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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

Selected clinical adverse reactions that occurred in adult patients in clinical studies with VIDEX are provided in Tables 3 and 4.

Table 3: 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 4: Selected Clinical Adverse Reactions from Combination Studies

Adverse Reactions Percent of Patientsa,c
AI 454-148b 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.

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 [see WARNINGS AND PRECAUTIONS].

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 5-7.

Table 5: 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 6: Selected Laboratory Abnormalities from Combination Studies (Grades 3-4)

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.

Table 7: Selected Laboratory Abnormalities from Combination Studies (All Grades)

Parameter Percent of Patientsa
AI454-148b START 2 b
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.

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 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, and redistribution/accumulation of body fat [see WARNINGS AND PRECAUTIONS].

Digestive Disorders – anorexia, dyspepsia, and flatulence.

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

Hepatobiliary Disorders – symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis [see BOXED WARNING, WARNINGS AND PRECAUTIONS]; non-cirrhotic portal hypertension [see WARNINGS AND PRECAUTIONS]; 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 [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 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 and hydroxyurea, with or without stavudine, should be avoided.

Read the Videx (didanosine pediatric powder for oral solution) 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 8. Pharmacokinetic results of drug interaction studies are shown in Tables 12 and 13 [see CONTRAINDICATIONS, CLINICAL PHARMACOLOGY].

Table 8: Established Drug Interactions with VIDEX

Drug Effect Clinical Comment
ciprofloxacin ↓ciprofloxacin concentration Administer VIDEX at least 2 hours after or 6 hours before ciprofloxacin.
delavirdine ↓delavirdine concentration Administer VIDEX 1 hour after delavirdine.
ganciclovir ↑didanosine concentration If there is no suitable alternative to ganciclovir, then use in combination with VIDEX with caution. Monitor for didanosine-associated toxicity.
indinavir ↓indinavir concentration Administer VIDEX 1 hour after indinavir.
methadone ↓didanosine concentration Do not coadminister methadone with VIDEX pediatric powder due to significant decreases in didanosine concentrations. 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.
nelfinavir No interaction 1 hour after didanosine Administer nelfinavir 1 hour after VIDEX.
tenofovir disoproxil fumarate ↑didanosine concentration A dose reduction of VIDEX to the following dosage once daily 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)
VIDEX and tenofovir disoproxil fumarate may be taken together in the fasted state. If tenofovir disoproxil fumarate is taken with food, VIDEX should be taken on an empty stomach (at least 30 minutes before food or 2 hours after food). Patients should be monitored for didanosine­associated toxicities and clinical response.
↑ Indicates increase.
↓Indicates decrease.
a The dosing recommendation for coadministration of VIDEX EC and tenofovir disoproxil fumarate with respect to meal consumption differs from that of VIDEX. See the complete prescribing information for VIDEX EC.

Exposure to didanosine is increased when coadministered with tenofovir disoproxil fumarate [Table 8 and see CLINICAL PHARMACOKINETICS, Table 12)]. 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 should be undertaken with caution, and patients should be monitored closely for didanosine-related toxicities and clinical response. VIDEX 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 are listed in Table 9.

Table 9: Predicted Drug Interactions with VIDEX

Drug or Drug Class Effect Clinical Comment
Drugs that may cause pancreatic toxicity ↑risk of pancreatitis Use only with extreme cautiona
Neurotoxic drugs ↑risk of neuropathy Use with caution b
Antacids containing magnesium or aluminum ↑side effects associated with antacid components Use caution with VIDEX Pediatric Powder for Oral Solution
Azole antifungals ↓ketoconazole or itraconazole concentration Administer drugs such as ketoconazole or itraconazole at least 2 hours before VIDEX.
Quinolone antibiotics (see also ciprofloxacin in Table 8) ↓quinolone concentration Consult package insert of the quinolone.
Tetracycline antibiotics ↓antibiotic concentration Consult package insert of the tetracycline.
↑Indicates increase.
↓Indicates decrease.
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 is recommended [see WARNINGS AND PRECAUTIONS].
b [See WARNINGS AND PRECAUTIONS]

Last reviewed on RxList: 12/6/2011
This monograph has been modified to include the generic and brand name in many instances.

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