Drug Detail

Didanosine

Last Updated June 10, 2016

Trade Names

Deladex, Videx, Aspen Didanosine, Sonke Didanosine

Drug Classification

Nucleoside reverse transcriptase inhibitor antiretroviral

Formulations

25 mg, 50 mg, 100 mg, 150 mg tablets; 250 mg, 400 mg capsules; 250 mg, 400 mg enteric-coated (EC) capsules

Indications and Pharmacology

Indication: treatment of HIV infection in combination with other antiretrovirals.

Mechanism of action*: an adenosine analogue that is phosphorylated intracellularly to dideoxyadenosine triphosphate, which interferes with HIV viral RNA-dependent DNA polymerase inhibiting viral replication.

Pharmacokinetics*: renal excretion 50%. Half-life: serum = 1.5 hours; intracellular = > 20 hours; subject to degradation by acidic pH of the stomach. Oral availability decreased with food. Cerebrospinal fluid penetration ~ 20% in adults.

Dosage

Adult Dose:

  • Administer at least one-half hour before or 1-2 hours after a meal.
  • Oral:
    • ≥ 60 kg: 400 mg daily in 1-2 divided doses.
    • < 60 mg: 250 mg daily in 1-2 divided doses.
  • EC formulation is prescribed as a single daily dose.
    • Dose can be reduced from 400 mg/day to 250 mg/day in adults > 60 kg when administered with tenofovir, but this dose is less effective than other NRTIs and is best avoided.
  • Non-EC formulations can be chewed or dissolved in water. Dissolve in at least 30 mL (15 mL per tablet). Each dose should consist of ≥ 2 tablets to ensure adequate antacid for effective buffering.

Use in Renal or Hepatic Insufficiency: Reduce dose in renal or hepatic impairment.

Dosage for patients with chronic kidney disease or end-stage renal disease:

Buffered tablets
Body weight ≥ 60 kg usual dose: 200 mg twice daily.

  • Creatinine clearance ≥ 60 mL/min: no adjustment.
  • Creatinine clearance 30-59 mL/min: 200 mg daily orally.
  • Creatinine clearance 10-29 mL/min: 150 mg daily orally.
  • Creatinine clearance < 10 mL/min: 100 mg daily orally.
  • Receiving haemodialysis: 100 mg once daily (dose didanosine after dialysis).
  • Receiving peritoneal dialysis: 100 mg daily orally.

Body weight < 60 kg usual dosage: 125 mg twice daily orally.
Dosage for patients with chronic kidney disease or end-stage renal disease:

  • Creatinine clearance ≥ 60 mL/min: no adjustment.
  • Creatinine clearance 30-59 mL/min: 150 mg daily orally.
  • Creatinine clearance 10-29 mL/min: 100 mg daily orally.
  • Creatinine clearance < 10 mL/min: 75 mg daily orally.
  • Receiving haemodialysis: 75 mg daily orally (dose didanosine after dialysis).
  • Receiving peritoneal dialysis: 75 mg daily orally.

Didanosine EC
Body weight ≥ 60 kg usual dosage: 400 mg/day orally.

  • Creatinine clearance ≥ 60 mL/min: no adjustment.
  • Creatinine clearance 30-59 mL/min: 200 mg once daily orally.
  • Creatinine clearance 10-29 mL/min: 125 mg once daily orally.
  • Creatinine clearance < 10 mL/min: 125 mg once daily orally.
  • Receiving haemodialysis 125 mg once daily orally (dose didanosine after dialysis).
  • Receiving peritoneal dialysis 125 mg once daily orally.

Body weight < 60 kg usual dosage: 250 mg once daily orally.

  • Creatinine clearance ≥ 60 ml/min: no adjustment.
  • Creatinine clearance 30-59 mL/min: 125 mg once daily orally.
  • Creatinine clearance 10-29 mL/min: 125 mg once daily orally.
  • Creatinine clearance < 10 mL/min: do not use; use buffered tablets instead.
  • Receiving haemodialysis: do not use; use buffered tablets instead.
  • Receiving peritoneal dialysis: do not use; use buffered tablets instead.

Use in Pregnancy and Breastfeeding: Category B. Excretion into breast milk is not known. Infants of mothers taking didanosine should not be breast-fed.

Use in Children: 180-240 mg/m2 daily in 1-2 divided doses. Maximum: 400 mg/day.

Warnings

US Prescribing Information Boxed Warning*: fatal and nonfatal pancreatitis has occurred and should be discontinued in anyone with suspected pancreatitis.

US Prescribing Information Boxed Warning*: lactic acidosis/hepatomegaly with steatosis has been reported with nucleoside analogues with fatal cases reported. Use in caution with patients with risk factors for liver disease and suspend treatment if a patient develops signs and symptoms. Fatal  lactic  acidosis has  been reported in pregnant women who received the combination of didanosine and stavudine.

Infants of mothers taking didanosine should not be breast-fed.

Drug–Drug Interactions

Contraindicated*: ribavirin, allopurinol.

Precautions:

  • Atazanavir*: administer (with food) 2 hours before or 1 hour after didanosine.
  • Tipranavir*: separate doses by at least 2 hours.
  • Other drugs in which absorption is impaired by increased gastric pH: administer 2 hours before or 2 hours after buffered formulation of didanosine.

Considerations for Special Populations

See above for pregnancy and lactation.

Administration to children may be difficult because drug must be taken on an empty stomach.

Mothers taking didanosine should not breast-feed their infants.

Adverse Effects

Peripheral neuropathy, retinal changes (optic neuritis), nausea, vomiting, insulin resistance/diabetes mellitus, potential association with noncirrhotic portal hypertension.*

Pancreatitis (see Warnings).*

Lactic acidosis/hepatomegaly (see Warnings).*

*Information from US prescribing information.
Recommendation from South African Renal Society, 2008.