knotted up [100,000:<12 years of age and an alternative regimen for initial treatment in adolescents ≥12 years of age who are not sexually mature. 201 Efavirenz is not recommended for initial treatment in those 3 months to> <3 years of age. 201 Usually avoid efavirenz in pregnant women during first trimester; 1 avoid in women of childbearing age who may become pregnant. 1 202 (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Efavirenz/emtricitabine/tenofovir DF fixed combination (Atripla ) can be used in adults, adolescents, and children ≥12 years of age weighing ≥40 kg to decrease pill burden and improve adherence; 232 used alone as a complete treatment regimen or used in conjunction with other antiretrovirals. 232 Postexposure Prophylaxis following Occupational Exposure to HIV (PEP) Postexposure prophylaxis of HIV infection following occupational exposure † (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV. 199 USPHS recommends 3-drug regimen of raltegravir in conjunction with emtricitabine and tenofovir DF as the preferred regimen for PEP following occupational exposures to HIV. 199 Efavirenz and 2 NRTIs can be considered an alternative regimen, but use for PEP only with expert consultation. 199 Preferred dual NRTI option for PEP regimens is emtricitabine and tenofovir DF (may be given as emtricitabine/tenofovir DF; Truvada ); alternative dual NRTIs are tenofovir DF and lamivudine, lamivudine and zidovudine (may be given as lamivudine/zidovudine; Combivir ), or zidovudine and emtricitabine. 199 Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible. 199 Do not delay initiation of PEP while waiting for expert consultation. 199 Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP) Postexposure prophylaxis of HIV infection following nonoccupational exposure † (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when the exposure represents a substantial risk for HIV transmission. 198 Used in conjunction with other antiretrovirals. 198 When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, CDC states preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF; Truvada ); 198 recommended alternative in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF (Truvada ). 198 CDC states efavirenz is an alternative antiretroviral that can be used in nPEP regimens, but use in such regimens only with expert consultation. 198 Consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals. 198 Do not delay initiation of nPEP while waiting for expert consultation. 198 Efavirenz Dosage and Administration Administration Oral Administration Administer efavirenz (Sustiva ) or efavirenz/emtricitabine/tenofovir DF (Atripla ) orally once daily on an empty stomach, preferably at bedtime. 1 232 Administration at bedtime may make adverse CNS effects (dizziness, insomnia, impaired concentration, somnolence, abnormal dreams) more tolerable. 1 232 Efavirenz (Sustiva ): Use in conjunction with other antiretrovirals. 1 Efavirenz/emtricitabine/tenofovir DF (Atripla ): Use alone as a complete treatment regimen or use in conjunction with other antiretrovirals. 232 Because antiretrovirals in the fixed combination also are available in single-entity or other fixed-combination preparations, take care to ensure that therapy is not duplicated if used in conjunction with other antiretrovirals. 232 (See Use of Fixed Combinations under Cautions.) Do not use single-entity efavirenz (Sustiva ) and efavirenz/emtricitabine/tenofovir DF (Atripla ) concomitantly, unless needed for adjustment of efavirenz dosage (e.g., when fixed combination used concomitantly with rifampin). 1 232 Capsules (Sustiva ) Swallow capsules whole on an empty stomach. 1 For adults and pediatric patients ≥3 months of age not able to swallow capsules or tablets, administer capsule contents by mixing with small amount (1 2 teaspoonfuls) of soft food (capsule sprinkle method). 1 Consider mixing with infant formula only if infant cannot consume solid foods. 1 Administer efavirenz mixture within 30 minutes after preparation; do not consume any additional food or infant formula for 2 hours after the mixture. 1 Mixing capsule contents into food: Add 1 2 teaspoonfuls of age-appropriate soft food (e.g., applesauce, grape jelly, yogurt) to a small container. 1 Hold appropriate number of capsules (see Table 1) horizontally over the small container, twist open, and empty onto the food. 1 Gently mix with a spoon; feed entire mixture to patient. 1 Then, add additional 2 teaspoonfuls of soft food to the small container, stir to disperse remaining efavirenz residue, and feed to patient. 1 Mixing capsule contents into infant formula: Add 10 mL (2 teaspoonfuls) of reconstituted room temperature infant formula to a 30-mL medicine cup. 1 Hold appropriate number of capsules (see Table 1) horizontally over the medicine cup, twist open, and empty onto the formula. 1 Gently mix with small spoon. 1 Draw up infant formula mixture into 10-mL oral dosing syringe; administer into infant's right or left inner cheek. 1 Then, add additional 2 teaspoonfuls of infant formula to the medicine cup, stir to disperse remaining efavirenz residue, draw up into oral dosing syringe, and administer to infant. 1 Tablets (Sustiva , Atripla ) Swallow tablets whole on an empty stomach; do not break or crush. 1 Dosage Pediatric Patients Treatment of HIV Infection Oral Efavirenz (Sustiva ): Dosage in children ≥3 months of age weighing 3.5 to> <40 kg is based on weight. 1 (See Table 1.) Adolescents and children weighing ≥40 kg may receive usual adult dosage. 1 Table 1. Efavirenz (Sustiva) Dosage in Children ≥3 Months of Age Weighing ≥3.5 kg1 Weight in kg Efavirenz Dosage Number of Capsules or Tablets 3.5 to> <5 100 mg once daily Two 50-mg capsules 5 to> <7.5 150 mg once daily Three 50-mg capsules 7.5 to> <15 200 mg once daily One 200-mg capsule 15 to> <20 250 mg once daily One 200-mg and one 50-mg capsule 20 to> <25 300 mg once daily One 200-mg and two 50-mg capsules 25 to> <32.5 350 mg once daily One 200-mg and three 50-mg capsules 32.5 to> <40 400 mg once daily Two 200-mg capsules ≥40 600 mg once daily One 600-mg tablet or three 200-mg capsules Efavirenz/emtricitabine/tenofovir DF (Atripla ) in children ≥12 years of age weighing ≥40 kg: 1 tablet (600 mg of efavirenz, 200 mg of emtricitabine, and 300 mg of tenofovir DF) once daily. 232 Adults Treatment of HIV Infection Oral Efavirenz (Sustiva ): 600 mg once daily. 1 Efavirenz/emtricitabine/tenofovir DF (Atripla ): 1 tablet (efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg) once daily. 232 Treatment of HIV Infection in Patients Weighing ≥50 kg Receiving Rifampin Oral Efavirenz (Sustiva ): 800 mg once daily. 1 (See Specific Drugs and Laboratory Tests under Interactions.) Efavirenz/emtricitabine/tenofovir DF (Atripla ): 1 tablet (efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg) once daily and 200 mg of single-entity efavirenz (Sustiva ) once daily to provide total efavirenz dosage of 800 mg daily. 232 Postexposure Prophylaxis of HIV following Occupational Exposure † Oral Efavirenz (Sustiva ): 600 mg once daily. 199 Use in conjunction with 2 NRTIs (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses). 199 Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated. 199 Special Populations Hepatic Impairment Treatment of HIV Infection Efavirenz (Sustiva ): Dosage adjustments not needed in patients with mild hepatic impairment; 1 do not use in those with moderate or severe hepatic impairment. 1 (See Hepatic Impairment under Cautions.) Efavirenz/emtricitabine/tenofovir DF (Atripla ): Use usual dosage in patients with mild hepatic impairment; however, caution advised. 232 Do not use in those with moderate or severe hepatic impairment. 232 Renal Impairment Treatment of HIV Infection Efavirenz (Sustiva ): Dosage adjustments not needed. 200 Efavirenz/emtricitabine/tenofovir DF (Atripla ): Use usual dosage in patients with Cl cr ≥50 mL/minute; 232 do not use in those with Cl cr> <50 mL/minute. 232 Geriatric Patients Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. 1 232 Cautions for Efavirenz Contraindications Efavirenz and efavirenz/emtricitabine/tenofovir DF: History of clinically important hypersensitivity reaction (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic skin eruption) to efavirenz or any ingredient in the formulation. 1 232 Efavirenz/emtricitabine/tenofovir DF: Consider contraindications associated with each drug in the fixed combination. 232 Warnings/Precautions Interactions Efavirenz plasma concentrations may be altered if CYP3A substrates, inhibitors, or inducers used concomitantly. 1 In addition, efavirenz may alter plasma concentrations of drugs metabolized by CYP3A or 2B6. 1 (See Interactions.) Psychiatric Symptoms Serious adverse psychiatric symptoms (severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions) reported rarely in efavirenz clinical studies. 1 232 Depression, anxiety, and nervousness also reported in clinical studies. 1 Although causal relationship not established, there have been occasional postmarketing reports of delusions, psychosis-like behavior, catatonia, and death by suicide in patients receiving efavirenz. 1 Aggressive reactions, 1 agitation, 1 emotional lability, 1 mania, 1 neurosis, 1 and paranoia 1 also reported during postmarketing surveillance. Factors associated with increased occurrence of psychiatric symptoms include history of injection drug use, history of psychiatric disorders, and treatment with antipsychotic drugs at study entry. 1 232 If serious psychiatric adverse events occur, evaluate to determine if symptoms are related to efavirenz; if so, determine whether risks of continued efavirenz outweigh benefits. 1 232 Nervous System Effects Dizziness or insomnia reported frequently; abnormal dreams, hallucinations, or impaired concentration also reported. 1 These adverse effects generally begin during first 1 2 days of therapy, improve with continued therapy, and usually resolve after first 2 4 weeks. 1 Seizures reported, 1 generally in those with a history of seizures. 1 Use with caution in patients with history of seizures. 1 Monitor anticonvulsant plasma concentrations if used in patients receiving anticonvulsants that are metabolized principally by the liver (e.g., phenytoin, phenobarbital). 1 (See Specific Drugs and Laboratory Tests under Interactions.) Fetal/Neonatal Morbidity and Mortality May cause fetal harm if administered during first trimester of pregnancy. 1 232 Teratogenicity demonstrated in animals. 1 Birth defects (including neural tube defects) reported in humans, usually with first-trimester exposure. 1 (See Pregnancy under Cautions.) Advise women of childbearing potential about the teratogenic potential of efavirenz; 1 232 perform test to rule out pregnancy before initiating efavirenz or fixed combination containing efavirenz. 1 232 Avoid pregnancy during therapy and for 12 weeks after discontinuance of efavirenz or fixed combination containing efavirenz. 1 232 Women of childbearing potential should use a reliable method of barrier contraception in addition to or instead of a hormonal contraceptive (oral or other hormonal contraceptive). 1 200 202 232 (See Specific Drugs and Laboratory Tests under Interactions.) Dermatologic and Sensitivity Reactions Rash (maculopapular skin eruptions) reported frequently. 1 2 Pruritus; rash associated with blistering, moist desquamation, or ulceration; allergic reaction; photoallergic dermatitis; erythema multiforme; and Stevens-Johnson syndrome also reported. 1 2 Median time to rash onset 11 days in adults and 28 days in pediatric patients; median duration 16 days. 1 Mild to moderate rash generally resolves within 1 month with continued efavirenz. 1 May be reinitiated after temporary interruption for rash. 1 Antihistamines and/or corticosteroids may improve tolerability and hasten resolution of rash. 1 Discontinue in patients with life-threatening cutaneous reactions (e.g., Stevens-Johnson syndrome) and consider alternative therapy. 1 232 Discontinue in patients with serious rash (e.g., rash associated with blistering, desquamation, mucosal involvement, or fever). 1 Hepatotoxicity Substantial increases in serum AST or ALT concentrations (>5 times ULN) reported in clinical studies in HIV-infected patients coinfected with HBV and/or HCV. 1 Hepatic failure and hepatitis reported, some with a fulminant course requiring transplantation or resulting in death. 1 Hepatic failure has occurred in some patients with no preexisting hepatic disease or other identifiable risk factors. 1 Use with caution in patients with hepatic impairment. 1 232 (See Hepatic Impairment under Cautions.) Assess serum liver enzyme concentrations prior to and during efavirenz treatment in patients with underlying hepatic disease (including those with HBV and/or HCV infection), patients with markedly increased serum transaminase concentrations, and patients receiving other drugs associated with liver toxicity. 1 232 Also consider monitoring serum liver enzymes in patients without preexisting hepatic dysfunction or other risk factors. 1 232 In patients with serum hepatic enzyme concentrations >5 times ULN, consider whether benefits of continued efavirenz therapy outweigh risks of hepatotoxicity. 1 232 Use of Fixed Combinations Efavirenz/emtricitabine/tenofovir DF: Consider cautions, precautions, contraindications, and interactions associated with each drug in the fixed combination. 232 Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug. 232 Do not use efavirenz/emtricitabine/tenofovir DF concomitantly with single-entity efavirenz, unless needed for adjustment of efavirenz dosage (e.g., when fixed combination used concomitantly with rifampin). 1 232 (See Specific Drugs and Laboratory Tests under Interactions.) Because the antiretrovirals contained in efavirenz/emtricitabine/tenofovir DF also are available in single-entity or other fixed-combination preparations, take care to ensure that therapy is not duplicated if the fixed combination is used in conjunction with other antiretrovirals. 232 Do not use efavirenz/emtricitabine/tenofovir DF concomitantly with any preparation containing emtricitabine or tenofovir DF. 232 In addition, do not use concomitantly with any preparation containing lamivudine or with adefovir. 232 Cardiovascular and Lipid Effects Prolongation of QT interval corrected for rate (QT c ) reported. 1 Consider alternative antiretroviral in patients at increased risk of torsades de pointes and in those receiving a drug known to increase risk of torsades de pointes. 1 (See Interactions.) Increased serum concentrations of total cholesterol and triglycerides reported. 1 Assess serum cholesterol and triglycerides prior to and periodically during therapy. 1 Adipogenic Effects Redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement ( buffalo hump ), peripheral wasting, breast enlargement, and general cushingoid appearance, reported in patients receiving antiretroviral therapy. 1 Mechanism and long-term consequences of fat redistribution unknown; 1 causal relationship not established. 1 Immune Reconstitution Syndrome During initial treatment, HIV-infected patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis , cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii ]); 1 this may necessitate further evaluation and treatment. 1 Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) also reported in the setting of immune reconstitution; 1 time to onset is more variable and can occur many months after initiation of antiretroviral therapy. 1 Specific Populations Pregnancy Efavirenz may cause fetal harm if administered during first trimester of pregnancy. 1 232 There are retrospective case reports of neural tube defects in infants born to mothers with first trimester exposure to efavirenz, 1 but prospective pregnancy data not sufficient to adequately assess this risk. 1 202 Efavirenz/emtricitabine/tenofovir DF (Atripla ): Category D. 232 Antiretroviral Pregnancy Registry at 800-258-4263 or . 1 202 Data from the Antiretroviral Pregnancy Registry show no difference in the risk of overall birth defects for efavirenz compared with background rate for birth defects. 1 Women of childbearing potential should use effective contraceptive measures during therapy and for 12 weeks after discontinuance of efavirenz or efavirenz/emtricitabine/tenofovir DF. 1 232 (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Manufacturer states avoid use during first trimester of pregnancy. 1 Experts state efavirenz in conjunction with 2 NRTIs is an alternative NNRTI-based regimen for initial treatment in antiretroviral-naive pregnant women, 202 but may be a preferred NNRTI-based regimen for initial treatment when drug interactions with PI-based regimens are a concern or when the convenience of a fixed-combination, single-tablet, once-daily regimen is advantageous. 202 However, these experts state efavirenz should be avoided during first 8 weeks of pregnancy. 202 Experts also state that antiretroviral regimens that do not include efavirenz should be strongly considered in women who are planning to become pregnant or are sexually active and not using effective contraception, provided such regimens are acceptable to the provider and not expected to compromise the health of the woman. 202 If a pregnant woman already receiving an efavirenz-containing regimen presents for antenatal care during first trimester, some experts suggest the regimen can be continued if well tolerated and providing adequate virologic suppression. 202 This strategy recognizes that risk of neural tube defects is limited to first 5 6 weeks of pregnancy and pregnancy rarely recognized until after 4 6 weeks and that unnecessary changes in antiretroviral regimens during pregnancy may be associated with loss of virologic control and increased risk of perinatal HIV transmission. 202 If efavirenz or a fixed combination containing efavirenz is used during first trimester or if pregnancy occurs, apprise patient of potential harm to the fetus. 1 232 Lactation Efavirenz distributed into human milk. 202 Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant. 1 202 232 Pediatric Use Efavirenz (Sustiva ): Safety and efficacy not evaluated in neonates and infants> <3 months of age or who weigh> <3.5 kg; 1 not recommended in these pediatric patients. 1 201 Some experts state efavirenz not recommended for initial treatment in antiretroviral-naive pediatric patients 3 months to> <3 years of age. 201 Efavirenz/emtricitabine/tenofovir DF (Atripla ): Safety and efficacy not established in pediatric patients> <12 years of age or weighing> <40 kg. 232 Adverse effects reported with efavirenz in pediatric patients 3 months to 21 years of age are similar to those reported in adults with the exception of rash. 1 Rash reported more frequently in children than adults and the incidence of moderate to severe rash has been greater in children than adults. 1 Not recommended in sexually active adolescent females of childbearing potential who desire to become pregnant or when reliable contraception cannot be ensured. 201 (See Pregnancy under Cautions.) Geriatric Use Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults. 1 232 Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. 1 232 Hepatic Impairment Efavirenz (Sustiva ): Use with caution in mild hepatic impairment; 1 do not use in moderate or severe hepatic impairment. 1 Efavirenz/emtricitabine/tenofovir DF (Atripla ): Use with caution in mild hepatic impairment; 232 do not use in moderate or severe hepatic impairment. 232 Monitor hepatic enzyme concentrations in patients with known or suspected HBV or HCV infection, patients with substantially increased transaminase concentrations, and in patients receiving other drugs associated with hepatotoxicity. 1 (See Hepatotoxicity under Cautions.) Renal Impairment Efavirenz (Sustiva ): Pharmacokinetics not specifically studied; clinically important decreases in clearance not anticipated. 1 (See Renal Impairment under Dosage and Administration.) Efavirenz/emtricitabine/tenofovir DF (Atripla ): Do not use in those with Cl cr> <50 mL/minute. 232 Common Adverse Effects Rash, dizziness, nausea, headache, fatigue, insomnia, vomiting. 1 Interactions for Efavirenz Metabolized by CYP3A and CYP2B6. 1 Inhibits CYP2C9 and CYP2C19 and, to a lesser extent, CYP2D6 and CYP1A2. 1 Does not inhibit CYP2E1. 1 Induces CYP3A and CYP2B6. 1 The following drug interactions are based on studies using efavirenz. 1 Drug interaction studies not performed using efavirenz/emtricitabine/tenofovir DF. 232 When fixed combinations are used, consider interactions associated with each drug in the fixed combination. 232 Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP isoenzymes 3A, 2B6, 2C9, or 2C19 with possible alteration in metabolism of efavirenz and/or other drug. 1 Specific Drugs and Laboratory Tests Drug Interaction Comments Abacavir Clinically important interactions not expected 1 In vitro evidence of additive antiretroviral effects 1 Dosage adjustments not needed 1 Alcohol Potential for additive CNS effects 1 Antacids (aluminum hydroxide, magnesium hydroxide, simethicone) Pharmacokinetic interaction unlikely 1 Dosage adjustments not needed 1 Anticoagulants, oral Warfarin concentrations likely to be affected 1 Use with caution; closely monitor INR 1 200 Anticonvulsants (carbamazepine, phenobarbital, phenytoin) Carbamazepine: Decreased concentrations and AUCs of efavirenz and carbamazepine 1 200 Phenobarbital, phenytoin: Possible decreased concentrations of phenobarbital and phenytoin and/or efavirenz 1 200 Carbamazepine: Data insufficient to make dosage recommendations for concomitant use with efavirenz; 1 use with caution and monitor anticonvulsant concentrations; 1 200 consider alternative anticonvulsant 200 Phenobarbital, phenytoin: Use caution and monitor anticonvulsant concentrations if used with efavirenz; 1 200 consider alternative anticonvulsant 200 Efavirenz/emtricitabine/tenofovir DF: Data insufficient to make dosage recommendations for concomitant use with carbamazepine; 232 use alternative anticonvulsant 232 Antifungals, azoles (fluconazole, isavuconazonium, itraconazole, ketoconazole, posaconazole, voriconazole) Fluconazole: No clinically important pharmacokinetic interactions 1 200 Isavuconazonium (prodrug of isavuconazole): Possible decreased isavuconazole concentrations 200 Itraconazole: Decreased concentrations of itraconazole; no change in efavirenz concentrations 1 Ketoconazole: Possible decreased concentrations of the antifungal 1 Posaconazole: Decreased posaconazole concentrations and AUC; 1 200 does not affect efavirenz concentrations 200 Voriconazole: Decreased voriconazole concentrations; increased efavirenz concentrations 1 200 Fluconazole: Dosage adjustments not needed 1 Isavuconazonium: Consider monitoring isavuconazole concentrations and antifungal efficacy; 200 isavuconazonium dosage adjustments may be needed 200 Itraconazole: Dosage recommendation for concomitant use not available; 1 consider alternative antifungal; 1 experts state avoid concomitant use; 200 if used concomitantly, closely monitor itraconazole concentrations and adjust antifungal dosage accordingly 200 Posaconazole: Avoid concomitant use unless potential benefits outweigh risks; 1 200 if used concomitantly, monitor posaconazole concentrations and adjust antifungal dosage accordingly 200 Voriconazole: Increase voriconazole maintenance dosage to 400 mg every 12 hours and decrease efavirenz dosage to 300 mg once daily (use efavirenz capsules; do not divide tablet); 1 200 do not use usual voriconazole dosage with usual efavirenz dosage; 1 200 concomitant use with efavirenz/emtricitabine/tenofovir DF contraindicated 232 Antihistamines Decreased cetirizine concentrations; no change in efavirenz concentrations 1 When used with cetirizine, dosage adjustments not needed 1 Antimalarials Fixed combination of artemether and lumefantrine (artemether/lumefantrine): Decreased concentrations and AUC of artemether and active metabolite of artemether; decreased lumefantrine AUC; may decrease antimalarial effect of artemether/lumefantrine; 1 200 possible QT interval prolongation 1 Fixed combination of atovaquone and proguanil (atovaquone/proguanil): Decreased AUC of atovaquone and proguanil; 200 Artemether/lumefantrine: Consider alternative antimalarial agent; 1 200 experts state if used concomitantly, monitor for antimalarial efficacy and malaria recurrence 200 Atovaquone/proguanil: Concomitant use not recommended; 1 experts state consider alternative for malaria prophylaxis, if possible 200 Antimycobacterials (bedaquiline, rifabutin, rifampin, rifapentine) Bedaquiline: Possible decreased bedaquiline concentrations 200 Rifabutin: Decreased rifabutin concentrations; no change in efavirenz AUC 1 54 200 Rifampin: Decreased efavirenz concentrations and AUC 1 200 Bedaquiline: Concomitant use not recommended 200 Rifabutin: Manufacturer of efavirenz states increase daily rifabutin dosage by 50% and consider doubling rifabutin dosage when given 2 or 3 times weekly; experts suggest increase rifabutin dosage to 450 600 mg once daily or 600 mg 3 times weekly, provided regimen does not include a PI 1 200 Rifampin: Manufacturer states increase efavirenz dosage to 800 mg once daily in those weighing ≥50 kg; 1 experts recommend efavirenz 600 mg once daily for patients weighing> <60 kg and efavirenz 800 mg once daily in those weighing >60 kg and state virologic response should be monitored and therapeutic drug monitoring considered; 200 if using efavirenz/emtricitabine/tenofovir DF, use 1 tablet of fixed combination (see Preparations) and 200 mg of single-entity efavirenz once daily to provide efavirenz dosage of 800 mg daily 232 Rifapentine: Do not use concomitantly 200 Antipsychotics (pimozide) Pimozide: Do not use concomitantly 200 Atazanavir Ritonavir-boosted atazanavir: Possible increased atazanavir concentrations and AUC depending on specific regimen 1 203 Cobicistat-boosted atazanavir: Decreased atazanavir and cobicistat concentrations; no change in efavirenz concentrations 200 238 239 Unboosted atazanavir: Substantially decreased atazanavir concentrations and AUC; 1 203 no clinically important change in efavirenz concentrations 200 No in vitro evidence of antagonistic antiretroviral effects 203 Ritonavir-boosted atazanavir in treatment-naive adults: Use atazanavir 400 mg and ritonavir 100 mg once daily (with food) and efavirenz 600 mg once daily (without food, preferably at bedtime) 1 200 203 Cobicistat-boosted atazanavir in antiretroviral-naive adults: Use single-entity atazanavir 400 mg and single-entity cobicistat 150 mg once daily (with food) and efavirenz 600 mg once daily (without food, preferably at bedtime) 200 239 Ritonavir-boosted or cobicistat-boosted atazanavir in antiretroviral-experienced adults: Concomitant use not recommended 1 200 203 Unboosted atazanavir: Do not use with efavirenz 200 203 Efavirenz/emtricitabine/tenofovir DF: Concomitant use with atazanavir (with or without low-dose ritonavir) not recommended 232 Atovaquone Decreased atovaquone AUC 200 Consider alternative treatment for Pneumocystis jirovecii pneumonia (PCP) or toxoplasmosis or consider alternative antiretroviral regimen; 200 if used concomitantly, monitor for atovaquone efficacy 200 Avanafil Data not available 200 Concomitant use not recommended 200 Benzodiazepines Midazolam, triazolam: Possible increased midazolam or triazolam concentrations 200 Lorazepam: Increased lorazepam concentrations, but no effect on lorazepam AUC 1 200 Alprazolam: Data not available 200 Midazolam (oral), triazolam: Do not use concomitantly 200 Midazolam (parenteral): Experts state a single parenteral midazolam dose can be used with caution in a monitored situation for procedural sedation 200 Lorazepam: Dosage adjustments not needed 1 200 Alprazolam: Monitor for benzodiazepine effectiveness 200 Buprenorphine Buprenorphine (sublingual or buccal): Decreased buprenorphine and norbuprenorphine AUCs 200 Buprenorphine (subdermal implant): Data not available 200 Buprenorphine (sublingual or buccal): Some experts state dosage adjustments not recommended, but monitor for withdrawal symptoms 200 Buprenorphine (subdermal implant): If efavirenz initiated after insertion of implant, clinical monitoring recommended 200 Bupropion Decreased bupropion concentrations and AUC; 1 200 increased concentrations of hydroxybupropion (an active metabolite) 1 Titrate bupropion dosage based on clinical response; 200 do not exceed maximum recommended bupropion dosage 1 Calcium-channel blocking agents Diltiazem: Decreased diltiazem concentrations; 1 slightly increased efavirenz concentrations 1 Other calcium-channel blocking agents that are substrates of CYP 3A4 (e.g., felodipine, nicardipine, nifedipine, verapamil): Possible decreased concentrations of the calcium-channel blocking agent 1 Diltiazem: Titrate diltiazem dosage based on clinical response; 1 200 232 adjustment of efavirenz or efavirenz/emtricitabine/tenofovir DF dosage not needed 1 232 Other calcium-channel blocking agents that are substrates of CYP 3A4: Titrate dosage of calcium-channel blocking agent according to clinical response 1 200 Cisapride Do not use concomitantly 200 Corticosteroids Dexamethasone: Possible decreased efavirenz concentrations 200 Dexamethasone: Monitor virologic response; 200 consider alternative corticosteroids for long-term use 200 Daclatasvir Decreased daclatasvir trough concentrations 178 200 Use daclatasvir dosage of 90 mg once daily 178 200 Darunavir Ritonavir-boosted darunavir: Increased efavirenz AUC; decreased darunavir AUC; 200 204 clinical importance unknown 200 Cobicistat-boosted darunavir: Possible decreased darunavir and cobicistat concentrations; 200 239 possible loss of therapeutic effect and development of resistance to darunavir 239 No in vitro evidence of antagonistic antiretroviral effects 204 Ritonavir-boosted darunavir: Usual dosage can be used; 204 some experts recommend close monitoring; 200 consider monitoring plasma concentrations of darunavir and efavirenz 200 Cobicistat-boosted darunavir: Concomitant use not recommended 200 239 Delavirdine Conco really apt
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