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Efavirenz

Medically reviewed by Drugs.com. Last updated on Aug 17, 2020.

Pronunciation

(e FAV e renz)

Dosage Forms

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

Capsule, Oral:

Sustiva: 50 mg, 200 mg

Generic: 50 mg, 200 mg

Tablet, Oral:

Sustiva: 600 mg

Generic: 600 mg

Brand Names: U.S.

  • Sustiva

Pharmacologic Category

  • Antiretroviral, Reverse Transcriptase Inhibitor, Non-nucleoside (Anti-HIV)

Pharmacology

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

Metabolism

Hepatic via CYP3A and 2B6 to inactive hydroxylated metabolites which then undergo glucuronidation; induces P450 enzymes and its own metabolism

Excretion

Feces (16% to 61% primarily as unchanged drug); urine (~14% to 34% as metabolites; <1% unchanged drug)

Time to Peak

3 to 5 hours

Half-Life Elimination

Single dose: 52 to 76 hours; Multiple doses: 40 to 55 hours

Protein Binding

>99%, primarily to albumin

Use: Labeled Indications

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

Contraindications

Hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions) to efavirenz or any component of the formulation; concurrent administration with elbasvir or grazoprevir

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

Dosing: Adult

HIV-1 infection, treatment:

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. Note: Do not use efavirenz plus abacavir and lamivudine in patients with a pre-antiretroviral therapy HIV RNA ≥100,000 copies/mL (HHS [adult] 2019).

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

HIV-1 infection, treatment: Use in combination with other antiretroviral agents:

Infants <3 months or <3 kg: Not recommended for use.

Infants ≥3 months weighing ≥3 kg and Children <3 years: Oral:

AIDSinfo recommendation: Very limited data available: Note: In general, current guidelines do not recommend efavirenz use 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. The following doses are under investigation and have been suggested by the expert panel based on pharmacokinetic data (HHS [pediatric] 2016).

Extensive metabolizers (CYP2B6 516 G/G or G/T genotypes):

3 kg to <5 kg: 200 mg once daily.

5 kg to <7 kg: 300 mg once daily.

7 kg to <14 kg: 400 mg once daily.

14 kg to <17 kg: 500 mg once daily.

≥17 kg: 600 mg once daily.

Slow metabolizer (CYP 2B6 516 T/T genotype):

3 kg to <7 kg: 50 mg once daily.

7 kg to <14 kg: 100 mg once daily.

≥14 kg: 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 dosing may result in subtherapeutic levels in extensive metabolizers and supratherapeutic in slow metabolizers and use should be avoided (HHS [pediatric] 2016).

3.5 kg to <5 kg: 100 mg once daily.

5 kg to <7.5 kg: 150 mg once daily.

7.5 kg to <15 kg: 200 mg once daily.

15 kg to <20 kg: 250 mg once daily.

Children ≥3 years and Adolescents:

Weight-directed dosing: Oral:

10 kg to <15 kg: 200 mg once daily.

15 kg to <20 kg: 250 mg once daily.

20 kg to <25 kg: 300 mg once daily.

25 kg to <32.5 kg: 350 mg once daily.

32.5 kg to <40 kg: 400 mg once daily.

≥40 kg: 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 (HHS [pediatric] 2016).

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

Administration

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.

Dietary Considerations

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.

Storage

Store at 25°C (77°F); excursion permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Abametapir: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Avoid combination

Abemaciclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abemaciclib. Avoid combination

Abiraterone Acetate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abiraterone Acetate. Monitor therapy

Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Acalabrutinib. Monitor therapy

Alcohol (Ethyl): Efavirenz may enhance the adverse/toxic effect of Alcohol (Ethyl). Efavirenz may decrease the serum concentration of Alcohol (Ethyl). 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. Consider therapy modification

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Amodiaquine: Efavirenz may enhance the hepatotoxic effect of Amodiaquine. Efavirenz may increase the serum concentration of Amodiaquine. Avoid combination

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

Apremilast: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Apremilast. Monitor therapy

Aprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Aprepitant. Monitor therapy

ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole. Monitor therapy

ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole Lauroxil. Monitor therapy

Artemether: Efavirenz may decrease the serum concentration of Artemether. Concentrations of dihydroartemisinin (active metabolite of artemether) may also be decreased by efavirenz Monitor therapy

Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Avoid combination

Atazanavir: Efavirenz may decrease the serum concentration of Atazanavir. Management: When used with efavirenz, the adult atazanavir dose should be 400 mg daily, boosted with ritonavir 100 mg daily or cobicistat 150 mg daily, for treatment-naive patients only; treatment-experienced patients should not use atazanavir with efavirenz. Consider therapy modification

AtorvaSTATin: Efavirenz may decrease the serum concentration of AtorvaSTATin. 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. Consider therapy modification

Avanafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avanafil. Avoid combination

Avapritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avapritinib. Avoid combination

Axitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib. Avoid combination

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Consider therapy modification

Bortezomib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bortezomib. Monitor therapy

Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Avoid combination

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brexpiprazole. 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. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: Efavirenz may decrease serum concentrations of the active metabolite(s) of Buprenorphine. Efavirenz may decrease the serum concentration of Buprenorphine. Monitor therapy

BuPROPion: CYP2B6 Inducers (Moderate) may decrease the serum concentration of BuPROPion. Monitor therapy

Cabozantinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cabozantinib. Monitor therapy

Calcium Channel Blockers: Efavirenz may decrease the serum concentration of Calcium Channel Blockers. Monitor therapy

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Capmatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Capmatinib. Avoid combination

CarBAMazepine: May decrease the serum concentration of Efavirenz. Efavirenz may decrease the serum concentration of CarBAMazepine. 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. Consider therapy modification

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Clarithromycin: Efavirenz may enhance the QTc-prolonging effect of Clarithromycin. Efavirenz may decrease the serum concentration of Clarithromycin. Additionally, efavirenz may increase the active metabolite of clarithromycin Management: Consider using an alternative antibiotic in patients taking efavirenz. If concomitant therapy cannot be avoided, monitor for decreased therapeutic effect of clarithromycin and for QT interval prolongation. Consider therapy modification

CloZAPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CloZAPine. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Cobimetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib. Avoid combination

Copanlisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Copanlisib. Monitor therapy

Crizotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Crizotinib. Monitor therapy

Cyclophosphamide: CYP2B6 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Cyclophosphamide. Monitor therapy

CycloSPORINE (Systemic): Efavirenz may decrease the serum concentration of CycloSPORINE (Systemic). Management: Increase monitoring of cyclosporine concentrations when starting, stopping, or adjusting doses of concurrent efavirenz, particularly within the first 2 weeks. Cyclosporine dose adjustment may be required. Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Substrates (High risk with Inducers): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Exceptions: Apixaban; Bromperidol; Rivaroxaban. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

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. Consider therapy modification

Dapsone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dapsone (Systemic). Monitor therapy

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. Consider therapy modification

Dasabuvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dasabuvir. Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deflazacort: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Avoid combination

DilTIAZem: Efavirenz may decrease the serum concentration of DilTIAZem. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. 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. See interaction monograph for details. Not recommended with Dovato or Juluca combo products. Seek alternatives if INSTI resistance. Consider therapy modification

Doravirine: Efavirenz may decrease the serum concentration of Doravirine. Avoid combination

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Elbasvir: Efavirenz may decrease the serum concentration of Elbasvir. Avoid combination

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

Elvitegravir: Efavirenz may decrease the serum concentration of Elvitegravir. Avoid combination

Encorafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Encorafenib. Avoid combination

Entrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Entrectinib. Avoid combination

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. 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. Avoid combination

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Estriol (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Systemic). Monitor therapy

Estriol (Topical): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Topical). Monitor therapy

Etoposide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide. Monitor therapy

Etoposide Phosphate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide Phosphate. Monitor therapy

Etravirine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Etravirine. This has been observed with the NNRTIs efavirenz and nevirapine. Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Etravirine. This has been observed with delavirdine. Avoid combination

Everolimus: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Everolimus. Monitor therapy

Fedratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fedratinib. Avoid combination

Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Consider therapy modification

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. 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. Monitor therapy

Fosphenytoin: May decrease the serum concentration of Efavirenz. Efavirenz may increase the serum concentration of Fosphenytoin. Monitor therapy

Ginkgo Biloba: May decrease the serum concentration of Efavirenz. 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. Consider therapy modification

Glecaprevir and Pibrentasvir: Efavirenz may decrease the serum concentration of Glecaprevir and Pibrentasvir. Avoid combination

Grazoprevir: Efavirenz may decrease the serum concentration of Grazoprevir. 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. Consider therapy modification

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Ibrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrutinib. 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. 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. Consider therapy modification

Istradefylline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Istradefylline. Monitor therapy

Itraconazole: Efavirenz may decrease the serum concentration of Itraconazole. Avoid combination

Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ivacaftor. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Ketamine: CYP2B6 Inducers (Moderate) may decrease the serum concentration of Ketamine. Monitor therapy

Ketoconazole (Systemic): Efavirenz may decrease the serum concentration of Ketoconazole (Systemic). Avoid combination

Lapatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lapatinib. Monitor therapy

Larotrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Larotrectinib. Monitor therapy

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. 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. Consider therapy modification

Lemborexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lemborexant. Avoid combination

Lercanidipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lercanidipine. Monitor therapy

Letermovir: May increase the serum concentration of UGT1A1 Inducers. Avoid combination

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

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. See lopinavir/ritonavir prescribing information for specific recommended dose increases in particular patient populations. 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, monitor AST, ALT, and bilirubin within 48 hours of starting the combination and at least three times within the first week of combined use. Consider therapy modification

Lovastatin: Efavirenz may decrease the serum concentration of Lovastatin. Monitor therapy

Lumateperone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumateperone. Avoid combination

Lumefantrine: Efavirenz may decrease the serum concentration of Lumefantrine. Monitor therapy

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. Consider therapy modification

Lurbinectedin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurbinectedin. Avoid combination

Macimorelin: Efavirenz may diminish the diagnostic effect of Macimorelin. Monitor therapy

Macitentan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Macitentan. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Maraviroc: Efavirenz may decrease the serum concentration of Maraviroc. Of note, this effect only applies in the absence of a strong CYP3A4 inhibitor Management: Increase maraviroc adult dose to 600mg twice/day, but only in the absence of a concurrent strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Do not use in patients with CrCl less than 30 mL/min. Consider therapy modification

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirodenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mirodenafil. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Naldemedine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naldemedine. Monitor therapy

Naloxegol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naloxegol. Monitor therapy

Neratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Neratinib. Avoid combination

Nevirapine: May enhance the adverse/toxic effect of Efavirenz. Efavirenz may enhance the adverse/toxic effect of Nevirapine. Nevirapine may decrease the serum concentration of Efavirenz. Avoid combination

NiMODipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NiMODipine. Monitor therapy

Nisoldipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nisoldipine. Avoid combination

Norgestimate: Efavirenz may decrease serum concentrations of the active metabolite(s) of Norgestimate. Management: Use a reliable barrier contraceptive if efavirenz is used in combination with norgestimate. Continue using barrier contraception for 12 weeks after discontinuation of efavirenz. Consider therapy modification

Olaparib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olaparib. Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interupt oxybate salt treatment during short-term opioid use. Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Palbociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palbociclib. Management: The US label does not provide specific recommendations concerning use with moderate CYP3A4 inducers, but the Canadian label recommends avoiding use of moderate CYP3A4 inducers. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

PAZOPanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PAZOPanib. Monitor therapy

Pemigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pemigatinib. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Perampanel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Monitor perampanel response closely, particularly with changes to CYP3A4 inducer therapy. Consider therapy modification

Pexidartinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pexidartinib. Monitor therapy

Phenytoin: May decrease the serum concentration of Efavirenz. Efavirenz may increase the serum concentration of Phenytoin. Monitor therapy

Pimavanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pimavanserin. Avoid combination

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pitolisant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pitolisant. Monitor therapy

Posaconazole: Efavirenz may decrease the serum concentration of Posaconazole. Avoid combination

Pralsetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pralsetinib. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Pravastatin: Efavirenz may decrease the serum concentration of Pravastatin. Monitor therapy

Pretomanid: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pretomanid. Avoid combination

Progestins (Contraceptive): Efavirenz may decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification

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. Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) 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. Monitor therapy

Ranolazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ranolazine. Avoid combination

Reverse Transcriptase Inhibitors (Non-Nucleoside): May increase the serum concentration of Efavirenz. Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Efavirenz. Avoid combination

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. Consider therapy modification

RifAMPin: May decrease the serum concentration of Efavirenz. Management: Closely monitor virologic response to efavirenz when used with 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. Monitor therapy

Rilpivirine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Rilpivirine. This mechanism applies to coadministration of delavirdine. Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Rilpivirine. This mechanism applies to coadministration of efavirenz, etravirine, and nevirapine. Avoid combination

Rimegepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rimegepant. Avoid combination

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. Monitor therapy

Rolapitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. 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. Avoid combination

Saquinavir: May enhance the adverse/toxic 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. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Selpercatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selpercatinib. Avoid combination

Selumetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selumetinib. Avoid combination

Sertraline: Efavirenz may decrease the serum concentration of Sertraline. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir. Avoid combination

Simvastatin: Efavirenz may decrease the serum concentration of Simvastatin. Monitor therapy

Sirolimus: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sirolimus. Monitor therapy

Sonidegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sonidegib. Avoid combination

St John's Wort: May decrease the serum concentration of Efavirenz. Avoid combination

SUNItinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SUNItinib. Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tacrolimus (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tacrolimus (Systemic). Monitor therapy

Tazemetostat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tazemetostat. Avoid combination

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

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

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Ulipristal: Efavirenz may decrease the serum concentration of Ulipristal. Avoid combination

Upadacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Upadacitinib. Monitor therapy

Velpatasvir: CYP2B6 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Avoid combination

Velpatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Avoid combination

Vemurafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vemurafenib. Monitor therapy

Venetoclax: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Venetoclax. Avoid combination

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. Monitor therapy

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. Consider therapy modification

Vortioxetine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vortioxetine. Monitor therapy

Voxelotor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If concomitant use is unavoidable, increase the voxelotor dose to 2,500 mg once daily. Consider therapy modification

Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zanubrutinib. Avoid combination

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Test Interactions

False-positive tests for cannabinoids have been reported when the CEDIA DAU Multilevel THC assay is used. False-positive results with other assays for cannabinoids have not been observed. False-positive tests for benzodiazepines have been reported and are likely due to the 8-hydroxy-efavirenz major metabolite.

Adverse Reactions

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

Warnings/Precautions

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.

Monitoring Parameters

Serum transaminases; cholesterol and triglycerides (prior to therapy and periodically during); signs and symptoms of infection; psychiatric effects

Reproductive Considerations

The Health and Human Services (HHS) perinatal HIV guidelines consider efavirenz an alternative antiretroviral therapy for females living with HIV who are not yet pregnant but are trying to conceive.

Females living with HIV 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 (HHS [perinatal] 2019). The manufacturer recommends women of reproductive potential undergo pregnancy testing prior to initiation of efavirenz. Barrier contraception should be used in combination with other (hormonal) methods of contraception during therapy and for 12 weeks after efavirenz is discontinued. However, current HHS perinatal HIV guidelines do not restrict use in females planning a pregnancy.

For males and females living with HIV and planning a pregnancy, maximum viral suppression below the limits of detection with antiretroviral therapy (ART), modification of therapy (if needed), optimization of the woman's health, and a discussion of the potential risks and benefits of ART therapy during pregnancy is recommended prior to conception (HHS [perinatal] 2019).

Pregnancy Considerations

Efavirenz has a moderate level of transfer across the human placenta.

Based on data from the Antiretroviral Pregnancy Registry, an increased risk of overall birth defects has not been observed following first trimester exposure to efavirenz. Neural tube and other CNS defects have been reported; however, a meta-analysis 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. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm delivery, stillbirth, 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 without HIV but who were exposed to ART in utero and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction. Hypersensitivity reactions (including hepatic toxicity and rash) are more common in women on non-nucleoside reverse transcriptase inhibitor therapy; it is not known if pregnancy increases this risk.

The Health and Human Services (HHS) perinatal HIV guidelines consider efavirenz an alternative ART for pregnant females living 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). Females who become pregnant while taking efavirenz may continue if viral suppression is effective and the regimen is well tolerated. Pharmacokinetic data from available studies do not suggest dose alterations are needed during pregnancy.

Use may be considered for females having drug interactions with other medications or who require the convenience of once daily dosing (and are not eligible for dolutegravir or rilpivirine); 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.

In general, ART is recommended for all pregnant females living with HIV to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of pregnant females is more frequent than in nonpregnant adults. ART should be continued postpartum for all females living with HIV and can be modified after delivery.

Health care providers are encouraged to enroll pregnant females exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant females living with HIV and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2019).

Patient Education

What is this drug used for?

• It is used to treat HIV infection.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Diarrhea

• Headache

• Loss of strength and energy

• Fatigue

• Trouble sleeping

• Trouble focusing

• Abnormal dreams

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes

• Depression like thoughts of suicide, anxiety, emotional instability, agitation, irritability, panic attacks, mood changes, behavioral changes, or confusion

• Change in body fat

• Behavioral changes

• Sensing things that seem real but are not

• Trouble with memory

• Confusion

• Seizures

• Mood changes

• Change in balance

• Abnormal movements

• Abnormal heartbeat

• Fast heartbeat

• Severe dizziness

• Passing out

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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