zerit and Didanosine delayed release capsule Interactions

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Interactions between zerit(stavudine) and Didanosine delayed release capsule (didanosine)

Major Drug-Drug Interaction didanosine and stavudine (Major Drug-Drug)

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.


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