Side Effects of Videx (didanosine)

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

• diarrhea,
• chills,
• fever,
• rash,
• stomach pain,
• headache,
• nausea, and
• vomiting.

Serious side effects of Videx include

• inflammation of the pancreas (pancreatitis),
• liver failure, and
• nerve damage in the arms and legs (peripheral neuropathy, symptoms include tingling, numbness and pain in the feet or hands).

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.

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:

• diarrhea,
• chills,
• fever,
• rash, stomach pain,
• headache,
• nausea and vomiting.

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 3 and 4.

Table 3: Selected Clinical Adverse Reactions from Monotherapy Studies

Table 4: Selected Clinical Adverse Reactions from Combination Studies

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

Table 6: Selected Laboratory Abnormalities from Combination Studies

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

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 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.

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

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