir/ritonavir dose adjustments are required for patients taking twice daily lopinavir/ritonavir. See full monograph. Risk D: Consider Therapy Modification

Lorlatinib: CYP3A4 Inducers (Moderate) may increase hepatotoxic effects of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with moderate CYP3A4 inducers. If such a combination must be used, increase lorlatinib to 125 mg daily. Monitor for reduced lorlatinib efficacy and consider closer monitoring of AST, ALT, and bilirubin. Risk D: Consider Therapy Modification

Lovastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lovastatin. Risk C: Monitor

Lovotibeglogene Autotemcel: Antiretroviral Agents may decrease therapeutic effects of Lovotibeglogene Autotemcel. Risk X: Avoid

Lumacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lumacaftor and Ivacaftor. Risk C: Monitor

Lumacaftor and Ivacaftor: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Risk C: Monitor

Lumateperone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lumateperone. Risk X: Avoid

Lurasidone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lurasidone. Management: After chronic treatment (7 days or more) with a moderate CYP3A4 inducer, lurasidone dose increases may be needed. Monitor closely for decreased lurasidone effects and increase the lurasidone dose as needed. Risk D: Consider Therapy Modification

Macimorelin: Coadministration of Efavirenz and Macimorelin may alter diagnostic results. Risk C: Monitor

Macitentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Macitentan. Risk C: Monitor

Maraviroc: CYP3A4 Inducers (Moderate) may decrease serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider Therapy Modification

Maribavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Maribavir. Risk C: Monitor

Mavacamten: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mavacamten. Risk X: Avoid

Mavorixafor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mavorixafor. Risk C: Monitor

Mefloquine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mefloquine. Risk C: Monitor

Meperidine: CYP2B6 Inducers (Moderate) may decrease serum concentration of Meperidine. CYP2B6 Inducers (Moderate) may increase active metabolite exposure of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. Risk C: Monitor

Methadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase metabolism of Methadone. Management: Methadone dosage adjustments will likely be required with efavirenz and nevirapine, and may be necessary with rilpivirine as well. Risk C: Monitor

Methoxyflurane: CYP2B6 Inducers (Moderate) may increase metabolism of Methoxyflurane. Specifically, this increased metabolism may lead to increased production of nephrotoxic metabolites. Risk X: Avoid

MethylPREDNISolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of MethylPREDNISolone. Risk C: Monitor

Mianserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mianserin. Risk C: Monitor

Midazolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of Midazolam. Risk C: Monitor

Midostaurin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Midostaurin. Risk C: Monitor

MiFEPRIStone: CYP3A4 Inducers (Moderate) may decrease serum concentration of MiFEPRIStone. Management: Avoid combined use in patients treated for Cushing's disease. When used for pregnancy termination, mifepristone efficacy may be reduced and an alternative pregnancy termination procedure may be warranted. Ensure a follow-up assessment after combined use. Risk D: Consider Therapy Modification

Mirodenafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mirodenafil. Risk C: Monitor

Mitapivat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mitapivat. Management: Consider alternatives to this combination when possible. If combined, monitor hemoglobin and titrate mitapivat beyond 50 mg twice daily, if needed, but do not exceed doses of 100 mg twice daily. Risk D: Consider Therapy Modification

Mobocertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mobocertinib. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Mobocertinib. Risk X: Avoid

Montelukast: CYP3A4 Inducers (Moderate) may decrease serum concentration of Montelukast. Risk C: Monitor

Naldemedine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Naldemedine. Risk C: Monitor

Naloxegol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Naloxegol. Risk C: Monitor

Nelfinavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nelfinavir. Risk C: Monitor

Neratinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Neratinib. Risk X: Avoid

Netupitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Netupitant. Risk C: Monitor

NIFEdipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of NIFEdipine. Risk C: Monitor

Nilotinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nilotinib. Risk C: Monitor

Nilvadipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nilvadipine. Risk C: Monitor

NiMODipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of NiMODipine. Risk C: Monitor

Nirmatrelvir and Ritonavir: Efavirenz may increase adverse/toxic effects of Nirmatrelvir and Ritonavir. Efavirenz may decrease serum concentration of Nirmatrelvir and Ritonavir. Specifically, efavirenz may decrease concentration of nirmatrelvir. Efavirenz may increase serum concentration of Nirmatrelvir and Ritonavir. Specifically, efavirenz may increase concentration of ritonavir. Nirmatrelvir and Ritonavir may increase serum concentration of Efavirenz. Risk C: Monitor

Nirogacestat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nirogacestat. Risk X: Avoid

Nisoldipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nisoldipine. Risk X: Avoid

Nonsteroidal Anti-Inflammatory Agents (Topical): May increase nephrotoxic effects of Tenofovir Products. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents: May increase nephrotoxic effects of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider Therapy Modification

Olaparib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olaparib. Risk X: Avoid

Oliceridine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Oliceridine. Risk C: Monitor

Olmutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olmutinib. Risk C: Monitor

Olutasidenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olutasidenib. Risk X: Avoid

Omaveloxolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Omaveloxolone. Risk X: Avoid

Orlistat: May decrease serum concentration of Antiretroviral Agents. Risk C: Monitor

Osimertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Osimertinib. Risk C: Monitor

Osimertinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Oteseconazole: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

OxyCODONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of OxyCODONE. Risk C: Monitor

P-glycoprotein/ABCB1 Inhibitors: May increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor

PACLitaxel (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of PACLitaxel (Conventional). Risk C: Monitor

PACLitaxel (Protein Bound): CYP3A4 Inducers (Moderate) may decrease serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor

Pacritinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pacritinib. Risk C: Monitor

Palbociclib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Palbociclib. Risk C: Monitor

Paliperidone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Paliperidone. Risk C: Monitor

Palovarotene: CYP3A4 Inducers (Moderate) may decrease serum concentration of Palovarotene. Risk X: Avoid

PAZOPanib: CYP3A4 Inducers (Moderate) may decrease serum concentration of PAZOPanib. Risk C: Monitor

Pemigatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pemigatinib. Risk X: Avoid

Perampanel: CYP3A4 Inducers (Moderate) may decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with moderate CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider Therapy Modification

Pimavanserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pimavanserin. Risk X: Avoid

Piperaquine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Piperaquine. Risk C: Monitor

Pirtobrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pirtobrutinib. Management: Avoid concomitant use if possible. If combined, if the current pirtobrutinib dose is 200 mg once daily, increase to 300 mg once daily. If current pirtobrutinib dose is 50 mg or 100 mg once daily, increase the dose by 50 mg. Risk D: Consider Therapy Modification

PONATinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of PONATinib. Risk C: Monitor

Posaconazole: Efavirenz may decrease serum concentration of Posaconazole. Risk X: Avoid

Pralsetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pralsetinib. Management: If this combo cannot be avoided, increase pralsetinib dose from 400 mg daily to 600 mg daily; from 300 mg daily to 500 mg daily; and from 200 mg daily to 300 mg daily. Risk D: Consider Therapy Modification

Pravastatin: Efavirenz may decrease serum concentration of Pravastatin. Risk C: Monitor

Praziquantel: CYP3A4 Inducers (Moderate) may decrease serum concentration of Praziquantel. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced praziquantel efficacy. If possible, stop the moderate CYP3A4 inducer 2 to 4 weeks before praziquantel initiation. Risk D: Consider Therapy Modification

PrednisoLONE (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of PrednisoLONE (Systemic). Risk C: Monitor

PredniSONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of PredniSONE. Risk C: Monitor

Pretomanid: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pretomanid. Risk X: Avoid

Proguanil: Efavirenz may decrease serum concentration of Proguanil. Efavirenz may decrease active metabolite exposure of Proguanil. Efavirenz may increase serum concentration of Proguanil. Risk C: Monitor

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

QUEtiapine: CYP3A4 Inducers (Moderate) may decrease serum concentration of QUEtiapine. Risk C: Monitor

QuiNIDine: CYP3A4 Inducers (Moderate) may decrease serum concentration of QuiNIDine. Risk C: Monitor

QuiNINE: CYP3A4 Inducers (Moderate) may decrease serum concentration of QuiNINE. Risk C: Monitor

Quizartinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Quizartinib. Risk X: Avoid

Ranolazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ranolazine. Risk X: Avoid

Red Yeast Rice: Efavirenz may decrease serum concentration of Red Yeast Rice. Risk C: Monitor

Regorafenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Regorafenib. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Regorafenib. Risk C: Monitor

Regorafenib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Repaglinide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Repaglinide. Risk C: Monitor

Repotrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Repotrectinib. Risk X: Avoid

Reverse Transcriptase Inhibitors (Non-Nucleoside): May increase adverse/toxic effects of Reverse Transcriptase Inhibitors (Non-Nucleoside). Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease serum concentration of Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, efavirenz and nevirapine may decrease the serum concentrations of other non-nucleoside reverse transcriptase inhibitors. Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase serum concentration of Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, delavirdine may increase the serum concentration of etravirine. Risk X: Avoid

Revumenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Revumenib. Risk X: Avoid

Ribociclib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ribociclib. Risk C: Monitor

Rifabutin: Efavirenz may decrease serum concentration of Rifabutin. Rifabutin may decrease serum concentration of Efavirenz. Management: If efavirenz is to be used with daily rifabutin, increase the planned rifabutin dose by 50% to a dose of 450 mg to 600 mg daily. If used with regimens where rifabutin is administered 2 to 3 times per week, consider doubling the rifabutin dose. Risk D: Consider Therapy Modification

RifAMPin: May decrease serum concentration of Efavirenz. Efavirenz may decrease serum concentration of RifAMPin. Management: Monitor for reduced response to efavirenz and rifampin. Guidelines suggest no efavirenz dose adjustments are required when combined, while labeling recommends an efavirenz dose increase to 800 mg daily in adults weighing more than 50 kg. Risk C: Monitor

Rimegepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rimegepant. Risk X: Avoid

Ripretinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ripretinib. Management: Avoid this combination if possible. If concomitant use is required, increase ripretinib to 150 mg twice daily. Decrease ripretinib to 150 mg once daily 14 days after stopping a moderate CYP3A4 inducer. Monitor patients for ripretinib response and toxicity Risk D: Consider Therapy Modification

RisperiDONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of RisperiDONE. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of RisperiDONE. Risk C: Monitor

Ritlecitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ritlecitinib. Risk C: Monitor

Ritonavir: Efavirenz may increase adverse/toxic effects of Ritonavir. Efavirenz may increase serum concentration of Ritonavir. Ritonavir may increase serum concentration of Efavirenz. Risk C: Monitor

Roflumilast (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Roflumilast (Systemic). CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Roflumilast (Systemic). Risk C: Monitor

Rolapitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rolapitant. Risk C: Monitor

Rolapitant: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Monitor patients receiving rolapitant for increased exposure to and/or effects of BCRP/ABCG2 substrates. Use the lowest effective rosuvastatin dose when used in combination with rolapitant. Risk C: Monitor

Sacituzumab Govitecan: UGT1A1 Inducers may decrease active metabolite exposure of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be decreased. Risk X: Avoid

Samidorphan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Samidorphan. Risk C: Monitor

Saquinavir: May increase hepatotoxic effects of Efavirenz. Efavirenz may decrease serum concentration of Saquinavir. Management: When used together with efavirenz, saquinavir should not be used as the sole protease inhibitor. Appropriate doses of the combination of efavirenz with saquinavir/ritonavir have not been established. Risk X: Avoid

Selpercatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Selpercatinib. Risk X: Avoid

Selumetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Selumetinib. Risk X: Avoid

Sertraline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sertraline. Risk C: Monitor

Sildenafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sildenafil. Risk C: Monitor

Simeprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Simeprevir. Risk X: Avoid

Simvastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Simvastatin. Risk C: Monitor

Sirolimus (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of Sirolimus (Conventional). Risk C: Monitor

Sirolimus (Protein Bound): CYP3A4 Inducers (Moderate) may decrease serum concentration of Sirolimus (Protein Bound). Risk C: Monitor

Sonidegib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sonidegib. Risk X: Avoid

SORAfenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of SORAfenib. Risk C: Monitor

Sotorasib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sotorasib. Risk C: Monitor

Sparsentan: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid

SUFentanil: CYP3A4 Inducers (Moderate) may decrease serum concentration of SUFentanil. Risk C: Monitor

SUNItinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of SUNItinib. Risk C: Monitor

Suvorexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Suvorexant. Risk C: Monitor

Suzetrigine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Suzetrigine. Risk X: Avoid

Tacrolimus (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Tacrolimus (Systemic). Risk C: Monitor

Tacrolimus (Systemic): Tenofovir Products may increase nephrotoxic effects of Tacrolimus (Systemic). Risk C: Monitor

Tadalafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tadalafil. Risk C: Monitor

Tafamidis: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Tamoxifen: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tamoxifen. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Tamoxifen. Risk C: Monitor

Tasimelteon: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tasimelteon. Risk C: Monitor

Taurursodiol: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid

Tazemetostat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tazemetostat. Risk X: Avoid

Tedizolid: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Temsirolimus: CYP3A4 Inducers (Moderate) may decrease serum concentration of Temsirolimus. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Temsirolimus. Specifically, sirolimus concentrations may be decreased. Risk C: Monitor

Teniposide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Teniposide. Risk C: Monitor

Teriflunomide: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor

Tetrahydrocannabinol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tetrahydrocannabinol. Risk C: Monitor

Tezacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tezacaftor and Ivacaftor. Risk C: Monitor

Thiotepa: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Thiotepa. CYP3A4 Inducers (Moderate) may decrease serum concentration of Thiotepa. Risk C: Monitor

Thiotepa: May increase serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor

Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Ticagrelor. Risk C: Monitor

Tipranavir: Tenofovir Disoproxil Fumarate may decrease serum concentration of Tipranavir. Tipranavir may decrease serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor

Tivozanib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tivozanib. Risk C: Monitor

Tofacitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tofacitinib. Risk C: Monitor

Tolvaptan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tolvaptan. Risk C: Monitor

Toremifene: CYP3A4 Inducers (Moderate) may decrease serum concentration of Toremifene. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Toremifene. Risk C: Monitor

Trabectedin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Trabectedin. Risk C: Monitor

TraMADol: CYP3A4 Inducers (Moderate) may decrease serum concentration of TraMADol. Risk C: Monitor

TraZODone: CYP3A4 Inducers (Moderate) may decrease serum concentration of TraZODone. Risk C: Monitor

Tretinoin (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Tretinoin (Systemic). Risk C: Monitor

Triazolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of Triazolam. Risk C: Monitor

Tucatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tucatinib. Risk C: Monitor

Ubrogepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Risk D: Consider Therapy Modification

Ulipristal: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ulipristal. Risk X: Avoid

Upadacitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Upadacitinib. Risk C: Monitor

Vadadustat: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor

Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Valbenazine. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Valbenazine. Risk C: Monitor

Valoctocogene Roxaparvovec: May increase hepatotoxic effects of Efavirenz. Efavirenz may decrease therapeutic effects of Valoctocogene Roxaparvovec. Risk X: Avoid

Vandetanib: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Vandetanib. CYP3A4 Inducers (Moderate) may decrease serum concentration of Vandetanib. Risk C: Monitor

Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Risk X: Avoid

Velpatasvir: CYP2B6 Inducers (Moderate) may decrease serum concentration of Velpatasvir. Risk X: Avoid

Velpatasvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Velpatasvir. Risk X: Avoid

Vemurafenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vemurafenib. Risk C: Monitor

Venetoclax: CYP3A4 Inducers (Moderate) may decrease serum concentration of Venetoclax. Risk X: Avoid

Verapamil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Verapamil. Risk C: Monitor

Vilazodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vilazodone. Risk C: Monitor

Vimseltinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Management: Avoid concomitant use of vimseltinib and P-gp substrates when possible. If combined, administer vimseltinib at least 4 hours before the P-gp substrate. Risk D: Consider Therapy Modification

VinCRIStine: CYP3A4 Inducers (Moderate) may decrease serum concentration of VinCRIStine. Risk C: Monitor

Vitamin K Antagonists: Efavirenz may decrease serum concentration of Vitamin K Antagonists. Efavirenz may increase serum concentration of Vitamin K Antagonists. Risk C: Monitor

Voclosporin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voclosporin. Risk X: Avoid

Vonoprazan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vonoprazan. Risk X: Avoid

Vorapaxar: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vorapaxar. Risk X: Avoid

Voriconazole: Efavirenz may decrease serum concentration of Voriconazole. Voriconazole may increase serum concentration of Efavirenz. Management: Use of standard doses of these drugs is contraindicated. The voriconazole oral maintenance dose should be increased to 400 mg every 12 hours, and the efavirenz dose should be reduced to 300 mg daily. Risk D: Consider Therapy Modification

Vortioxetine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vortioxetine. Risk C: Monitor

Voxelotor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,000 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider Therapy Modification

Voxilaprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voxilaprevir. Risk X: Avoid

Zaleplon: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zaleplon. Risk C: Monitor

Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zanubrutinib. Management: Avoid this combination if possible. If coadministration of zanubrutinib and a moderate CYP3A4 inducer is required, increase the zanubrutinib dose to 320 mg twice daily. Risk D: Consider Therapy Modification

Zolpidem: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zolpidem. Risk C: Monitor

Zopiclone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zopiclone. Risk C: Monitor

Zuranolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zuranolone. Risk X: Avoid

Food Interactions

See individual agents.

Reproductive Considerations

The manufacturer's labeling recommends pregnancy testing prior to therapy, and effective contraception in patients who may become pregnant during treatment and for 12 weeks after therapy is discontinued. However, available guidelines note contraception is not required to initiate or continue antiretroviral therapy (ART). Patients with HIV not planning to become pregnant may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. Consult drug interactions database for more detailed information specific to use of this combination and specific contraceptives.

This fixed-dose combination of efavirenz, emtricitabine, and tenofovir disoproxil fumarate is an alternative regimen for patients with HIV who are not yet pregnant but are trying to conceive (HHS [perinatal] 2024).

Refer to individual monographs for additional information.

Pregnancy Considerations

This fixed-dose combination of efavirenz, emtricitabine, and tenofovir disoproxil fumarate is an alternative regimen for pregnant patients with HIV who are antiretroviral-naive, who have had antiretroviral therapy (ART) in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). Patients who become pregnant while taking this fixed-dose combination may continue if viral suppression is effective and the regimen is well tolerated. This fixed dose combination may be considered for patients when significant drug interactions would occur with preferred agents or in patients who need the convenience of a co-formulated single dose tablet in a once daily regimen but are not eligible for preferred agents (HHS [perinatal] 2024).

Refer to individual monographs for additional information.

Breastfeeding Considerations

Efavirenz, emtricitabine, and tenofovir are present in breast milk.

Refer to individual monographs for additional information.

Dietary Considerations

Consider calcium and vitamin D supplementation.

Monitoring Parameters

Test for hepatitis B virus infection prior to the initiation of antiretroviral therapy.

CBC with differential, reticulocyte count, creatine kinase, CD4 count, HIV RNA plasma levels; serum creatinine, estimated creatine clearance, urine glucose, and urine protein (prior to initiation and as clinically indicated during therapy); serum phosphorus at baseline and periodically during therapy in patients with chronic kidney disease; hepatic function tests prior to initiation and during treatment (discontinuation of treatment should be considered for persistent serum transaminase elevations >5 times ULN; discontinue if signs or symptoms of hepatitis or hepatic decompensation occur with serum transaminase elevation); bone density (patients with a history of bone fracture or have risk factors for bone loss).

Patients with HIV and HBV coinfection should have hepatic function monitored for several months following discontinuation.

Mechanism of Action

Efavirenz: Non-nucleoside reverse transcriptase inhibitor of HIV-1. It consequently blocks the RNA-dependent and DNA-dependent DNA polymerase activities including HIV-1 replication.

Emtricitabine: Nucleoside reverse transcriptase inhibitor; cytidine analogue that is phosphorylated intracellularly to emtricitabine 5'-triphosphate which interferes with HIV viral RNA dependent DNA polymerase resulting in inhibition of viral replication.

Tenofovir disoproxil fumarate: Nucleotide reverse transcriptase inhibitor; analog of adenosine 5'-monophosphate that interferes with the HIV viral RNA dependent DNA polymerase resulting in inhibition of viral replication. TDF is first converted intracellularly by hydrolysis to tenofovir and subsequently phosphorylated to the active tenofovir diphosphate. Tenofovir inhibits replication of HBV by inhibiting HBV polymerase.

Pharmacokinetics (Adult Data Unless Noted)

See individual agents.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (EC) Ecuador: Calprega forte | Trivirox;
  • (MX) Mexico: Goltrec | Tremixclar;
  • (RU) Russian Federation: Trakten n;
  • (ZM) Zambia: Efavirenz + emtricitabine + tenofovir
  1. Atripla (efavirenz/emtricitabine/tenofovir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; December 2021.
  2. Atripla (efavirenz/emtricitabine/tenofovir) [product monograph]. Mississauga, Ontario, Canada: Gilead Sciences Canada, Inc; February 2020.
  3. Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med. 2006;354(3):251-260. [PubMed 16421366]
  4. Lucas GM, Ross MJ, Stock PG, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(9): e96-e138. [PubMed 25234519]
  5. Puthanakit T, Tanpaiboon P, Aurpibul L, Cressey TR, Sirisanthana V. Plasma efavirenz concentrations and the association with CYP2B6-516G >T polymorphism in HIV-infected Thai children. Antivir Ther. 2009;14(3):315-320. [PubMed 19474465]
  6. Rawala MS, Wright J, King J, Howell D, Martin S. Membranous nephropathy in a patient with human immunodeficiency virus shortly after initiation of HAART with atripla. Cureus. 2019;11(1):e3932. doi:10.7759/cureus.3932 [PubMed 30931200]
  7. Shubber Z, Calmy A, Andrieux-Meyer I, et al. Adverse events associated with nevirapine and efavirenz-based first-line antiretroviral therapy: a systematic review and meta-analysis. AIDS. 2013;27(9):1403-1412. doi:10.1097/QAD.0b013e32835f1db0 [PubMed 23343913]
  8. US Department of Health and Human Services (HHS) Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/whats-new-guidelines. Updated April 11, 2022. Accessed July 1, 2022.
  9. US Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new. Updated March 23, 2023. Accessed May 16, 2023.
  10. US Department of Health and Human Services (HHS) Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. https://clinicalinfo.hiv.gov/en/guidelines/perinatal/whats-new. Updated December 19, 2024. Accessed December 30, 2024.
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