Version May 2024
HIV-1 infection, treatment:
Note: Do not use efavirenz plus abacavir and lamivudine in patients with a pre-antiretroviral therapy HIV RNA ≥100,000 copies/mL (Ref).
Oral: 600 mg once daily, in combination with other appropriate agents; 400 mg once daily may be used in combination with tenofovir disoproxil fumarate and lamivudine (Ref). The 400 mg once daily dose is not recommended in patients who are pregnant (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary (Ref).
Mild impairment (Child-Pugh class A): No dosage adjustment necessary; use with caution.
Moderate-to-severe impairment (Child-Pugh class B or C): Use is not recommended.
Refer to adult dosing.
(For additional information see "Efavirenz: Pediatric drug information")
HIV-1 infection, treatment: Note: Use in combination with other antiretroviral (ARV) agents; gene mutation and ARV resistance patterns should be evaluated (refer to https://www.iasusa.org and https://hivdb.stanford.edu/ for more information).
Infants ≥3 months and Children <3 years:
Dosing based on CYP2B6 genotype: Very limited data available: Note: Efavirenz use is not recommended in patients <3 years of age unless use is unavoidable due to the clinical situation; CYP2B6 genotype testing should be performed prior to therapy initiation, and therapeutic drug monitoring is recommended. The following dosing is investigational but suggested for use in current guidelines (Ref).
Extensive metabolizers (CYP2B6-516-G/G or -G/T genotypes):
5 to <7 kg: Oral: 300 mg once daily.
7 to <14 kg: Oral: 400 mg once daily
14 to ≤17 kg: Oral: 500 mg once daily.
Slow metabolizers (CYP2B6-516-T/T genotype):
5 to <7 kg: Oral: 50 mg once daily.
7 to <14 kg: Oral: 100 mg once daily.
14 to ≤17 kg: Oral: 150 mg once daily.
Manufacturer's labeling: Note: Although FDA approved in pediatric patients ≥3 months of age and weighing ≥3.5 kg, pharmacokinetic data suggest that the FDA-approved regimen may result in underexposure in extensive metabolizers and overexposure in slow metabolizers; dosing is not recommended by expert panel for patients <3 years of age; therapeutic drug monitoring is recommended in this age group regardless of dosing regimen used (Ref).
3.5 to <5 kg: Oral: 100 mg once daily.
5 to <7.5 kg: Oral: 150 mg once daily.
7.5 to <15 kg: Oral: 200 mg once daily.
15 to <20 kg: Oral: 250 mg once daily.
Children ≥3 years and Adolescents:
Fixed dosing (Ref):
7.5 to <15 kg: Oral: 200 mg once daily.
15 to <20 kg: Oral: 250 mg once daily.
20 to <25 kg: Oral: 300 mg once daily.
25 to <32.5 kg: Oral: 350 mg once daily.
32.5 to <40 kg: Oral: 400 mg once daily.
≥40 kg: Oral: 600 mg once daily.
BSA-directed dosing: Oral: 367 mg/m2/dose once daily, maximum dose: 600 mg/dose; recommended by some experts due to concern of underdosing at the upper end of each weight range (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in manufacturer's labeling; however, drug undergoes minimal renal excretion elimination.
Infants ≥3 months, Children, and Adolescents:
Baseline hepatic impairment:
Mild impairment: No dosage adjustment necessary; use with caution.
Moderate to severe impairment: Use not recommended (has not been studied).
Hepatotoxicity during therapy:
Serum transaminases >5 × ULN (persistently): Consider discontinuing therapy.
Serum transaminase elevation AND clinical signs or symptoms of hepatitis or hepatic decompensation: Discontinue therapy.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency of adverse events is as reported for patients receiving combination antiretroviral therapy.
>10%:
Dermatologic: Skin rash (5% to 32%)
Endocrine & metabolic: Increased serum cholesterol (20% to 40%), increased HDL cholesterol (25% to 35%), increased serum triglycerides (≥751 mg/dL: 6% to 11%)
Gastrointestinal: Diarrhea (3% to 14%)
Nervous system: Central nervous system toxicity (53%), dizziness (2% to 28%), depression (3% to 19%), insomnia (7% to 16%), anxiety (2% to 13%), pain (1% to 13%)
1% to 10%:
Dermatologic: Pruritus (≤9%), erythema multiforme (≤2%)
Endocrine & metabolic: Increased gamma-glutamyl transferase (grades 3/4: 5% to 8%), increased amylase (grades 3/4: grades 3/4: 4% to 6%), hyperglycemia (>250 mg/dL: 2% to 5%)
Gastrointestinal: Nausea (2% to 10%), vomiting (3% to 6%), dyspepsia (4%), abdominal pain (2% to 3%), anorexia (≤2%)
Hematologic & oncologic: Neutropenia (grades 3/4: 2% to 10%)
Hepatic: Increased serum aspartate aminotransferase (grades 3/4: 5% to 8%; incidence higher with hepatitis B and/or C coinfection), increased serum alanine aminotransferase (grades 3/4: 2% to 8%; incidence higher with hepatitis B and/or C coinfection)
Nervous system: Lack of concentration (3% to 8%), fatigue (2% to 8%), headache (2% to 8%), drowsiness (2% to 7%), nervousness (2% to 7%), abnormal dreams (1% to 6%), severe depression (2%), hallucination (1%)
Frequency not defined: Cardiovascular: Prolonged QT interval on ECG
<1%, postmarketing, and/or case reports: Aggressive behavior, agitation, arthralgia, asthenia, ataxia, catatonia, cerebellar ataxia, constipation, delusion, dyspnea, emotional lability, encephalopathy, flushing, fulminant hepatitis, gynecomastia, hepatic failure, hepatitis, hypersensitivity reaction, hypoesthesia, immune reconstitution syndrome, lipotrophy, loss of balance, malabsorption, mania, myalgia, myopathy, neuropathy, palpitations, pancreatitis, paranoid ideation, paresthesia, photodermatitis, psychoneurosis, psychosis, redistribution of body fat, seizure, Stevens-Johnson syndrome, suicidal ideation, suicidal tendencies, tinnitus, tremor, vertigo, visual disturbance
Hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions) to efavirenz or any component of the formulation; concurrent administration with elbasvir or 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): Concurrent administration with cisapride (not available in Canada), ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine), midazolam, pimozide, St. John's wort, triazolam
Concerns related to adverse effects:
• CNS effects: May cause CNS effects (eg, abnormal dreams, insomnia, impaired concentration, hallucinations, dizziness, drowsiness); symptoms usually begin within 1 to 2 days after starting efavirenz, and generally resolve within 2 to 4 weeks of continued therapy; dosing at bedtime may improve tolerability; avoid potentially hazardous tasks such as driving or operating machinery. CNS effects may be potentiated when used concomitantly with other psychoactive drugs or ethanol. 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 increased efavirenz levels at standard doses). Promptly assess patients with signs and symptoms of serious neurologic adverse effects and consider discontinuation of therapy.
• Fat redistribution: May cause redistribution/accumulation of fat (eg, central obesity, dorsocervical fat enlargement [buffalo hump], peripheral wasting, facial wasting, breast enlargement, cushingoid appearance).
• Hepatotoxicity: Hepatitis, including fulminant hepatitis progressing to hepatic failure (sometimes fatal or requiring transplantation), has been reported, including patients with no preexisting hepatic disease or other identifiable risk factors. Monitor liver function tests in all patients; consider discontinuing treatment in patients with persistent serum transaminase elevations >5 x ULN or if serum transaminase elevations are accompanied by signs/symptoms of hepatitis or hepatic decompensation.
• Hypercholesterolemia: Increases in total cholesterol and triglycerides have been reported; screening should be done prior to therapy and periodically throughout treatment.
• 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.
• Psychiatric effects: Serious psychiatric side effects have been associated with use, including aggressive behavior, delusions, severe depression, suicidal ideation, fatal and nonfatal suicide attempts, paranoia, psychosis-like behavior, and mania; use with caution in patients with a history of mental illness/drug abuse (predisposition to psychological reactions). Patients should be instructed to contact healthcare provider if serious psychiatric effects occur.
• Rash: May cause mild to moderate maculopapular rash; usually occurs within 2 weeks of starting therapy; most resolve within 1 month with continued therapy. Treatment may be reinitiated in patients interrupting therapy for mild to moderate rashes. Discontinue use if severe rash (involving blistering, desquamation, mucosal involvement, or fever) develops; use is contraindicated in patients with a history of a severe cutaneous reaction (eg, Stevens-Johnson syndrome). Pediatric patients are more susceptible to development of rash; prophylactic antihistamines/corticosteroids may be used.
• QT prolongation: QT prolongation has been reported; consider alternative therapy in patients at risk of torsades de pointes or when coadministered with medications with known risk of torsades de pointes.
Disease-related concerns:
• Hepatic impairment: Not recommended in moderate to severe hepatic impairment (Child-Pugh class B or C); use with caution in patients with mild hepatic impairment (Child-Pugh class A), including known or suspected hepatitis B or C infection; monitoring is recommended.
• 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] 2019).
• Seizure disorder: Use with caution in patients with a history of seizure disorder; seizures have been associated with use.
Concurrent drug therapy issues:
• Duplicate therapy: Concomitant use of other efavirenz-containing products should be avoided (unless needed for dosage adjustment with concomitant rifampin treatment).
Other warnings/precautions:
• Resistance: Efavirenz administered as monotherapy or added on to a failing regimen may result in rapid viral resistance to efavirenz. Consider cross-resistance when adding antiretroviral agents on to efavirenz therapy.
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: ~1%, 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; if therapy is interrupted due to non-severe rash, efavirenz can typically be reinitiated. Discontinue if severe rash (involving blistering, desquamation, mucosal involvement, ulceration, or fever) occurs. Consider prophylaxis with antihistamines in children due to frequency and severity of rash reported in children (HHS [pediatric] 2023; manufacturer's labeling).
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. Alternate agents are recommended for initial use in pediatric patients; avoid use in patients with psychiatric illness (including depression) or concomitant use with psychoactive drugs. If benefits of use are determined to outweigh risks, administer at bedtime on an empty stomach to lower the risk of and severity of neuropsychiatric effects. Consider evaluation of efavirenz serum concentrations if patient experiences CNS/neuropsychiatric symptoms; may require drug substitution if a suitable alternative exists. Alternatively, after consultation with an expert in pediatric HIV, consider initial dose reduction followed by trough concentration monitoring and potential additional dose adjustment. One study reported an 11% incidence of new-onset seizures in children <36 months of age; late-onset neurologic symptoms (eg, ataxia, encephalopathy) may occur months to years after therapy initiation (HHS [pediatric] 2023).
Efavirenz use is associated with low serum vitamin D levels and low bone mineral density in adults, possibly due to the induction of CYP3A4 and CYP24 enzymes, which impact vitamin D homeostasis. Ensure that calcium, vitamin D, and total caloric intake are sufficient and supplement with vitamin D3 to achieve serum 25-OH-vitamin D concentrations of >30 ng/mL if necessary (HHS [pediatric] 2023].
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Sustiva: 50 mg [DSC], 200 mg [DSC]
Generic: 50 mg [DSC], 200 mg [DSC]
Tablet, Oral:
Sustiva: 600 mg [DSC]
Generic: 600 mg
Yes
Tablets (Efavirenz Oral)
600 mg (per each): $20.27 - $37.26
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Sustiva: 50 mg [DSC], 200 mg [DSC] [contains fd&c blue #2 (indigotine,indigo carmine)]
Tablet, Oral:
Sustiva: 600 mg [DSC]
Generic: 600 mg
Oral: Administer on an empty stomach. Dosing at bedtime is recommended to limit central nervous system effects. Tablets must not be broken.
Capsule contents may be sprinkled onto a small amount of soft food (eg, applesauce, grape jelly, yogurt) for patients who cannot swallow capsules. Place 1 to 2 teaspoonfuls of food in a small container. Hold capsule horizontally over container and carefully twist in opposite directions to open, sprinkling contents over food. If more than 1 capsule is needed for a dose, add contents of all capsules needed to 1 to 2 teaspoonfuls of food; do not add more food. Use a small spoon to gently mix capsule contents with food and administer all of mixture to patient. To ensure entire capsule contents are administered, add another 2 teaspoonfuls of food to the container, mix to incorporate any drug residue, and administer. Administer within 30 minutes of mixing. Patient should not consume any additional food or administer additional formula for 2 hours after administration.
Oral: Administer dose at bedtime to decrease CNS adverse effects; administer with water on an empty stomach (administration with food may increase efavirenz concentrations and adverse effects). Capsules and tablets should be swallowed intact.
Patients unable to swallow: The capsules may be opened and added to 1 to 2 teaspoons (5 to 10 mL) of age-appropriate soft food (eg, applesauce, grape jelly, yogurt) or 10 mL of room temperature infant formula. After placing food in a small container, hold capsule horizontally over container and carefully twist in opposite directions to open, sprinkling contents over food. After administration, an additional small amount (2 teaspoons [10 mL]) of food or formula must be added to the empty mixing container, stirred to disperse any remaining efavirenz residue, and administered to the patient. Administer the efavirenz food or formula mixture within 30 minutes of mixing; do not save for future use. No additional food should be consumed for 2 hours after administration. Refer to the detailed "Instructions for Use" (found in the product labeling) for preparing a dose of efavirenz using the capsule sprinkle method. Note: Efavirenz tastes peppery and mixing with grape jelly may improve palatability (Ref).
HIV-1 infection: Treatment of HIV-1 infection in combination with other antiretroviral agents in adults and pediatric patients at least 3 months old and weighing at least 3.5 kg
Substrate of CYP2B6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP2B6 (moderate), CYP2C19 (weak), CYP3A4 (moderate), UGT1A1, UGT1A4
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abemaciclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abemaciclib. Risk X: Avoid combination
Abiraterone Acetate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abiraterone Acetate. Risk C: Monitor therapy
Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Acalabrutinib. Risk C: Monitor therapy
Alcohol (Ethyl): Efavirenz may enhance the adverse/toxic effect of Alcohol (Ethyl). Efavirenz may decrease the serum concentration of Alcohol (Ethyl). Risk C: Monitor therapy
ALfentanil: CYP3A4 Inducers (Moderate) may decrease the 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
ALPRAZolam: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ALPRAZolam. Risk C: Monitor therapy
AmLODIPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy
Amodiaquine: Efavirenz may enhance the hepatotoxic effect of Amodiaquine. Efavirenz may increase the 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 the serum concentration of Antihepaciviral Combination Products. Risk X: Avoid combination
Apremilast: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Apremilast. Risk C: Monitor therapy
Aprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Aprepitant. Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole. Risk C: Monitor therapy
ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor therapy
Artemether and Lumefantrine: Efavirenz may decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. Efavirenz may decrease the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy
Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Risk X: Avoid combination
Atazanavir: Efavirenz may decrease the serum concentration of Atazanavir. Management: Only use atazanavir/ritonavir (400/100 mg daily with food) an efavirenz (600 mg daily on empty stomach at bedtime) in treatment-naive patients. Use in treatment-experienced patients, or other combination of atazanavir and efavirenz, are not recommended. Risk D: Consider therapy modification
Atogepant: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Atorvastatin. Risk C: Monitor therapy
Atovaquone: Efavirenz may decrease the 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
Avacopan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avacopan. Risk X: Avoid combination
Avanafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avanafil. Risk X: Avoid combination
Avapritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avapritinib. Risk X: Avoid combination
Axitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib. Risk X: Avoid combination
Bedaquiline: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination
Belumosudil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Belumosudil. Risk C: Monitor therapy
Benzhydrocodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor therapy
Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
Bictegravir: UGT1A1 Inducers may decrease the serum concentration of Bictegravir. Risk C: Monitor therapy
Bortezomib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bortezomib. Risk C: Monitor therapy
Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Risk C: Monitor therapy
Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brexpiprazole. Risk C: Monitor therapy
Brigatinib: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Buprenorphine. Risk C: Monitor therapy
BuPROPion: CYP2B6 Inducers (Moderate) may decrease the serum concentration of BuPROPion. Risk C: Monitor therapy
BusPIRone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of BusPIRone. Risk C: Monitor therapy
Cabotegravir: UGT1A1 Inducers may decrease the serum concentration of Cabotegravir. Risk X: Avoid combination
Cabozantinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cabozantinib. Risk C: Monitor therapy
Cannabis: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor therapy
Capivasertib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Capivasertib. Risk X: Avoid combination
Capmatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Capmatinib. Risk X: Avoid combination
CarBAMazepine: May decrease the serum concentration of Efavirenz. Efavirenz may decrease the serum concentration of CarBAMazepine. Risk X: Avoid combination
Cariprazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cariprazine. Risk X: Avoid combination
Caspofungin: Inducers of Drug Clearance may decrease the 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 the serum concentration of Ceritinib. Risk C: Monitor therapy
Clarithromycin: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Moderate) may decrease the serum concentration 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 the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy
CloZAPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy
Cobicistat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobicistat. Risk C: Monitor therapy
Cobimetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib. Risk X: Avoid combination
Codeine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
Copanlisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Copanlisib. Risk C: Monitor therapy
Crizotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Crizotinib. Risk C: Monitor therapy
CycloPHOSphamide: CYP2B6 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of CycloPHOSphamide. Risk C: Monitor therapy
CycloSPORINE (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Efavirenz. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Efavirenz. Risk C: Monitor therapy
Daclatasvir: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Dapsone (Systemic). Risk C: Monitor therapy
Daridorexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Daridorexant. Risk X: Avoid combination
Darunavir: May increase the serum concentration of Efavirenz. Efavirenz may decrease the 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 the serum concentration of Dasabuvir. Risk X: Avoid combination
Dasatinib: CYP3A4 Inducers (Moderate) may increase the serum concentration of Dasatinib. Risk C: Monitor therapy
Deferasirox: UGT1A1 Inducers may decrease the 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 serum concentrations of the active metabolite(s) of Deflazacort. Risk X: Avoid combination
DexAMETHasone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapy
DiazePAM: CYP3A4 Inducers (Moderate) may decrease the serum concentration of DiazePAM. Risk C: Monitor therapy
Dienogest: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dienogest. Risk C: Monitor therapy
DilTIAZem: CYP3A4 Inducers (Moderate) may decrease the serum concentration of DilTIAZem. Risk C: Monitor therapy
Disopyramide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Disopyramide. Risk C: Monitor therapy
Dolutegravir: Efavirenz may decrease the 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 the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DroNABinol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of DroNABinol. Risk C: Monitor therapy
Dronedarone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dronedarone. Risk C: Monitor therapy
Duvelisib: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Dydrogesterone. Risk C: Monitor therapy
Elacestrant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elacestrant. Risk X: Avoid combination
Elbasvir and Grazoprevir: Efavirenz may decrease the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor therapy
Eliglustat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Eliglustat. Risk C: Monitor therapy
Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect 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 combination
Elvitegravir: Efavirenz may decrease the serum concentration of Elvitegravir. Risk X: Avoid combination
Encorafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Encorafenib. Risk C: Monitor therapy
Entrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Entrectinib. Risk X: Avoid combination
Enzalutamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Enzalutamide. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Enzalutamide. Risk C: Monitor therapy
Erdafitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. Risk D: Consider therapy modification
Ergonovine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the 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 combination
Erlotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erlotinib. Risk C: Monitor therapy
Estrogen Derivatives: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Etoposide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Everolimus: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Everolimus. Risk C: Monitor therapy
Exemestane: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Exemestane. Risk C: Monitor therapy
Fedratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fedratinib. Risk X: Avoid combination
Felodipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Felodipine. Risk C: Monitor therapy
FentaNYL: CYP3A4 Inducers (Moderate) may decrease the serum concentration of FentaNYL. Risk C: Monitor therapy
Fexinidazole: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Fexinidazole. Risk X: Avoid combination
Finerenone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Finerenone. Risk X: Avoid combination
Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Risk X: Avoid combination
Fosamprenavir: Efavirenz may decrease serum concentrations of the active metabolite(s) 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 the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Risk C: Monitor therapy
Fosnetupitant: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Fosnetupitant. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: May decrease the serum concentration of Efavirenz. Efavirenz may decrease the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy
Fostamatinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Fostamatinib. Risk C: Monitor therapy
Fruquintinib: CYP3A4 Inducers (Moderate) may decrease the 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
Ganaxolone: CYP3A4 Inducers (Moderate) may decrease the 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
Gefitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gefitinib. Risk C: Monitor therapy
Gemigliptin: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gemigliptin. Risk C: Monitor therapy
Gepirone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gepirone. Risk C: Monitor therapy
Ginkgo Biloba: May decrease the serum concentration of Efavirenz. Risk C: Monitor therapy
Glasdegib: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination
GuanFACINE: CYP3A4 Inducers (Moderate) may decrease the 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 enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Hormonal Contraceptives: Efavirenz may decrease the 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 diminish the therapeutic effect of Efavirenz. Risk C: Monitor therapy
HYDROcodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of HYDROcodone. Risk C: Monitor therapy
Hydrocortisone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
Ibrexafungerp: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrexafungerp. Risk X: Avoid combination
Ibrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrutinib. Risk C: Monitor therapy
Idelalisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Idelalisib. Risk C: Monitor therapy
Ifosfamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy
Imatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Imatinib. Risk C: Monitor therapy
Indinavir: Efavirenz may decrease the 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
Infigratinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Infigratinib. Risk X: Avoid combination
Irinotecan Products: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. Risk C: Monitor therapy
Isavuconazonium Sulfate: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Moderate) may decrease isavuconazole serum concentrations. Risk C: Monitor therapy
Isradipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Isradipine. Risk C: Monitor therapy
Istradefylline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Istradefylline. Risk C: Monitor therapy
Itraconazole: Efavirenz may decrease serum concentrations of the active metabolite(s) of Itraconazole. Efavirenz may decrease the serum concentration of Itraconazole. Risk X: Avoid combination
Ivabradine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ivabradine. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ivacaftor. Risk C: Monitor therapy
Ixabepilone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ixabepilone. Risk C: Monitor therapy
Ixazomib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ixazomib. Risk C: Monitor therapy
Ketamine: CYP2B6 Inducers (Moderate) may decrease the serum concentration of Ketamine. Risk C: Monitor therapy
Ketoconazole (Systemic): Efavirenz may decrease the 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 the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: CYP3A4 Inducers (Moderate) may decrease the 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
Lefamulin: CYP3A4 Inducers (Moderate) may decrease the 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
Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease the 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
Lemborexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lemborexant. Risk X: Avoid combination
Lenacapavir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lenacapavir. Risk X: Avoid combination
Leniolisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Leniolisib. Risk X: Avoid combination
Lercanidipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lercanidipine. Risk C: Monitor therapy
Letermovir: UGT1A1 Inducers may decrease the serum concentration of Letermovir. Risk X: Avoid combination
Levamlodipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Levamlodipine. Risk C: Monitor therapy
Levoketoconazole: Efavirenz may decrease the serum concentration of Levoketoconazole. Risk X: Avoid combination
Levomethadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the 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 therapy
Levomethadone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy
LinaGLIPtin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of LinaGLIPtin. Risk C: Monitor therapy
Lonafarnib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lonafarnib. Risk X: Avoid combination
Lopinavir: Efavirenz may decrease the 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 enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Lovastatin. Risk C: Monitor therapy
Lovotibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Lumacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumacaftor and Ivacaftor. Risk C: Monitor therapy
Lumateperone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumateperone. Risk X: Avoid combination
Lurasidone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurasidone. Management: Monitor for decreased lurasidone effects if combined with moderate CYP3A4 inducers and consider increasing the lurasidone dose if coadministered with a moderate CYP3A4 inducer for 7 or more days. Risk D: Consider therapy modification
Macimorelin: Efavirenz may diminish the diagnostic effect of Macimorelin. Risk C: Monitor therapy
Macitentan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Macitentan. Risk C: Monitor therapy
Maraviroc: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Maribavir. Risk C: Monitor therapy
Mavacamten: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mavacamten. Risk X: Avoid combination
Mefloquine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mefloquine. Risk C: Monitor therapy
Meperidine: CYP2B6 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. CYP2B6 Inducers (Moderate) may decrease the serum concentration of Meperidine. Risk C: Monitor therapy
Methadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the 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 therapy
MethylPREDNISolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy
Mianserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mianserin. Risk C: Monitor therapy
Midazolam: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Midazolam. Risk C: Monitor therapy
Midostaurin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Midostaurin. Risk C: Monitor therapy
MiFEPRIStone: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Mirodenafil. Risk C: Monitor therapy
Mitapivat: CYP3A4 Inducers (Moderate) may decrease the 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 concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination
Naldemedine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naldemedine. Risk C: Monitor therapy
Naloxegol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naloxegol. Risk C: Monitor therapy
Nelfinavir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nelfinavir. Risk C: Monitor therapy
Neratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Neratinib. Risk X: Avoid combination
Netupitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Netupitant. Risk C: Monitor therapy
NIFEdipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NIFEdipine. Risk C: Monitor therapy
Nilotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nilotinib. Risk C: Monitor therapy
Nilvadipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nilvadipine. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: Efavirenz may enhance the adverse/toxic effect of Nirmatrelvir and Ritonavir. Efavirenz may decrease the serum concentration of Nirmatrelvir and Ritonavir. Specifically, efavirenz may decrease concentration of nirmatrelvir. Efavirenz may increase the serum concentration of Nirmatrelvir and Ritonavir. Specifically, efavirenz may increase concentration of ritonavir. Nirmatrelvir and Ritonavir may increase the serum concentration of Efavirenz. Risk C: Monitor therapy
Nirogacestat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nirogacestat. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nisoldipine. Risk X: Avoid combination
Olaparib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olaparib. Risk X: Avoid combination
Oliceridine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olmutinib. Risk C: Monitor therapy
Olutasidenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olutasidenib. Risk X: Avoid combination
Omaveloxolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Omaveloxolone. Risk X: Avoid combination
Orelabrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Orelabrutinib. Risk X: Avoid combination
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
Osimertinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Osimertinib. Risk C: Monitor therapy
OxyCODONE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy
PACLitaxel (Conventional): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
Pacritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pacritinib. Risk X: Avoid combination
Palbociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palbociclib. Risk C: Monitor therapy
Palovarotene: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palovarotene. Risk X: Avoid combination
PAZOPanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PAZOPanib. Risk C: Monitor therapy
Pemigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pemigatinib. Risk X: Avoid combination
Perampanel: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Pimavanserin. Risk X: Avoid combination
Piperaquine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Piperaquine. Risk C: Monitor therapy
Pirtobrutinib: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of PONATinib. Risk C: Monitor therapy
Posaconazole: Efavirenz may decrease the serum concentration of Posaconazole. Risk X: Avoid combination
Pralsetinib: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Pravastatin. Risk C: Monitor therapy
Praziquantel: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of PrednisoLONE (Systemic). Risk C: Monitor therapy
PredniSONE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PredniSONE. Risk C: Monitor therapy
Pretomanid: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pretomanid. Risk X: Avoid combination
Proguanil: Efavirenz may decrease serum concentrations of the active metabolite(s) of Proguanil. Efavirenz may decrease the serum concentration of Proguanil. Efavirenz may increase the serum concentration of Proguanil. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect 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 therapy
QUEtiapine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of QUEtiapine. Risk C: Monitor therapy
QuiNIDine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy
QuiNINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of QuiNINE. Risk C: Monitor therapy
Quizartinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Quizartinib. Risk X: Avoid combination
Ranolazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination
Red Yeast Rice: Efavirenz may decrease the serum concentration of Red Yeast Rice. Risk C: Monitor therapy
Regorafenib: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Regorafenib. Risk C: Monitor therapy
Repaglinide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Repaglinide. Risk C: Monitor therapy
Repotrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Repotrectinib. Risk X: Avoid combination
Reverse Transcriptase Inhibitors (Non-Nucleoside): May enhance the adverse/toxic effect of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of other 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 the serum concentration of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, delavirdine may increase the serum concentration of etravirine. Risk X: Avoid combination
Ribociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ribociclib. Risk C: Monitor therapy
Rifabutin: Efavirenz may decrease the serum concentration of Rifabutin. Rifabutin may decrease the 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 the serum concentration of Efavirenz. Efavirenz may decrease the 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 therapy
Rimegepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rimegepant. Risk X: Avoid combination
Ripretinib: CYP3A4 Inducers (Moderate) may decrease the 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 concentrations of the active metabolite(s) of RisperiDONE. CYP3A4 Inducers (Moderate) may decrease the serum concentration of RisperiDONE. Risk C: Monitor therapy
Ritlecitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ritlecitinib. Risk C: Monitor therapy
Ritonavir: Efavirenz may enhance the adverse/toxic effect of Ritonavir. Efavirenz may increase the serum concentration of Ritonavir. Ritonavir may increase the serum concentration of Efavirenz. Risk C: Monitor therapy
Roflumilast (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Roflumilast (Systemic). CYP3A4 Inducers (Moderate) may decrease the serum concentration of Roflumilast (Systemic). Risk C: Monitor therapy
Rolapitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant. Risk C: Monitor therapy
Sacituzumab Govitecan: UGT1A1 Inducers may decrease serum concentrations of the active metabolite(s) of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be decreased. Risk X: Avoid combination
Samidorphan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Samidorphan. Risk C: Monitor therapy
Saquinavir: May enhance the hepatotoxic effect of Efavirenz. Efavirenz may decrease the 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 combination
Selpercatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selpercatinib. Risk X: Avoid combination
Selumetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selumetinib. Risk X: Avoid combination
Sertraline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sertraline. Risk C: Monitor therapy
Sildenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sildenafil. Risk C: Monitor therapy
Simeprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir. Risk X: Avoid combination
Simvastatin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simvastatin. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: Monitor therapy
Sonidegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sonidegib. Risk X: Avoid combination
SORAfenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SORAfenib. Risk C: Monitor therapy
Sotorasib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sotorasib. Risk C: Monitor therapy
Sparsentan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sparsentan. Risk C: Monitor therapy
SUFentanil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SUFentanil. Risk C: Monitor therapy
SUNItinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SUNItinib. Risk C: Monitor therapy
Suvorexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Suvorexant. Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tadalafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tadalafil. Risk C: Monitor therapy
Tamoxifen: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tamoxifen. Risk C: Monitor therapy
Tasimelteon: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tasimelteon. Risk C: Monitor therapy
Tazemetostat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tazemetostat. Risk X: Avoid combination
Temsirolimus: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, sirolimus concentrations may be decreased. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Temsirolimus. Risk C: Monitor therapy
Tetrahydrocannabinol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy
Tezacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tezacaftor and Ivacaftor. Risk C: Monitor therapy
Thiotepa: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Thiotepa: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Thiotepa. Risk C: Monitor therapy
Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ticagrelor. Risk C: Monitor therapy
Tivozanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tivozanib. Risk C: Monitor therapy
Tofacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tofacitinib. Risk C: Monitor therapy
Tolvaptan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tolvaptan. Risk C: Monitor therapy
Toremifene: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Toremifene. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Toremifene. Risk C: Monitor therapy
Trabectedin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Trabectedin. Risk C: Monitor therapy
TraMADol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of TraMADol. Risk C: Monitor therapy
TraZODone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of TraZODone. Risk C: Monitor therapy
Triazolam: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Triazolam. Risk C: Monitor therapy
Tucatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tucatinib. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Ulipristal. Risk X: Avoid combination
Upadacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Upadacitinib. Risk C: Monitor therapy
Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Valbenazine. Risk C: Monitor therapy
Valoctocogene Roxaparvovec: May enhance the hepatotoxic effect of Efavirenz. Efavirenz may diminish the therapeutic effect of Valoctocogene Roxaparvovec. Risk X: Avoid combination
Vandetanib: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Vandetanib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vandetanib. Risk C: Monitor therapy
Velpatasvir: CYP2B6 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Risk X: Avoid combination
Velpatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Risk X: Avoid combination
Vemurafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vemurafenib. Risk C: Monitor therapy
Venetoclax: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Venetoclax. Risk X: Avoid combination
Verapamil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Verapamil. Risk C: Monitor therapy
Vilazodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vilazodone. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Efavirenz may decrease the serum concentration of Vitamin K Antagonists. Efavirenz may increase the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Voclosporin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voclosporin. Risk X: Avoid combination
Vonoprazan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vonoprazan. Risk X: Avoid combination
Vorapaxar: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vorapaxar. Risk X: Avoid combination
Voriconazole: Efavirenz may decrease the serum concentration of Voriconazole. Voriconazole may increase the 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 the serum concentration of Vortioxetine. Risk C: Monitor therapy
Voxelotor: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Voxilaprevir. Risk X: Avoid combination
Zaleplon: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zaleplon. Risk C: Monitor therapy
Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Zolpidem. Risk C: Monitor therapy
Zopiclone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zopiclone. Risk C: Monitor therapy
Zuranolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zuranolone. Risk X: Avoid combination
High-fat/high-caloric meals increase the absorption of efavirenz. CNS effects are possible. Management: Avoid high-fat/high-caloric meals. Administer at or before bedtime on an empty stomach unless using capsule sprinkle method in patients unable to swallow capsules or tablets. If capsule sprinkle method is used, patient should not consume additional food for 2 hours after administration.
The manufacturer recommends patients of reproductive potential undergo pregnancy testing prior to initiation of efavirenz. The manufacturer also recommends barrier contraception be used in combination with other (hormonal) methods of contraception during therapy and for 12 weeks after efavirenz is discontinued. However, current Health and Human Services (HHS) perinatal HIV guidelines do not restrict use of efavirenz in patients who are planning to become pregnant and note contraception is not required to initiate or continue antiretroviral therapy (ART). Patients with HIV who may become pregnant but who are not planning a pregnancy 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 efavirenz and specific contraceptives, particularly if efficacy of the contraceptive method is of primary importance (HHS [perinatal] 2023).
HHS perinatal HIV guidelines consider efavirenz an alternative ART for patients with HIV who are not yet pregnant but are trying to conceive.
Maximum viral suppression sustained below the limits of detection prior to conception is recommended for all persons with HIV who are planning a pregnancy. Optimization of the health of the person who will become pregnant is recommended. Selection of or changes to a specific antiretroviral regimen prior to pregnancy should be done as part of a shared decision-making process. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.
Health care providers caring for couples planning a pregnancy when one or both partners are diagnosed with HIV may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2023).
Efavirenz has a moderate level of transfer across the human placenta.
Based on data from the Antiretroviral Pregnancy Registry, an increased risk of overall teratogenic effects has not been observed following first trimester exposure to efavirenz. Neural tube and other CNS defects have been reported; however, data collected by the registry has shown that the risk for neural tube defects after efavirenz exposure in the first trimester are not greater than those in the general population. Additional data are needed to evaluate the potential risks of microcephaly and developmental delay. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm birth, low birth weight, and small for gestational age infants. Actual risks may be influenced by maternal factors, such as disease severity, gestational age at initiation of therapy, and specific ART regimen, therefore close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential metabolic dysfunction.
The Health and Human Services (HHS) perinatal HIV guidelines consider efavirenz an alternative ART for pregnant patients with HIV who are antiretroviral-naive, who have had ART therapy 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 efavirenz may continue if viral suppression is effective and the regimen is well tolerated.
The pharmacokinetics of efavirenz may be altered in pregnancy, particularly during the third trimester in patients who are extensive CYP2B6 metabolizers. The standard adult doses should be used until pharmacokinetic data are available for the use of reduced doses in patients who are pregnant.
Use may be considered for patients having drug interactions with other medications or who require the convenience of once daily dosing (and are not eligible for dolutegravir); screening for antenatal and postpartum depression is recommended. Although not recommended by the manufacturer, HHS guidelines do not restrict the use of efavirenz in the first trimester.
ART is recommended for all pregnant people with HIV to maximize their health, maintain the viral load below the limit of detection, and reduce the risk of perinatal transmission. Selection of or changes to a specific antiretroviral regimen during pregnancy should be done as part of a shared decision-making process. Patients on fully suppressive regimens prior to pregnancy generally may continue the same regimen considering known pregnancy outcomes and pharmacokinetic data. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.
Data collection to monitor pregnancy and infant outcomes following exposure to ART is ongoing. Health care providers should enroll all patients exposed to antiretroviral medications during pregnancy in the Antiretroviral Pregnancy Registry (1-800-258-4263). Enrollment should be done as early in pregnancy as possible.
Health care providers caring for pregnant patients with HIV and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2023).
Efavirenz is present in breast milk.
Plasma concentrations of efavirenz in breastfeeding infants have been reported as ~13% of maternal plasma concentrations. Infants in this study (n=13) were exposed to efavirenz during the last trimester of pregnancy and 6 months postpartum.
Maintaining maximum viral suppression during pregnancy and postpartum decreases but does not eliminate the risk of HIV transmission via breast milk. In addition, multiclass-resistant virus has been detected in breastfeeding infants who acquire HIV despite maternal therapy. In the United States, where formula is usually accessible, affordable, safe, and sustainable, and the risk of infant mortality due to diarrhea and respiratory infections is low, the Health and Human Services perinatal HIV guidelines do not recommend breastfeeding for patients with HIV when safer infant feeding options are available. Persons with HIV who maintain an undetectable viral load while taking antiretroviral therapy (ART) should evaluate infant feeding options (formula, banked donor milk, or breastfeeding) as part of a shared decision-making process (if breastfeeding is being considered, see guidelines for measures to reduce the risk of HIV transmission). When the HIV status at delivery is not known, breastmilk may be expressed and stored until a negative test is available. If HIV infection is diagnosed after breastfeeding has been initiated, breastfeeding should be discontinued immediately. Breastfeeding is not recommended for persons with HIV who are not taking ART and/or who do not have sustained viral suppression.
Information is available for counseling and managing patients with HIV who are considering breastfeeding (1-888-448-8765). In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth (HHS [perinatal] 2023).
Should be taken on an empty stomach unless using capsule sprinkle method in patients unable to swallow capsules or tablets. If capsule sprinkle method is used, do not consume additional food for 2 hours after administration.
Serum transaminases; cholesterol and triglycerides (prior to therapy and periodically during); signs and symptoms of infection; psychiatric effects
As a non-nucleoside reverse transcriptase inhibitor, efavirenz has activity against HIV-1 by binding to reverse transcriptase. It consequently blocks the RNA-dependent and DNA-dependent DNA polymerase activities including HIV-1 replication. It does not require intracellular phosphorylation for antiviral activity.
Absorption: Increased by high-fat/high-caloric meals
Distribution: CSF concentrations are 0.69% of plasma (range: 0.26% to 1.2%); however, CSF:plasma concentration ratio is 3 times higher than free fraction in plasma
Protein binding: >99%, primarily to albumin
Metabolism: Hepatic via CYP3A and 2B6 to inactive hydroxylated metabolites which then undergo glucuronidation; induces P450 enzymes and its own metabolism
Bioavailability: 42%
Half-life elimination: Single dose: 52 to 76 hours; Multiple doses: 40 to 55 hours
Time to peak: 3 to 5 hours
Excretion: Feces (16% to 61% primarily as unchanged drug); urine (~14% to 34% as metabolites; <1% unchanged drug)
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