VIDEX SIDE EFFECTS
- Generic Name: didanosine pediatric powder for oral solution
- Brand Name: Videx
- Drug Class: HIV, NNRTIs
SIDE EFFECTS
The following serious adverse reactions are described below and elsewhere in the labeling:
- Pancreatitis
- Lactic acidosis/severe hepatomegaly with steatosis
- Hepatic toxicity
- Non-cirrhotic portal hypertension
- Peripheral neuropathy
- Retinal changes and optic neuritis
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Clinical Trials Experience In Adults
Selected clinical adverse reactions that occurred in adult patients in clinical studies with VIDEX are provided in Tables 1 and 2.
Table 1: Selected Clinical Adverse Reactions from Monotherapy Studies
| Adverse Reactions | Percent of Patients* | |||
| ACTG 116A | ACTG 116B/117 | |||
| VIDEX n=197 |
zidovudine n=212 |
VIDEX n=298 |
zidovudine n=304 |
|
| Diarrhea | 19 | 15 | 28 | 21 |
| Peripheral Neurologic Symptoms/Neuropathy | 17 | 14 | 20 | 12 |
| Abdominal Pain | 13 | 8 | 7 | 8 |
| Rash/Pruritus | 7 | 8 | 9 | 5 |
| Pancreatitis | 7 | 3 | 6 | 2 |
| * The incidences reported included all severity grades and all reactions regardless of causality. | ||||
Table 2: Selected Clinical Adverse Reactions from Combination Studies
| Adverse Reactions | Percent of Patientsa,c | |||
| AI454-148b | START 2b | |||
| VIDEX + stavudine + nelfinavir n=482 |
zidovudine + lamivudine + nelfinavir n=248 |
VIDEX + stavudine + indinavir n=102 |
zidovudine + lamivudine + indinavir n=103 |
|
| Diarrhea | 70 | 60 | 45 | 39 |
| Nausea | 28 | 40 | 53 | 67 |
| Peripheral Neurologic Symptoms/Neuropathy | 26 | 6 | 21 | 10 |
| Headache | 21 | 30 | 46 | 37 |
| Rash | 13 | 16 | 30 | 18 |
| Vomiting | 12 | 14 | 30 | 35 |
| Pancreatitis (see below) | 1 | * | less than 1 | * |
| a Percentages based on treated subjects. b Median duration of treatment 48 weeks. c The incidences reported included all severity grades and all reactions regardless of causality. * This event was not observed in this study arm. |
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Pancreatitis resulting in death was observed in one patient who received VIDEX (didanosine) plus stavudine plus nelfinavir in Study AI454-148 and in one patient who received VIDEX plus stavudine plus indinavir in the START 2 study. In addition, pancreatitis resulting in death was observed in 2 of 68 patients who received VIDEX plus stavudine plus indinavir plus hydroxyurea in an ACTG clinical trial.
The frequency of pancreatitis is dose related. In phase 3 studies, incidence ranged from 1% to 10% with doses higher than are currently recommended and from 1% to 7% with recommended dose.
Selected laboratory abnormalities in clinical studies with VIDEX are shown in Tables 3-4.
Table 3: Selected Laboratory Abnormalities from Monotherapy Studies
| Parameter | Percent of Patients | |||
| ACTG 116A | ACTG 116B/117 | |||
| VIDEX n=197 |
zidovudine n=212 |
VIDEX n=298 |
zidovudine n=304 |
|
| SGOT (AST) (greater than 5 x ULN) | 9 | 4 | 7 | 6 |
| SGPT (ALT) (greater than 5 x ULN) | 9 | 6 | 6 | 6 |
| Alkaline phosphatase (greater than 5 x ULN) | 4 | 1 | 1 | 1 |
| Amylase (at least 1.4 x ULN) | 17 | 12 | 15 | 5 |
| Uric acid (greater than 12 mg/dL) | 3 | 1 | 2 | 1 |
| ULN = upper limit of normal. | ||||
Table 4: Selected Laboratory Abnormalities from Combination Studies
| Parameter | Percent of Patientsa | |||
| AI454-148b | START 2b | |||
| VIDEX + stavudine + nelfinavir n=482 |
zidovudine + lamivudine + nelfinavir n=248 |
VIDEX + stavudine + indinavir n=102 |
zidovudine + lamivudine + indinavir n=103 |
|
| Bilirubin (greater than 2.6 x ULN) | less than 1 | less than 1 | 16 | 8 |
| SGOT (AST) (greater than 5 x ULN) | 3 | 2 | 7 | 7 |
| SGPT (ALT) (greater than 5 x ULN) | 3 | 3 | 8 | 5 |
| GGT (greater than 5 x ULN) | NC | NC | 5 | 2 |
| Lipase (greater than 2 x ULN) | 7 | 2 | 5 | 5 |
| Amylase (greater than 2 x ULN) | NC | NC | 8 | 2 |
| ULN = upper limit of normal. NC = Not Collected. a Percentages based on treated subjects. b Median duration of treatment 48 weeks. |
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Table 5: Selected Laboratory Abnormalities from Combination Studies (All Grades)
| Parameter | Percent of Patientsa | |||
| AI454-148b | START 2b | |||
| VIDEX + stavudine + nelfinavir n=482 |
zidovudine + lamivudine + nelfinavir n=248 |
VIDEX + stavudine + indinavir n=102 |
zidovudine + lamivudine + indinavir n=103 |
|
| Bilirubin | 7 | 3 | 68 | 55 |
| SGOT (AST) | 42 | 23 | 53 | 20 |
| SGPT (ALT) | 37 | 24 | 50 | 18 |
| GGT | NC | NC | 28 | 12 |
| Lipase | 17 | 11 | 26 | 19 |
| Amylase | NC | NC | 31 | 17 |
| NC = Not Collected. a Percentages based on treated subjects. b Median duration of treatment 48 weeks. |
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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 dosesbelow 300 mg per m2 per 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 per m2 every 12 hours and in less than 1% of the 274 pediatric patients who received didanosine 90 mg per m2 every 12 hours in combination with zidovudine.
Retinal changes and optic neuritis have been reported in pediatric patients.
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, it is not always possible to reliably estimate their frequency. These reactions have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to VIDEX, or a combination of these factors.
Blood and Lymphatic System Disorders – anemia, leukopenia, and thrombocytopenia.
Body as a Whole – alopecia, anaphylactoid reaction, asthenia, chills/fever, pain.
Digestive Disorders – anorexia, dyspepsia, and flatulence.
Exocrine Gland Disorders – pancreatitis (including fatal cases), sialadenitis, parotid gland enlargement, dry mouth, and dry eyes.
Hepatobiliary Disorders – symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis; non-cirrhotic portal hypertension; hepatitis and liver failure.
Metabolic Disorders – diabetes mellitus, 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.
SRC: NLM .