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Home > Treatment > Charts & Tables > Renal Dosing
Dosing of Antiretroviral Drugs in Adults with Chronic Kidney Disease and Hemodialysis
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Introduction
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Tables
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transparent imageNucleoside/Nucleotide Analogues
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transparent imageFixed-Dose Combinations
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transparent imageNonnucleoside Reverse Transcriptase Inhibitors
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transparent imageProtease Inhibitors
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transparent imageFusion Inhibitors
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transparent imageChemokine Coreceptor Antagonists
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transparent imageIntegrase Inhibitors
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References
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Related Resources
transparent imageRenal Manifestations of HIV
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Introduction
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Several nucleoside and nucleotide analogue reverse transcriptase inhibitors are excreted primarily through the kidney and must be dose adjusted for patients with chronic kidney disease, and for those who are on hemodialysis. Although there are few data on the pharmacokinetic properties of the nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, fusion inhibitors, chemokine coreceptor antagonists, or integrase inhibitors in patients with chronic kidney disease, the pharmacokinetic profiles of these drugs suggest that renal function has minimal effect on drug elimination. Despite this, protease inhibitors and the NNRTI nevirapine may require modified dosing strategies in patients on hemodialysis, and the chemokine coreceptor antagonist maraviroc and the pharmacokinetic booster cobicistat should not be used in certain patients with chronic kidney disease (see below). These tables summarize antiretroviral drug dose recommendations for patients with impaired renal function.

For further information, see the Renal Manifestations of HIV Knowledge Base Chapter.

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Tables
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Nucleoside/Nucleotide Analogues
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Drug Standard Dosage Dosing in Chronic Kidney Disease and Hemodialysis References
Abacavir 300 mg PO BID Dosage adjustment for chronic kidney disease does not appear necessary Ziagen package insert ( 1 )
Didanosine (enteric-coated capsules) 250 mg to 400 mg PO QD, depending on wt ClCr (mL/min) Wt ≥60 kg Wt <60 kg Videx EC package insert ( 2 , 3 )
≥60 400 mg QD 250 mg QD
30-59 200 mg QD 125 mg QD
10-29 125 mg QD 125 mg QD
<10 125 mg QD formulation not suitable
HD 125 mg QD formulation not suitable
Emtricitabine 200 mg PO QD ClCr (mL/min) Emtriva package insert
≥50 200 mg QD
30-49 200 mg Q 48 H
15-29 200 mg Q 72 H
<15 200 mg Q 96 H
HD 200 mg Q 96 H, give dose after dialysis
Lamivudine 150 mg PO BID or 300 mg PO QD ClCr (mL/min) Epivir package insert ( 4 , 5 , 6 )
≥50 150 mg BID or 300 mg QD
30-49 150 mg QD
15-29 150 mg first dose, then 100 mg QD
5-14 150 mg first dose, then 50 mg QD
<5 50 mg first dose, then 25 mg QD
Stavudine 20 mg to 40 mg PO BID, depending on wt ClCr (mL/min) Wt ≥60 kg Wt <60 kg Zerit package insert ( 7 )
>50 40 mg BID 30 mg BID
26-50 20 mg BID 15 mg BID
10-25 20 mg QD 15 mg QD
HD 20 mg QD 15 mg QD
Tenofovir 300 mg PO QD Experience in patients with ClCr <60 mL/min is limited. Preliminary data suggest: Viread package insert ( 8 )
ClCr (mL/min)
≥50 300 mg QD
30-49 300 mg Q 48 H
10-29 300 mg twice weekly (ie, Q 3-4 days)
HD 300 mg QW
Zidovudine 300 mg PO BID ClCr (mL/min) Retrovir package insert ( 9 , 10 , 11 )
<15 100 mg Q 6-8 H
HD 100 mg TID
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Fixed-Dose Combinations
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Drug Standard Dosage Dosing in Chronic Kidney Disease and Hemodialysis References

Abbreviations: BID = 2 times daily; ClCr = creatinine clearance; H = hours; HD = hemodialysis; PO = by mouth; Q = every; QD = 1 time daily; QHS = at bedtime; QW = once a week; TID = 3 times daily; Wt = weight

Atripla (efavirenz/emtricitabine/ tenofovir) 1 tab PO QHS Substitute component drugs, adjusting dosage of each drug for ClCr Atripla package insert
Combivir (zidovudine/lamivudine) 1 tab PO BID Substitute component drugs, adjusting dosage of each drug for ClCr Combivir package insert
Complera (rilpivirine/emtricitabine/tenofovir) 1 tab PO QD Substitute component drugs, adjusting dosage of each drug for ClCr Complera package insert
Epzicom or Kivexa (abacavir/lamivudine) 1 tab PO QD Substitute component drugs, adjusting dosage of each drug for ClCr Epzicom package insert
Trizivir (zidovudine/lamivudine/abacavir) 1 tab PO BID Substitute component drugs, adjusting dosage of each drug for ClCr Trizivir package insert
Truvada (emtricitabine/tenofovir) 1 tab PO QD ClCr (mL/min) Truvada package insert
≥50 1 tab QD
30-49 1 tab Q 48 H
<30 Substitute component drugs, adjusting dosage of each drug for ClCr
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Nonnucleoside Reverse Transcriptase Inhibitors
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Drug(s)ManagementReferences
Delavirdine, efavirenzDosage adjustment for chronic kidney disease does not appear necessary.
Nevirapine
  • For patients with chronic kidney disease (not on hemodialysis): Dosage adjustment does not appear necessary.

  • For patients on hemodialysis: An additional 200 mg dose of nevirapine following each dialysis treatment is recommended

Viramune package insert (12)
RilpivirineDosage adjustment not necessary in mild chronic kidney disease; no data in advanced kidney disease. Edurent package insert (13)
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Protease Inhibitors
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Drug(s)ManagementReferences
Amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir, tipranavir
  • For patients with chronic kidney disease (not on hemodialysis): Dosage adjustment does not appear necessary.

  • For patients on hemodialysis: Hemodialysis normally would not be expected to change serum levels of drugs that are hepatically cleared, such as protease inhibitors. However, pharmacokinetic studies suggest that levels of atazanavir, lopinavir, and ritonavir are reduced significantly in patients on hemodialysis; the mechanism for this is not clear. Pharmacokinetic evaluations of most other protease inhibitors in hemodialysis patients have not been conducted. Further studies are needed to describe protease inhibitor levels in patients on hemodialysis and to define dosing recommendations.

AtazanavirAlthough atazanavir is not cleared by hemodialysis, patients on hemodialysis have substantially lower plasma atazanavir concentrations compared with controls.
  • Unboosted atazanavir should not be used.

  • For treatment-naive patients receiving hemodialysis, atazanavir must be boosted by ritonavir.

  • For treatment-experienced patients receiving hemodialysis, atazanavir (boosted or unboosted) is not recommended.

Reyataz package insert (14 , 15)
Lopinavir/ritonavirLopinavir and ritonavir also are not cleared by hemodialysis, but a recent study found that levels of both agents were lower than those of historical controls (C min was 44% lower).
  • For patients receiving hemodialysis, once-daily dosing should not be used (consider twice-daily dosing; dosage adjustments have not been studied).

  • Exercise caution in patients with resistance to protease inhibitors; lopinavir and ritonavir levels may not be adequate for viral suppression.

(16)
Other PIsThe pharmacokinetics of other protease inhibitors in the setting of hemodialysis have not been studied, and it is not known whether the finding of lower-than-expected drug levels in dialysis patients is a drug-class effect.
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Fusion Inhibitors
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Drug(s)ManagementReferences
EnfuvirtideDosage adjustment for chronic kidney disease does not appear necessary.
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Chemokine Coreceptor Antagonists
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Drug(s)ManagementReferences
MaravirocDosage adjustment for patients with mild or moderate chronic kidney disease does not appear necessary. Maraviroc should not be used in patients with severe renal impairment or end-stage renal disease (CrCl <30 mL/min) who are taking a potent CYP3A inhibitor or inducer. Selzentry package insert (17)
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Integrase Inhibitors
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Drug(s)ManagementReferences
RaltegravirDosage adjustment for chronic kidney disease does not appear necessary. Isentress package insert (18)
Elvitegravir/cobicistatDo not initiate combination of elvitegravir/cobicistat/tenofovir/emtricitabine if ClCr <70 mL/min. Discontinue if ClCr decreases to <50 mL/min.Stribild package insert (19)
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References

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1.   Izzedine H, Launay-Vacher V, Aymard G, Legrand M, Deray G. Pharmacokinetics of abacavir in HIV-1-infected patients with impaired renal function. Nephron 2001; 89:62-7.
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2.   Singlas E, Taburet AM, Borsa Lebas F, Parent de Curzon O, Sobel A, Chauveau P, Viron B, al Khayat R, Poignet JL, Mignon F, et al. Didanosine pharmacokinetics in patients with normal and impaired renal function: influence of hemodialysis. Antimicrob Agents Chemother 1992; 36:1519-24.
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3.   Knupp CA, Hak LJ, Coakley DF, Falk RJ, Wagner BE, Raasch RH, van der Horst CM, Kaul S, Barbhaiya RH, Dukes GE. Disposition of didanosine in HIV-seropositive patients with normal renal function or chronic renal failure: influence of hemodialysis and continuous ambulatory peritoneal dialysis. Clin Pharmacol Ther 1996; 60:535-42.
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4.   Bohjanen PR, Johnson MD, Szczech LA, Wray DW, Petros WP, Miller CR, Hicks CB. Steady-state pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with end-stage renal disease receiving chronic dialysis. Antimicrob Agents Chemother 2002; 46:2387-92.
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5.   Izzedine H, Launay-Vacher V, Deray G. Dosage of lamivudine in a haemodialysis patient. Nephron 2000; 86:553.
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6.   Johnson MA, Verpooten GA, Daniel MJ, Plumb R, Moss J, Van Caesbroeck D, De Broe ME. Single dose pharmacokinetics of lamivudine in subjects with impaired renal function and the effect of haemodialysis. Br J Clin Pharmacol 1998; 46:21-7.
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7.   Grasela DM, Stoltz RR, Barry M, Bone M, Mangold B, O'Grady P, Raymond R, Haworth SJ. Pharmacokinetics of single-dose oral stavudine in subjects with renal impairment and in subjects requiring hemodialysis. Antimicrob Agents Chemother 2000; 44:2149-53.
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8.  Personal communication with J. Flaherty. 2002.
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9.   Kimmel PL, Lew SQ, Umana WO, Li PP, Gordon AM, Straw J. Pharmacokinetics of zidovudine in HIV-infected patients with end-stage renal disease. Blood Purif 1995; 13:340-6.
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10.   Pachon J, Cisneros JM, Castillo JR, Garcia-Pesquera F, Canas E, Viciana P. Pharmacokinetics of zidovudine in end-stage renal disease: influence of haemodialysis. Aids 1992; 6:827-30.
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11.   Tartaglione TA, Holeman E, Opheim K, Smith T, Collier AC. Zidovudine disposition during hemodialysis in a patient with acquired immunodeficiency syndrome. J Acquir Immune Defic Syndr 1990; 3:32-4.
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12.  Viramune [prescribing information]. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT. June 2010. Accessed July 27, 2010.
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13.  Edurant [package insert]. Raritan, NJ: Tibotec Theraputics; June 2011. Accessed June 21, 2011.
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14.  Agarwala S et al. Pharmacokinetics of atazanavir in severely renally impaired subjects including those on hemodialysis. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention. In: Program and abstracts of the 8th International Workshop on Clinical Pharmacology of HIV Therapy. April 16-18, 2007; Budapest. Abstract 2.
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15.  Reyataz [patient information]. Princeton, NJ: Bristol-Myers Squibb; April 2009. Accessed June 22, 2009.
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16.   Gupta SK, Rosenkranz SL, Cramer YS, et al. The pharmacokinetics and pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected persons requiring hemodialysis. AIDS. 2008 Oct 1;22(15):1919-27.
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17.  Selzentry [prescribing information]. Pfizer, Inc. New York, NY: Pfizer, Inc. May 2010. Accessed July 20, 2010.
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18.  Isentress [package insert]. Merck & Co. Whitehouse Station, New Jersey: Merck & Co. October 2007. Accessed October 19, 2012.
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19.  Stribild [package insert]. Gilead Sciences. Foster City, CA: Gilead Sciences. August 2012. Accessed October 19, 2012.
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