Nucleoside Reverse Transcriptase Inhibitors: Didanosine
Contents Introduction Information card Pharmacokinetics Dosing Pediatric dose Side effects Drug interactions

Introduction

The information represented on this drug does not necessarily correspond with the information that can be found in the Belgian scientific leaflet.
Didanosine is a purine analog and was the second drug to be approved by the FDA for the treatment of HIV-1 infection. This drug is a  potent Nucleoside Reverse Transcriptase Inhibitor, and, in some studies, has been shown to be superior to zidovudine as initial monotherapy (120) (before it became clear that monotherapy should be avoided). When combined with zidovudine or stavudine, its benefit is augmented. In addition, didanosine can be safely combined with NNRTIs and PIs.(100)

Abbreviation(s):  Generic name: Brand name: ddI didanosine Videx®		USA (FDA) Adult approval date: Pediatric approval date: October 9, 1991 October 9, 1991
Pharmaceutical co.: Bristol Myers-Squibb		Belgium: Reimbursable since April 1994
	Active Ingredient	Dosage form; Route		Strength
	Didanosine	Powder For Reconstitution; Oral		10MG/ML
	Didanosine	Tablet, Chewable; Oral		100MG

Pharmacokinetics

Didanosine is inactivated by an acidic environment; therefore, the oral formulation contains a buffering agent (containing aluminium and magnesium(100)) designed to increase gastric pH. Because administration with a meal leads to a 50% decrease in serum concentrations, didanosine should be taken on an empty stomach. (121) Although the plasma half-life of didanosine is only slightly longer than that of zidovudine, the intracellular half-life of the active metabolite is much longer (8 to 24 hours), which allows twice daily dosing. Based on these observations, studies are underway evaluating once daily dosing of didanosine. (106)

Dosing

Didanosine dosing is based on body weight. Patients weighing 60 kg or more should receive a dose of 200 mg (tablet form) every 12 hours. Patients weighing less than 60 kg should receive 125 mg every 12 hours. (106)

Pediatric Dose:

• 120 mg/m² every 12 hours.

Although didanosine is generally well tolerated, two potentially serious side effects are associated with its use: pancreatitis and peripheral neuropathy. In large phase III studies, approximately 7% of subjects developed clinical evidence of pancreatitis during 1 year of therapy.(122) Fatal cases have been reported. Factors that increase the risk of pancreatitis include prior episodes of pancreatitis and active alcohol abuse. Patients receiving didanosine are also at risk for developing peripheral neuropathy. In one clinical trial the incidence over 1 year of treatment was approximately 13%, but in large studies, the incidence of peripheral neuropathy related to didanosine use has been relatively low. Symptoms are intermittent initially, becoming permanent with continued use of the drug. Because advanced neuropathy can be painful and disabling, didanosine should be discontinued immediately if signs or symptoms develop. (106)
Optic neuritis and fulminant hepatitis are associated with ddI therapy. (114)
Other common side effects include mild to moderate diarrhea, which may be due to the large amount of buffer used in the didanosine formulation. Mild nausea occurs occasionally. Skin rash has been reported in 5 to 10% of patients. Elevation of liver aminotransferase levels occurs in a small number of patients, but this effect is rarely dose limiting. Asymptomatic elevations in amylase levels are common. (106)

Drug interactions

Drugs requiring an acidic environment for absorption (e.g., ketoconazole, itraconazole) should be ingested at least 1 hour before or 2 hours after didanosine administration. The buffered vehicle for didanosine (i.e., a magnesium/aluminum antacid) produces an acutely alkaline gastric environment that may decrease the absorption of these drugs. Patients should not ingest didanosine concurrently with tetracycline or the quinolone antibiotics, because absorption of antimicrobials may be impaired. These drugs should be taken 2 hours after didanosine. (114)
 

Interactions with other antiretroviral agents

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