didanosine (ddI)
Videx, Videx EC

Available forms
Available by prescription only
Capsules (delayed-release): 125 mg, 200 mg, 250 mg, 400 mg
Powder for oral solution (buffered): 100 mg/packet, 167 mg/packet, 250 mg/packet
Powder for oral solution (pediatric): 2 g and 4 g in 4- and 8-oz bottles, respectively
Tablets (chewable): 25 mg, 50 mg, 100 mg, 150 mg, 200 mg

Indications and dosages
 Treatment of HIV infection when antiretroviral therapy is warranted. Adults who weigh 60 kg (132 lb) or more: 200 mg (tablets) P.O. b.i.d. Or, 400 mg (as two 200-mg chewable tablets or one 400-mg delayed-release capsule) once daily. Or, 250 mg buffered powder P.O. b.i.d.
Adults who weigh less than 60 kg: 125 mg (tablets) P.O. b.i.d. Or, 250 mg (as chewable tablets or delayed-release capsule) once daily. Or, 167 mg buffered powder P.O. b.i.d.
Children: 120 mg/m² P.O. b.i.d. To prevent gastric acid degradation, children older than age 1 should receive a 2-tablet dose, and children younger than age 1 should receive a 1-tablet dose. Videx EC isn’t for use in children.
≡ Dosage adjustment. Patients with renal or hepatic impairment may need dosage adjustment.

Pharmacodynamics
Antiviral action: Didanosine is a synthetic purine analogue of deoxyadenosine. After it enters the cell, it’s converted to its active form dideoxyadenosine triphosphate (ddATP), which inhibits replication of HIV by preventing DNA replication. In addition, ddATP inhibits the enzyme HIV-RNA dependent DNA polymerase (reverse transcriptase).

Pharmacokinetics
Absorption: Degrades rapidly in gastric acid. Commercially available preparations contain buffers to raise stomach pH. Bioavailability averages about 33%; tablets may exhibit better bioavailability than buffered powder for oral solution. Food can decrease absorption by 50%.
Distribution: Widely distributed; drug penetration into the CNS varies, but CSF levels average 46% of concurrent plasma levels.
Metabolism: Metabolism isn’t fully understood, but is probably similar to that of endogenous purines.
Excretion: Excreted in urine as allantoin, hypoxanthine, xanthine, and uric acid. Serum half-life averages 0.8 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or its components. Use very cautiously in patients with history of pancreatitis. Use cautiously in patients with peripheral neuropathy, impaired renal or hepatic function, or hyperuricemia.

Interactions
Drug-drug. Allopurinol: Increases didanosine level. Avoid use together.
Antacids containing magnesium or aluminum hydroxides: May produce enhanced adverse effects, such as diarrhea or constipation. Avoid use together.
Dapsone, drugs that need gastric acid for adequate absorption, ketoconazole: Decreases buffering action of didanosine. Give such drugs 2 hours before didanosine.
Fluoroquinolones, tetracyclines: Decreases antibiotic absorption from buffering agents in didanosine tablets or antacids in pediatric suspension. Separate administration times.
Ganciclovir: Increases didanosine level. Monitor patient for toxicity.
Itraconazole: May decrease serum itraconazole levels. Avoid use together.
Methadone: Decreases didanosine level. Monitor patient closely for effect if drugs must be given together. Dosage adjustment may be needed.
Stavudine: May increase incidence of fatal lactic acidosis in women when stavudine, didanosine, and other antivirals are administered together. Use together cautiously. Monitor laboratory studies.
Drug-food. Any food: Decreases absorption. Give drug on an empty stomach at least 30 minutes before a meal.
Drug-lifestyle. Alcohol use: Increases risk of pancreatitis. Discourage alcohol use.

Adverse reactions
CNS: headache, seizures, confusion, anxiety, nervousness, asthenia, abnormal thinking, twitching, depression, peripheral neuropathy, pain, fever.
EENT: blurred vision, retinal changes, optic neuritis.
GI: diarrhea, nausea, vomiting, abdominal pain, pancreatitis, dry mouth, anorexia.
Hematologic: leukopenia, granulocytosis, thrombocytopenia, anemia.
Hepatic: hepatic failure, hepatomegaly.
Metabolic: increased serum uric acid levels, lactic acidosis.
Musculoskeletal: myopathy.
Respiratory: pneumonia, dyspnea.
Skin: rash, pruritus, sarcoma.
Other: infection, allergic reactions, chills.

Effects on lab test results
• May increase uric acid, AST, ALT, alkaline phosphatase, and bilirubin levels.
• May decrease hemoglobin and WBC, granulocyte, and platelet counts.

Overdose and treatment
Possible effects of overdose include diarrhea, pancreatitis, peripheral neuropathy, hyperuricemia, and hepatic dysfunction.
 Treatment is supportive. No specific antidote is known. Drug isn’t dialyzable by peritoneal dialysis, but some is cleared by hemodialysis.

Special considerations
 ALERT Didanosine shouldn’t be used as monotherapy.
• The 200-mg chewable tablet should be used only as a component of a once-daily regimen.
 ALERT Pediatric powder for oral solution must be prepared by the pharmacist before dispensing. It must be constituted with water and then diluted with antacid (manufacturer recommends either Mylanta Double Strength Liquid or Maalox TC) to a final concentration of 10 mg/ml. Admixture is stable for 30 days if kept at 36° to 46° F (2° to 8° C). Shake well before measuring the dose.
 ALERT Don’t confuse drug with other antivirals that use abbreviations for identification.
• Most patients older than age 1 should receive two tablets per dose. Tablets contain buffers that raise stomach pH to levels that prevent degradation of the active drug. Tablets should be thoroughly chewed before swallowing, and patient should drink at least 1 oz of water with each dose. If tablets are manually crushed, mix drug in 1 oz (30 ml) water or clear apple juice; stir to disperse uniformly and have patient drink it immediately. Single-dose packets containing buffered powder for oral solution are available.
• To administer buffered powder for oral solution, carefully open packet and pour contents into 4 oz (120 ml) water. Don’t use fruit juice or other acidic beverages. Stir for 2 or 3 minutes until powder dissolves completely. Administer immediately.
• When preparing powder or crushing tablets, avoid excessive dispersal of drug particles into the air.
• Each packet of buffered powder contains 1,380 mg sodium; use with caution in patients on a sodium-restricted diet.
• Consider substituting the chewable tablets if diarrhea occurs.
• The major toxicity of drug use is pancreatitis, which has been fatal in some cases. It must be considered when abdominal pain, nausea, and vomiting develop or biochemical markers are elevated. Discontinue drug until pancreatitis is excluded. If pancreatitis is confirmed, don’t use drug again.
• Monitor patient for signs of lactic acidosis and hepatotoxicity, including weakness, lethargy, abdominal pain, feeling cold, dizziness, light-headedness, and a slow, irregular heartbeat. Lactic acidosis occurs generally in women.
• Obtain periodic retinal examinations to watch for retinal changes or optic neuritis.
Pregnant patients
• Fatal lactic acidosis has occurred in women who have taken didanosine alone or with stavudine or other antiretrovirals. This combination should only be used in pregnant women if the benefit outweighs the potential risk.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. Because of risk of serious adverse effects in the infant, breast-feeding isn’t recommended. The Centers for Disease Control and Prevention recommends that drug not be used in HIV + mothers who are breast-feeding.
Pediatric patients
• Retinal depigmentation has occurred in some children receiving drug. Children should receive dilated retinal examinations at least every 6 months or if vision changes. Videx EC isn’t for use in children.
Geriatric patients
• Pancreatitis is seen more often in elderly patients.
• Monitor renal function closely and adjust dosage as needed to prevent toxicity.

Patient education
• Tell patient to take drug on an empty stomach to ensure adequate absorption, to chew tablets thoroughly before swallowing, and to drink at least 1 oz (30 ml) water with each dose.
• Tell patient not to crush or break the capsule form.
• Remind patient using buffered powder for oral solution not to use fruit juice or other acidic beverages, to allow 3 minutes for powder to dissolve completely, and to take immediately. Make sure patient understands how to mix the solution.
• Explain possible adverse effects and how to watch for them. Remind patient that there may be increased adverse effects and toxicities while on multidrug therapy.
• Explain importance of drug compliance for treatment of HIV.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use