FDA label e0c9df53-bc95-591f-e053-2a95a90a1dc6

WARNING: HYPERSENSITIVITY REACTIONS, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, and EXACERBATIONS OF HEPATITIS B Hypersensitivity Reactions Serious and sometimes fatal hypersensitivity reactions, with multiple organ involvement, have occurred with abacavir, a component of abacavir and lamivudine tablets. Patients who carry the HLA-B*5701 allele are at a higher risk of a hypersensitivity reaction to abacavir; although, hypersensitivity reactions have occurred in patients who do not carry the HLA-B*5701 allele [see Warnings and Precautions ( 5.1 )] . Abacavir and lamivudine tablets are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )] . All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with abacavir and lamivudine tablets or reinitiation of therapy with abacavir and lamivudine tablets, unless patients have a previously documented HLA-B*5701 allele assessment. Discontinue abacavir and lamivudine tablets immediately if a hypersensitivity reaction is suspected, regardless of HLA-B*5701 status and even when other diagnoses are possible [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )]. Following a hypersensitivity reaction to abacavir and lamivudine tablets, NEVER restart abacavir and lamivudine tablets or any other abacavir-containing product because more severe symptoms, including death, can occur within hours. Similar severe reactions have also occurred rarely following the reintroduction of abacavir-containing products in patients who have no history of abacavir hypersensitivity [see Warnings and Precautions ( 5.1 )]. Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Discontinue abacavir and lamivudine tablets if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions ( 5.2 )]. Exacerbations of Hepatitis B Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine, which is a component of abacavir and lamivudine tablets. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue abacavir and lamivudine tablets and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions ( 5.3 )] . WARNING: HYPERSENSITIVITY REACTIONS, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, and EXACERBATIONS OF HEPATITIS B . See full prescribing information for complete boxed warning . Hypersensitivity Reactions Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir-containing products. ( 5.1 ) Hypersensitivity to abacavir is a multi-organ clinical syndrome. ( 5.1 ) Patients who carry the HLA-B*5701 allele are at a higher risk of experiencing a hypersensitivity reaction to abacavir. ( 5.1 ) Abacavir and lamivudine tablets are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients. ( 4 ) Discontinue abacavir and lamivudine tablets as soon as a hypersensitivity reaction is suspected. Regardless of HLA-B*5701 status, permanently discontinue abacavir and lamivudine tablets if hypersensitivity cannot be ruled out, even when other diagnoses are possible. ( 5.1 ) Following a hypersensitivity reaction to abacavir and lamivudine tablets, NEVER restart abacavir and lamivudine tablets or any other abacavir-containing product. ( 5.1 ) Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues. ( 5.2 ) Exacerbations of Hepatitis B Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine, a component of abacavir and lamivudine tablets. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment. ( 5.3 )

5 WARNINGS AND PRECAUTIONS Hepatic decompensation, some fatal, has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy and interferon alfa with or without ribavirin. Discontinue abacavir and lamivudine tablets as medically appropriate and consider dose reduction or discontinuation of interferon alfa, ribavirin, or both. ( 5.4 ) Immune reconstitution syndrome and redistribution/accumulation of body fat have been reported in patients treated with combination antiretroviral therapy. ( 5.5 , 5.6 ) 5.1 Hypersensitivity Reactions Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir, a component of abacavir and lamivudine tablets. These hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during treatment [see Adverse Reactions ( 6.1 )]. Patients who carry the HLA-B*5701 allele are at a higher risk of abacavir hypersensitivity reactions; although, patients who do not carry the HLA-B*5701 allele have developed hypersensitivity reactions. Hypersensitivity to abacavir was reported in approximately 206 (8%) of 2,670 patients in 9 clinical trials with abacavir-containing products where HLA-B*5701 screening was not performed. The incidence of suspected abacavir hypersensitivity reactions in clinical trials was 1% when subjects carrying the HLA-B*5701 allele were excluded. In any patient treated with abacavir, the clinical diagnosis of hypersensitivity reaction must remain the basis of clinical decision making. Due to the potential for severe, serious, and possibly fatal hypersensitivity reactions with abacavir: All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with abacavir and lamivudine tablets or reinitiation of therapy with abacavir and lamivudine tablets, unless patients have a previously documented HLA-B*5701 allele assessment. Abacavir and lamivudine tablets are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients. Before starting abacavir and lamivudine tablets, review medical history for prior exposure to any abacavir- containing product. NEVER restart abacavir and lamivudine tablets or any other abacavir-containing product following a hypersensitivity reaction to abacavir, regardless of HLA-B*5701 status. To reduce the risk of a life-threatening hypersensitivity reaction, regardless of HLA-B*5701 status, discontinue abacavir and lamivudine tablets immediately if a hypersensitivity reaction is suspected, even when other diagnoses are possible (e.g., acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or influenza; gastroenteritis; or reactions to other medications). If a hypersensitivity reaction cannot be ruled out, do not restart abacavir and lamivudine tablets or any other abacavir-containing products because more severe symptoms, which may include life-threatening hypotension and death, can occur within hours. If a hypersensitivity reaction is ruled out, patients may restart abacavir and lamivudine tablets. Rarely, patients who have stopped abacavir for reasons other than symptoms of hypersensitivity have also experienced life-threatening reactions within hours of reinitiating abacavir therapy. Therefore, reintroduction of abacavir and lamivudine tablets or any other abacavir-containing product is recommended only if medical care can be readily accessed. A Medication Guide and Warning Card that provide information about recognition of hypersensitivity reactions should be dispensed with each new prescription and refill. 5.2 Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. See full prescribing information for ZIAGEN ® (abacavir) and EPIVIR ® (lamivudine). Treatment with abacavir and lamivudine tablets should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations). 5.3 Patients with Hepatitis B Virus Co-infection Posttreatment Exacerbations of Hepatitis Clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of lamivudine. See full prescribing information for EPIVIR® (lamivudine). Patients should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. Emergence of Lamivudine-resistant HBV Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in subjects dually infected with HIV-1 and HBV. Emergence of hepatitis B virus variants associated with resistance to lamivudine has been reported in HIV-1-infected subjects who have received lamivudine-containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus. See full prescribing information for EPIVIR® (lamivudine). 5.4 Use with Interferon- and Ribavirin-based Regimens Patients receiving interferon alfa with or without ribavirin and abacavir and lamivudine tablets should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. See full prescribing information for EPIVIR® (lamivudine). Discontinuation of abacavir and lamivudine tablets should be considered as medically appropriate. Dose reduction or discontinuation of interferon alfa, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6) (see full prescribing information for interferon and ribavirin). 5.5 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including abacavir and lamivudine tablets. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], 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. 5.6 Fat Redistribution 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. 5.7 Myocardial Infarction In a published prospective, observational, epidemiological trial designed to investigate the rate of myocardial infarction (MI) in patients on combination antiretroviral therapy, the use of abacavir within the previous 6 months was correlated with an increased risk of MI. In a sponsor-conducted pooled analysis of clinical trials, no excess risk of MI was observed in abacavir-treated subjects as compared with control subjects. In totality, the available data from the observational cohort and from clinical trials are inconclusive. As a precaution, the underlying risk of coronary heart disease should be considered when prescribing antiretroviral therapies, including abacavir, and action taken to minimize all modifiable risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking).

6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Serious and sometimes fatal hypersensitivity reactions [see Boxed Warning , Warnings and Precautions ( 5.1 )] . Lactic acidosis and severe hepatomegaly with steatosis [see Boxed Warning , Warnings and Precautions ( 5.2 )] . Exacerbations of hepatitis B [see Boxed Warning , Warnings and Precautions ( 5.3 )] . Hepatic decompensation in patients co-infected with HIV-1 and Hepatitis C [see Warnings and Precautions ( 5.4 )] . Immune reconstitution syndrome [see Warnings and Precautions ( 5.5 )] . Fat redistribution [see Warnings and Precautions ( 5.6 )] . Myocardial infarction [see Warnings and Precautions ( 5.7 )] . The most commonly reported adverse reactions of at least moderate intensity (incidence greater than 5%) in an adult HIV-1 clinical trial were drug hypersensitivity, insomnia, depression/depressed mood, headache/migraine, fatigue/malaise, dizziness/vertigo, nausea, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE, Inc. at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience in Adult Subjects Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Serious and Fatal Abacavir-associated Hypersensitivity Reactions In clinical trials, serious and sometimes fatal hypersensitivity reactions have occurred with abacavir, a component of abacavir and lamivudine tablets [see Boxed Warning , Warnings and Precautions ( 5.1 )]. These reactions have been characterized by 2 or more of the following signs or symptoms: (1) fever; (2) rash; (3) gastrointestinal symptoms (including nausea, vomiting, diarrhea, or abdominal pain); (4) constitutional symptoms (including generalized malaise, fatigue, or achiness); (5) respiratory symptoms (including dyspnea, cough, or pharyngitis). Almost all abacavir hypersensitivity reactions include fever and/or rash as part of the syndrome. Other signs and symptoms have included lethargy, headache, myalgia, edema, arthralgia, and paresthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, myolysis, and death have occurred in association with these hypersensitivity reactions. Physical findings have included lymphadenopathy, mucous membrane lesions (conjunctivitis and mouth ulcerations), and maculopapular or urticarial rash (although some patients had other types of rashes and others did not have a rash). There were reports of erythema multiforme. Laboratory abnormalities included elevated liver chemistries, elevated creatine phosphokinase, elevated creatinine, and lymphopenia and abnormal chest x-ray findings (predominantly infiltrates, which were localized). Additional Adverse Reactions with Use of Abacavir and Lamivudine Tablets Therapy-Naive Adults: Treatment-emergent clinical adverse reactions (rated by the investigator as moderate or severe) with greater than or equal to 5% frequency during therapy with ZIAGEN ® 600 mg once daily or ZIAGEN ® 300 mg twice daily, both in combination with lamivudine 300 mg once daily and efavirenz 600 mg once daily, are listed in Table 1. Table 1. Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate Intensity (Grades 2 to 4, Greater than or Equal to 5% Frequency) in Therapy-Naive Adults (CNA30021) through 48 Weeks of Treatment Adverse Event ZIAGEN ® 600 mg q.d. plus EPIVIR ® plus Efavirenz (n = 384) ZIAGEN ® 300 mg b.i.d. plus EPIVIR ® plus Efavirenz (n = 386) Drug hypersensitivity Subjects receiving ZIAGEN ® 600 mg once daily, experienced a significantly higher incidence of severe drug hypersensitivity reactions and severe diarrhea compared with subjects who received ZIAGEN ® 300 mg twice daily. Five percent (5%) of subjects receiving ZIAGEN ® 600 mg once daily had severe drug hypersensitivity reactions compared with 2% of subjects receiving ZIAGEN ® 300 mg twice daily. Two percent (2%) of subjects receiving ZIAGEN ® 600 mg once daily had severe diarrhea while none of the subjects receiving ZIAGEN ® 300 mg twice daily had this event. , CNA30024 was a multi-center, double-blind, controlled trial in which 649 HIV-1-infected, therapy-naive adults were randomized and received either ZIAGEN ® (300 mg twice daily), EPIVIR ® (150 mg twice daily), and efavirenz (600 mg once daily); or zidovudine (300 mg twice daily), EPIVIR ® (150 mg twice daily), and efavirenz (600 mg once daily). CNA30024 used double-blind ascertainment of suspected hypersensitivity reactions. During the blinded portion of the trial, suspected hypersensitivity to abacavir was reported by investigators in 9% of 324 subjects in the abacavir group and 3% of 325 subjects in the zidovudine group. 9% 7% Insomnia 7% 9% Depression/Depressed mood 7% 7% Headache/Migraine 7% 6% Fatigue/Malaise 6% 8% Dizziness/Vertigo 6% 6% Nausea 5% 6% Diarrhea 5% 6% Rash 5% 5% Pyrexia 5% 3% Abdominal pain/gastritis 4% 5% Abnormal dreams 4% 5% Anxiety 3% 5% Laboratory Abnormalities: Laboratory abnormalities observed in clinical trials of ZIAGEN ® were anemia, neutropenia, liver function test abnormalities, and elevations of CPK, blood glucose, and triglycerides. Additional laboratory abnormalities observed in clinical trials of EPIVIR ® were thrombocytopenia and elevated levels of bilirubin, amylase, and lipase. The frequencies of treatment-emergent laboratory abnormalities were comparable between treatment groups in CNA30021. Other Adverse Events: In addition to adverse reactions listed above, other adverse events observed in the expanded access program for abacavir were pancreatitis and increased GGT. 6.2 Clinical Trials Experience in Pediatric Subjects The safety of once-daily compared with twice-daily dosing of abacavir and lamivudine, administered as either single products or as abacavir and lamivudine tablets, was assessed in the ARROW trial (n = 336). Primary safety assessment in the ARROW (COL105677) trial was based on Grade 3 and Grade 4 adverse events. The frequency of Grade 3 and 4 adverse events was similar among subjects randomized to once-daily dosing compared with subjects randomized to twice-daily dosing. One event of Grade 4 hepatitis in the once-daily cohort was considered as uncertain causality by the investigator and all other Grade 3 or 4 adverse events were considered not related by the investigator. No additional safety issues were identified in pediatric subjects receiving abacavir and lamivudine once-daily compared with historical data in adults [see Adverse Reactions ( 6.1 )]. 6.3 Postmarketing Experience The following adverse reactions have been identified during postmarketing use. 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. Abacavir Cardiovascular: Myocardial infarction. Skin: Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving abacavir primarily in combination with medications known to be associated with SJS and TEN, respectively. Because of the overlap of clinical signs and symptoms between hypersensitivity to abacavir and SJS and TEN, and the possibility of multiple drug sensitivities in some patients, abacavir should be discontinued and not restarted in such cases. There have also been reports of erythema multiforme with abacavir use [see Adverse Reactions ( 6.1 )]. Abacavir and Lamivudine Body as a Whole: Redistribution/accumulation of body fat [see Warnings and Precautions ( 5.6 )]. Digestive: Stomatitis. Endocrine and Metabolic : Hyperglycemia. General: Weakness. Hemic and Lymphatic: Aplastic anemia, anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, splenomegaly. Hepatic: Lactic acidosis and hepatic steatosis [see Warnings and Precautions ( 5.2 )], posttreatment exacerbations of hepatitis B [see Warnings and Precautions ( 5.3 )]. Hypersensitivity: Sensitization reactions (including anaphylaxis), urticaria. Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis. Nervous: Paresthesia, peripheral neuropathy, seizures. Respiratory: Abnormal breath sounds/wheezing. Skin: Alopecia, erythema multiforme, Stevens-Johnson syndrome. To report SUSPECTED ADVERSE REACTIONS contact AvKARE, Inc. at 1-855-361-3993; email drugsafety@avkare.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

<table ID="_RefID67B34DA8108040B6911B10F5E11A74FE" width="100%"><caption>Table 1. Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate Intensity (Grades 2 to 4, Greater than or Equal to 5% Frequency) in Therapy-Naive Adults (CNA30021) through 48 Weeks of Treatment </caption><col width="24%"/><col width="38%"/><col width="39%"/><tbody><tr><td align="center" styleCode="Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold"> Adverse Event </content></paragraph></td><td align="center" styleCode="Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold"> ZIAGEN</content>^&#xAE;<content styleCode="bold"> 600 mg q.d. plus EPIVIR</content>^&#xAE;<content styleCode="bold"> plus Efavirenz (n = 384) </content></paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold"> ZIAGEN</content>^&#xAE;<content styleCode="bold"> 300 mg b.i.d. plus EPIVIR</content>^&#xAE;<content styleCode="bold"> plus Efavirenz (n = 386) </content></paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Drug hypersensitivity</content><footnote ID="_RefID12962CA7630341938CAD94F42DE2AADD">Subjects receiving ZIAGEN &#xAE; 600 mg once daily, experienced a significantly higher incidence of severe drug hypersensitivity reactions and severe diarrhea compared with subjects who received ZIAGEN &#xAE; 300 mg twice daily. Five percent (5%) of subjects receiving ZIAGEN &#xAE; 600 mg once daily had severe drug hypersensitivity reactions compared with 2% of subjects receiving ZIAGEN &#xAE; 300 mg twice daily. Two percent (2%) of subjects receiving ZIAGEN &#xAE; 600 mg once daily had severe diarrhea while none of the subjects receiving ZIAGEN &#xAE; 300 mg twice daily had this event. </footnote>^,<footnote ID="_RefID372805EF46C94566AA19804D54DFDD83">CNA30024 was a multi-center, double-blind, controlled trial in which 649 HIV-1-infected, therapy-naive adults were randomized and received either ZIAGEN &#xAE; (300 mg twice daily), EPIVIR &#xAE; (150 mg twice daily), and efavirenz (600 mg once daily); or zidovudine (300 mg twice daily), EPIVIR &#xAE; (150 mg twice daily), and efavirenz (600 mg once daily). CNA30024 used double-blind ascertainment of suspected hypersensitivity reactions. During the blinded portion of the trial, suspected hypersensitivity to abacavir was reported by investigators in 9% of 324 subjects in the abacavir group and 3% of 325 subjects in the zidovudine group. </footnote></paragraph></td><td align="center" styleCode="Lrule Botrule " valign="top"><paragraph> 9% </paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 7% </paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Insomnia </paragraph></td><td align="center" styleCode="Lrule Botrule " valign="top"><paragraph> 7% </paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 9% </paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Depression/Depressed mood </paragraph></td><td align="center" styleCode="Lrule Botrule " valign="top"><paragraph> 7% </paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 7% </paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Headache/Migraine </paragraph></td><td align="center" styleCode="Lrule Botrule " valign="top"><paragraph> 7% </paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 6% </paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Fatigue/Malaise </paragraph></td><td align="center" styleCode="Lrule Botrule " valign="top"><paragraph> 6% </paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 8% </paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Dizziness/Vertigo </paragraph></td><td align="center" styleCode="Lrule Botrule " valign="top"><paragraph> 6% </paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 6% </paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Nausea </paragraph></td><td align="center" styleCode="Lrule Botrule " valign="top"><paragraph> 5% </paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 6% </paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Diarrhea <footnoteRef IDREF="_RefID12962CA7630341938CAD94F42DE2AADD"/></paragraph></td><td align="center" styleCode="Lrule Botrule " valign="top"><paragraph> 5% </paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 6% </paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Rash </paragraph></td><td align="center" styleCode="Lrule Botrule " valign="top"><paragraph> 5% </paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 5% </paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Pyrexia </paragraph></td><td align="center" styleCode="Lrule Botrule " valign="top"><paragraph> 5% </paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 3% </paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Abdominal pain/gastritis </paragraph></td><td align="center" styleCode="Lrule Botrule " valign="top"><paragraph> 4% </paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 5% </paragraph></td></tr><tr><td styleCode="Lrule Botrule " valign="top"><paragraph>Abnormal dreams </paragraph></td><td align="center" styleCode="Lrule Botrule " valign="top"><paragraph> 4% </paragraph></td><td align="center" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> 5% </paragraph></td></tr><tr><td styleCode="Botrule Lrule " valign="top"><paragraph>Anxiety </paragraph></td><td align="center" styleCode="Botrule Lrule " valign="top"><paragraph> 3% </paragraph></td><td align="center" styleCode="Rrule Botrule Lrule " valign="top"><paragraph> 5% </paragraph></td></tr></tbody></table>