ddI, d4T and Hydroxyurea Side Effect Warning!

The FDA recently issued a warning that when using ddI (didanosine, Videx), some people may develop pancreatitis (a potentially life-threatening inflammation of the pancreas). An early symptom includes severe abdominal pain, which should be carefully diagnosed. Adding d4T (stavudine, Zerit) and/or hydroxyurea (Hydrea, Droxia) to ddI may further increase the risk of pancreatitis.

Results from ACTG A5025 suggest that people taking ddI, d4T and hydroxyurea together are more likely to develop this side effect than those taking AZT (zidovudine, Retrovir) and 3TC (lamivudine, Epivir). All people had been on stable treatment with AZT+3TC+indinavir, and after six months, either stayed on AZT+3TC+indinavir or switched to d4T+ddI+indinavir with or without hydroxyurea.

After 24 weeks there were no differences in viral load changes among the groups, but people taking ddI+d4T+hydroxyurea+indinavir were more likely to have side effects. These included pancreatitis, neuropathy and increased liver enzymes. Further, the group taking hydroxyurea had about a hundred CD4+ cell loss compared to a slight increase in the other two groups.

There are several possible reasons why those taking hydroxyurea had more side effects. The most obvious is that they took four drugs while the others used three. Another is that the dose of hydroxyurea used was higher than the standard dose (1,200 mg vs. 1,000 mg) and it was not adjusted for weight. Also, hydroxyurea causes more ddI to get into cells, increasing the risk of ddI-related side effects, like pancreatitis. Additionally, regular monitoring was not done by the researchers but by their primary physicians, who may have been less familiar with the procedures for monitoring and responding to early signs of pancreatitis.

These findings suggest that people should be cautious if they're taking ddI and hydroxyurea together. If they experience any type of pain in the stomach, they should immediately notify their healthcare provider.

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