Stavudine Ribavirin

Drugs that may interact with stavudine include didanosine, doxorubicin, hydroxyurea, methadone, ribavirin, and zidovudine. 

Drugs that may affect zidovudine include acetaminophen, atovaquone, bone marrow suppressive/cytotoxic agents (eg, adriamycin, dapsone), clarithromycin, doxorubicin, fluconazole, ganciclovir, methadone, nelfinavir/ritonavir, phenytoin, probenecid, ribavirin, rifamycins, stavudine, trimethoprim, and valproic acid. 

Little information on the drug interactions of ribavirin is available. In vitro, ribavirin inhibits the phosphorylation reactions that are required for activation of zidovudine and stavudine. 

Zidovudine should be used cautiously with any other agent that causes bone marrow suppression, such as interferon-a, trimethoprim-sulfamethoxazole, dap-sone, foscarnet, flucytosine, ganciclovir, and valganci-clovir. Probenecid and interferon-p inhibit the elimination of zidovudine therefore, a dosage reduction of zidovudine is necessary when the drugs are administered concurrently. Ribavirin inhibits the phosphorylation reactions that activate zidovudine, and zidovudine similarly inhibits the activation of stavudine thus, the coadministration of zidovudine with ribavirin or stavudine is contraindicated. 

Didanosine (ddl) NRTT1 Tablets, 400 mg daily,3 adjusted for weight. 30 min before or 2 h after meals. Separate dosing from fluoroquinolones and tetracyclines by 2 h Peripheral neuropathy, pancreatitis, diarrhea, nausea, hyperuricemia. Possible increase in myocardial infarction Avoid concurrent neuropathic drugs (eg, stavudine, zalcitabine, isoniazid), ribavirin, and alcohol. Do not administer with tenofovir... 

Zidovudine NRTI1 200 mg tid or 300 mg bid3 Macrocytic anemia, neutropenia, nausea, headache, insomnia, asthenia Avoid concurrent stavudine and myelosuppressive drugs (eg, ganciclovir, ribavirin)... 

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS RIBAVIRIN 1. t side-effects, risk of lactic acidosis, peripheral neuropathy, pancreatitis, hepatic decompensation, mitochondrial toxicity and anaemia with didanosine and stavudine 2.1 efficacy of lamivudine 1. Additive side-effects t intracellular activation of didanosine and stavudine 2. J intracellular activation of lamivudine 1. Not recommended. Use with extreme caution monitor lactate, LFTs and amylase closely. Stop co-administration if peripheral neuropathy occurs. Stavudine and didanosine carry a higher risk 2. Monitor HIV RNA levels if they T, review treatment combination... 

Coinfection with HIV is common in patients with HCV given the shared risk factors for transmission. Patients coinfected with these viruses have a more accelerated progression of their HCV disease. Most trials to date have excluded patients with HIV or limited them to patients with stable HTV infection. Combination therapy using ribavirin is considered to be superior however, enhancement of antiretroviral adverse events such as lactic acidosis limits therapy. Concurrent use of ribavirin therapy with didanosine, stavudine, or zidovudine is relatively contraindicated. ... 

Ribavirin inhibits the phosphorylation and antiviral activity of pyrimidine nucleoside HIV reverse-transcriptase inhibitors such as zidovudine and stavudine but increases the activity of purine nucleoside reverse-transcriptase inhibitors (e.g., didanosine) in vitro. It appears to increase the risk of mitochondrial toxicity from didanosine (see Chapter 50). 

In vitro, ribavirin reduced the intracellular activation and antiretroviral activity of stavudine. However, in a study in 5 HIV-positive patients with hepatitis C, ribavirin 800 mg daily had no statistically significant effect on the pharmacokinetics of stavudine (a 45% increase in AUC), and no effect on intracellular activation of stavudine, when compared with similar patients who received placebo. Similarly, no decrease in antiviral activity of stavudine (as assessed by plasma HIV-RNA levels) has been seen when ribavirin was given with interferon for hepatitis C infection in patients with HIV. " Nevertheless, the UK manufacturers of ribavirin continue to recommend that plasma HIV-RNA levels are closely monitored in patients taking ribavirin with stavudine to ensure continued efficacy. In contrast, based on an analysis of data from the adverse event reporting system of the FDA in the US, (see didanosine above), the UK manufacturers of ribavirin consider that concurrent use of stavudine should be avoided to limit the risk of mitochondrial toxicity. The UK manufacturer of stavudine notes that patients co-infected with hepatitis C and treated with interferon alfa and ribavirin may be at increased risk ofNRTI-associated lactic acidosis. Patients at increased risk should be monitored closely. Similarly, the US manufacturer of stavudine states that patients receiving interferon with or without ribavirin and stavudine should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. ... 

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