ADVERSE REACTIONS
A SERIOUS TOXICITY OF DIDANOSINE IS PANCREATITIS, WHICH MAY BE FATAL (see WARNINGS). OTHER IMPORTANT TOXICITIES INCLUDE LACTIC ACIDOSIS/ SEVERE HEPATOMEGALY WITH STEATOSIS; RETINAL CHANGES AND OPTIC NEURITIS; AND PERIPHERAL NEUROPATHY (see WARNINGS and PRECAUTIONS).
When didanosine is used in combination with other agents with similar toxicities, the incidence of these toxicities may be higher than when didanosine is used alone. Thus, patients treated with VIDEX EC in combination with stavudine, with or without hydroxyurea, may be at increased risk for pancreatitis, which may be fatal, and hepatotoxicity (see WARNINGS). Patients treated with VIDEX EC in combination with stavudine may also be at increased risk for peripheral neuropathy (see PRECAUTIONS).
Selected clinical adverse events that occurred in a study of VIDEX EC in combination with other antiretroviral agents are provided in Table 10.
Table 10
Selected Clinical Adverse Events, Study AI454-152 a
|
|
Percent of Patients b |
| Adverse Events |
VIDEX EC+
stavudine+
nelfinavir n=258 |
zidovudine/
lamivudine c +
nelfinavir n=253 |
|
Diarrhea
|
57
|
58
|
|
Peripheral Neurologic Symptoms/Neuropathy
|
25
|
11
|
|
Nausea
|
24
|
36
|
|
Headache
|
22
|
17
|
|
Rash
|
14
|
12
|
|
Vomiting
|
14
|
19
|
|
Pancreatitis (see below)
|
<1
|
* |
| a Median duration of treatment was 62 weeks in the VIDEX EC (didanosine) + stavudine + nelfinavir group and 61 weeks in the zidovudine/lamivudine + nelfinavir group.
|
| b Percentages based on treated patients. |
| c Zidovudine/lamivudine combination tablet.
|
|
*This event was not observed in this study arm. |
|
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 (didanosine) plus stavudine plus hydroxyurea plus ritonavir plus indinavir plus efavirenz (see WARNINGS).
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 11.
Table 11
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 |
|
SGOT (AST)
|
5
|
46
|
5
|
19
|
|
SGPT (ALT)
|
6
|
44
|
5
|
22
|
|
Lipase
|
5
|
23
|
2
|
13
|
|
Bilirubin
|
<1
|
9
|
<1
|
3
|
| a Median duration of treatment was 62 weeks in the VIDEX EC (didanosine) + stavudine + nelfinavir group and 61 weeks in the zidovudine/lamivudine + nelfinavir group.
|
| b Percentages based on treated patients. |
| c Zidovudine/lamivudine combination tablet.
|
| d>5 × ULN for SGOT and SGPT, >/=2.1 × ULN for lipase, and >/=2.6 × ULN for bilirubin (ULN = upper limit of normal).
|
|
Observed During Clinical Practice: The following events have been identified during postapproval use of didanosine buffered formulations. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to didanosine, or a combination of these factors.
Body as a Whole --abdominal pain, alopecia, anaphylactoid reaction, asthenia, chills/fever, pain, and redistribution/accumulation of body fat (see PRECAUTIONS: Fat Redistribution).
Digestive Disorders --anorexia, dyspepsia, and flatulence.
Exocrine Gland Disorders --pancreatitis (including fatal cases) (see WARNINGS), sialoadenitis, parotid gland enlargement, dry mouth, and dry eyes. Hematologic Disorders --anemia, leukopenia, and thrombocytopenia.
Liver --symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis (see WARNINGS); 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).
|
