[3] The most common adverse events with didanosine are diarrhea, nausea, vomiting, abdominal pain, fever, headache, and rash.

[5] Pancreatitis is rarely observed but has caused occasional fatalities, and has black box warning status.

In February 2010, the United States Food and Drug Administration issued a statement that patients using didanosine (Videx) are at risk for a rare but potentially fatal liver disorder, non-cirrhotic portal hypertension.

Like other anti-HIV nucleoside analogs, it acts as a chain terminator by incorporation and inhibits viral reverse transcriptase by competing with natural dATP.

Elimination is predominantly renal; the kidneys actively secrete didanosine, the amount being 20% of the oral dose.

Subsequently, Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan in the National Cancer Institute (NCI) found that ddA and ddI could inhibit HIV replication in the test tube and conducted initial clinical trials showing that didanosine had activity in patients infected with HIV.

Therefore, the original formula approved by the FDA used chewable tablets that included an antacid buffering compound to neutralize stomach acid.