Inadequacy of antiretroviral drugs dosage adjustment in HIV patients receiving dialysis

Abstract

Letter to the Editor: Szczech et al [1.Szczech L.A. Kalayjian R. Rodriguez R. et al.The clinical characteristics and antiretroviral dosing patterns of HIV-infected patients receiving dialysis.Kindey Int. 2003; 63: 2295-2301Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar] reported an interesting study in a recent issue of Kidney International. The authors reported the antiretroviral drugs dosing regimens they observed in their hemodialyzed patients. We further analyzed these dosing regimens and it appeared that dosage adjustement were most often inadequate for those patients with end-stage renal disease. Table 1Comparison of antiretroviral dosage reported in Szczech's study and available dosing recommendations for hemodialysis patients 2.Izzedine H. Launay-Vacher V. Baumelou A. Deray G. An appraisal of antiretroviral drugs in hemodialysis.Kidney Int. 2001; 60: 821-830Abstract Full Text Full Text PDF PubMed Scopus (42) Google ScholarDrugNDosageRecommended dosageNucleoside reverse transcriptase inhibitorsAbacaviraDrug for which dosage adjustment is not necessary in hemodialyzed patients.3300 to 600 mg/day1200 mg/dayDidanosine7100 to 400 mg/day50 to 100 mg/dayLamivudine3625 to 300 mg/day150 mg first dose then 25 to 50 mg/dayStavudine3310 to 40 mg/day15 to 20 mg/dayZidovudine11100 mg 3 × a week to 600 mg/day300 mg/dayCombivir®8Lamivudine150 to 450 mg/day150 mg first dose then 25 to 50 mg/dayZidovudine300 to 900 mg/day300 mg/dayNon-nucleoside reverse transcriptase inhibitorsEfavirenzaDrug for which dosage adjustment is not necessary in hemodialyzed patients.13200 to 600 mg/day600 mg/dayNevirapineaDrug for which dosage adjustment is not necessary in hemodialyzed patients.11200 to 400 mg/day200 to 400 mg/dayProtease inhibitorsIndinaviraDrug for which dosage adjustment is not necessary in hemodialyzed patients.61600 to 2400 mg/day2400 mg/dayNelfinaviraDrug for which dosage adjustment is not necessary in hemodialyzed patients.21500 to 2500 mg/day2250 mg/dayRitonaviraDrug for which dosage adjustment is not necessary in hemodialyzed patients.5200 to 1000 mg/day1200 mg/daySaquinaviraDrug for which dosage adjustment is not necessary in hemodialyzed patients.2800 to 3600 mg/day1800 mg/dayN = Number of patients in Szczech's study.Combivir®, 1 capsule contains 150 mg lamivudine and 300 mg zidovudine.a Drug for which dosage adjustment is not necessary in hemodialyzed patients. Open table in a new tab N = Number of patients in Szczech's study. Combivir®, 1 capsule contains 150 mg lamivudine and 300 mg zidovudine. We read with great interest Szczech's article [1.Szczech L.A. Kalayjian R. Rodriguez R. et al.The clinical characteristics and antiretroviral dosing patterns of HIV-infected patients receiving dialysis.Kindey Int. 2003; 63: 2295-2301Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar], in which they concluded that antiretroviral medications were not used at their optimal dose in the human immunodeficiency virus (HIV) hemodialysis patients they studied because data on these drugs' pharmacokinetics and dosage adjustment in patients with renal insufficiency are lacking. However, we would like to outline that most antiretroviral drugs' pharmacokinetics have been studied in patients with renal insufficiency. Based on those publications and our personal data, we have recently published precise guidelines on antiretroviral drug dosage adjustment in hemodialysis patients [2.Izzedine H. Launay-Vacher V. Baumelou A. Deray G. An appraisal of antiretroviral drugs in hemodialysis.Kidney Int. 2001; 60: 821-830Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar]. Among the 11 antiretroviral drugs reported in Szczech's article, only 1 was administered at the correct dose (nevirapine). The other drugs that should have been prescribed at their usual dosage were either underdosed (abacavir, efavirenz, indinavir, nelfinavir, ritonavir, saquinavir) or overdosed (saquinavir). For the latter, the usual recommended dose for hemodialysis patients is 1800 mg/day [2.Izzedine H. Launay-Vacher V. Baumelou A. Deray G. An appraisal of antiretroviral drugs in hemodialysis.Kidney Int. 2001; 60: 821-830Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar]; the dosing range reported by Szczech is 800 to 3600 mg/day. Among the drugs that should have had their dose adjusted according to the patients' renal function, didanosine was clearly overdosed. Stavudine, lamivudine, and zidovudine administered alone were either under- or overdosed. Finally, the use of the lamivudine-zidovudine combination drug Combivir® led to a large overdose in all cases. Consequently, although we agree that further pharmacokinetic, tolerance, and efficacy studies are mandatory for these patients, dose adjustment recommendations exist [2.Izzedine H. Launay-Vacher V. Baumelou A. Deray G. An appraisal of antiretroviral drugs in hemodialysis.Kidney Int. 2001; 60: 821-830Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar] and should already be routinely applied.