FDA label 2f36e505-bf65-2fb2-e054-00144ff88e88

WARNINGS AND PRECAUTIONS See Table 3 for a listing of drugs that are contraindicated for use with REYATAZ (atazanavir sulfate) due to potentially life-threatening adverse events, significant drug interactions, or loss of virologic activity. [See Contraindications (4) .] Please refer to Table 13 for established and other potentially significant drug interactions [see Drug Interactions (7.3) ]. Atazanavir has been shown to prolong the PR interval of the electrocardiogram in some patients. In healthy volunteers and in patients, abnormalities in atrioventricular (AV) conduction were asymptomatic and generally limited to first-degree AV block. There have been reports of second-degree AV block and other conduction abnormalities [see Adverse Reactions (6.4) and Overdosage (10) ]. In clinical trials that included electrocardiograms, asymptomatic first-degree AV block was observed in 5.9% of atazanavir-treated patients (n=920), 5.2% of lopinavir/ritonavir-treated patients (n=252), 10.4% of nelfinavir-treated patients (n=48), and 3.0% of efavirenz-treated patients (n=329). In Study AI424-045, asymptomatic first-degree AV block was observed in 5% (6/118) of atazanavir/ritonavir-treated patients and 5% (6/116) of lopinavir/ritonavir-treated patients who had on-study electrocardiogram measurements. Because of limited clinical experience in patients with preexisting conduction system disease (eg, marked first-degree AV block or second- or third-degree AV block), atazanavir should be used with caution in these patients. [See Clinical Pharmacology (12.2) .] Atazanavir in combination with diltiazem increased diltiazem plasma concentration by 2-fold with an additive effect on the PR interval. When used in combination with atazanavir, a dose reduction of diltiazem by one-half should be considered and ECG monitoring is recommended. In a pharmacokinetic study between atazanavir 400 mg once daily and atenolol 50 mg once daily, no clinically significant additive effect of atazanavir and atenolol on the PR interval was observed. Dose adjustment of atenolol is not required when used in combination with atazanavir. [See Drug Interactions (7) and Clinical Pharmacology (12.2) .] Pharmacokinetic studies between atazanavir and other drugs that prolong the PR interval including beta blockers [other than atenolol, see Drug Interactions (7) ], verapamil, and digoxin have not been performed. An additive effect of atazanavir and these drugs cannot be excluded; therefore, caution should be exercised when atazanavir is given concurrently with these drugs, especially those that are metabolized by CYP3A (eg, verapamil). In controlled clinical trials, rash (all grades, regardless of causality) occurred in approximately 20% of patients treated with REYATAZ. The median time to onset of rash in clinical studies was 7.3 weeks and the median duration of rash was 1.4 weeks. Rashes were generally mild-to-moderate maculopapular skin eruptions. Treatment-emergent adverse reactions of moderate or severe rash (occurring at a rate of ≥2%) are presented for the individual clinical studies [see Adverse Reactions (6.1) ]. Dosing with REYATAZ (atazanavir sulfate) was often continued without interruption in patients who developed rash. The discontinuation rate for rash in clinical trials was <1%. REYATAZ should be discontinued if severe rash develops. Cases of Stevens-Johnson syndrome, erythema multiforme, and toxic skin eruptions , including drug rash, eosinophilia and systemic symptoms (DRESS) syndrome, have been reported in patients receiving REYATAZ. [See Contraindications (4) .] Most patients taking REYATAZ experience asymptomatic elevations in indirect (unconjugated) bilirubin related to inhibition of UDP-glucuronosyl transferase (UGT). This hyperbilirubinemia is reversible upon discontinuation of REYATAZ. Hepatic transaminase elevations that occur with hyperbilirubinemia should be evaluated for alternative etiologies. No long-term safety data are available for patients experiencing persistent elevations in total bilirubin >5 times ULN. Alternative antiretroviral therapy to REYATAZ may be considered if jaundice or scleral icterus associated with bilirubin elevations presents cosmetic concerns for patients. Dose reduction of atazanavir is not recommended since long-term efficacy of reduced doses has not been established. [See Adverse Reactions (6.1 , 6.2) .] Caution should be exercised when administering REYATAZ to patients with hepatic impairment because atazanavir concentrations may be increased. [See Dosage and Administration (2.5) .] Patients with underlying hepatitis B or C viral infections or marked elevations in transaminases before treatment may be at increased risk for developing further transaminase elevations or hepatic decompensation. In these patients, hepatic laboratory testing should be conducted prior to initiating therapy with REYATAZ and during treatment. [See Adverse Reactions (6.3) and Use in Specific Populations (8.8) .] Cases of nephrolithiasis and/or cholelithiasis have been reported during postmarketing surveillance in HIV-infected patients receiving REYATAZ therapy. Some patients required hospitalization for additional management and some had complications. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made. If signs or symptoms of nephrolithiasis and/or cholelithiasis occur, temporary interruption or discontinuation of therapy may be considered. [See Adverse Reactions (6.4) .] New-onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and hyperglycemia have been reported during postmarketing surveillance in HIV-infected patients receiving protease inhibitor therapy. Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycemia persisted in some cases. Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between protease inhibitor therapy and these events has not been established. [See Adverse Reactions (6.4) .] Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including REYATAZ. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia, or tuberculosis), which may necessitate further evaluation and treatment. Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment. Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established. There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis, in patients with hemophilia type A and B treated with protease inhibitors. In some patients additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced. A causal relationship between protease inhibitor therapy and these events has not been established. Various degrees of cross-resistance among protease inhibitors have been observed. Resistance to atazanavir may not preclude the subsequent use of other protease inhibitors. [See Clinical Pharmacology (12.4) .]

ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: cardiac conduction abnormalities [see Warnings and Precautions (5.2) ] rash [see Warnings and Precautions (5.3) ] hyperbilirubinemia [see Warnings and Precautions (5.4) ] nephrolithiasis and cholelithiasis [see Warnings and Precautions (5.6) ] 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. Treatment-Emergent Adverse Reactions in Treatment-Naive Patients The safety profile of REYATAZ in treatment-naive adults is based on 1625 HIV-1 infected patients in clinical trials. 536 patients received REYATAZ 300 mg with ritonavir 100 mg and 1089 patients received REYATAZ 400 mg or higher (without ritonavir). The most common adverse reactions are nausea, jaundice/scleral icterus, and rash. Selected clinical adverse reactions of moderate or severe intensity reported in ≥2% of treatment-naive patients receiving combination therapy including REYATAZ 300 mg with ritonavir 100 mg and REYATAZ 400 mg (without ritonavir) are presented in Tables 4 and 5 , respectively. Table 4: Selected Treatment-Emergent Adverse Reactions a of Moderate or Severe Intensity Reported in ≥2% of Adult Treatment-Naive Patients, b Study AI424-138 96 weeks c 96 weeks c REYATAZ 300 mg with ritonavir 100 mg (once daily) and tenofovir with emtricitabine d lopinavir 400 mg with ritonavir 100 mg (twice daily) and tenofovir with emtricitabine d (n=441) (n=437) Digestive System Nausea 4% 8% Jaundice/scleral icterus 5% * Diarrhea 2% 12% Skin and Appendages Rash 3% 2% Table 5: Selected Treatment-Emergent Adverse Reactions a of Moderate or Severe Intensity Reported in ≥2% of Adult Treatment-Naive Patients, b Studies AI424-034, AI424-007, and AI424-008 Study AI424-034 Studies AI424-007, -008 64 weeks c REYATAZ 400 mg once daily + lamivudine + zidovudine e 64 weeks c efavirenz 600 mg once daily + lamivudine + zidovudine e 120 weeks c,d REYATAZ 400 mg once daily + stavudine + lamivudine or didanosine 73 weeks c,d nelfinavir 750 mg TID or 1250 mg BID + stavudine + lamivudine or didanosine (n=404) (n=401) (n=279) (n=191) Body as a Whole Headache 6% 6% 1% 2% Digestive System Nausea 14% 12% 6% 4% Jaundice/scleral icterus 7% * 7% * Vomiting 4% 7% 3% 3% Abdominal pain 4% 4% 4% 2% Diarrhea 1% 2% 3% 16% Nervous System Insomnia 3% 3% <1% * Dizziness 2% 7% <1% * Peripheral neurologic symptoms <1% 1% 4% 3% Skin and Appendages Rash 7% 10% 5% 1% Treatment-Emergent Adverse Reactions in Treatment-Experienced Patients The safety profile of REYATAZ in treatment-experienced adults is based on 119 HIV-1 infected patients in clinical trials. The most common adverse reactions are jaundice/scleral icterus and myalgia. Selected clinical adverse reactions of moderate or severe intensity reported in ≥2% of treatment-experienced patients receiving REYATAZ/ritonavir are presented in Table 6 . Table 6: Selected Treatment-Emergent Adverse Reactions a of Moderate or Severe Intensity Reported in ≥2% of Adult Treatment-Experienced Patients, b Study AI424-045 48 weeks c REYATAZ/ritonavir 300/100 mg once daily + tenofovir + NRTI 48 weeks c lopinavir/ritonavir 400/100 mg twice daily d + tenofovir + NRTI (n=119) (n=118) Body as a Whole Fever 2% * Digestive System Jaundice/scleral icterus 9% * Diarrhea 3% 11% Nausea 3% 2% Nervous System Depression 2% <1% Musculoskeletal System Myalgia 4% * Laboratory Abnormalities in Treatment-Naive Patients The percentages of adult treatment-naive patients treated with combination therapy including REYATAZ (atazanavir sulfate) 300 mg with ritonavir 100 mg and REYATAZ 400 mg (without ritonavir) with Grade 3–4 laboratory abnormalities are presented in Tables 7 and 8 , respectively. Table 7: Grade 3–4 Laboratory Abnormalities Reported in ≥2% of Adult Treatment-Naive Patients, a Study AI424-138 Variable Limit c 96 weeks b 96 weeks b REYATAZ 300 mg with ritonavir 100 mg (once daily) and tenofovir with emtricitabine d lopinavir 400 mg with ritonavir 100 mg (twice daily) and tenofovir with emtricitabine d (n=441) (n=437) Chemistry High SGOT/AST ≥5.1 x ULN 3% 1% SGPT/ALT ≥5.1 x ULN 3% 2% Total Bilirubin ≥2.6 x ULN 44% <1% Lipase ≥2.1 x ULN 2% 2% Creatine Kinase ≥5.1 x ULN 8% 7% Total Cholesterol ≥240 mg/dL 11% 25% Hematology Low Neutrophils <750 cells/mm 3 5% 2% a Based on the regimen containing REYATAZ. b Median time on therapy. c ULN = upper limit of normal. d As a fixed-dose combination: 300 mg tenofovir, 200 mg emtricitabine once daily. Table 8: Grade 3–4 Laboratory Abnormalities Reported in ≥2% of Adult Treatment-Naive Patients, a Studies AI424-034, AI424-007, and AI424-008 Variable Limit d Study AI424-034 Studies AI424-007, -008 64 weeks b 64 weeks b 120 weeks b,c 73 weeks b,c REYATAZ 400 mg once daily + lamivudine + zidovudine e efavirenz 600 mg once daily + lamivudine + zidovudine e REYATAZ 400 mg once daily + stavudine + lamivudine or + stavudine + didanosine nelfinavir 750 mg TID or 1250 mg BID + stavudine + lamivudine or + stavudine + didanosine (n=404) (n=401) (n=279) (n=191) Chemistry High SGOT/AST ≥5.1 x ULN 2% 2% 7% 5% SGPT/ALT ≥5.1 x ULN 4% 3% 9% 7% Total Bilirubin ≥2.6 x ULN 35% <1% 47% 3% Amylase ≥2.1 x ULN * * 14% 10% Lipase ≥2.1 x ULN <1% 1% 4% 5% Creatine Kinase ≥5.1 x ULN 6% 6% 11% 9% Total Cholesterol ≥240 mg/dL 6% 24% 19% 48% Triglycerides ≥751 mg/dL <1% 3% 4% 2% Hematology Low Hemoglobin <8.0 g/dL 5% 3% <1% 4% Neutrophils <750 cells/mm 3 7% 9% 3% 7% Laboratory Abnormalities in Treatment-Experienced Patients The percentages of adult treatment-experienced patients treated with combination therapy including REYATAZ/ritonavir with Grade 3–4 laboratory abnormalities are presented in Table 9 . Table 9: Grade 3–4 Laboratory Abnormalities Reported in ≥2% of Adult Treatment-Experienced Patients, Study AI424-045 a Variable Limit c 48 weeks b 48 weeks b REYATAZ/ritonavir 300/100 mg once daily + tenofovir + NRTI lopinavir/ritonavir 400/100 mg twice daily d + tenofovir + NRTI (n=119) (n=118) Chemistry High SGOT/AST ≥5.1 x ULN 3% 3% SGPT/ALT ≥5.1 x ULN 4% 3% Total Bilirubin ≥2.6 x ULN 49% <1% Lipase ≥2.1 x ULN 5% 6% Creatine Kinase ≥5.1 x ULN 8% 8% Total Cholesterol ≥240 mg/dL 25% 26% Triglycerides ≥751 mg/dL 8% 12% Glucose ≥251 mg/dL 5% <1% Hematology Low Platelets <50,000 cells/mm 3 2% 3% Neutrophils <750 cells/mm 3 7% 8% Lipids, Change from Baseline in Treatment-Naive Patients For Study AI424-138 and Study AI424-034, changes from baseline in LDL-cholesterol, HDL-cholesterol, total cholesterol, and triglycerides are shown in Tables 10 and 11 , respectively. Table 10: Lipid Values, Mean Change from Baseline, Study AI424-138 REYATAZ/ritonavir a,b lopinavir/ritonavir b,c Baseline Week 48 Week 96 Baseline Week 48 Week 96 mg/dL mg/dL Change d mg/dL Change d mg/dL mg/dL Change d mg/dL Change d (n=428 e ) (n=372 e ) (n=372 e ) (n=342 e ) (n=342 e ) (n=424 e ) (n=335 e ) (n=335 e ) (n=291 e ) (n=291 e ) LDL-Cholesterol f 92 105 +14% 105 +14% 93 111 +19% 110 +17% HDL-Cholesterol f 37 46 +29% 44 +21% 36 48 +37% 46 +29% Total Cholesterol f 149 169 +13% 169 +13% 150 187 +25% 186 +25% Triglycerides f 126 145 +15% 140 +13% 129 194 +52% 184 +50% Table 11: Lipid Values, Mean Change from Baseline, Study AI424-034 REYATAZ a,b efavirenz b,c Baseline Week 48 Week 48 Baseline Week 48 Week 48 mg/dL mg/dL Change d mg/dL mg/dL Change d (n=383 e ) (n=283 e ) (n=272 e ) (n=378 e ) (n=264 e ) (n=253 e ) LDL-Cholesterol f 98 98 +1% 98 114 +18% HDL-Cholesterol 39 43 +13% 38 46 +24% Total Cholesterol 164 168 +2% 162 195 +21% Triglycerides f 138 124 -9% 129 168 +23% Lipids, Change from Baseline in Treatment-Experienced Patients For Study AI424-045, changes from baseline in LDL-cholesterol, HDL-cholesterol, total cholesterol, and triglycerides are shown in Table 12 . The observed magnitude of dyslipidemia was less with REYATAZ/ritonavir than with lopinavir/ritonavir. However, the clinical impact of such findings has not been demonstrated. Table 12: Lipid Values, Mean Change from Baseline, Study AI424-045 REYATAZ/ritonavir a,b lopinavir/ritonavir b,c Baseline Week 48 Week 48 Baseline Week 48 Week 48 mg/dL mg/dL Change d mg/dL mg/dL Change d (n=111 e ) (n=75 e ) (n=74 e ) (n=108 e ) (n=76 e ) (n=73 e ) LDL-Cholesterol f 108 98 -10% 104 103 +1% HDL-Cholesterol 40 39 -7% 39 41 +2% Total Cholesterol 188 170 -8% 181 187 +6% Triglycerides f 215 161 -4% 196 224 +30% The safety and tolerability of REYATAZ Capsules with and without ritonavir have been established in pediatric patients at least 6 years of age from the open-label, multicenter clinical trial PACTG 1020A. Use of REYATAZ in pediatric patients less than 6 years of age is under investigation. The safety profile of REYATAZ in pediatric patients (6 to less than 18 years of age) was generally similar to that observed in clinical studies of REYATAZ in adults. The most common Grade 2–4 adverse events (≥5%, regardless of causality) reported in pediatric patients were cough (21%), fever (18%), jaundice/scleral icterus (15%), rash (14%), vomiting (12%), diarrhea (9%), headache (8%), peripheral edema (7%), extremity pain (6%), nasal congestion (6%), oropharyngeal pain (6%), wheezing (6%), and rhinorrhea (6%). Asymptomatic second-degree atrioventricular block was reported in <2% of patients. The most common Grade 3–4 laboratory abnormalities occurring in pediatric patients were elevation of total bilirubin (≥3.2 mg/dL, 58%), neutropenia (9%), and hypoglycemia (4%). All other Grade 3–4 laboratory abnormalities occurred with a frequency of less than 3%. Liver function tests should be monitored in patients with a history of hepatitis B or C. In study AI424-138, 60 patients treated with REYATAZ/ritonavir 300 mg/100 mg once daily, and 51 patients treated with lopinavir/ritonavir 400 mg/100 mg twice daily, each with fixed dose tenofovir-emtricitabine, were seropositive for hepatitis B and/or C at study entry. ALT levels >5 times ULN developed in 10% (6/60) of the REYATAZ/ritonavir-treated patients and 8% (4/50) of the lopinavir/ritonavir-treated patients. AST levels >5 times ULN developed in 10% (6/60) of the REYATAZ/ritonavir-treated patients and none (0/50) of the lopinavir/ritonavir-treated patients. In study AI424-045, 20 patients treated with REYATAZ/ritonavir 300 mg/100 mg once daily, and 18 patients treated with lopinavir/ritonavir 400 mg/100 mg twice daily, were seropositive for hepatitis B and/or C at study entry. ALT levels >5 times ULN developed in 25% (5/20) of the REYATAZ/ritonavir-treated patients and 6% (1/18) of the lopinavir/ritonavir-treated patients. AST levels >5 times ULN developed in 10% (2/20) of the REYATAZ/ritonavir-treated patients and 6% (1/18) of the lopinavir/ritonavir-treated patients. In studies AI424-008 and AI424-034, 74 patients treated with 400 mg of REYATAZ (atazanavir sulfate) once daily, 58 who received efavirenz, and 12 who received nelfinavir were seropositive for hepatitis B and/or C at study entry. ALT levels >5 times the upper limit of normal (ULN) developed in 15% of the REYATAZ-treated patients, 14% of the efavirenz-treated patients, and 17% of the nelfinavir-treated patients. AST levels >5 times ULN developed in 9% of the REYATAZ-treated patients, 5% of the efavirenz-treated patients, and 17% of the nelfinavir-treated patients. Within atazanavir and control regimens, no difference in frequency of bilirubin elevations was noted between seropositive and seronegative patients. [See Warnings and Precautions (5.5) .] The following events have been identified during postmarketing use of REYATAZ. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Body as a Whole: edema Cardiovascular System: second-degree AV block, third-degree AV block, left bundle branch block, QTc prolongation [see Warnings and Precautions (5.2) ] Gastrointestinal System: pancreatitis Hepatic System: hepatic function abnormalities Hepatobiliary Disorders: cholelithiasis [see Warnings and Precautions (5.6) ], cholecystitis, cholestasis Metabolic System and Nutrition Disorders: diabetes mellitus, hyperglycemia [see Warnings and Precautions (5.7) ] Musculoskeletal System: arthralgia Renal System: nephrolithiasis [see Warnings and Precautions (5.6) ], interstitial nephritis Skin and Appendages: alopecia, maculopapular rash [see Contraindications (4) and Warnings and Precautions (5.3) ], pruritus

<table ID="table4" width="100%"> <caption>Table 4: Selected Treatment-Emergent Adverse Reactions ^a of Moderate or Severe Intensity Reported in &#x2265;2% of Adult Treatment-Naive Patients, ^b Study AI424-138 </caption> <col span="1" width="30%"/> <col span="1" width="35%"/> <col span="1" width="35%"/> <tbody> <tr> <th colspan="1"> </th> <th colspan="1"> <content styleCode="bold">96 weeks ^c </content> </th> <th colspan="1"> <content styleCode="bold">96 weeks ^c </content> </th> </tr> <tr> <th colspan="1"> </th> <th colspan="1"> <content styleCode="bold">REYATAZ 300 mg with ritonavir 100 mg (once daily) and tenofovir with emtricitabine ^d </content> </th> <th colspan="1"> <content styleCode="bold">lopinavir 400 mg with ritonavir 100 mg (twice daily) and tenofovir with emtricitabine ^d </content> </th> </tr> <tr> <th colspan="1"> </th> <th colspan="1"> <content styleCode="bold">(n=441)</content> </th> <th colspan="1"> <content styleCode="bold">(n=437)</content> </th> </tr> <tr> <td> <content styleCode="bold">Digestive System</content> </td> <td> </td> <td> </td> </tr> <tr> <td> Nausea</td> <td>4%</td> <td>8%</td> </tr> <tr> <td> Jaundice/scleral icterus</td> <td>5%</td> <td>*</td> </tr> <tr> <td> Diarrhea</td> <td>2%</td> <td>12%</td> </tr> <tr> <td> <content styleCode="bold">Skin and Appendages</content> </td> <td> </td> <td> </td> </tr> <tr> <td> Rash</td> <td>3%</td> <td>2%</td> </tr> </tbody> </table>

<table ID="table5" width="100%"> <caption>Table 5: Selected Treatment-Emergent Adverse Reactions ^a of Moderate or Severe Intensity Reported in &#x2265;2% of Adult Treatment-Naive Patients, ^b Studies AI424-034, AI424-007, and AI424-008 </caption> <col span="1" width="20%"/> <col span="1" width="20%"/> <col span="1" width="20%"/> <col span="1" width="20%"/> <col span="1" width="20%"/> <tbody> <tr> <th colspan="1"> </th> <th colspan="2"> <content styleCode="bold">Study AI424-034</content> </th> <th colspan="2"> <content styleCode="bold">Studies AI424-007, -008</content> </th> </tr> <tr> <th colspan="1"> <content styleCode="bold">64 weeks ^c REYATAZ 400 mg once daily + lamivudine + zidovudine ^e </content> </th> <th colspan="1"> <content styleCode="bold">64 weeks ^c efavirenz 600 mg once daily + lamivudine + zidovudine ^e </content> </th> <th colspan="1"> <content styleCode="bold">120 weeks ^c,d REYATAZ 400 mg once daily + stavudine + lamivudine or didanosine </content> </th> <th colspan="1"> <content styleCode="bold">73 weeks ^c,d nelfinavir 750 mg TID or 1250 mg BID + stavudine + lamivudine or didanosine </content> </th> </tr> <tr> <th colspan="1"> <content styleCode="bold">(n=404)</content> </th> <th colspan="1"> <content styleCode="bold">(n=401)</content> </th> <th colspan="1"> <content styleCode="bold">(n=279) </content> </th> <th colspan="1"> <content styleCode="bold">(n=191)</content> </th> </tr> <tr> <td> <content styleCode="bold">Body as a Whole</content> </td> </tr> <tr> <td> Headache</td> <td>6%</td> <td>6%</td> <td>1%</td> <td>2%</td> </tr> <tr> <td> <content styleCode="bold">Digestive System</content> </td> </tr> <tr> <td> Nausea</td> <td>14%</td> <td>12%</td> <td>6%</td> <td>4%</td> </tr> <tr> <td> Jaundice/scleral icterus </td> <td>7%</td> <td>*</td> <td>7%</td> <td>*</td> </tr> <tr> <td> Vomiting</td> <td>4%</td> <td>7%</td> <td>3%</td> <td>3%</td> </tr> <tr> <td> Abdominal pain</td> <td>4%</td> <td>4%</td> <td>4%</td> <td>2%</td> </tr> <tr> <td> Diarrhea</td> <td>1%</td> <td>2%</td> <td>3%</td> <td>16%</td> </tr> <tr> <td> <content styleCode="bold">Nervous System</content> </td> </tr> <tr> <td> Insomnia</td> <td>3%</td> <td>3%</td> <td>&lt;1%</td> <td>*</td> </tr> <tr> <td> Dizziness</td> <td>2%</td> <td>7%</td> <td>&lt;1%</td> <td>*</td> </tr> <tr> <td> Peripheral neurologic symptoms </td> <td>&lt;1%</td> <td>1%</td> <td>4%</td> <td>3%</td> </tr> <tr> <td> <content styleCode="bold">Skin and Appendages</content> </td> </tr> <tr> <td> Rash</td> <td>7%</td> <td>10%</td> <td>5%</td> <td>1%</td> </tr> </tbody> </table>

<table ID="table6" width="100%"> <caption>Table 6: Selected Treatment-Emergent Adverse Reactions ^a of Moderate or Severe Intensity Reported in &#x2265;2% of Adult Treatment-Experienced Patients, ^b Study AI424-045 </caption> <col span="1" width="28%"/> <col span="1" width="36%"/> <col span="1" width="35%"/> <tbody> <tr> <th colspan="1"> </th> <th colspan="1"> <content styleCode="bold">48 weeks ^c REYATAZ/ritonavir 300/100 mg once daily + tenofovir + NRTI </content> </th> <th colspan="1"> <content styleCode="bold">48 weeks ^c lopinavir/ritonavir 400/100 mg twice daily ^d + tenofovir + NRTI </content> </th> </tr> <tr> <th colspan="1"> <content styleCode="bold">(n=119) </content> </th> <th colspan="1"> <content styleCode="bold">(n=118)</content> </th> </tr> <tr> <td> <content styleCode="bold">Body as a Whole</content> </td> </tr> <tr> <td> Fever</td> <td>2%</td> <td>*</td> </tr> <tr> <td> <content styleCode="bold">Digestive System</content> </td> </tr> <tr> <td> Jaundice/scleral icterus</td> <td>9%</td> <td>*</td> </tr> <tr> <td> Diarrhea</td> <td>3%</td> <td>11%</td> </tr> <tr> <td> Nausea</td> <td>3%</td> <td>2%</td> </tr> <tr> <td> <content styleCode="bold">Nervous System</content> </td> </tr> <tr> <td> Depression</td> <td>2%</td> <td>&lt;1%</td> </tr> <tr> <td> <content styleCode="bold">Musculoskeletal System</content> </td> </tr> <tr> <td> Myalgia</td> <td>4%</td> <td>*</td> </tr> </tbody> </table>