Ribavirin Zidovudine

Fig. 5.22 Thymidine (A), guanosine (B) and some nucleoside analogues (C-J). C, idoxuridine D, cytarabine E, ribavirin F, zidovudine (AZT) G, dideoxycytidine (DDC) H, dideoxyinosine (DDI) I, acyclovir J, ganciclovir.

Currently, amantadine, vidarabine, trifluridine, idoxuridine, sciclovir, ribavirin, and zidovudine are used as antiviral drugs. An analysis of the mechanisms of action of existing and used viral drugs permits the conclusion to be made that they can increase resistance of... 

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. 

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)... 

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. ... 

Zidovudine Ribavirin Ribavirin inhibits phosphorylation of Avoid... 

IFN reduces the metabolism of various drugs by hepatic CYPs. IFNs can increase the hematological toxicity of drugs such as zidovudine and ribavirin, as well as the neuro- and cardiotoxicity of other drugs. 

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 central role played by nucleic acid replication in biology has been exploited in medicine. Many hundreds of synthetically modified bases and nucleosides have been prepared and their effects on nucleic acid synthesis investigated. Some of them in clinical use include 5-fiuorouracil (fluracil), an anticancer agent, 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir), which is active against two strains of herpes simplex virus, 3 -azido-3 -deoxythymidine (zidovudine, or AZT), the first approved drug (in 1987) that combats the AIDS virus, and l-/3-D-ribofuranosyl-l,2,4-triazole-3-carboxamide (ribavirin), used to treat hepatitis C and respiratory viral infections. 

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