Videx Side Effects, and Drug Interactions - Didanosine

Videx Side Effects, and Drug Interactions - Didanosine

SIDE EFFECTS

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).

Selected clinical adverse events that occurred in a study of VIDEXEC in combination with other antiretroviral agents are provided in Table 10.

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.

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).

DRUG INTERACTIONS

(see also CLINICAL PHARMACOLOGY: Drug Interactions)

Drug interactions that have been established based on drug interaction studies are listed with the pharmacokinetic results in CLINICAL PHARMACOLOGY: Drug Interactions (Tables 3-6). The clinical recommendations based on the results of these studies are listed in Table 8.

Coadministration of VIDEX EC with drugs that are known to cause pancreatitis may increase the risk of this toxicity (see WARNINGS: Pancreatitis). Predicted drug interactions with VIDEX EC are listed in Table 9.

Nucleoside/nucleotide analogues

Tenofovir disoproxil fumarate. Exposure to didanosine is increased when coadministered with tenofovir (see Tables 3, 5, and 8). Increased exposure may cause or worsen didanosine-related clinical toxicities, including pancreatitis, symptomatic hyperlactatemia/lactic acidosis, and peripheral neuropathy. Coadministration of tenofovir with VIDEX EC should be undertaken with caution, and patients should be monitored closely for didanosine-related toxicities. VIDEX EC should be suspended if signs or symptoms of pancreatitis, symptomatic hyperlactatemia, or lactic acidosis develop (see WARNINGS). Administration of reduced doses of VIDEX EC with tenofovir and a light meal resulted in didanosine exposures (AUC) similar to the recommended doses of VIDEX EC given alone in the fasted state (see Table 3). Therefore, when administered with tenofovir, a dose reduction of VIDEX EC to 250 mg (adults weighing ³60 kg with creatinine clearance ³60 mL/min) or 200 mg (adults weighing <60 kg with creatinine clearance ³60 mL/min) once daily is recommended, and both drugs may be taken together with a light meal (£400 kcalories, £20% fat) or in the fasted state (see DOSAGE AND ADMINISTRATION). 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.

Ribavirin : Exposure to the active metabolite of didanosine (dideoxyadenosine 5’-triphosphate) is increased when didanosine is coadministered with ribavirin (see Table 9). Fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in patients receiving both didanosine and ribavirin. Coadministration of didanosine and ribavirin is not recommended.