No

Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)

Treatment of HIV infection; always to be used in combination with at least two other antiretroviral agents

B

Clinical effects on the fetus: Administer during pregnancy only if benefits to mother outweigh risks to the fetus

Breast-feeding/lactation: HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV

Hypersensitivity to any component

Peripheral neuropathy occurs in ~35% of patients receiving the drug; pancreatitis (sometimes fatal) occurs in ~9%; risk factors for developing pancreatitis include a previous history of the condition, concurrent cytomegalovirus or Mycobacterium avium-intracellulare infection, and concomitant use of pentamidine or co-trimoxazole; discontinue didanosine if clinical signs of pancreatitis occur. Didanosine may cause retinal depigmentation in children receiving doses >300 mg/m²/day. Patients should undergo retinal examination every 6-12 months. Use with caution in patients with decreased renal or hepatic function, phenylketonuria, sodium-restricted diets, or with edema, congestive heart failure or hyperuricemia; in high concentrations, didanosine is mutagenic. Lactic acidosis and severe hepatomegaly have occurred with antiretroviral nucleoside analogues.

>10%:

Central nervous system: Anxiety, headache, irritability, insomnia, restlessness

Gastrointestinal: Abdominal pain, nausea, diarrhea

Neuromuscular & skeletal: Peripheral neuropathy

1% to 10%:

Central nervous system: Depression

Dermatologic: Rash, pruritus

Gastrointestinal: Pancreatitis (2% to 3%)

<1%: Seizures, anemia, granulocytopenia, leukopenia, thrombocytopenia, hepatitis, lactic acidosis/hepatomegaly, alopecia, anaphylactoid reaction, diabetes mellitus, optic neuritis, retinal depigmentation, renal impairment, hypersensitivity

Chronic overdose may cause pancreatitis, peripheral neuropathy, diarrhea, hyperuricemia, and hepatic impairment

There is no known antidote for didanosine overdose; treatment is asymptomatic

Drugs whose absorption depends on the level of acidity in the stomach such as ketoconazole, itraconazole, and dapsone should be administered at least 2 hours prior to didanosine

Increased toxicity: Concomitant administration of other drugs which have the potential to cause peripheral neuropathy or pancreatitis may increase the risk of these toxicities

Tablets should be stored in tightly closed bottles at 15°C to 30°C; undergoes rapid degradation when exposed to an acidic environment; tablets dispersed in water are stable for 1 hour at room temperature; reconstituted buffered solution is stable for 4 hours at room temperature; reconstituted pediatric solution is stable for 30 days if refrigerated; unbuffered powder for oral solution must be reconstituted and mixed with an equal volume of antacid at time of preparation

Didanosine, a purine nucleoside analogue and the deamination product of dideoxyadenosine (ddA), inhibits HIV replication in vitro in both T cells and monocytes. Didanosine is converted within the cell to the mono-, di-, and triphosphates of ddA. These ddA triphosphates act as substrate and inhibitor of HIV reverse transcriptase substrate and inhibitor of HIV reverse transcriptase thereby blocking viral DNA synthesis and suppressing HIV replication.

Absorption: Subject to degradation by the acidic pH of the stomach; buffered to resist the acidic pH; as much as 50% reduction in the peak plasma concentration is observed in the presence of food

Distribution: V_d: 1.08 L/kg; children: 35.6 L/m²

Protein binding: <5%

Metabolism: Has not been evaluated in man; studies conducted in dogs, shows didanosine extensively metabolized with allantoin, hypoxanthine, xanthine, and uric acid being the major metabolites found in the urine

Bioavailability: 42%

Half-life:

Children and Adolescents: 0.8 hour

Adults:

Normal renal function: 1.5 hours; however, its active metabolite ddATP has an intracellular half-life >12 hours in vitro; this permits the drug to be dosed at 12-hour intervals; total body clearance averages 800 mL/minute

Impaired renal function: Half-life is increased, with values ranging from 2.5-5 hours

Elimination: ~55% of drug is eliminated unchanged in urine

Oral (administer on an empty stomach):

BSA less than or equal to 0.4 m²: 25 mg twice daily (tablets)

BSA 0.5-0.7 m²: 50 mg twice daily (tablets)

BSA 0.8-1.0 m²: 75 mg twice daily (tablets)

BSA 1.1-1.4 m² :100 mg twice daily (tablets)

Adults: Dosing based on patient weight:

35-49 kg: 125 mg twice daily (tablets)

50-74 kg: 200 mg twice daily (tablets)

greater than or equal to 75 kg: 300 mg twice daily (tablets)

Note: Children >1 year and Adults should receive 2 tablets per dose and children <1 year should receive 1 tablet per dose for adequate buffering and absorption; tablets should be chewed; didanosine has also been used as 300 mg once daily

Dosing adjustment in renal impairment[Dosing based on creatinine clearance, patient weight, and dosage form (tablet* or solution**)]:

Dosing for patients greater than or equal to 60 kg with

Cl_cr greater than or equal to 60 mL/minute:

200 mg tablet* OR 250 mg solution** every 12 hours

Cl_cr 30-59 mL/minute:

100 mg tablet* OR 100 mg solution** every 12 hours

Cl_cr 10-29 mL/minute:

150 mg tablet* OR 167 mg solution** every 24 hours

Cl_cr <10 mL/minute:

100 mg tablet* OR 100 mg solution** every 24 hours

Dosing for patients <60 kg with

Cl_cr greater than or equal to 60 mL/minute:

125 mg tablet* OR 167 mg solution** every 12 hours

Cl_cr 30-59 mL/minute:

75 mg tablet* OR 100 mg solution** every 12 hours

Cl_cr 10-29 mL/minute:

100 mg tablet* OR 100 mg** solution every 24 hours

Cl_cr <10 mL/minute:

75 mg tablet* OR 100 mg** solution every 24 hours

*Chewable/dispersible buffered tablet; 2 tablets must be taken with each dose; different strengths of tablets may be combined to yield the recommended dose.

**Buffered powder for oral solution

Hemodialysis: Removed by hemodialysis (40% to 60%)

Dosing adjustment in hepatic impairment: Should be considered

Do not mix with fruit juice or other acid containing liquid; administer at least 1 hour before or 2 hours after eating

Serum potassium, uric acid, creatinine; hemoglobin, CBC with neutrophil and platelet count, CD4 cells; viral load; liver function tests, amylase; weight gain; perform dilated retinal exam every 6 months

Anxiety; irritability and insomnia are common; may produce depression

May cause granulocytopenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Take as directed, 1 hour before or 2 hours after eating. Chew tablets thoroughly and/or dissolve in water. Pour powder into 4 oz of liquid, stir, and drink immediately. Do not mix with fruit juice or other acid-containing liquids. You may experience dizziness; use caution when driving or engaging in tasks that require alertness until response to drug is known. You will be susceptible to infection; avoid crowds. Report numbness or tingling of fingers, toes, or feet; abdominal pain; or persistent nausea or vomiting. Should have a retinal exam every 6-12 months. Breast-feeding precautions: Do not breast-feed.

Administer liquified powder immediately after dissolving; avoid creating dust if powder spilled, use wet mop or damp sponge

Powder for oral solution:

Buffered (single dose packet): 100 mg, 167 mg, 250 mg, 375 mg

Pediatric: 2 g, 4 g

Tablet, buffered, chewable (mint flavor): 25 mg, 50 mg, 100 mg, 150 mg, 200 mg

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Bissuel F, Cotte L, Cruneel F, et al, "Didanosine-Induced Fulminant Hepatitis," 10th Internal Conference on AIDS, Abstract, 1994, 2:204.

Bouvet E, Casalino E, Prevost MH, et al, "Fatal Case of 2',3'-Dideoxyinosine-Associated Pancreatitis," Lancet, 1990, 336(8729):1515.

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Knupp CA, Hak LJ, Coakley DF, et al, "Disposition of Didanosine in HIV-Seropositive Patients With Normal Renal Function of Chronic Renal Failure: Influence of Hemodialysis and Continuous Ambulatory Peritoneal Dialysis," Clin Pharmacol Ther, 1996, 60(5):535-42.

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