Ribavirin Didanosine

SLC28A2 CNT2 Purine nucleosides, uridine Didanosine, ribavirin Kidney, liver, heart, brain. Gray et al., 2004 Kong... 

Tablets - Coadministration of ribavirin and didanosine is not recommended. Reports of fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in clinical trials. 

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

Drugs that may interact with zalcitabine include antacids, chloramphenicol, cisplatin, dapsone, didanosine, disulfiram, ethionamide, glutethimide, gold, hydralazine, iodoquinol, isoniazid, metronidazole, nitrofurantoin, phenytoin, ribavirin, vincristine, cimetidine, metoclopramide, amphotericin, aminoglycosides, foscarnet, antiretroviral nucleoside analogs, pentamidine, and probenecid. 

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... 

Allopurinol increases didanosine plasma concentrations and their coadministration is not recommended. Ganciclovir, tenofovir and disoproxil also increase didanosine plasma concentrations, and dose reduction is recommended. Conversely, methadone decreases didanosine plasma concentrations, and appropriate doses for the combination have not been established. Didanosine should not be administered with drugs that cause pancreatic or neurotoxicity. Ribavirin increases its risk of toxicity and should not be coadministered. 

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... 

Multisystem organ dysfunction and lactic acidemia occurred in two of 15 patients with HIV and hepatitis C infections who received interferon alfa, didanosine, and ribavirin (23). Co-administration of didanosine with ribavirin can lead to increased toxicity secondary to raised intracellular concentrations of phosphorylated didanosine (ddA-TP) (24,25). Thus, the evidence suggests that the combination of didanosine plus ribavirin increases the risk of lactic acidosis. 

Japour AJ, Lertora JJ, Meehan PM, Erice A, Connor JD, Griffith BP, Clax PA, Holden-Wiltse J, Hussey S, Walesky M, Cooney E, Pollard R, Timpone J, McLaren C, Johanneson N, Wood K, Booth D, Bassiakos Y, Crumpacker CS. A phase-I study of the safety, pharmacokinetics, and antiviral activity of combination didanosine and ribavirin in patients with HIV-1 disease. AIDS Clinical Trials Group 231 Protocol Team. J Acquir Immune Defic Syndr Hum Retrovirol 1996 13(3) 235-46. 

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). 

Interferon alfa does not alter the pharmacokinetics of didanosine or lamivudine to a clinically relevant extent. Interferon alfa and, particularly, interferon beta can cause an increase in the serum levels of zidovudine. HIV-positive patients infected with hepatitis C and treated with interferon alfa and ribavirin may be at special risk of NRTI-associated lactic acidosis. Interleukin-2 appears not to interact significantly with zidovudine. 

The use of ribavirin with the NRTIs may result in increased toxicity (lactic acidosis, blood dyscrasias and hepatotoxicity), which may be more frequent with didanosine than other NRTIs. These effects may also be exacerbated by the additional use of interferon for hepatitis C. Early in vitro data su ested that ribavirin may reduce the antiretroviral effects of some NRTIs but this does not appear to have been demonstrated in practice. 

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. ... 

Butt AA Fatal lactic acidosis and pancreatitis associated with ribavirin and didanosine therapy AIDSRead(2m) 13,344-8... 

Moreno A, Quereda C, Mcceno L, Perez-Elias MJ, Muriel A, Casado JL, Antela A, Dronda F, Navas E, Barcena R, Moreno S High rate of didanosine-related mitochondrial toxicity in HIV/HCV-coinfected patients receiving ribavirin Antivir Ther (2004) 9,133-8. 

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