Tolerability of enteric-coated didanosine capsules compared with didanosine tablets in adults with HIV infection.
BACKGROUND
A new enteric-coated (EC) didanosine (ddI) formulation (Videx EC; Bristol-Myers Squibb, Princeton, NJ, U.S.A.) may be better tolerated than the tablet form because it lacks the buffer component thought to be responsible for diarrhea and other gastrointestinal (GI) side effects.


OBJECTIVE
To evaluate the frequency and magnitude of GI side effects (nausea, bloating, GI upset, diarrhea, abdominal cramps, gas [flatus]) before and after switching the formulation of ddI, in study subjects who were experiencing one or more GI symptom(s) of at least moderate severity.


METHODS
A 6-week open label crossover study of current didanosine tablet users comparing daily symptom scores (7 point scale, 0 = absent to 6 = very severe) during weeks 1 to 2 (on tablets) to weeks 4 and 6 (on EC capsules). Formulation palatability and preference, lifestyle effects, and use of antidiarrheals or other medications for symptom relief were also assessed.


RESULTS
GI symptom scores (7-day means) on tablets were diarrhea 2.11, gas 2.00, bloating 1.23, abdominal cramps 0.74, GI upset 0.69, nausea 0.66. After switching to EC (week 4 and week 6), mean scores decreased for diarrhea (mean scores 0.99 week 4, 0.79 week 6), gas (0.95, 0.79), bloating (0.49, 0.32), abdominal cramps (0.21, 0.05), GI upset (0.16, 0.14), and nausea (0.32, 0.22). Severity of all GI symptoms was significantly reduced after 4 weeks on EC capsules ( p <.01 by paired t- test). Negative impact of side effects on routine activities was significantly reduced (41% on tablet vs. 7% on EC; p <.01). All 42 study subjects preferred the EC form.


CONCLUSIONS
According to patients' diary scores, switching to ddI in EC form significantly reduces nausea, bloating, GI upset, diarrhea, abdominal cramps, and gas for individuals who experienced GI side effects while taking the buffered tablet form. The striking tolerability advantages appear to support routine switching to EC for such patients and may suggest that widespread preferential selection of the EC form is appropriate to enhance didanosine tolerability and promote treatment adherence.
Kunches
L M
LM
JSI Clinical Research, Inc., Boston, Massachusetts 02210, USA. lkunches@jsi.com
Reinhalter
N E
NE
Marquis
A
A
Coakley
E
E
Cohen
C
C
Morris
A B
AB
Mazzullo
J M
JM
D000328:Adult; D000681:Amylases / Q000097:blood; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001900:Boston; D018791:CD4 Lymphocyte Count; D002214:Capsules; D018592:Cross-Over Studies; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D016049:Didanosine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004361:Drug Tolerance / Q000502:physiology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D018579:Patient Selection; D013607:Tablets
D019380:Anti-HIV Agents; D002214:Capsules; D013607:Tablets; D000681:Amylases; D016049:Didanosine