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Drug Interactions between didanosine and stavudine

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

didanosine stavudine

Applies to: didanosine and stavudine

MONITOR CLOSELY: The concomitant use of the nucleoside reverse transcriptase inhibitors (NRTIs), didanosine (ddI) and stavudine (d4T), has been associated with an increased risk of certain toxicities related to mitochondrial damage, and the addition of hydroxyurea to the combination may further increase that risk. Specifically, concurrent use of ddI and d4T has been associated with an increased risk of pancreatitis, several cases of which have been fatal. Additionally, the risk and severity of NRTI-related peripheral neuropathy may be additively or synergistically increased. Although rare, the syndrome of lactic acidosis and severe hepatomegaly with steatosis (with or without pancreatitis) may also occur more frequently with this combination than with antiretroviral regimens containing either drug alone or other combinations of NRTIs. Fatal lactic acidosis has been reported in pregnant women receiving ddI and d4T with other antiretroviral agents, although it is unclear if pregnancy is a specific risk factor.

MANAGEMENT: Close observation for signs and symptoms of toxicity is recommended if ddI and d4T must be used together, particularly in patients with advanced HIV disease and/or elderly patients. Both drugs should be suspended if pancreatitis is suspected, and ddI discontinued permanently if pancreatitis is confirmed. Reinstitution of d4T, if necessary, should be undertaken with caution following recovery. Prompt withdrawal of these drugs is also essential in patients who develop peripheral neuropathy to avoid irreversible damage. Therapy may be reinstituted following resolution of neuropathy symptoms, but reduced dosages are recommended. Likewise, treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity, and permanent discontinuation considered if the syndrome is confirmed. In pregnant women, the manufacturers recommend that the combination of ddI and d4T be used with caution and only if potential benefit clearly outweighs the risks. Patients should be advised to seek medical attention promptly if symptoms of toxicity occur such as nausea, vomiting, abdominal pain/distention, fatigue, unexplained weight loss, tachypnea, dyspnea, motor weakness, numbness, tingling, and pain in hands and feet.

References

  1. (2002) "Product Information. Videx (didanosine)." Bristol-Myers Squibb
  2. (2001) "Product Information. Zerit (stavudine)." Bristol-Myers Squibb
  3. Rutschmann OT, Opravil M, Iten A, Malinverni R, Vernazza PL, Bucher HC, Bernasconi E, Sudre P, Leduc D, Yerly S, Perrin LH, (1998) "A placebo-controlled trial of didanosine plus stavudine, with and without hydroxyurea, for HIV infection." AIDS, 12, f71-7
  4. Moore RD, Wong WME, Keruly JC, McArthur JC (2000) "Incidence of neuropathy in HIV-infected patients on monotherapy versus those on combination therapy with didanosine, stavudine and hydroxyurea." Aids, 14, p. 273-8
  5. Cepeda JA, Wilks D (2000) "Excess peripheral neuropathy in patients treated with hydroxyurea plus didanosine and stavudine for HIV infection." Aids, 14, p. 332-3
  6. Rutschmann OT, Vernazza PL, Bucher HC, Opravil M, Ledergerber B, Telenti A, Malinverni R, Bernasconi E, Fagard C, Leduc D, Perr (2000) "Long-term hydroxyurea in combination with didanosine and stavudine for the treatment of HIV-1 infection." Aids, 14, p. 2145-51
  7. Lonergan JT, Behling C, Pfander H, Hassanein TI, Mathews WC (2000) "Hyperlactatemia and hepatic abnormalities in 10 human immunodeficiency virus-infected patients receiving nucleoside analogue combination regimens." Clin Infect Dis, 31, p. 162-6
  8. Moore RD, Keruly JC, Chaisson RE (2001) "Incidence of pancreatitis in HIV-infected patients receiving nucleoside reverse transcriptase inhibitor drugs." Aids, 15, p. 617-20
  9. Kronenberg A, Riehle HM, Gunthard HF (2001) "Liver failure after long-term nucleoside antiretroviral therapy." Lancet, 358, p. 759-601
  10. Havlir DV, Gilbert PB, Bennett K, et al. (2001) "Effects of treatment intensification with hydroxyurea in HIV-infected patients with virologic suppression." AIDS, 15, p. 1379-88
  11. Boubaker K, Flepp M, Sudre P, et al. (2001) "Hyperlactatemia and Antiretroviral Therapy: The Swiss HIV Cohort Study." Clin Infect Dis, 33, p. 1931-7
  12. Coghlan ME, Sommadossi JP, Jhala NC, Many WJ, Saag MS, Johnson VA (2001) "Symptomatic lactic acidosis in hospitalized antiretroviral-treated patients with human immunodeficiency virus infection: a report of 12 cases." Clin Infect Dis, 33, p. 1914-21
View all 12 references

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Drug and food interactions

Moderate

didanosine food

Applies to: didanosine

ADJUST DOSING INTERVAL: Didanosine bioavailability is decreased when administered with food. Loss of efficacy may result.

MANAGEMENT: Didanosine should be administered in the fasting state, at least 30 minutes before or more than 2 hours after eating.

References

  1. (2002) "Product Information. Videx (didanosine)." Bristol-Myers Squibb

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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