Does Videx (didanosine) cause side effects?

Videx (didanosine) is a type of antiviral medication called a reverse transcriptase inhibitor used to treat infections with the human immunodeficiency virus (HIV). 

During infection with HIV, the HIV virus multiplies within the body's cells. The newly-formed viruses then are released from the cells and spread throughout the body where they infect other cells. 

In this manner, the infection spreads to new, uninfected cells that the body is continually producing, and HIV infection is perpetuated. When producing new viruses, the HIV virus must manufacture new DNA for each virus. Reverse transcriptase is the enzyme that the virus uses to form this new DNA. 

Specifically, didanosine is converted within the body to its active form (dideoxyadenosine triphosphate). This active form is similar to a chemical, deoxyadenosine triphosphate, that is required by the HIV virus to make new DNA. 

The reverse transcriptase uses dideoxyadenosine triphosphate instead of deoxyadenosine triphosphate for making DNA, and the dideoxyadenosine triphosphate that interferes with the reverse transcriptase. Videx does not kill existing HIV virus and it is not a cure for HIV. 

Common side effects of Videx include

Serious side effects of Videx include

Drug interactions of Videx include allopurinol, tenofovir, and ganciclovir, which increase blood levels of Videx by reducing its elimination.

  • Videx powder contains an antacid which reduces the absorption of tetracycline, ketoconazole, fluoroquinolone antibiotics, and other drugs that need stomach acid for absorption.
  • Therefore, these drugs should be administered at least two hours before or after administration of Videx solution. 

There are no adequate and well-controlled studies of Videx in pregnant women. Videx should be used during pregnancy only if the potential benefit justifies the potential risk. An Antiretroviral Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnant women exposed to Videx and other antiretroviral agents.

Although it is unknown if Videx is excreted in breast milk, HIV-infected mothers should not breastfeed because of the potential risk of transmitting HIV to an infant that is not infected.

What are the important side effects of Videx (didanosine)?

The most severe side effects of didanosine are:

  • inflammation of the pancreas (pancreatitis),
  • liver failure, and
  • nerve damage in the arms and legs (peripheral neuropathy).

Symptoms of peripheral neuropathy are tingling, numbness and pain in the feet or hands.

Other important side effects include:

Videx (didanosine) side effects list for healthcare professionals

The following serious adverse reactions are described below and elsewhere in the labeling:

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 3 and 4.

Table 3: Selected Clinical Adverse Reactions from Monotherapy Studies

Adverse ReactionsPercent of Patients*
ACTG 116AACTG 116B/117
Videx
n=197
zidovudine
n=212
Videx
n=298
zidovudine
n=304
Diarrhea19152821
Peripheral Neurologic Symptoms/Neuropathy17142012
Abdominal Pain13878
Rash/Pruritus7895
Pancreatitis7362
* The incidences reported included all severity grades and all reactions regardless of causality.

Table 4: Selected Clinical Adverse Reactions from Combination Studies

Adverse ReactionsPercent of Patientsa,c
AI454-148bSTART 2b
Videx + stavudine + nelfinavir
n=482
zidovudine + lamivudine + nelfinavir
n=248
Videx + stavudine + indinavir
n=102
zidovudine + lamivudine + indinavir
n=103
Diarrhea70604539
Nausea28405367
Peripheral Neurologic Symptoms/Neuropathy2662110
Headache21304637
Rash13163018
Vomiting12143035
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.

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

ParameterPercent of Patients
ACTG 116AACTG 116B/117
Videx
n=197
zidovudine
n=212
Videx
n=298
zidovudine
n=304
SGOT (AST) (greater than 5 x ULN)9476
SGPT (ALT) (greater than 5 x ULN)9666
Alkaline phosphatase (greater than 5 x ULN)4111
Amylase (at least 1.4 x ULN)1712155
Uric acid (greater than 12 mg/dL)3121
ULN = upper limit of normal.

Table 6: Selected Laboratory Abnormalities from Combination Studies

ParameterPercent of Patientsa
AI454-148bSTART 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 1less than 1168
SGOT (AST) (greater than 5 x ULN)3277
SGPT (ALT) (greater than 5 x ULN)3385
GGT (greater than 5 x ULN)NCNC52
Lipase (greater than 2 x ULN)7255
Amylase (greater than 2 x ULN)NCNC82
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)

ParameterPercent of Patientsa
AI454-148bSTART 2b
Videx + stavudine + nelfinavir
n=482
zidovudine + lamivudine + nelfinavir
n=248
Videx + stavudine + indinavir
n=102
zidovudine + lamivudine + indinavir
n=103
Bilirubin736855
SGOT (AST)42235320
SGPT (ALT)37245018
GGTNCNC2812
Lipase17112619
AmylaseNCNC3117
NC = Not Collected.
a Percentages based on treated subjects.
b Median duration of treatment 48 weeks.

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 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 Disordersanemia, leukopenia, and thrombocytopenia.

Body as a Wholealopecia, anaphylactoid reaction, asthenia, chills/fever, pain.

Digestive Disordersanorexia, 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 Disordersdiabetes mellitus, hypoglycemia, and hyperglycemia.

Musculoskeletal Disordersmyalgia (with or without increases in creatine kinase), rhabdomyolysis including acute renal failure and hemodialysis, arthralgia, and myopathy.

Ophthalmologic Disorders – retinal depigmentation and optic neuritis.

What drugs interact with Videx (didanosine)?

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.

Table 8: Established Drug Interactions with Videx

DrugEffectClinical Comment
ciprofloxacin↓ ciprofloxacin concentrationAdminister Videx at least 2 hours after or 6 hours before ciprofloxacin.
delavirdine↓ delavirdine concentrationAdminister Videx 1 hour after delavirdine.
ganciclovir↑ didanosine concentrationIf there is no suitable alternative to ganciclovir, then use in combination with Videx with caution. Monitor for didanosine-associated toxicity.
indinavir↓ indinavir concentrationAdminister Videx 1 hour after indinavir.
methadone↓ didanosine concentrationDo 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.
nelfinavirNo interaction 1 hour after didanosineAdminister nelfinavir 1 hour after Videx.
tenofovir disoproxil fumarate↑ didanosine concentrationA 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. 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. 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 ClassEffectClinical Comment
Drugs that may cause pancreatic toxicity↑ risk of pancreatitisUse only with extreme cautiona
Neurotoxic drugs↑ risk of neuropathyUse with cautionb
Antacids containing magnesium or aluminum↑ side effects associated with antacid componentsUse caution with Videx Pediatric Powder for Oral Solution
Azole antifungalsketoconazole or itraconazole concentrationAdminister drugs such as ketoconazole or itraconazole at least 2 hours before Videx.
Quinolone antibiotics (see also ciprofloxacin in Table 8)↓ quinolone concentrationConsult package insert of the quinolone.
Tetracycline antibioticsantibiotic concentrationConsult package insert of the tetracycline.
Hydroxyurea↑ risk of pancreatitis, fatal hepatotoxicity, and severe peripheral neuropathyUse should be avoided.
↑ 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.
b See prescribing information.

Treatment & Diagnosis

Medications & Supplements

FDA Logo

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 12/14/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.