Brands, Medical Use, Clinical Data
Drug Category
- Anti-HIV Agents
- Antimetabolites
- Reverse Transcriptase Inhibitors
Dosage Forms
- Capsule (enteric-coated)
- Powder for solution
- Tablet
Brands / Synonyms
,3’ -dideoxy-; -Dideoxyinosine; -Dideoxyinosine, hydrate; 2’ ddI
; DDI, Didanosine; Didanosine (JAN/USAN); Dideoxyinosine; Inosine, 2’ Videx; Videx (TN); Videx EC
Indications
For use, in combination with other antiretroviral agents, in the treatment of HIV-1 infection in adults.
Pharmacology
Didanosine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Didanosine differs from other nucleoside analogues, as it does not have any of the regular bases, instead it has hypoxanthine attached to the sugar ring. Didanosine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. Didanosine is effective against HIV, and usually used in combination with other antiviral therapy. Switching from long term AZT treatment to didanosine has been shown to be beneficial. Didanosine has weak acid stability and therefore, it is often combined with an antacid.
Mechanism of Action
Didanosine (ddI) is metabolized intracellularly by a series of cellular enzymes to its active moiety, dideoxyadenosine triphosphate (ddATP), which inhibits the HIV reverse transcriptase enzyme competitively by competing with natural dATP. It also acts as a chain terminator by its incorporation into viral DNA as the lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.
Absorption
Rapidly absorbed (bioavailability 30-40%) with peak plasma concentrations appearing within 0.5 and 1.5 hrs.
Toxicity
Side effects include pancreatitis, peripheral neuropathy, diarrhea, hyperuricemia and hepatic dysfunction
Biotrnasformation / Drug Metabolism
Rapidly metabolized intracellularly to its active moiety, 2,3-dideoxyadenosine-5-triphosphate (ddA-TP). It is then further metabolized hepatically to yield hypoxanthine, xanthine, and uric acid.
Contraindications
VIDEXEC (didanosine) is contraindicated in patients with previously demonstrated clinically
significant hypersensitivity to any component of the formulation.
Drug Interactions
Coadministration of VIDEX with drugs that are known to cause pancreatitis may increase the risk of this toxicity (see WARNINGS) and should be done with extreme caution, only if other alternatives are not available, and only if clearly indicated. Neuropathy has occurred more frequently in patients with a history of neuropathy or neurotoxic drug therapy, including stavudine, and these patients may be at increased risk of neuropathy during VIDEX therapy (see ADVERSE REACTIONS).
Allopurinol: The AUC of didanosine was increased about 4-fold when allopurinol at 300 mg/day was coadministered with a single 200-mg dose of VIDEX to two patients with renal impairment (CLcr=15 and 18 mL/min). The effects of allopurinol on didanosine pharmacokinetics in subjects with normal renal function are not known.
Antacids: Concomitant administration of antacids containing magnesium or aluminum with VIDEX Chewable/Dispersible Buffered Tablets or Pediatric Powder for Oral Solution may potentiate adverse events associated with the antacid components.
Drugs Whose Absorption Can Be Affected by the Level of Acidity in the Stomach: Drugs such as ketoconazole and itraconazole should be administered at least 2 hours prior to dosing with VIDEX.
Ganciclovir: Administration of VIDEX 2 hours prior to or concurrent with oral ganciclovir was associated with a 111 (114)% increase in the steady-state AUC of didanosine (n = 12). A 21 (17)% decrease in the steady-state AUC of ganciclovir was observed when VIDEX was administered 2 hours prior to ganciclovir, but not when the two drugs were administered simultaneously (n = 12).
Quinolone Antibiotics: VIDEX should be administered at least 2 hours after or 6 hours before dosing with ciprofloxacin because plasma concentrations of ciprofloxacin are decreased when administered with antacids containing magnesium, calcium, or aluminum. In eight HIV-infected patients, the steady-state AUC of ciprofloxacin was decreased an average of 26% (95% CI = 14%, 37%) when ciprofloxacin was administered 2 hours prior to a marketed chewable/dispersible tablet formulation of VIDEX. The AUC of ciprofloxacin was decreased an average of 15-fold in 12 healthy subjects given ciprofloxacin and didanosine-placebo tablets concurrently. In a single subject given one dose of ciprofloxacin 2 hours after a dose of didanosine-placebo tablets, a greater than 50% reduction in the AUC of ciprofloxacin was observed.
Plasma concentrations of quinolone antibiotics are decreased when administered with antacids containing magnesium, calcium, or aluminum. The optimal dosing interval for coadministration with VIDEX should be determined by consulting the appropriate quinolone package insert.
Interactions with Other Antiretroviral Drugs: Significant decreases in the AUC of delavirdine (20%) and indinavir (84%) occurred following simultaneous administration of these agents with VIDEX. To avoid this interaction, delavirdine or indinavir should be given 1 hour prior to dosing with VIDEX. The pharmacokinetics of nelfinavir are not altered to a clinically significant degree when it is administered with a light meal 1 hour after VIDEX.
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