(e FAV e renz, em trye SYE ta been, & ten OF oh vir dye soe PROX il FUE ma rate)
Treatment of HIV-1 infection
History of clinically-significant hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin reactions) to efavirenz; concurrent use of bepridil, cisapride, midazolam, triazolam, voriconazole, ergot alkaloids (includes dihydroergotamine, ergotamine, ergonovine, methylergonovine), St Johns wort, pimozide
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to any component of the formulation; concomitant use with astemizole or terfenadine (not marketed in Canada)
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including tenofovir disoproxil fumarate, in combination with other antiretrovirals.
Hepatitis B coinfection:Efavirenz/emtricitabine/tenofovir disoproxil fumarate is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy have not been established in patients coinfected with HBV and HIV-1. Severe, acute exacerbations of hepatitis B have been reported in patients who have discontinued emtricitabine or tenofovir disoproxil fumarate. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who discontinue therapy and are coinfected with HIV-1 and HBV. If appropriate, initiation of anti " “hepatitis B therapy may be warranted.
Note: Prior to initiation, patients should be tested for hepatitis B infection, and baseline estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein should be assessed in all patients.
HIV infection: Oral: One tablet once daily.
Refer to adult dosing.
Note: Prior to initiation, patients should be tested for hepatitis B infection, and baseline estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein should be assessed in all patients.
HIV infection:
US labeling: Children ≥12 years and ≥40 kg and Adolescents: Oral: Refer to adult dosing.
Canadian labeling: Use is not approved in pediatric patients.
Moderate-to-severe renal impairment (CrCl <50 mL/minute): Use not recommended.
Mild hepatic impairment (Child-Pugh class A): Use with caution.
Moderate or severe hepatic impairment (Child-Pugh class B, C): Not recommended.
Should be taken on an empty stomach, normally at bedtime to increase gastrointestinal tolerance and decrease nervous system manifestations.
Should be taken on an empty stomach. In patients with history of bone fracture or osteopenia, consider calcium and vitamin D supplementation.
Store at 25 ‚ °C (77 ‚ °F); excursions permitted between 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Dispense only in original container; do not use if seal on bottle is broken or missing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral:
Atripla: Efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg
Acyclovir-Valacyclovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Monitor therapy
Adefovir: May diminish the therapeutic effect of Tenofovir Products. Adefovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Adefovir. Avoid combination
Alcohol (Ethyl): Efavirenz may enhance the adverse/toxic effect of Alcohol (Ethyl). Efavirenz may decrease the serum concentration of Alcohol (Ethyl). Monitor therapy
Aminoglycosides: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. 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
ARIPiprazole: CYP3A4 Inducers may decrease the serum concentration of ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor response. Reduce oral aripiprazole dose to 10-15 mg/day (for adults) if the inducer is discontinued. Avoid use of CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Consider therapy modification
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: Tenofovir Disoproxil Fumarate may decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Must use ritonavir-boosting in adults; give combo (atazanavir/ritonavir 300mg/100mg and tenofovir 300mg) as a single daily dose with food. Pediatric patients, pregnant patients, and users of H2-blockers require other dose changes. Consider therapy modification
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
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. Consider therapy modification
Boceprevir: Efavirenz may decrease the serum concentration of Boceprevir. Boceprevir may increase the serum concentration of Efavirenz. Avoid combination
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosentan: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy
Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Avoid combination
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Buprenorphine: Efavirenz may decrease serum concentrations of the active metabolite(s) of Buprenorphine. Efavirenz may decrease the serum concentration of Buprenorphine. Monitor therapy
BuPROPion: Efavirenz may decrease the serum concentration of BuPROPion. Management: Monitor for decreased response to bupropion in patients treated with efavirenz. Increased bupropion doses may be required. Avoid the use of naltrexone/bupropion for weight management in patients receiving efavirenz. Monitor therapy
Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Monitor therapy
Calcium Channel Blockers: Efavirenz may decrease the serum concentration of Calcium Channel Blockers. Monitor therapy
Canagliflozin: Efavirenz may decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2. Consider therapy modification
Cannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Monitor therapy
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
CarBAMazepine: May decrease the serum concentration of Efavirenz. Efavirenz may decrease the serum concentration of CarBAMazepine. Avoid combination
Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Monitor therapy
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
Cidofovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Monitor therapy
Cilostazol: CYP2C19 Inhibitors may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19. Consider therapy modification
Citalopram: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a moderate CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (e.g., serotonin syndrome, QT prolongation, etc.). Consider therapy modification
Clarithromycin: Efavirenz may decrease the serum concentration of Clarithromycin. Management: Consider using an alternative antibiotic, such as azithromycin, for patients taking efavirenz. If concomitant therapy cannot be avoided, monitor for decreased therapeutic effect of clarithromycin and increased incidence of skin rash. Consider therapy modification
Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a moderate CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
Cobicistat: May enhance the adverse/toxic effect of Tenofovir Products. More specifically, cobicistat may impair proper tenofovir monitoring and dosing. Monitor therapy
Cobimetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib. Avoid combination
Contraceptives (Progestins): Efavirenz may decrease the serum concentration of Contraceptives (Progestins). 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
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
CYP2B6 Substrates: CYP2B6 Inducers (Moderate) may decrease the serum concentration of CYP2B6 Substrates. Monitor therapy
CYP2C19 Substrates: CYP2C19 Inhibitors (Moderate) may decrease the metabolism of CYP2C19 Substrates. Monitor therapy
CYP2C8 Substrates: CYP2C8 Inhibitors (Moderate) may decrease the metabolism of CYP2C8 Substrates. Monitor therapy
CYP2C9 Substrates: CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates. Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. 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: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. 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
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
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Diclofenac (Systemic): May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to this combination whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification
Didanosine: Tenofovir Disoproxil Fumarate may diminish the therapeutic effect of Didanosine. Tenofovir Disoproxil Fumarate may increase the serum concentration of Didanosine. Management: Avoid concomitant treatment with tenofovir disoproxil fumarate and didanosine. Consider altering even existing, stable treatment to avoid this combination. Avoid combination
DiltiaZEM: Efavirenz may decrease the serum concentration of DiltiaZEM. Monitor therapy
Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Dolutegravir: Efavirenz may decrease the serum concentration of Dolutegravir. Management: Increase dolutegravir dose to 50 mg twice daily in adults or children. Consider alternatives to efavirenz for INSTI experienced patients with clinically suspected INSTI resistance or certain INSTI associated resistance substitutions. Consider therapy modification
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: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. 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 (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
Elbasvir: Efavirenz may decrease the serum concentration of Elbasvir. Avoid combination
Elvitegravir: Efavirenz may decrease the serum concentration of Elvitegravir. Avoid combination
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. 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
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
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
Etonogestrel: Efavirenz may diminish the therapeutic effect of Etonogestrel. Management: Use a reliable barrier contraceptive if efavirenz is used in combination with etonogestrel. Continue using barrier contraception for 12 weeks after discontinuation of efavirenz. Consider therapy modification
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: Efavirenz may decrease the serum concentration of Everolimus. Management: Closely monitor everolimus serum concentrations when starting, stopping, or changing doses of efavirenz, particularly during the first 2 weeks after any change. Dose adjustment of everolimus may be required. Consider therapy modification
FentaNYL: CYP3A4 Inducers (Moderate) may decrease the serum concentration of FentaNYL. Monitor therapy
Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
Fosamprenavir: Efavirenz may decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Management: For once-daily fosamprenavir/ritonavir with efavirenz, an increased ritonavir dose to 300 mg/day is recommended in adult patients. No ritonavir dose adjustment is required if using twice-daily fosamprenavir/ritonavir. Consider therapy modification
Fosphenytoin: May decrease the serum concentration of Efavirenz. Efavirenz may increase the serum concentration of Fosphenytoin. Consider therapy modification
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity with zidovudine is of particular concern. Ganciclovir-Valganciclovir may increase the serum concentration of Reverse Transcriptase Inhibitors (Nucleoside). Management: Monitor patients receiving any of these combination closely for toxicity of the reverse transcriptase inhibitor. Avoid zidovudine. Intravitreal implants would not be affected. Consider therapy modification
Ginkgo Biloba: May decrease the serum concentration of Efavirenz. Monitor therapy
Grazoprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Grazoprevir. Avoid combination
GuanFACINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating concomitant therapy with moderate CYP3A4 inducers. Increase guanfacine dose gradually over 1-2 weeks if moderate CYP3A4 inducer therapy is just beginning. Consider therapy modification
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Ibrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrutinib. Management: Although moderate CYP3A inducers are not specifically contraindicated with ibrutinib, prescribing information indicates that they may decrease AUC up to 3-fold. If possible, alternatives with less CYP3A induction should be considered. Consider therapy modification
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
Itraconazole: Efavirenz may decrease the serum concentration of Itraconazole. Avoid combination
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Ketoconazole (Systemic): Efavirenz may decrease the serum concentration of Ketoconazole (Systemic). Avoid combination
LamiVUDine: May enhance the adverse/toxic effect of Emtricitabine. Avoid combination
Ledipasvir: May increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Avoidance of this combination is recommended under some circumstances. Refer to full monograph for details. Consider therapy modification
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
Lovastatin: Efavirenz may decrease the serum concentration of Lovastatin. 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 600 mg twice daily if used with efavirenz. This does not apply to patients also receiving strong CYP3A4 inhibitors. This combination is contraindicated in patients with CrCl less than 30 mL/min. Consider therapy modification
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. Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP2B6 Substrates. Monitor therapy
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirodenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mirodenafil. Monitor therapy
Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. 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
Nevirapine: Efavirenz may enhance the adverse/toxic effect of Nevirapine. Nevirapine may enhance the adverse/toxic effect of Efavirenz. Nevirapine may decrease the serum concentration of Efavirenz. Avoid combination
Nilotinib: May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy
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
Nonsteroidal Anti-Inflammatory Agents: May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification
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
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. 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
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
Phenytoin: May decrease the serum concentration of Efavirenz. Efavirenz may increase the serum concentration of Phenytoin. Consider therapy modification
Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy
Posaconazole: Efavirenz may decrease the serum concentration of Posaconazole. Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Pravastatin: Efavirenz may decrease the serum concentration of Pravastatin. Monitor therapy
Proguanil: Efavirenz may decrease serum concentrations of the active metabolite(s) of Proguanil. Efavirenz may increase the serum concentration of Proguanil. Efavirenz may decrease the serum concentration of Proguanil. 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
Ribavirin (Oral Inhalation): May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Monitor therapy
Ribavirin (Systemic): May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). 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 adult dose by 50%. If used with regimens where rifabutin is administered 2-3 times per week, consider doubling the rifabutin dose. Consider therapy modification
RifAMPin: May decrease the serum concentration of Efavirenz. Management: Increase efavirenz adult dose to 800 mg daily in patients weighing over 50 kg. Consider therapy modification
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
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. Management: Monitor for reduced rolapitant response. Recommended dexamethasone regimens should be used with rolapitant. Higher dexamethasone doses or more prolonged use may increase the potential for a significant interaction. 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
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
SAXagliptin: CYP3A4 Inducers may decrease the serum concentration of SAXagliptin. Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Sertraline: Efavirenz may decrease the serum concentration of Sertraline. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. 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: Efavirenz may decrease the serum concentration of Sirolimus. Management: Closely monitor sirolimus serum concentrations when starting, stopping, or changing doses of efavirenz, particularly during the first 2 weeks after any change. Dose adjustment of sirolimus may be required. Consider therapy modification
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
Sonidegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sonidegib. Avoid combination
St Johns Wort: May decrease the serum concentration of Efavirenz. Avoid combination
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): Efavirenz may decrease the serum concentration of Tacrolimus (Systemic). Management: Closely monitor tacrolimus serum concentrations when starting, stopping, or changing doses of efavirenz, particularly during the first 2 weeks after any change. Dose adjustment of tacrolimus may be required. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Telaprevir: Efavirenz may decrease the serum concentration of Telaprevir. Telaprevir may decrease the serum concentration of Efavirenz. Management: Initiate telaprevir at a dose of 1125 mg every 8 hours in patients receiving efavirenz (per adult/adolescent HIV guidelines). Consider therapy modification
Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Thiotepa: May increase the serum concentration of CYP2B6 Substrates. Monitor therapy
Tipranavir: Tenofovir Disoproxil Fumarate may decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Ulipristal: Efavirenz may decrease the serum concentration of Ulipristal. Avoid combination
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
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/day. Consider therapy modification
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
Testing for HBV is recommended prior to the initiation of antiretroviral therapy. CBC with differential, reticulocyte count, creatine kinase, CD4 count, HIV RNA plasma levels, serum phosphorus; serum creatinine (prior to initiation and as clinically indicated during therapy), urine glucose and urine protein (in patients at risk for renal impairment or who experienced renal impairment while taking adefovir), hepatic function tests (discontinuation of treatment should be considered for persistent serum transaminase elevations >5 times ULN), bone density (patients with a history of bone fracture or have risk factors for bone loss).
Patients with HIV and HBV coinfection should have hepatic function monitored for several months following discontinuation.
False-positive test for cannabinoids have been reported with some screening assays used in HIV-infected and uninfected subjects receiving efavirenz. Confirmation of screening tests for cannabinoids by a more specific method is recommended.
Frequency not always defined. The complete adverse reaction profile of combination therapy has not been established. See individual agents. The following adverse effects were noted in clinical trials with combination therapy.
>10%: Endocrine & metabolic: Hypercholesterolemia (22%)
1% to 10%:
Central nervous system: Depression (9%), fatigue (9%), dizziness (8%), headache (6%), anxiety (5%), insomnia (5%), drowsiness (4%), abnormal dreams
Dermatologic: Skin rash (7%)
Endocrine & metabolic: Increased serum triglycerides (4%), hyperglycemia (2%)
Gastrointestinal: Diarrhea (9%), nausea (9%), increased serum amylase (8%), vomiting (2%)
Genitourinary: Hematuria (3%)
Hematologic & oncologic: Neutropenia (3%)
Hepatic: Increased serum AST (3%), increased serum ALT (2%), increased serum alkaline phosphatase (1%)
Neuromuscular & skeletal: Increased creatine phosphokinase (9%)
Respiratory: Sinusitis (8%), upper respiratory tract infection (8%), nasopharyngitis (5%)
<1% (Limited to important or life-threatening): Glycosuria
Concerns related to adverse effects:
- CNS depression: May cause CNS depression (eg, impaired concentration, dizziness or drowsiness); avoid potentially hazardous tasks such as driving or operating machinery.
- Decreased bone mineral density: In clinical trials, tenofovir has been associated with decreases in bone mineral density in HIV-1 infected adults and increases in bone metabolism markers. Serum parathyroid hormone and 1,25 vitamin D levels were also higher. Decreases in bone mineral density have also been observed in clinical trials of HIV-1 infected pediatric patients. Observations in chronic hepatitis B infected pediatric patients (aged 12-18 years) were similar. In all pediatric clinical trials, skeletal growth (height) appears unaffected. Consider monitoring of bone density in adult and pediatric patients with a history of pathologic fractures or with other risk factors for bone loss or osteoporosis. Consider calcium and vitamin D supplementation for all patients; effect of supplementation has not been studied but may be beneficial. Long-term bone health and fracture risk unknown. If abnormalities are suspected, expert assessment is recommended.
- Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).
- 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-Barre syndrome) later in therapy; further evaluation and treatment may be required.
- Lactic acidosis/hepatomegaly: [US Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis). Some cases of hepatotoxicity have occurred in patients with no hepatic disease prior to treatment. Persistent elevations of serum transaminases >5 times the upper limit of normal should prompt evaluation - benefit of continued therapy should be weighed against possible risk of hepatotoxicity.
- Osteomalacia and renal dysfunction: May cause osteomalacia with proximal renal tubulopathy. Bone pain, extremity pain, fractures, arthralgias, weakness, and muscle pain have been reported. In patients at risk for renal dysfunction, persistent or worsening bone or muscle symptoms should be evaluated for hypophosphatemia and osteomalacia.
- Psychiatric effects: Serious psychiatric side effects have been associated with use, including severe depression, suicide, paranoia, and mania; use with caution in patients with a history of mental illness/drug abuse (predisposition to psychological reactions).
- Rash: Discontinue if severe rash (involving blistering, desquamation, mucosal involvement or fever) develops. Children are more susceptible to development of rash (median time to onset: 28 days); prophylactic antihistamines may be used. Consider alternative therapy in the case of life-threatening cutaneous reactions (see Contraindications).
- Renal toxicity: May cause renal toxicity (acute renal failure and/or Fanconi syndrome); avoid use with concurrent or recent nephrotoxic therapy (including high-dose or multiple NSAID use). Acute renal failure has occurred in HIV-infected patients with risk factors for renal impairment who were on a stable tenofovir regimen to which a high dose or multiple NSAID therapy was added. Consider alternatives to NSAIDS in patients taking tenofovir and at risk for renal impairment. Calculate estimated creatinine clearance (CrCl) prior to initiation of therapy and monitor renal function (including recalculation of CrCl and serum phosphorus) during therapy. In patients at risk for renal dysfunction, including patients who have experienced renal events while taking adefovir, assess serum phosphorus, urine glucose, and urine protein prior to and periodically during treatment. Use with caution in patients with low body weight or concurrent medications which increase tenofovir levels. IDSA guidelines recommend discontinuing tenofovir (and substituting with alternative antiretroviral therapy) in HIV-infected patients who develop a decline in GFR (a >25% decrease in GFR from baseline and to a level of <60 mL/minute/1.73 m2) during use, particularly in presence of proximal tubular dysfunction (eg, euglycemic glycosuria, increased urinary phosphorus excretion and hypophosphatemia, proteinuria [new onset or worsening]) (IDSA [Lucas 2014]).
Disease-related concerns:
- Chronic hepatitis B: [US Boxed Warning]: Safety and efficacy during coinfection of HIV and HBV have not been established; acute, severe exacerbations of HBV have been reported following discontinuation of antiretroviral therapy. Not indicated for treatment of chronic hepatitis B. All patients with HIV should be tested for HBV prior to initiation of treatment. Caution in patients with known or suspected hepatitis B or C infection (monitoring of liver function is recommended). In HBV coinfected patients, monitor hepatic function closely for several months following discontinuation.
- Hepatic impairment: Not recommended in patients with moderate or severe hepatic impairment (Child-Pugh class B, C). Use caution in patients with mild hepatic impairment (Child-Pugh class A), HBV or HCV coinfection, elevated transaminases or use of concomitant hepatotoxic drugs. Monitor liver function tests before and during treatment; some cases of hepatic failure have developed in patients with no hepatic disease prior to treatment. Ethanol may increase hepatotoxic potential; instruct patients to limit or avoid alcohol.
- 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] 2015).
- Renal impairment: Product is a fixed-dose combination and is not appropriate for use in renal impairment (CrCl <50 mL/minute).
- Seizure disorder: Use with caution in patients with a history of seizure disorder; seizures have been associated with use.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- Duplicate therapy: Do not use concurrently with efavirenz emtricitabine, tenofovir, or any combination of these drugs; however, coadministration with efavirenz may be required for dose-adjustment with concomitant rifampin therapy.
- Sedatives: CNS effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
- Pediatric: Fixed-dose combination product; safety and efficacy have not been established in patients <12 years of age and <40 kg. In children <40 kg, the dose of efavirenz would be excessive.
- Pregnancy: Avoid pregnancy; women of childbearing potential should undergo pregnancy testing prior to initiation of therapy. Two forms of contraception should be used during and for 12 weeks after discontinuation of therapy.
D
Adverse events have been observed in some animal reproduction studies. The manufacturer of this combination recommends pregnancy testing prior to therapy and effective contraception in women of reproductive potential during treatment and for 12 weeks after therapy is discontinued. The HHS Perinatal HIV Guidelines consider efavirenz in combination with emtricitabine and tenofovir disoproxil fumarate as a preferred regimen in antiretroviral-naive pregnant women who require co-administration of drugs without significant interactions with protease inhibitors, or for the convenience of once daily dosing (initiate after the first 8 weeks of pregnancy) (HHS [perinatal] 2016). Postpartum contraception is recommended. See individual agents.
See individual agents.
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, fatigue, nightmares, dizziness, nausea, vomiting, diarrhea, insomnia, or skin discoloration. Have patient report immediately to prescriber signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of too much lactic acid in the blood (lactic acidosis; fast breathing, fast heartbeat, abnormal heartbeat, vomiting, drowsiness, shortness of breath, feeling very tired or weak, severe dizziness, feeling cold, or muscle pain or cramps), signs of depression (suicidal ideation, anxiety, emotional instability, illogical thinking), bone pain, muscle pain, painful extremities, seizures, change in body fat, signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes), or signs of infection (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.