didanosine (Rx)

>10%

Diarrhea (19-28%)

Peripheral neuropathy (17-20%)

Increased amylase (15-17%)

Abdominal pain (7-13%)

1-10%

Increased LFT

Increased uric acid

Pancreatitis (patients >65 years had higher frequency of pancreatitis than younger patients)

Pruritus

Rash

Postmarking Reports

Noncirrhotic portal hypertension

Contraindications

Hypersensitivity

Coadministration with allopurinol (may increase didanosine toxicity)

Coadministration with ribavirin (increases actrive metabolite dideoxyadenosine 5’-triphosphate levels, causing fatal hepatic failure, peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis)

Coadministration with stavudine

Cautions

(All NRTIs): Risk of potentially fatal lactic acidosis & severe hepatomegaly with steatosis when used alone or in combination with other antiretrovirals

Risk of potentially fatal pancreatitis, increases if used in combo with stavudine

Risk of potentially fatal bleeding from esophageal varices in patients with non-cirrhotic portal hypertension

Discontinue if pancreatitis occurs; reduce dose for other ADR's

Risk of immune reconstitution syndrome if used in combination w/ other antiretroviral drugs

Risk of retinal changes and optic neuritis

Rapidly degrades in acidic pH, however, EC is protected from stomach acids

Noncirrhotic portal hypertension reported; discontinue if signs/symptoms occur (eg, elevated liver enzymes, esophageal varices, hematemesis, ascites, splenomegaly)

Coadministration of methadone with Videx pediatric powder may significant decrease didanosine concentrations

Patients treated in combination with stavudine may be at increased risk for pancreatitis, lactic acidosis, and hepatic toxicity; coadministration is contraindicated

Treatment has been associated with loss of subcutaneous fat, which is most evident in the face, limbs, and buttocks; incidence and severity of lipoatrophy are related to cumulative exposure, and is often not reversible when treatment is stopped; patients receiving therapy should be frequently examined and questioned for signs of lipoatrophy, and if feasible, therapy should be switched to an alternative regimen if there is suspicion of lipoatrophy

Pregnancy

To monitor maternal-fetal outcomes of pregnant women exposed to didanosine and other antiretroviral agents, an Antiretroviral Pregnancy Registry has been established; physicians are encouraged to register patients by calling 1-800-258-4263

There are no adequate and well-controlled studies of didanosine in pregnant women; drug should be used during pregnancy only if potential benefit justifies potential risk

Lactation

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed infants to avoid risking postnatal transmission of HIV; a study in rats showed that following oral administration, didanosine and/or its metabolites were excreted into the milk of lactating rats; it is not known if didanosine is excreted in human milk; because of both potential for HIV transmission and potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving didanosine

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Nucleoside Reverse Transcriptase Inhibitor (NRTI)

Inhibits in vitro replication of HIV via chain termination & interference with HIV-RNA dependent DNA polymerase

Pharmacokinetics

Bioavailability: 42% (adults); 25% (children)

Protein Bound: <5%

Metabolism: Liver

Excretion: Urine

Vd: 28 L/m² (children); 1.08 L/kg

Half-life elimination: 0.8 hr (children and adolescents); 1.5 hr (adults)

Powder for Oral Solution Preparation

Prior to dispensing, the pharmacist must reconstitute dry powder to an initial concentration of 20 mg/mL and immediately mix the resulting solution with antacid to a final concentration of 10 mg/mL

Initial solution (20 mg/mL): Reconstitute the product to 20 mg per mL by adding 100 mL or 200 mL of purified water USP, to the 2 g or 4 g of powder, respectively

Final solution (10 mg/mL): Immediately mix one part of the 20 mg/mL initial solution with one part of any commercially available antacid that contains as active ingredients aluminum hydroxide (400 mg/5 mL), magnesium hydroxide (400 mg/5 mL), and simethicone (40 mg/5 mL) for a final dispensing concentration of 10 mg/mL

Oral Administration

Oral solution dispensed as 10 mg/mL with antacid as diluent

Take on empty stomach, at least 30 minutes before food or 2 hr after food; Cmax and AUC reduced by ~46% and 19% respectively in the presence of food

EC not approved for aged <6 yr and for children who weigh <20 kg and unable to swallow capsule whole

Storage

Reconstituted oral solution (10 mg/mL): Refrigerate for up to 30 days at 36-46°F (2-8°C); discard any unused portion after 30 days