Didanosine with ganciclovir

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. 

Buffering agents that are compounded with didanosine to counteract its degradation by gastric acid may interfere with the absorption of other drugs that require acidity (e.g., indinavir, delavirdine, ketoconazole, fluoroquinolones, tetracyclines, dapsone). An enteric-coated formulation Videx EC) that dissolves in the basic pH of the small intestine is not susceptible to these interactions. Ganciclovir and valganciclovir can increase blood levels of didanosine. The use of zalcitabine with didanosine is not recommended because that combination carries an additive risk of peripheral neuropathy. The combination of didanosine with stavudine increases the risk of pancreatitis, hepatotoxicity, and peripheral neuropa-... 

Fluoroquinolones and tetracyclines should be administered at least 2 hours before or after didanosine in order to avoid decreased antibiotic plasma concentrations due to chelation. Coadministration with ganciclovir results in an increased AUC of didanosine and a decreased AUC... 

Clinically important, potentially hazardous interactions with chloroquine, didanosine, furazolidone, ganciclovir, hydroxychloroquine, methotrexate, pyrimethamine, rifabutin, rifampin, sulfonamides, ursodeoxycholic 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. 

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. 

The buffer in didanosine tablets and powder interferes with absorption of indinavir, delavirdine, atazanavir, dapsone, itraconazole, and fluoroquinolone agents therefore, administration should be separated in time. Serum levels of didanosine are increased when -administered with tenofovir or ganciclovir, and are decreased by atazanavir, delavirdine, ritonavir, tipranavir, and methadone (Table 49-4). 

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 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... 

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). 

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. 

The interactions between ganciclovir and didanosine or zidovudine would appear to be established, but the clinical importance is uncertain. Zidovudine seems to be associated with greater toxicity than didanosine. However, there is also some evidence suggesting reduced ganciclovir efficacy in the presence of didanosine, and this requires further study. Close and careful monitoring is required if either combination is used. 

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. 

Jacobson MA, Owen W, Campbell J, Brosgart C, Abrams DI. Tolerability of combined ganciclovir and didanosine for the tteataient of cytomegalovirus disease associated with AIDS. Clin InfectDis 0-993) 16 (Suppl 1), S69-S73. 

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