Probenecid Ganciclovir

Drugs that may interact with imipenem-cilastatin include ganciclovir, probenecid, and cyclosporine. 

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. 

Drugs that may affect mycophenolate include acyclovir, antacids, azathioprine, cholestyramine, ganciclovir, iron, probenecid, and salicylates. 

Uses Serious Infxns d/t susceptible bacteria Action Bactericidal X cell wall synth Dose Adults. 250-1000 mg (imipenem) IV q6-8h, 500-750 mg IM 1/2 h Peds. 60-100 mg/kg/24 h IV q6h -1- if CrCl is <70 mL/min Caution [C, +/-] Probenecid T tox Contra Ped pts w/ CNS Infxn (t Sz risk) <30 kg w/ renal impair Disp Inj SE Szs if drug accumulates, GI upset, thromboc5rtopenia Interactions T Risks of Szs W/ cyclosporine, ganciclovir T effects W/ probenecid EMS Monitor for S/Sxs of sup Infxn T Sz risk w/ high doses monitor for signs of electrolyte disturbances and hypovolemia d/t D OD May cause N/V/D symptomatic and supportive... 

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. 

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. 

Levels of ganciclovir may rise in patients concurrently taking probenecid or trimethoprim. Concurrent use of ganciclovir with didanosine may result in increased levels of didanosine. 

PROBENECID ANTIVIRALS t levels of acidovir, valacidovir and ganciclovir Competitive inhibition of renal excretion Care with co-administering probenecid with /r/g/r-dose antivirals... 

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

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. 

Zidovudine and probably other cytotoxic agents increase the risk of myelosuppression, as do nephrotoxic drugs that impair ganciclovir excretion. Probenecid and possibly acyclovir reduce renal clearance of ganciclovir. Zalcitabine increases oral ganciclovir exposure by -22%. Oral ganciclovir doubles the absorption and peak plasma concentrations of didanosine and increases zidovudine by -20%. 

Probenecid reduces the renal excretion and increases the plasma levels of aciclovir, valaciclovir, and ganciclovir. Famciclovir and valganciclovir are predicted to interact similarly. 

A pharmacokinetic study in HIV-positive patients found that probenecid 500 mg every 6 hours increased the AUC of oral ganciclovir 1 g every 8 hours by 53.1%, and reduced the renal clearance by 12.3%. 

The increases in aciclovir and ganciclovir AUCs are attributable to a reduction in their renal excretion by probenecid, probably due to competition for secretion by the kidney tubules. - The effects on aciclovir of combining probenecid and cimetidine , (p.774) were greater than either drug alone. ... 

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. 

Cimoch PJ, Lavelle J, Pollard R, Griffy KG, Wong R, Tarnowsld TL, Casserella S, Jung D. Pharmacokinetics of oral ganciclovir alone and in combination with zidovudine, didanosine, and probenecid in HIV-infected subjects. J Acquir Immune Defic Syndr Hum Retroviral (1998) 17, 227-34. 

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