Zidovudine Ganciclovir

Gaines K, Wong Jung D, Cimoch P, Lavelle J, Pollard R. Pharmacokinetic interactions with oral ganciclovir zidovudine, didanosine, probenecid. 10th Int Conf AIDS, Yokohama (J )an), 1994. Abstract p7. 

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.

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. 

Antibodies against the virus but also amantadine and derivatives, interfere with host cell penetration. There are nucleoside analogues such as aciclovir and ganciclovir, which interfere with DNA synthesis, especially of herpes viruses. Others like zidovudine and didanosine, inhibit reverse transcriptase of retroviruses. Recently a number of non-nucleoside reverse transcriptase inhibitors was developed for the treatment of HIV infections. Foscarnet, a pyrophosphate analogue, inhibits both reverse transcriptase and DNA synthesis. Protease inhibitors, also developed for the treatment of HIV infections, are active during the fifth step of virus replication. They prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new vi-rons. 

Ganciclovir interacts with a number of medications, some of which are used to treat HIV or transplant patients. Ganciclovir may cause severe neutropenia when used in combination with zidovudine. Ganciclovir increases serum levels of didanosine, whereas probenecid decreases ganciclovir elimination. Nephrotoxicity may result if other nephrotoxic agents (e.g., amphotericin B, cyclosporine, NSAIDs) are administered in conjunction with ganciclovir. 

A. Ganciclovir commonly causes myelosuppression and may produce severe neutropenia when given in combination with zidovudine. Fomivirsen is most commonly associated with iritis and other ocular information rimantadine with nausea, vomiting, anorexia, and dizziness famciclovir with headache, nausea, diarrhea, and CNS effects and zanamivir with bronchospasm. 

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)... 

Adverse effects Adverse effects include severe, dose-dependent neutropenia. [Note Combined treatment with zidovudine can result in additive neutropenia.] Ganciclovir is carcinogenic as well as embryotoxic and teratogenic in experimental animals. 

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS GANCICLOVIRAfALGANCIC LOVIR 1. T adverse effects with tenofovir, zidovudine and possibly didanosine, lamivudine and zalcitabine 2. Possibly 1 efficacy of ganciclovir 1. Uncertain possibly additive toxicity. Lamivudine may compete for active tubular secretion in the kidneys 2. Uncertain L bioavailability 1. Avoid if possible otherwise monitor FBC and renal function weekly. It has been suggested that the dose of zidovudine should be halved from 600 mg to 300 mg daily. Monitor for peripheral neuropathy, particularly with zalcitabine 2. Uncertain clinical significance if in doubt, consider alternative cytomegalovirus prophylaxis... 

P-Lactam antibiotics Cephalosporins Cidofovir Furosemide Ganciclovir Methotrexate NSAIDs Probenecid Tetracycline Zidovudine KW-3902 ... 

Hochster H, Dieterich D, Bozzette S et al. Toxicity of combined ganciclovir and zidovudine for cytomegalovirus disease associated with AIDS An AIDS clinical trials group study. Ann Intern Med 1990 113 111-17. 

Zidovudine and ganciclovir have overlapping toxicity profiles with respect to adverse hematological effects. Severe life-threatening hematological toxicity has been reported in 82% of patients treated with a combination of zidovudine and ganciclovir (18). The combination of ganciclovir with didanosine was much better tolerated (19). 

Oat2 Benzylpenicillin, erythromycin, tetracycline, rifampicin, glibenclamide, tolbutamide, zidovudine, ganciclovir, digoxin, enalapril, verapamil, methotrexate, acetylsalicylic add... 

Zidovudine, and probably other cytotoxic agents, increase the risk of myelosuppression, as do nephrotoxic agents that impair ganciclovir excretion. Probenecid and... 

Probenecid but not cidofovir alters zidovudine pharmacokinetics such that zidovudine doses should be reduced when probenecid is present, as should the doses of drugs similarly affected by probenecid fe.g., /i-lactam antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], acyclovir, lorazepam, furosemide, methotrexate, theophylline, and rifampin). Concurrent nephrotoxic agents are contraindicated, and an interval of 1 week before beginning cidofovir treatment is recommended after prior exposure to aminoglycosides, intravenous pentamidine, amphotericin foscamet, NSAIDs, or contrast dye. Cidofovir and oral ganciclovir in combination are poorly tolerated at full doses. 

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