FDA label ef8e48eb-df78-465d-9748-b3c1c8e1e2d3

WARNING: PANCREATITIS, LACTIC ACIDOSIS and HEPATOMEGALY with STEATOSIS Fatal and nonfatal pancreatitis has occurred during therapy with didanosine used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. VIDEX EC should be suspended in patients with suspected pancreatitis and discontinued in patients with confirmed pancreatitis [ see Warnings and Precautions (5.1) ]. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including didanosine and other antiretrovirals. Fatal lactic acidosis has been reported in pregnant individuals who received the combination of didanosine and stavudine with other antiretroviral agents. Coadministration of VIDEX EC and stavudine is contraindicated because of increased risk of serious and/or life-threatening events [ see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 ) ]. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occurs. WARNING: PANCREATITIS, LACTIC ACIDOSIS and HEPATOMEGALY with STEATOSIS See full prescribing information for complete boxed warning. Fatal and nonfatal pancreatitis. VIDEX EC should be suspended in patients with suspected pancreatitis and discontinued in patients with confirmed pancreatitis. (5.1) Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur. Fatal lactic acidosis has been reported in pregnant individuals who received the combination of didanosine and stavudine. (5.2) Coadministration of VIDEX EC with stavudine is contraindicated. (4)

5 WARNINGS AND PRECAUTIONS Pancreatitis: Suspension or discontinuation of didanosine may be necessary. ( 5.1 ) Coadministration of VIDEX EC with stavudine is contraindicated. ( 4 ) Lactic acidosis and severe hepatomegaly with steatosis: Suspend didanosine in patients who develop clinical symptoms or signs with or without laboratory findings. (5.2) Hepatic toxicity: Interruption or discontinuation of didanosine must be considered upon worsening of liver disease. ( 5.3 ) Coadministration of VIDEX EC with stavudine is contraindicated. ( 4 ) Non-cirrhotic portal hypertension: Discontinue didanosine in patients with evidence of non-cirrhotic portal hypertension. (5.4) Patients may develop peripheral neuropathy (5.5) , retinal changes and optic neuritis (5.6) , immune reconstitution syndrome (5.7) , and lipoatrophy (5.8) . 5.1 Pancreatitis Fatal and nonfatal pancreatitis has occurred during therapy with didanosine used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. VIDEX EC should be suspended in patients with signs or symptoms of pancreatitis and discontinued in patients with confirmed pancreatitis. Patients treated with VIDEX EC in combination with stavudine may be at increased risk for pancreatitis; the coadministration of VIDEX EC and stavudine is contraindicated [ see Contraindications (4) ]. When treatment with life-sustaining drugs known to cause pancreatic toxicity is required, suspension of VIDEX EC (didanosine) therapy is recommended. In patients with risk factors for pancreatitis, VIDEX EC should be used with extreme caution and only if clearly indicated. Patients with advanced HIV-1 infection, especially the elderly, are at increased risk of pancreatitis and should be followed closely. Patients with renal impairment may be at greater risk for pancreatitis if treated without dose adjustment. The frequency of pancreatitis is dose related. [ see Adverse Reactions (6) ]. 5.2 Lactic Acidosis/Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including didanosine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Fatal lactic acidosis has been reported in pregnant individuals who received the combination of didanosine and stavudine with other antiretroviral agents. Coadministration of VIDEX EC and stavudine is contraindicated [ see Contraindications (4) and Use in Specific Populations (8.1) ]. Particular caution should be exercised when administering VIDEX EC to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with VIDEX EC should be suspended in any patient who develops clinical signs or symptoms with or without laboratory findings consistent with symptomatic hyperlactatemia, lactic acidosis, or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations). 5.3 Hepatic Toxicity The safety and efficacy of VIDEX EC have not been established in HIV-infected patients with significant underlying liver disease. During combination antiretroviral therapy, patients with preexisting liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities, including severe and potentially fatal hepatic adverse events, and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered. Hepatotoxicity and hepatic failure resulting in death were reported during postmarketing surveillance in HIV-infected patients treated with hydroxyurea and other antiretroviral agents. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. Coadministration of VIDEX EC and stavudine is contraindicated; the combination of VIDEX EC and hydroxyurea should be avoided. [ see Contraindications (4) and Drug Interactions (7.2 ) ]. 5.4 Non-cirrhotic Portal Hypertension Postmarketing cases of non-cirrhotic portal hypertension have been reported, including cases leading to liver transplantation or death. Cases of didanosine-associated non-cirrhotic portal hypertension were confirmed by liver biopsy in patients with no evidence of viral hepatitis. Onset of signs and symptoms ranged from months to years after start of didanosine therapy. Common presenting features included elevated liver enzymes, esophageal varices, hematemesis, ascites, and splenomegaly. Patients receiving VIDEX EC should be monitored for early signs of portal hypertension (e.g., thrombocytopenia and splenomegaly) during routine medical visits. Appropriate laboratory testing including liver enzymes, serum bilirubin, albumin, complete blood count, and international normalized ratio (INR) and ultrasonography should be considered. VIDEX EC should be discontinued in patients with evidence of non-cirrhotic portal hypertension. 5.5 Peripheral Neuropathy Peripheral neuropathy, manifested by numbness, tingling, or pain in the hands or feet, has been reported in patients receiving didanosine therapy. Peripheral neuropathy has occurred more frequently in patients with advanced HIV disease, in patients with a history of neuropathy, or in patients being treated with neurotoxic drug therapy. Discontinuation of VIDEX EC should be considered in patients who develop peripheral neuropathy [ see Contraindications (4) , Adverse Reactions (6) , and Drug Interactions (7.2) ]. 5.6 Retinal Changes and Optic Neuritis Retinal changes and optic neuritis have been reported in patients taking didanosine. Periodic retinal examinations should be considered for patients receiving VIDEX EC [ see Adverse Reactions (6) ]. 5.7 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including VIDEX EC. 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 [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. 5.8 Lipoatrophy Treatment with VIDEX EC has been associated with loss of subcutaneous fat, which is most evident in the face, limbs, and buttocks. The incidence and severity of lipoatrophy are related to cumulative exposure, and is often not reversible when VIDEX EC treatment is stopped. Patients receiving VIDEX EC should be frequently examined and questioned for signs of lipoatrophy, and if feasible, therapy should be switched to an alternative regimen if there is suspicion of lipoatrophy.

5.1 Pancreatitis Fatal and nonfatal pancreatitis has occurred during therapy with didanosine used alone or in combination regimens in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression. VIDEX EC should be suspended in patients with signs or symptoms of pancreatitis and discontinued in patients with confirmed pancreatitis. Patients treated with VIDEX EC in combination with stavudine may be at increased risk for pancreatitis; the coadministration of VIDEX EC and stavudine is contraindicated [ see Contraindications (4) ]. When treatment with life-sustaining drugs known to cause pancreatic toxicity is required, suspension of VIDEX EC (didanosine) therapy is recommended. In patients with risk factors for pancreatitis, VIDEX EC should be used with extreme caution and only if clearly indicated. Patients with advanced HIV-1 infection, especially the elderly, are at increased risk of pancreatitis and should be followed closely. Patients with renal impairment may be at greater risk for pancreatitis if treated without dose adjustment. The frequency of pancreatitis is dose related. [ see Adverse Reactions (6) ].

5.2 Lactic Acidosis/Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including didanosine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Fatal lactic acidosis has been reported in pregnant individuals who received the combination of didanosine and stavudine with other antiretroviral agents. Coadministration of VIDEX EC and stavudine is contraindicated [ see Contraindications (4) and Use in Specific Populations (8.1) ]. Particular caution should be exercised when administering VIDEX EC to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with VIDEX EC should be suspended in any patient who develops clinical signs or symptoms with or without laboratory findings consistent with symptomatic hyperlactatemia, lactic acidosis, or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

5.3 Hepatic Toxicity The safety and efficacy of VIDEX EC have not been established in HIV-infected patients with significant underlying liver disease. During combination antiretroviral therapy, patients with preexisting liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities, including severe and potentially fatal hepatic adverse events, and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered. Hepatotoxicity and hepatic failure resulting in death were reported during postmarketing surveillance in HIV-infected patients treated with hydroxyurea and other antiretroviral agents. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. Coadministration of VIDEX EC and stavudine is contraindicated; the combination of VIDEX EC and hydroxyurea should be avoided. [ see Contraindications (4) and Drug Interactions (7.2 ) ].

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections: Pancreatitis [ see Warnings and Precautions (5.1) ] Lactic acidosis/severe hepatomegaly with steatosis [ see Warnings and Precautions (5.2) ] Hepatic toxicity [ see Warnings and Precautions (5.3) ] Non-cirrhotic portal hypertension [ see Warnings and Precautions (5.4) ] Peripheral neuropathy [ see Warnings and Precautions (5.5) ] Retinal changes and optic neuritis [ see Warnings and Precautions (5.6) ] • In adults, the most common adverse reactions (greater than 10%, all grades) are diarrhea, peripheral neurologic symptoms/neuropathy, nausea, headache, rash, and vomiting. (6.1) • Adverse reactions in pediatric patients were consistent with those in adults. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 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 Adult Subjects Study AI454-152 was a 48-week, randomized, open-label study comparing VIDEX EC (400 mg once daily) plus stavudine (40 mg twice daily) plus nelfinavir (750 mg three times daily) to zidovudine (300 mg) plus lamivudine (150 mg) combination tablets twice daily plus nelfinavir (750 mg three times daily) in 511 treatment-naive patients. Selected clinical adverse reactions that occurred in combination with other antiretroviral agents are provided in Table 3 . Table 3: Selected Clinical Adverse Reactions, Study AI454-152 a Adverse Reactions Percent of Patients b,c VIDEX EC + stavudine + nelfinavir n=258 zidovudine/lamivudine d + nelfinavir n=253 a Median duration of treatment was 62 weeks in the VIDEX EC + stavudine + nelfinavir group and 61 weeks in the zidovudine/lamivudine + nelfinavir group. b Percentages based on treated patients. c The incidences reported included all severity grades and all reactions regardless of causality. d Zidovudine/lamivudine combination tablet. * This event was not observed in this study arm. Diarrhea 57 58 Peripheral Neurologic Symptoms/Neuropathy 25 11 Nausea 24 36 Headache 22 17 Rash 14 12 Vomiting 14 19 Pancreatitis (see below) less than 1 * In clinical trials using a buffered formulation of didanosine, pancreatitis resulting in death was observed in one patient who received didanosine plus stavudine plus nelfinavir, one patient who received didanosine plus stavudine plus indinavir, and 2 of 68 patients who received didanosine plus stavudine plus indinavir plus hydroxyurea. In an early access program, pancreatitis resulting in death was observed in one patient who received VIDEX EC plus stavudine plus hydroxyurea plus ritonavir plus indinavir plus efavirenz [ see Warnings and Precautions (5) ]. The frequency of pancreatitis is dose related. In phase 3 studies with buffered formulations of didanosine, incidence ranged from 1% to 10% with doses higher than are currently recommended and 1% to 7% with recommended dose. Selected laboratory abnormalities that occurred in a study of VIDEX EC in combination with other antiretroviral agents are shown in Table 4 . Table 4: Selected Laboratory Abnormalities, Study AI454-152 a Percent of Patients b VIDEX EC + stavudine + nelfinavir n=258 zidovudine/lamivudine c + nelfinavir n=253 Parameter Grades 3-4 d All Grades Grades 3-4 d All Grades a Median duration of treatment was 62 weeks in the VIDEX EC + stavudine + nelfinavir group and 61 weeks in the zidovudine/lamivudine + nelfinavir group. b Percentages based on treated patients. c Zidovudine/lamivudine combination tablet. d Greater than 5 × ULN for SGOT and SGPT, at least 2.1 × ULN for lipase, and at least 2.6 × ULN for bilirubin (ULN = upper limit of normal). SGOT (AST) 5 46 5 19 SGPT (ALT) 6 44 5 22 Lipase 5 23 2 13 Bilirubin less than 1 9 less than 1 3 Clinical Trials Experience in Pediatric Patients In clinical trials, 743 pediatric patients between 2 weeks and 18 years of age have been treated with didanosine. Adverse reactions and laboratory abnormalities reported to occur in these patients were generally consistent with the safety profile of didanosine in adults. In pediatric phase 1 studies, pancreatitis occurred in 2 of 60 (3%) patients treated at entry doses below 300 mg/m 2 /day and in 5 of 38 (13%) patients treated at higher doses. In study ACTG 152, pancreatitis occurred in none of the 281 pediatric patients who received didanosine 120 mg/m 2 every 12 hours and in less than 1% of the 274 pediatric patients who received didanosine 90 mg/m 2 every 12 hours in combination with zidovudine [ see Clinical Studies (14) ]. Retinal changes and optic neuritis have been reported in pediatric patients. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of didanosine. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to VIDEX EC, or a combination of these factors. Blood and Lymphatic System Disorders - anemia, leukopenia, and thrombocytopenia. Body as a Whole - abdominal pain, alopecia, anaphylactoid reaction, asthenia, chills/fever, pain. Digestive Disorders - anorexia, dyspepsia, and flatulence. Exocrine Gland Disorders - pancreatitis (including fatal cases) [ see Warnings and Precautions ( 5.1 ) ], sialoadenitis, parotid gland enlargement, dry mouth, and dry eyes. Hepatobiliary Disorders - symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis [ see Warnings and Precautions ( 5.2 ) ]; non-cirrhotic portal hypertension [ see Warnings and Precautions ( 5.4 ) ]; hepatitis and liver failure. Metabolic Disorders - diabetes mellitus, elevated serum alkaline phosphatase level, elevated serum amylase level, elevated serum gamma-glutamyltransferase level, elevated serum uric acid level, hypoglycemia, and hyperglycemia. Musculoskeletal Disorders - myalgia (with or without increases in creatine kinase), rhabdomyolysis including acute renal failure and hemodialysis, arthralgia, and myopathy. Ophthalmologic Disorders - retinal depigmentation and optic neuritis [ see Warnings and Precautions ( 5.6 ) ].

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 Adult Subjects Study AI454-152 was a 48-week, randomized, open-label study comparing VIDEX EC (400 mg once daily) plus stavudine (40 mg twice daily) plus nelfinavir (750 mg three times daily) to zidovudine (300 mg) plus lamivudine (150 mg) combination tablets twice daily plus nelfinavir (750 mg three times daily) in 511 treatment-naive patients. Selected clinical adverse reactions that occurred in combination with other antiretroviral agents are provided in Table 3 . Table 3: Selected Clinical Adverse Reactions, Study AI454-152 a Adverse Reactions Percent of Patients b,c VIDEX EC + stavudine + nelfinavir n=258 zidovudine/lamivudine d + nelfinavir n=253 a Median duration of treatment was 62 weeks in the VIDEX EC + stavudine + nelfinavir group and 61 weeks in the zidovudine/lamivudine + nelfinavir group. b Percentages based on treated patients. c The incidences reported included all severity grades and all reactions regardless of causality. d Zidovudine/lamivudine combination tablet. * This event was not observed in this study arm. Diarrhea 57 58 Peripheral Neurologic Symptoms/Neuropathy 25 11 Nausea 24 36 Headache 22 17 Rash 14 12 Vomiting 14 19 Pancreatitis (see below) less than 1 * In clinical trials using a buffered formulation of didanosine, pancreatitis resulting in death was observed in one patient who received didanosine plus stavudine plus nelfinavir, one patient who received didanosine plus stavudine plus indinavir, and 2 of 68 patients who received didanosine plus stavudine plus indinavir plus hydroxyurea. In an early access program, pancreatitis resulting in death was observed in one patient who received VIDEX EC plus stavudine plus hydroxyurea plus ritonavir plus indinavir plus efavirenz [ see Warnings and Precautions (5) ]. The frequency of pancreatitis is dose related. In phase 3 studies with buffered formulations of didanosine, incidence ranged from 1% to 10% with doses higher than are currently recommended and 1% to 7% with recommended dose. Selected laboratory abnormalities that occurred in a study of VIDEX EC in combination with other antiretroviral agents are shown in Table 4 . Table 4: Selected Laboratory Abnormalities, Study AI454-152 a Percent of Patients b VIDEX EC + stavudine + nelfinavir n=258 zidovudine/lamivudine c + nelfinavir n=253 Parameter Grades 3-4 d All Grades Grades 3-4 d All Grades a Median duration of treatment was 62 weeks in the VIDEX EC + stavudine + nelfinavir group and 61 weeks in the zidovudine/lamivudine + nelfinavir group. b Percentages based on treated patients. c Zidovudine/lamivudine combination tablet. d Greater than 5 × ULN for SGOT and SGPT, at least 2.1 × ULN for lipase, and at least 2.6 × ULN for bilirubin (ULN = upper limit of normal). SGOT (AST) 5 46 5 19 SGPT (ALT) 6 44 5 22 Lipase 5 23 2 13 Bilirubin less than 1 9 less than 1 3 Clinical Trials Experience in Pediatric Patients In clinical trials, 743 pediatric patients between 2 weeks and 18 years of age have been treated with didanosine. Adverse reactions and laboratory abnormalities reported to occur in these patients were generally consistent with the safety profile of didanosine in adults. In pediatric phase 1 studies, pancreatitis occurred in 2 of 60 (3%) patients treated at entry doses below 300 mg/m 2 /day and in 5 of 38 (13%) patients treated at higher doses. In study ACTG 152, pancreatitis occurred in none of the 281 pediatric patients who received didanosine 120 mg/m 2 every 12 hours and in less than 1% of the 274 pediatric patients who received didanosine 90 mg/m 2 every 12 hours in combination with zidovudine [ see Clinical Studies (14) ]. Retinal changes and optic neuritis have been reported in pediatric patients.

Clinical Trials Experience in Adult Subjects Study AI454-152 was a 48-week, randomized, open-label study comparing VIDEX EC (400 mg once daily) plus stavudine (40 mg twice daily) plus nelfinavir (750 mg three times daily) to zidovudine (300 mg) plus lamivudine (150 mg) combination tablets twice daily plus nelfinavir (750 mg three times daily) in 511 treatment-naive patients. Selected clinical adverse reactions that occurred in combination with other antiretroviral agents are provided in Table 3 . Table 3: Selected Clinical Adverse Reactions, Study AI454-152 a Adverse Reactions Percent of Patients b,c VIDEX EC + stavudine + nelfinavir n=258 zidovudine/lamivudine d + nelfinavir n=253 a Median duration of treatment was 62 weeks in the VIDEX EC + stavudine + nelfinavir group and 61 weeks in the zidovudine/lamivudine + nelfinavir group. b Percentages based on treated patients. c The incidences reported included all severity grades and all reactions regardless of causality. d Zidovudine/lamivudine combination tablet. * This event was not observed in this study arm. Diarrhea 57 58 Peripheral Neurologic Symptoms/Neuropathy 25 11 Nausea 24 36 Headache 22 17 Rash 14 12 Vomiting 14 19 Pancreatitis (see below) less than 1 * In clinical trials using a buffered formulation of didanosine, pancreatitis resulting in death was observed in one patient who received didanosine plus stavudine plus nelfinavir, one patient who received didanosine plus stavudine plus indinavir, and 2 of 68 patients who received didanosine plus stavudine plus indinavir plus hydroxyurea. In an early access program, pancreatitis resulting in death was observed in one patient who received VIDEX EC plus stavudine plus hydroxyurea plus ritonavir plus indinavir plus efavirenz [ see Warnings and Precautions (5) ]. The frequency of pancreatitis is dose related. In phase 3 studies with buffered formulations of didanosine, incidence ranged from 1% to 10% with doses higher than are currently recommended and 1% to 7% with recommended dose. Selected laboratory abnormalities that occurred in a study of VIDEX EC in combination with other antiretroviral agents are shown in Table 4 . Table 4: Selected Laboratory Abnormalities, Study AI454-152 a Percent of Patients b VIDEX EC + stavudine + nelfinavir n=258 zidovudine/lamivudine c + nelfinavir n=253 Parameter Grades 3-4 d All Grades Grades 3-4 d All Grades a Median duration of treatment was 62 weeks in the VIDEX EC + stavudine + nelfinavir group and 61 weeks in the zidovudine/lamivudine + nelfinavir group. b Percentages based on treated patients. c Zidovudine/lamivudine combination tablet. d Greater than 5 × ULN for SGOT and SGPT, at least 2.1 × ULN for lipase, and at least 2.6 × ULN for bilirubin (ULN = upper limit of normal). SGOT (AST) 5 46 5 19 SGPT (ALT) 6 44 5 22 Lipase 5 23 2 13 Bilirubin less than 1 9 less than 1 3

Clinical Trials Experience in Pediatric Patients In clinical trials, 743 pediatric patients between 2 weeks and 18 years of age have been treated with didanosine. Adverse reactions and laboratory abnormalities reported to occur in these patients were generally consistent with the safety profile of didanosine in adults. In pediatric phase 1 studies, pancreatitis occurred in 2 of 60 (3%) patients treated at entry doses below 300 mg/m 2 /day and in 5 of 38 (13%) patients treated at higher doses. In study ACTG 152, pancreatitis occurred in none of the 281 pediatric patients who received didanosine 120 mg/m 2 every 12 hours and in less than 1% of the 274 pediatric patients who received didanosine 90 mg/m 2 every 12 hours in combination with zidovudine [ see Clinical Studies (14) ]. Retinal changes and optic neuritis have been reported in pediatric patients.