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Adult patients: 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal. ( 2.1 , 2.2 , 2.4 ) Pregnant patients: 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal. ( 2.2 ) Pediatric patients (2 years to less than 18 years of age and weighing at least 10 kg): dosage of Etravirine is based on body weight and should not exceed the recommended adult dose. Etravirine tablets should be taken following a meal. ( 2.3 ) 2.1 Recommended Dosage in Adult Patients The recommended oral dosage of Etravirine for adult patients is 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal. The type of food does not affect the exposure to Etravirine [see Clinical Pharmacology (12.3) ] . 2.2 Recommended Dosage During Pregnancy The recommended oral dosage of Etravirine for pregnant individuals is 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal [see Use in Specific Populations (8.1) ] . 2.3 Recommended Dosage in Pediatric Patients (2 Years to Less Than 18 Years of Age) The recommended dosage of Etravirine for pediatric patients 2 years to less than 18 years of age and weighing at least 10 kg is based on body weight (see Table 1 ) not exceeding the recommended adult dosage. Etravirine should be taken orally, following a meal. The type of food does not affect the exposure to…

The following adverse reactions are described in greater detail in other sections: Severe skin and hypersensitivity reactions [see Warnings and Precautions (5.1) ] . Immune reconstitution syndrome [see Warnings and Precautions (5.3) ] . The most common adverse drug reactions of moderate to severe intensity (at least 2%) which occurred at a higher rate than placebo in adults are rash and peripheral neuropathy. ( 6.1 ) The most common adverse drug reactions in at least 2% of pediatric patients are rash and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Patriot Pharmaceuticals, LLC at 1-800-667-8570 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials Experience in Adults The safety assessment is based on all data from 1203 subjects in the Phase 3 placebo-controlled trials, TMC125-C206 and TMC125-C216, conducted in antiretroviral treatment-experienced HIV-1-infected adult subjects, 599 of whom received Etravirine (200 mg twice daily). In these pooled trials, the median exposure for subjects in the Etravirine arm and placebo arm was 52.3 and 51.0 weeks,…

None. None.

There is no specific antidote for overdose with Etravirine. Human experience of overdose with Etravirine is limited. The highest dose studied in healthy volunteers was 400 mg once daily. Treatment of overdose with Etravirine consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. Because etravirine is highly protein bound, dialysis is unlikely to result in significant removal of the active substance.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

Co-administration of Etravirine with other drugs can alter the concentrations of other drugs and other drugs may alter the concentrations of etravirine. The potential drug-drug interactions must be considered prior to and during therapy. ( 7 , 12.3 ) 7.1 Potential for Other Drugs to Affect Etravirine Etravirine is a substrate of CYP3A, CYP2C9, and CYP2C19. Therefore, co-administration of Etravirine with drugs that induce or inhibit CYP3A, CYP2C9, and CYP2C19 may alter the therapeutic effect or adverse reaction profile of Etravirine (see Table 4 ) [see Clinical Pharmacology (12.3) ]. 7.2 Potential for Etravirine to Affect Other Drugs Etravirine is an inducer of CYP3A and inhibitor of CYP2C9, CYP2C19 and P-glycoprotein (P-gp). Therefore, co-administration of drugs that are substrates of CYP3A, CYP2C9 and CYP2C19 or are transported by P-gp with Etravirine may alter the therapeutic effect or adverse reaction profile of the co-administered drug(s) (see Table 4 ) [see Clinical Pharmacology (12.3) ]. 7.3 Significant Drug Interactions Table 4 shows significant drug interactions based on which, alterations in dose or regimen of Etravirine and/or co-administered drug may be recommended. Drugs that are not recommended for co-administration with Etravirine are also included in Table 4 [see Clinical Pharmacology (12.3) ] . Table 4: Significant Drug Interactions Concomitant Drug Class: Drug Name Effect on Concentration of Etravirine or Concomitant Drug Clinical Comment ↑ = increase; ↓ = decrease; ↔ = no change HIV-antiviral agents: integrase strand inhibitors dolutegravir The interaction between Etravirine and the drug was evaluated in a clinical study. All other drug interactions shown are predicted. ↓ dolutegravir ↔ etravirine Etravirine significantly reduced plasma concentrations of dolutegravir. Using cross - study comparisons to historical pharmacokinetic data for etravirine, dolutegravir did not appear to affect the pharmacokinetics of etravirine. dolutegravir/darunavir /ritonavir ↓ dolutegravir ↔ etravirine The effect of etravirine on dolutegravir plasma concentrations was mitigated by co-administration of darunavir/ritonavir or lopinavir/ritonavir, and is expected to be mitigated by atazanavir/ritonavir. Dolutegravir should only be used with Etravirine when co-administered with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. dolutegravir/lopinavir /ritonavir ↔ dolutegravir ↔ etravirine HIV-antiviral agents: non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz nevirapine ↓ etravirine Combining two NNRTIs has not been shown to be beneficial. Concomitant use of Etravirine with efavirenz or nevirapine may cause a significant decrease in the plasma concentrations of etravirine and loss of therapeutic effect of Etravirine. Co-administration of Etravirine and other NNRTIs is not recommended. delavirdine ↑ etravirine Combining two NNRTIs has not been shown to be beneficial. Etravirine and delavirdine should not be co-administered. rilpivirine ↓ rilpivirine ↔ etravirine Combining two NNRTIs has not been shown to be beneficial. Co-administration of Etravirine and rilpivirine is not recommended. HIV-antiviral agents: protease inhibitors (PIs) atazanavir (without ritonavir) ↓ atazanavir Co-administration of Etravirine and atazanavir without low-dose ritonavir is not recommended. atazanavir/ritonavir ↓ atazanavir ↔ etravirine Concomitant use of Etravirine with atazanavir/ritonavir decreased atazanavir C min but it is not considered clinically relevant. The mean systemic exposure (AUC) of etravirine after co-administration of Etravirine with atazanavir/ritonavir in HIV-infected subjects was similar to the mean systemic exposure of etravirine observed in the Phase 3 trials after co-administration of Etravirine and darunavir/ritonavir (as part of the background regimen). Etravirine and atazanavir/ritonavir can be co-administered without dose adjustments. atazanavir/cobicistat ↓ atazanavir ↓ cobicistat Co-administration of Etravirine with atazanavir/cobicistat is not recommended because it may result in loss of therapeutic effect and development of resistance to atazanavir. darunavir/ritonavir ↓ etravirine The mean systemic exposure (AUC) of etravirine was reduced when Etravirine was co-administered with darunavir/ritonavir. Because all subjects in the Phase 3 trials received darunavir/ritonavir as part of the background regimen and etravirine exposures from these trials were determined to be safe and effective, Etravirine and darunavir/ritonavir can be co-administered without dose adjustments. darunavir/cobicistat ↓ cobicistat darunavir: effect unknown Co-administration of Etravirine with darunavir/cobicistat is not recommended because it may result in loss of therapeutic effect and development of resistance to darunavir. fosamprenavir (without ritonavir) ↑ amprenavir Concomitant use of Etravirine with fosamprenavir without low-dose ritonavir may cause a significant alteration in the plasma concentration of amprenavir. Co-administration of Etravirine and fosamprenavir without low-dose ritonavir is not recommended. fosamprenavir/ritonavir ↑ amprenavir Due to a significant increase in the systemic exposure of amprenavir, the appropriate doses of the combination of Etravirine and fosamprenavir/ritonavir have not been established. Co-administration of Etravirine and fosamprenavir/ritonavir is not recommended. indinavir (without ritonavir) ↓ indinavir Concomitant use of Etravirine with indinavir without low-dose ritonavir may cause a significant alteration in the plasma concentration of indinavir. Co-administration of Etravirine and indinavir without low-dose ritonavir is not recommended. lopinavir/ritonavir ↓ etravirine The mean systemic exposure (AUC) of etravirine was reduced after co-administration of Etravirine with lopinavir/ritonavir (tablet). Because the reduction in the mean systemic exposures of etravirine in the presence of lopinavir/ritonavir is similar to the reduction in mean systemic exposures of etravirine in the presence of darunavir/ritonavir, Etravirine and lopinavir/ritonavir can be co-administered without dose adjustments. nelfinavir (without ritonavir) ↑ nelfinavir Concomitant use of Etravirine with nelfinavir without low-dose ritonavir may cause a significant alteration in the plasma concentration of nelfinavir. Co-administration of Etravirine and nelfinavir without low-dose ritonavir is not recommended. ritonavir ↓ etravirine Concomitant use of Etravirine with ritonavir 600 mg twice daily may cause a significant decrease in the plasma concentration of etravirine and loss of therapeutic effect of Etravirine. Co-administration of Etravirine and ritonavir 600 mg twice daily is not recommended. saquinavir/ritonavir ↓ etravirine The mean systemic exposure (AUC) of etravirine was reduced when Etravirine was co-administered with saquinavir/ritonavir. Because the reduction in the mean systemic exposures of etravirine in the presence of saquinavir/ritonavir is similar to the reduction in mean systemic exposures of etravirine in the presence of darunavir/ritonavir, Etravirine and saquinavir/ritonavir can be co-administered without dose adjustments. tipranavir/ritonavir ↓ etravirine Concomitant use of Etravirine with tipranavir/ritonavir may cause a significant decrease in the plasma concentrations of etravirine and loss of therapeutic effect of Etravirine. Co-administration of Etravirine and tipranavir/ritonavir is not recommended. CCR5 antagonists maraviroc ↔ etravirine ↓ maraviroc When Etravirine is co-administered with maraviroc in the absence of a potent CYP3A inhibitor (e.g., ritonavir boosted protease inhibitor), the recommended dose of maraviroc is 600 mg twice daily. No dose adjustment of Etravirine is needed. maraviroc/darunavir/ ritonavir The reference for etravirine exposure is the pharmacokinetic parameters of etravirine in the presence of darunavir/ritonavir. ↔ etravirine ↑ maraviroc When Etravirine is co-administered with maraviroc in the presence of a potent CYP3A inhibitor (e.g., ritonavir boosted protease inhibitor), the recommended dose of maraviroc is 150 mg twice daily. No dose adjustment of Etravirine is needed. Other agents Antiarrhythmics : digoxin ↔ etravirine ↑ digoxin For patients who are initiating a combination of Etravirine and digoxin, the lowest dose of digoxin should initially be prescribed. For patients on a stable digoxin regimen and initiating Etravirine, no dose adjustment of either Etravirine or digoxin is needed. The serum digoxin concentrations should be monitored and used for titration of the digoxin dose to obtain the desired clinical effect. amiodarone bepridil disopyramide flecainide lidocaine (systemic) mexiletine propafenone quinidine ↓ antiarrhythmics Concentrations of these antiarrhythmics may be decreased when co-administered with Etravirine. Etravirine and antiarrhythmics should be co-administered with caution. Drug concentration monitoring is recommended, if available. Anticoagulant : warfarin ↑ anticoagulants Warfarin concentrations may be increased when co-administered with Etravirine. The international normalized ratio (INR) should be monitored when warfarin is combined with Etravirine. Anticonvulsants : carbamazepine phenobarbital phenytoin ↓ etravirine Carbamazepine, phenobarbital and phenytoin are inducers of CYP450 enzymes. Etravirine should not be used in combination with carbamazepine, phenobarbital, or phenytoin as co-administration may cause significant decreases in etravirine plasma concentrations and loss of therapeutic effect of Etravirine. Antifungals : fluconazole ↑ etravirine ↔ fluconazole Co-administration of etravirine and fluconazole significantly increased etravirine exposures. The amount of safety data at these increased etravirine exposures is limited, therefore, etravirine and fluconazole should be co-administered with caution. No dose adjustment of Etravirine or fluconazole is needed. voriconazole ↑ voriconazole Co-administration of etravirine and voriconazole significantly increased etravirine exposures. The amount of safety data at these increased etravirine exposures is limited, therefore, etravirine and voriconazole should be co-administered with caution. No dose adjustment of Etravirine or voriconazole is needed. Antifungals : itraconazole ketoconazole posaconazole ↑ etravirine ↓ itraconazole ↓ ketoconazole ↔ posaconazole Posaconazole, a potent inhibitor of CYP3A4, may increase plasma concentrations of etravirine. Itraconazole and ketoconazole are potent inhibitors as well as substrates of CYP3A4. Concomitant systemic use of itraconazole or ketoconazole and Etravirine may increase plasma concentrations of etravirine. Simultaneously, plasma concentrations of itraconazole or ketoconazole may be decreased by Etravirine. Dose adjustments for itraconazole, ketoconazole or posaconazole may be necessary depending on the other co-administered drugs. Antiinfective : clarithromycin ↑ etravirine ↓ clarithromycin ↑ 14-OH-clarithromycin Clarithromycin exposure was decreased by Etravirine; however, concentrations of the active metabolite, 14-hydroxy-clarithromycin, were increased. Because 14-hydroxy-clarithromycin has reduced activity against Mycobacterium avium complex (MAC), overall activity against this pathogen may be altered. Alternatives to clarithromycin, such as azithromycin, should be considered for the treatment of MAC. Antimalarial : artemether/lumefantrine ↔ etravirine ↓ artemether ↓ dihydroartemisinin ↓ lumefantrine Caution is warranted when co-administering Etravirine and artemether/lumefantrine as it is unknown whether the decrease in exposure of artemether or its active metabolite, dihydroartemisinin, could result in decreased antimalarial efficacy. No dose adjustment is needed for Etravirine. Antimycobacterials: rifampin rifapentine ↓ etravirine Rifampin and rifapentine are potent inducers of CYP450 enzymes. Etravirine should not be used with rifampin or rifapentine as co-administration may cause significant decreases in etravirine plasma concentrations and loss of therapeutic effect of Etravirine. Antimycobacterial: rifabutin ↓ etravirine ↓ rifabutin ↓ 25- O -desacetylrifabutin If Etravirine is NOT co-administered with a protease inhibitor/ritonavir, then rifabutin at a dose of 300 mg once daily is recommended. If Etravirine is co-administered with darunavir/ritonavir, lopinavir/ritonavir or saquinavir/ritonavir, then rifabutin should not be co-administered due to the potential for significant reductions in etravirine exposure. Benzodiazepine: diazepam ↑ diazepam Concomitant use of Etravirine with diazepam may increase plasma concentrations of diazepam. A decrease in diazepam dose may be needed. Corticosteroid : dexamethasone (systemic) ↓ etravirine Systemic dexamethasone induces CYP3A and can decrease etravirine plasma concentrations. This may result in loss of therapeutic effect of Etravirine. Systemic dexamethasone should be used with caution or alternatives should be considered, particularly for long-term use. Herbal products : St. John's wort ( Hypericum perforatum ) ↓ etravirine Concomitant use of Etravirine with products containing St. John's wort may cause significant decreases in etravirine plasma concentrations and loss of therapeutic effect of Etravirine. Etravirine and products containing St. John's wort should not be co-administered. Hepatitis C virus (HCV) direct-acting antivirals : daclatasvir ↓ daclatasvir Co-administration of Etravirine with daclatasvir may decrease daclatasvir concentrations. Increase the daclatasvir dose to 90 mg once daily. elbasvir/grazoprevir ↓ elbasvir ↓ grazoprevir Co-administration of Etravirine with elbasvir/grazoprevir may decrease elbasvir and grazoprevir concentrations, leading to reduced therapeutic effect of elbasvir/grazoprevir. Co-administration is not recommended. HMG-CoA reductase inhibitors : atorvastatin ↔ etravirine ↓ atorvastatin ↑ 2-OH-atorvastatin The combination of Etravirine and atorvastatin can be given without dose adjustments, however, the dose of atorvastatin may need to be altered based on clinical response. pravastatin rosuvastatin ↔ etravirine ↔ pravastatin ↔ rosuvastatin No interaction between pravastatin, rosuvastatin and Etravirine is expected. lovastatin simvastatin ↓ lovastatin ↓ simvastatin Lovastatin and simvastatin are CYP3A substrates and co-administration with Etravirine may result in lower plasma concentrations of the HMG-CoA reductase inhibitor. fluvastatin pitavastatin ↑ fluvastatin ↑ pitavastatin Fluvastatin and pitavastatin are metabolized by CYP2C9 and co-administration with Etravirine may result in higher plasma concentrations of the HMG-CoA reductase inhibitor. Dose adjustments for these HMG-CoA reductase inhibitors may be necessary. Immunosuppressants : cyclosporine sirolimus tacrolimus ↓ immunosuppressant Etravirine and systemic immunosuppressants should be co-administered with caution because plasma concentrations of cyclosporine, sirolimus, or tacrolimus may be affected. Narcotic analgesics/treatment of opioid dependence: buprenorphine buprenorphine/naloxone methadone ↔ etravirine ↓ buprenorphine ↔ norbuprenorphine ↔ methadone Etravirine and buprenorphine (or buprenorphine/naloxone) can be co-administered without dose adjustments, however, clinical monitoring for withdrawal symptoms is recommended as buprenorphine (or buprenorphine/naloxone) maintenance therapy may need to be adjusted in some patients. Etravirine and methadone can be co-administered without dose adjustments, however, clinical monitoring for withdrawal symptoms is recommended as methadone maintenance therapy may need to be adjusted in some patients. Phosphodiesterase type 5 (PDE-5) inhibitors : sildenafil tadalafil vardenafil ↓ sildenafil ↓ N-desmethyl-sildenafil Etravirine and sildenafil can be co-administered without dose adjustments, however, the dose of sildenafil may need to be altered based on clinical effect. Platelet aggregation inhibitors: clopidogrel ↓ clopidogrel (active) metabolite Activation of clopidogrel to its active metabolite may be decreased when clopidogrel is co-administered with Etravirine. Alternatives to clopidogrel should be considered. 7.4 Drugs Without Clinically Significant Interactions with Etravirine In addition to the drugs included in Table 4, the interaction between Etravirine and the following drugs were evaluated in clinical studies and no dose adjustment is needed for either drug [see Clinical Pharmacology (12.3) ] : didanosine, enfuvirtide (ENF), ethinylestradiol/norethindrone, omeprazole, paroxetine, raltegravir, ranitidine, and tenofovir disoproxil fumarate.