FDA label a5752782-044f-87e6-e053-2995a90a4511

WARNING: LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY, EXACERBATIONS OF HEPATITIS B, and DIFFERENT FORMULATIONS OF LAMIVUDINE. 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 LAMIVUDINE if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occurs [see Warnings and Precautions (5.1) ]. 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. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue LAMIVUDINE and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.2) ]. Important Differences among Lamivudine-containing Products LAMIVUDINE tablets (used to treat HIV-1 infection) contain a higher dose of the active ingredient (lamivudine) than LAMIVUDINE–HBV tablets (used to treat chronic HBV infection). Patients with HIV-1 infection should receive only dosage forms appropriate for treatment of HIV-1 [see Warnings and Precautions (5.2) ]. WARNING: LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY, EXACERBATIONS OF HEPATITIS B, and DIFFERENT FORMULATIONS OF LAMIVUDINE See full prescribing information for complete boxed warning Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues. (5.1) 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. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment. (5.2) Patients with HIV-1 infection should receive only dosage forms of LAMIVUDINE appropriate for treatment of HIV-1. (5.2)

5.4 Pancreatitis In pediatric patients with a history of prior antiretroviral nucleoside exposure, a history of pancreatitis, or other significant risk factors for the development of pancreatitis, LAMIVUDINE should be used with caution. Treatment with LAMIVUDINE should be stopped immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur [see Adverse Reactions (6.1) ] .

5.5 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including LAMIVUDINE. 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 Lower Virologic Suppression Rates and Increased Risk of Viral Resistance with Oral Solution Pediatric subjects who received LAMIVUDINE oral solution concomitantly with other antiretroviral oral solutions at any time in the ARROW trial had lower rates of virologic suppression, lower plasma lamivudine exposure, and developed viral resistance more frequently than those receiving LAMIVUDINE tablets [see Clinical Pharmacology (12.3) , Microbiology (12.4) , Clinical Studies (14.2) ]. LAMIVUDINE scored tablet is the preferred formulation for HIV-1-infected pediatric patients who weigh at least 14 kg and for whom a solid dosage form is appropriate. Consider more frequent monitoring of HIV-1 viral load when treating with LAMIVUDINE oral solution.

5.7 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.

6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Lactic acidosis and severe hepatomegaly with steatosis [see Boxed Warning , Warnings and Precautions (5.1) ]. Exacerbations of hepatitis B [see Boxed Warning, Warnings and Precautions (5.2) ]. Hepatic decompensation in patients co-infected with HIV-1 and hepatitis C [see Warnings and Precautions (5.3) ]. Pancreatitis [see Warnings and Precautions (5.4) ]. Immune reconstitution syndrome [see Warnings and Precautions (5.5) ]. Fat redistribution [see Warnings and Precautions (5.7) ]. The most common reported adverse reactions (incidence greater than equal to 15%) in adults were headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, and cough. (6.1) The most common reported adverse reactions (incidence greater than equal to 15%) in pediatric patients subjects were fever and cough. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Ingenus Pharmaceuticals, LLC at 1-877-748-1970 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Clinical Trials Experience in Adult SubjectsBecause 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.The safety profile of LAMIVUDINE in adults is primarily based on 3,568 HIV-1-infected subjects in 7 clinical trials.The most common adverse reactions are headache, nausea, malaise, fatigue, nasal signs and symptoms, diarrhea, and cough.Selected clinical adverse reactions in greater than or equal to 5% of subjects during therapy with LAMIVUDINE 150 mg twice daily plus RETROVIR® 200 mg 3 times daily for up to 24 weeks are listed in Table 3. Table 3. Selected Clinical Adverse Reactions (Greater than or Equal to 5% Frequency) in Four Controlled Clinical Trials (NUCA3001, NUCA3002, NUCB3001, NUCB3002)Adverse ReactionLAMIVUDINE 150 mgTwice Dailyplus RETROVIR(n = 251)RETROVIRaEither zidovudine monotherapy or zidovudine in combination with zalcitabine.(n = 230)Body as a WholeHeadache35%27%Malaise & fatigue27%23%Fever or chills10%12%DigestiveNausea33%29%Diarrhea18%22%Nausea & vomiting13%12%Anorexia and/or decreased appetite10%7%Abdominal pain9%11%Abdominal cramps6%3%Dyspepsia5%5%Nervous SystemNeuropathy12%10%Insomnia & other sleep disorders11%7%Dizziness10%4%Depressive disorders9%4%RespiratoryNasal signs & symptoms20%11%Cough18%13%SkinSkin rashes9%6%MusculoskeletalMusculoskeletal pain12%10%Myalgia8%6%Arthralgia5%5%Pancreatitis: Pancreatitis was observed in 9 out of 2,613 adult subjects (0.3%) who received LAMIVUDINE in controlled clinical trials EPV20001, NUCA3001, NUCB3001, NUCA3002, NUCB3002, and NUCB3007 [see Warnings and Precautions (5.4)].LAMIVUDINE 300 mg Once Daily: The types and frequencies of clinical adverse reactions reported in subjects receiving LAMIVUDINE 300 mg once daily or LAMIVUDINE 150 mg twice daily (in 3-drug combination regimens in EPV20001 and EPV40001) for 48 weeks were similar. Selected laboratory abnormalities observed during therapy are summarized in Table 4.Table 4. Frequencies of Selected Grade 3-4 Laboratory Abnormalities in Adults in Four 24-Week Surrogate Endpoint Trials (NUCA3001, NUCA3002, NUCB3001, NUCB3002) and a Clinical Endpoint Trial (NUCB3007)ULN = Upper limit of normal.ND = Not done.Test (Threshold Level)24-Week Surrogate EndpointClinical Endpoint TrialThe median duration on study was 12 months.LAMIVUDINE plus RETROVIREither zidovudine monotherapy or zidovudine in combination with zalcitabine.LAMIVUDINE plus Current TherapyCurrent therapy was either zidovudine, zidovudine plus didanosine, or zidovudine plus zalcitabine.Placebo plus Current TherapyAbsolute neutrophil count(<750/mm3)7.2%5.415%13%Hemoglobin (<8.0 g/dL)2.9%1.82.2%3.4%Platelets (<50,000/mm3)0.4%1.32.8%3.8%ALT (>5.0 x ULN)3.7%3.63.8%1.9%AST (>5.0 x ULN)1.7%1.84.0%2.1%Bilirubin (>2.5 x ULN)0.8%0.4NDNDAmylase (>2.0 x ULN)4.2%1.52.2%1.1%The frequencies of selected laboratory abnormalities reported in subjects receiving LAMIVUDINE 300 mg once daily or LAMIVUDINE 150 mg twice daily (in 3-drug combination regimens in EPV20001 and EPV40001) were similar. Clinical Trials Experience in Pediatric Subjects LAMIVUDINE oral solution has been studied in 638 pediatric subjects aged 3 months to 18 years in 3 clinical trials.Selected clinical adverse reactions and physical findings with a greater than or equal to 5% frequency during therapy with LAMIVUDINE 4 mg per kg twice daily plus RETROVIR 160 mg per m2 3 times daily in therapy-naive (less than or equal to 56 days of antiretroviral therapy) pediatric subjects are listed in Table 5. Table 5. Selected Clinical Adverse Reactions and Physical Findings (Greater than or Equal to 5% Frequency) in Pediatric Subjects in Trial ACTG300Adverse ReactionLAMIVUDINEplus RETROVIRDidanosine(n = 235)Body as a WholeFever25%32%DigestiveHepatomegaly11%11%Nausea & vomiting8%7%Diarrhea8%6%Stomatitis6%12%Splenomegaly5%8%RespiratoryCough15%18%Abnormal breath sounds/wheezing7%9%Ear, Nose and ThroatSigns or symptoms of earsaIncludes pain, discharge, erythema, or swelling of an ear.7%6%Nasal discharge or congestion8%11%OtherSkin rashes12%14%Lymphadenopathy9%11%Pancreatitis Pancreatitis, which has been fatal in some cases, has been observed in antiretroviral nucleoside-experienced pediatric subjects receiving LAMIVUDINE alone or in combination with other antiretroviral agents. In an open-label dose-escalation trial (NUCA2002), 14 subjects (14%) developed pancreatitis while receiving monotherapy with LAMIVUDINE. Three of these subjects died of complications of pancreatitis. In a second open-label trial (NUCA2005), 12 subjects (18%) developed pancreatitis. In Trial ACTG300, pancreatitis was not observed in 236 subjects randomized to LAMIVUDINE plus RETROVIR. Pancreatitis was observed in 1 subject in this trial who received open-label LAMIVUDINE in combination with RETROVIR and ritonavir following discontinuation of didanosine monotherapy [see Warnings and Precautions (5.4)].Paresthesias and Peripheral Neuropathies Paresthesias and peripheral neuropathies were reported in 15 subjects (15%) in Trial NUCA2002, 6 subjects (9%) in Trial NUCA2005, and 2 subjects (less than1%) in Trial ACTG300. Selected laboratory abnormalities experienced by therapy-naive (less than or equal to 56 days of antiretroviral therapy) pediatric subjects are listed in Table 6.Table 6. Frequencies of Selected Grade 3-4 Laboratory Abnormalities in Pediatric Subjects in Trial ACTG300ULN = Upper limit of normal.Test(Threshold Level)LAMIVUDINE plus RETROVIRDidanosineAbsolute neutrophil count (<400/mm3)8%3%Hemoglobin (<7.0 g/dL)4%2%Platelets (<50,000/mm3)1%3%ALT (>10 x ULN)1%3%AST (>10 x ULN)2%4%Lipase (>2.5 x ULN)3%3%Total Amylase (>2.5 x ULN)3%3%Additional pediatric use information for patients aged 3 months and above is approved for ViiV Healthcare Company’s EPIVIR® (lamivudine) tablets and oral solution. However, due to ViiV Healthcare Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.Neonates Limited short-term safety information is available from 2 small, uncontrolled trials in South Africa in neonates receiving lamivudine with or without zidovudine for the first week of life following maternal treatment starting at Week 38 or 36 of gestation [see Clinical Pharmacology (12.3)]. Selected adverse reactions reported in these neonates included increased liver function tests, anemia, diarrhea, electrolyte disturbances, hypoglycemia, jaundice and hepatomegaly, rash, respiratory infections, and sepsis; 3 neonates died (1 from gastroenteritis with acidosis and convulsions, 1 from traumatic injury, and 1 from unknown causes). Two other nonfatal gastroenteritis or diarrhea cases were reported, including 1 with convulsions; 1 infant had transient renal insufficiency associated with dehydration. The absence of control groups limits assessments of causality, but it should be assumed that perinatally exposed infants may be at risk for adverse reactions comparable to those reported in pediatric and adult HIV-1-infected patients treated with lamivudine-containing combination regimens. Long-term effects of in utero and infant lamivudine exposure are not known. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of LAMIVUDINE.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. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to lamivudine. Body as a Whole Redistribution/accumulation of body fat [see Warnings and Precautions (5.7) ] . Endocrine and Metabolic Hyperglycemia. a. General: Weakness. Hemic and Lymphatic Anemia (including pure red cell aplasia and severe anemias progressing on therapy). Hepatic and Pancreatic Lactic acidosis and hepatic steatosis, [see Warnings and Precautions (5.1) ], post treatment exacerbation of hepatitis B. [see Warnings and Precautions (5.2) ]. Hypersensitivity Anaphylaxis, urticaria. Musculoskeletal Muscle weakness, CPK elevation, rhabdomyolysis. Skin Alopecia, pruritus.

6.1 Clinical Trials Experience Clinical Trials Experience in Adult SubjectsBecause 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.The safety profile of LAMIVUDINE in adults is primarily based on 3,568 HIV-1-infected subjects in 7 clinical trials.The most common adverse reactions are headache, nausea, malaise, fatigue, nasal signs and symptoms, diarrhea, and cough.Selected clinical adverse reactions in greater than or equal to 5% of subjects during therapy with LAMIVUDINE 150 mg twice daily plus RETROVIR® 200 mg 3 times daily for up to 24 weeks are listed in Table 3. Table 3. Selected Clinical Adverse Reactions (Greater than or Equal to 5% Frequency) in Four Controlled Clinical Trials (NUCA3001, NUCA3002, NUCB3001, NUCB3002)Adverse ReactionLAMIVUDINE 150 mgTwice Dailyplus RETROVIR(n = 251)RETROVIRaEither zidovudine monotherapy or zidovudine in combination with zalcitabine.(n = 230)Body as a WholeHeadache35%27%Malaise & fatigue27%23%Fever or chills10%12%DigestiveNausea33%29%Diarrhea18%22%Nausea & vomiting13%12%Anorexia and/or decreased appetite10%7%Abdominal pain9%11%Abdominal cramps6%3%Dyspepsia5%5%Nervous SystemNeuropathy12%10%Insomnia & other sleep disorders11%7%Dizziness10%4%Depressive disorders9%4%RespiratoryNasal signs & symptoms20%11%Cough18%13%SkinSkin rashes9%6%MusculoskeletalMusculoskeletal pain12%10%Myalgia8%6%Arthralgia5%5%Pancreatitis: Pancreatitis was observed in 9 out of 2,613 adult subjects (0.3%) who received LAMIVUDINE in controlled clinical trials EPV20001, NUCA3001, NUCB3001, NUCA3002, NUCB3002, and NUCB3007 [see Warnings and Precautions (5.4)].LAMIVUDINE 300 mg Once Daily: The types and frequencies of clinical adverse reactions reported in subjects receiving LAMIVUDINE 300 mg once daily or LAMIVUDINE 150 mg twice daily (in 3-drug combination regimens in EPV20001 and EPV40001) for 48 weeks were similar. Selected laboratory abnormalities observed during therapy are summarized in Table 4.Table 4. Frequencies of Selected Grade 3-4 Laboratory Abnormalities in Adults in Four 24-Week Surrogate Endpoint Trials (NUCA3001, NUCA3002, NUCB3001, NUCB3002) and a Clinical Endpoint Trial (NUCB3007)ULN = Upper limit of normal.ND = Not done.Test (Threshold Level)24-Week Surrogate EndpointClinical Endpoint TrialThe median duration on study was 12 months.LAMIVUDINE plus RETROVIREither zidovudine monotherapy or zidovudine in combination with zalcitabine.LAMIVUDINE plus Current TherapyCurrent therapy was either zidovudine, zidovudine plus didanosine, or zidovudine plus zalcitabine.Placebo plus Current TherapyAbsolute neutrophil count(<750/mm3)7.2%5.415%13%Hemoglobin (<8.0 g/dL)2.9%1.82.2%3.4%Platelets (<50,000/mm3)0.4%1.32.8%3.8%ALT (>5.0 x ULN)3.7%3.63.8%1.9%AST (>5.0 x ULN)1.7%1.84.0%2.1%Bilirubin (>2.5 x ULN)0.8%0.4NDNDAmylase (>2.0 x ULN)4.2%1.52.2%1.1%The frequencies of selected laboratory abnormalities reported in subjects receiving LAMIVUDINE 300 mg once daily or LAMIVUDINE 150 mg twice daily (in 3-drug combination regimens in EPV20001 and EPV40001) were similar. Clinical Trials Experience in Pediatric Subjects LAMIVUDINE oral solution has been studied in 638 pediatric subjects aged 3 months to 18 years in 3 clinical trials.Selected clinical adverse reactions and physical findings with a greater than or equal to 5% frequency during therapy with LAMIVUDINE 4 mg per kg twice daily plus RETROVIR 160 mg per m2 3 times daily in therapy-naive (less than or equal to 56 days of antiretroviral therapy) pediatric subjects are listed in Table 5. Table 5. Selected Clinical Adverse Reactions and Physical Findings (Greater than or Equal to 5% Frequency) in Pediatric Subjects in Trial ACTG300Adverse ReactionLAMIVUDINEplus RETROVIRDidanosine(n = 235)Body as a WholeFever25%32%DigestiveHepatomegaly11%11%Nausea & vomiting8%7%Diarrhea8%6%Stomatitis6%12%Splenomegaly5%8%RespiratoryCough15%18%Abnormal breath sounds/wheezing7%9%Ear, Nose and ThroatSigns or symptoms of earsaIncludes pain, discharge, erythema, or swelling of an ear.7%6%Nasal discharge or congestion8%11%OtherSkin rashes12%14%Lymphadenopathy9%11%Pancreatitis Pancreatitis, which has been fatal in some cases, has been observed in antiretroviral nucleoside-experienced pediatric subjects receiving LAMIVUDINE alone or in combination with other antiretroviral agents. In an open-label dose-escalation trial (NUCA2002), 14 subjects (14%) developed pancreatitis while receiving monotherapy with LAMIVUDINE. Three of these subjects died of complications of pancreatitis. In a second open-label trial (NUCA2005), 12 subjects (18%) developed pancreatitis. In Trial ACTG300, pancreatitis was not observed in 236 subjects randomized to LAMIVUDINE plus RETROVIR. Pancreatitis was observed in 1 subject in this trial who received open-label LAMIVUDINE in combination with RETROVIR and ritonavir following discontinuation of didanosine monotherapy [see Warnings and Precautions (5.4)].Paresthesias and Peripheral Neuropathies Paresthesias and peripheral neuropathies were reported in 15 subjects (15%) in Trial NUCA2002, 6 subjects (9%) in Trial NUCA2005, and 2 subjects (less than1%) in Trial ACTG300. Selected laboratory abnormalities experienced by therapy-naive (less than or equal to 56 days of antiretroviral therapy) pediatric subjects are listed in Table 6.Table 6. Frequencies of Selected Grade 3-4 Laboratory Abnormalities in Pediatric Subjects in Trial ACTG300ULN = Upper limit of normal.Test(Threshold Level)LAMIVUDINE plus RETROVIRDidanosineAbsolute neutrophil count (<400/mm3)8%3%Hemoglobin (<7.0 g/dL)4%2%Platelets (<50,000/mm3)1%3%ALT (>10 x ULN)1%3%AST (>10 x ULN)2%4%Lipase (>2.5 x ULN)3%3%Total Amylase (>2.5 x ULN)3%3%Additional pediatric use information for patients aged 3 months and above is approved for ViiV Healthcare Company’s EPIVIR® (lamivudine) tablets and oral solution. However, due to ViiV Healthcare Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.Neonates Limited short-term safety information is available from 2 small, uncontrolled trials in South Africa in neonates receiving lamivudine with or without zidovudine for the first week of life following maternal treatment starting at Week 38 or 36 of gestation [see Clinical Pharmacology (12.3)]. Selected adverse reactions reported in these neonates included increased liver function tests, anemia, diarrhea, electrolyte disturbances, hypoglycemia, jaundice and hepatomegaly, rash, respiratory infections, and sepsis; 3 neonates died (1 from gastroenteritis with acidosis and convulsions, 1 from traumatic injury, and 1 from unknown causes). Two other nonfatal gastroenteritis or diarrhea cases were reported, including 1 with convulsions; 1 infant had transient renal insufficiency associated with dehydration. The absence of control groups limits assessments of causality, but it should be assumed that perinatally exposed infants may be at risk for adverse reactions comparable to those reported in pediatric and adult HIV-1-infected patients treated with lamivudine-containing combination regimens. Long-term effects of in utero and infant lamivudine exposure are not known.

Clinical Trials Experience in Pediatric Subjects LAMIVUDINE oral solution has been studied in 638 pediatric subjects aged 3 months to 18 years in 3 clinical trials.Selected clinical adverse reactions and physical findings with a greater than or equal to 5% frequency during therapy with LAMIVUDINE 4 mg per kg twice daily plus RETROVIR 160 mg per m2 3 times daily in therapy-naive (less than or equal to 56 days of antiretroviral therapy) pediatric subjects are listed in Table 5. Table 5. Selected Clinical Adverse Reactions and Physical Findings (Greater than or Equal to 5% Frequency) in Pediatric Subjects in Trial ACTG300Adverse ReactionLAMIVUDINEplus RETROVIRDidanosine(n = 235)Body as a WholeFever25%32%DigestiveHepatomegaly11%11%Nausea & vomiting8%7%Diarrhea8%6%Stomatitis6%12%Splenomegaly5%8%RespiratoryCough15%18%Abnormal breath sounds/wheezing7%9%Ear, Nose and ThroatSigns or symptoms of earsaIncludes pain, discharge, erythema, or swelling of an ear.7%6%Nasal discharge or congestion8%11%OtherSkin rashes12%14%Lymphadenopathy9%11%Pancreatitis Pancreatitis, which has been fatal in some cases, has been observed in antiretroviral nucleoside-experienced pediatric subjects receiving LAMIVUDINE alone or in combination with other antiretroviral agents. In an open-label dose-escalation trial (NUCA2002), 14 subjects (14%) developed pancreatitis while receiving monotherapy with LAMIVUDINE. Three of these subjects died of complications of pancreatitis. In a second open-label trial (NUCA2005), 12 subjects (18%) developed pancreatitis. In Trial ACTG300, pancreatitis was not observed in 236 subjects randomized to LAMIVUDINE plus RETROVIR. Pancreatitis was observed in 1 subject in this trial who received open-label LAMIVUDINE in combination with RETROVIR and ritonavir following discontinuation of didanosine monotherapy [see Warnings and Precautions (5.4)].Paresthesias and Peripheral Neuropathies Paresthesias and peripheral neuropathies were reported in 15 subjects (15%) in Trial NUCA2002, 6 subjects (9%) in Trial NUCA2005, and 2 subjects (less than1%) in Trial ACTG300. Selected laboratory abnormalities experienced by therapy-naive (less than or equal to 56 days of antiretroviral therapy) pediatric subjects are listed in Table 6.Table 6. Frequencies of Selected Grade 3-4 Laboratory Abnormalities in Pediatric Subjects in Trial ACTG300ULN = Upper limit of normal.Test(Threshold Level)LAMIVUDINE plus RETROVIRDidanosineAbsolute neutrophil count (<400/mm3)8%3%Hemoglobin (<7.0 g/dL)4%2%Platelets (<50,000/mm3)1%3%ALT (>10 x ULN)1%3%AST (>10 x ULN)2%4%Lipase (>2.5 x ULN)3%3%Total Amylase (>2.5 x ULN)3%3%Additional pediatric use information for patients aged 3 months and above is approved for ViiV Healthcare Company’s EPIVIR® (lamivudine) tablets and oral solution. However, due to ViiV Healthcare Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.Neonates Limited short-term safety information is available from 2 small, uncontrolled trials in South Africa in neonates receiving lamivudine with or without zidovudine for the first week of life following maternal treatment starting at Week 38 or 36 of gestation [see Clinical Pharmacology (12.3)]. Selected adverse reactions reported in these neonates included increased liver function tests, anemia, diarrhea, electrolyte disturbances, hypoglycemia, jaundice and hepatomegaly, rash, respiratory infections, and sepsis; 3 neonates died (1 from gastroenteritis with acidosis and convulsions, 1 from traumatic injury, and 1 from unknown causes). Two other nonfatal gastroenteritis or diarrhea cases were reported, including 1 with convulsions; 1 infant had transient renal insufficiency associated with dehydration. The absence of control groups limits assessments of causality, but it should be assumed that perinatally exposed infants may be at risk for adverse reactions comparable to those reported in pediatric and adult HIV-1-infected patients treated with lamivudine-containing combination regimens. Long-term effects of in utero and infant lamivudine exposure are not known.

6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of LAMIVUDINE.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. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to lamivudine. Body as a Whole Redistribution/accumulation of body fat [see Warnings and Precautions (5.7) ] . Endocrine and Metabolic Hyperglycemia. a. General: Weakness. Hemic and Lymphatic Anemia (including pure red cell aplasia and severe anemias progressing on therapy). Hepatic and Pancreatic Lactic acidosis and hepatic steatosis, [see Warnings and Precautions (5.1) ], post treatment exacerbation of hepatitis B. [see Warnings and Precautions (5.2) ]. Hypersensitivity Anaphylaxis, urticaria. Musculoskeletal Muscle weakness, CPK elevation, rhabdomyolysis. Skin Alopecia, pruritus.