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Videx EC

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Videx EC

Side Effects
Interactions

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections:

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.

Adults

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 AI454-152a

Adverse Reactions Percent of Patientsb,c
VIDEX EC + stavudine + nelfinavir
n=258
zidovudine/lamivudined +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) less than 1 *
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.

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].

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 AI454-152a

Parameter Percent of Patientsb
VIDEX EC + stavudine+ nelfinavir
n=258
zidovudine/lamivudinec +nelfinavir
n=253
Grades 3-4d All Grades Grades 3-4d All Grades
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
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 x ULN for SGOT and SGPT, at least 2.1 x ULN for lipase, and at least 2.6 x ULN for bilirubin (ULN = upper limit of normal).

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/m²/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/m² every 12 hours and in less than 1% of the 274 pediatric patients who received didanosine 90 mg/m² every 12 hours in combination with zidovudine [see Clinical Studies].

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, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to didanosine, 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, and redistribution/accumulation of body fat [see WARNINGS AND PRECAUTIONS].

Digestive Disorders - anorexia, dyspepsia, and flatulence.

Exocrine Gland Disorders - pancreatitis (including fatal cases) [see WARNINGS AND PRECAUTIONS], sialoadenitis, parotid gland enlargement, dry mouth, and dry eyes.

Hepatobiliary Disorders - symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis [see WARNINGS AND PRECAUTIONS]; non-cirrhotic portal hypertension [see WARNINGS AND PRECAUTIONS]; 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].

Use with Stavudine- and Hydroxyurea-Based Regimens

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 and hepatotoxicity, which may be fatal, and severe peripheral neuropathy [see WARNINGS AND PRECAUTIONS]. The combination of VIDEX EC and hydroxyurea, with or without stavudine, should be avoided.

Read the Videx EC (didanosine delayed-release capsules) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Established Drug Interactions

Clinical recommendations based on the results of drug interaction studies are listed in Table 5. Pharmacokinetic results of drug interaction studies are shown in Tables 9-12 [see CONTRAINDICATIONS, CLINICAL PHARMACOLOGY].

Table 5: Established Drug Interactions Based on Studies with VIDEX EC or Studies with Buffered Formulations of Didanosine and Expected to Occur with VIDEX EC

Drug Effect Clinical Comment
ganciclovir ↑didanosine concentration If there is no suitable alternative to ganciclovir, then use in combination with VIDEX EC with caution. Monitor for didanosine-associated toxicity.
methadone ↓didanosine concentration If coadministration of methadone and didanosine is necessary, the recommended formulation of didanosine is VIDEX EC. Patients should be closely monitored for adequate clinical response when VIDEX EC is coadministered with methadone, including monitoring for changes in HIV RNA viral load. Do not coadminister methadone with VIDEX pediatric powder due to significant decreases in didanosine concentrations.
nelfinavir No interaction 1 hour after didanosine Administer nelfinavir 1 hour after VIDEX EC.
tenofovir disoproxil fumarate ↑didanosine concentration A dose reduction of VIDEX EC to the following dosage once daily taken together with tenofovir disoproxil fumarate and a light meal (400 kcalories or less and 20% fat or less) or in the fasted state is recommended.a
  • 250 mg (adults weighing at least 60 kg with creatinine clearance of at least 60 mL/min)
  • 200 mg (adults weighing less than 60 kg with creatinine clearance of at least 60 mL/min)
Patients should be monitored for didanosine-associated toxicities and clinical response.
Indicates increase.
Indicates decrease.
a Coadministration of didanosine with food decreases didanosine concentrations. Thus, although not studied, it is possible that coadministration with heavier meals could reduce didanosine concentrations further.

Exposure to didanosine is increased when coadministered with tenofovir disoproxil fumarate [Table 5 and see CLINICAL PHARMACOKINETICS, Tables 9 and 10)]. Increased exposure may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. Coadministration of tenofovir disoproxil fumarate with VIDEX EC should be undertaken with caution, and patients should be monitored closely for didanosine-related toxicities and clinical response. VIDEX EC should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS]. Suppression of CD4 cell counts has been observed in patients receiving tenofovir disoproxil fumarate with didanosine at a dose of 400 mg daily.

Predicted Drug Interactions

Predicted drug interactions with VIDEX EC are listed in Table 6.

Table 6: Predicted Drug Interactions with VIDEX EC

Drug or Drug Class Effect Clinical Comment
Drugs that may cause pancreatic toxicity ↑risk of pancreatitis Use only with extreme caution.a
Neurotoxic drugs ↑risk of neuropathy Use with cautionb
↑ Indicates increase.
a Only if other drugs are not available and if clearly indicated. If treatment with life-sustaining drugs that cause pancreatic toxicity is required, suspension of VIDEX EC is recommended [see WARNINGS AND PRECAUTIONS].
b [See WARNINGS AND PRECAUTIONS]

Last reviewed on RxList: 2/19/2010
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
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