most farseeing [1%:<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 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; Note: Dosage adjustments may be necessary if patient receives certain concomitant medications. Alternate recommendations: Infants 3 months ( 3 kg) and Children> <3 years: Very limited data available; In general, current guidelines do not recommend efavirenz use in patients> <3 years unless use is unavoidable due to the clinical situation; CYP2B6 genotype testing should be performed prior to therapy initiation; consult pediatric HIV antiretroviral treatment guidelines for investigational dosing (HHS [pediatric] 2016) 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; Note: Dosage adjustments may be necessary if patient receives certain concomitant medications. BSA-directed dosing: Oral: 367 mg/ m 2 /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 rifampin: Pediatric patients weighing> <50 kg: There are no dosage adjustments provided in manufacturer's labeling; however, efavirenz dosage increase may be considered. Pediatric patients weighing 50 kg: Increase efavirenz dose to 800 mg once daily Dosage adjustment for concomitant voriconazole: Infants 3 months, Children, and Adolescents: There are no dosage adjustments provided in manufacturer's labeling; however, efavirenz dose reduction and voriconazole dosage increase may be considered. Dosing: Renal Impairment There are no dosage adjustment provided in manufacturer's labeling (has not been studied); however, undergoes minimal renal excretion. Dosing: Hepatic Impairment Mild impairment (Child-Pugh class A): No dosage adjustment necessary; use with caution. Moderate-to-severe impairment (Child-Pugh class B or C): Use is not recommended. 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 pediatric or adult 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. Capsule contents may also be mixed with infant formula only for young infants who cannot reliably consume solid foods. Combine entire contents of capsule(s) with 10 mL of reconstituted, room temperature infant formula in a 30 mL small container, stir carefully, then draw up mixture in a 10 mL oral syringe for administration. If more than 1 capsule is needed for a dose, add contents of all capsules needed to 10 mL of formula; do not add more formula. To ensure entire capsule contents are administered, add another 10 mL of formula to the cup, stir to incorporate any drug residue, draw up in oral syringe 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 Alcohol (Ethyl): Efavirenz may enhance the adverse/toxic effect of Alcohol (Ethyl). Efavirenz may decrease the serum concentration of Alcohol (Ethyl). 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 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 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 (High risk with Inducers). 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 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/m 2 , 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 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 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 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 (High risk with Inducers): CYP2B6 Inducers (Moderate) may decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Monitor therapy CYP2C8 Substrates (High risk with Inhibitors): CYP2C8 Inhibitors (Moderate) may decrease the metabolism of CYP2C8 Substrates (High risk with Inhibitors). Monitor therapy CYP2C9 Substrates (High risk with Inhibitors): CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates (High risk with Inhibitors). Monitor therapy 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). 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 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 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 (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 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 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 Ginkgo Biloba: May decrease the serum concentration of Efavirenz. Monitor therapy Glecaprevir and Pibrentasvir: Efavirenz may decrease the serum concentration of Glecaprevir and Pibrentasvir. Avoid combination 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: Avoid concomitant use of hydrocodone 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 Hydroxychloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination 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 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 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 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 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 enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination 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 (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 Neratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Neratinib. Avoid combination 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 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 Analgesics: CNS Depressants may enhance the CNS depressant effect of Opioid Analgesics. Management: Avoid concomitant use of opioid analgesics 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 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 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. Consider therapy modification Phenytoin: May decrease the serum concentration of Efavirenz. Efavirenz may increase the serum concentration of Phenytoin. Consider therapy modification Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification 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 Probucol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). 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 Promazine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination QTc-Prolonging Agents (Highest Risk): QTc-Prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Avoid combination QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy QTc-Prolonging Agents (Moderate Risk): May enhance the QTc-prolonging effect of other QTc-Prolonging Agents (Moderate Risk). Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification 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 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. 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 Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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 Selexipag: CYP2C8 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Selexipag. CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Selexipag. Management: If initiating selexipag in a patient on a moderate CYP2C8 inhibitor, consider a less frequent dosing regimen (ie, once daily). If initiating a moderate CYP2C8 inhibitor in a patient on selexipag, consider a selexipag dose reduction. Consider therapy modification 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: 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 John's 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: Avoid concomitant use of tapenta most beneficial
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