| | Dosing of Antiretroviral Drugs in Adults with Chronic Kidney Disease and Hemodialysis |  | | October 2009 |  | Ian R. McNicholl, PharmD, BCPS, University of California San Francisco Rudolph A. Rodriguez, MD, University of California San Francisco
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| Introduction |  | 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, 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 may require modified dosing strategies in patients on hemodialysis. 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. |  | | Tables |  |  | | Nucleoside/Nucleotide Analogues |  | | Drug | Standard Dosage | Dosing in Chronic Kidney Disease and Hemodialysis | References |
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| Abacavir |
300 mg PO BID
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Dosage adjustment for chronic kidney disease does not appear necessary
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Ziagen package insert (1)
| | Didanosine (enteric-coated capsules) |
250 mg to 400 mg PO QD, depending on wt
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ClCr (mL/min)
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Wt ≥60 kg
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Wt <60 kg
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Videx EC package insert (2, 3)
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≥60
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400 mg QD
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250 mg QD
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30-59
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200 mg QD
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125 mg QD
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10-29
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125 mg QD
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125 mg QD
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<10
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125 mg QD
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formulation not suitable
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HD
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125 mg QD
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formulation not suitable
| | Emtricitabine |
200 mg PO QD
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ClCr (mL/min)
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Emtriva package insert
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≥50
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200 mg QD
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30-49
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200 mg Q 48 H
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15-29
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200 mg Q 72 H
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<15
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200 mg Q 96 H
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HD
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200 mg Q 96 H, give dosage after dialysis
| | Lamivudine |
150 mg PO BID or 300 mg PO QD
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ClCr (mL/min)
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Epivir package insert (4, 5, 6)
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≥50
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150 mg BID or 300 mg QD
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30-49
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150 mg QD
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15-29
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150 mg first dose, then 100 mg QD
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5-14
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150 mg first dose, then 50 mg QD
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<5
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50 mg first dose, then 25 mg QD
| | Stavudine |
20 mg to 40 mg PO BID, depending on wt
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ClCr (mL/min)
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Wt ≥60 kg
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Wt <60 kg
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Zerit package insert (7)
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>50
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40 mg BID
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30 mg BID
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26-50
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20 mg BID
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15 mg BID
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10-25
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20 mg QD
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15 mg QD
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HD
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20 mg QD
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15 mg QD
| | Tenofovir |
300 mg PO QD
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Experience in patients with ClCr <60 mL/min is limited. Preliminary data suggest:
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Viread package insert (8)
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ClCr (mL/min)
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≥50
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300 mg QD
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30-49
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300 mg Q 48 H
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10-29
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300 mg twice weekly (ie, Q 3-4 days)
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HD
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300 mg QW
| | Zidovudine |
300 mg PO BID
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ClCr (mL/min)
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Retrovir package insert (9, 10, 11)
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<15
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100 mg Q 6-8 H
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HD
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100 mg TID
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 | | Fixed-Dose Combinations |  | | Drug | Standard Dosage | Dosing in Chronic Kidney Disease and Hemodialysis | References |
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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
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Substitute component drugs, adjusting dosage of each drug for ClCr
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Atripla package insert
| | Combivir (zidovudine/lamivudine) |
1 tab PO BID
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Substitute component drugs, adjusting dosage of each drug for ClCr
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Combivir package insert
| | Epzicom or Kivexa (abacavir/lamivudine) |
1 tab PO QD
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Substitute component drugs, adjusting dosage of each drug for ClCr
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Epzicom package insert
| | Trizivir (zidovudine/lamivudine/abacavir) |
1 tab PO BID
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Substitute component drugs, adjusting dosage of each drug for ClCr
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Trizivir package insert
| | Truvada (emtricitabine/tenofovir) |
1 tab PO QD
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ClCr (mL/min)
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Truvada package insert
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≥50
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1 tab QD
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30-49
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1 tab Q 48 H
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<30
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Substitute component drugs, adjusting dosage of each drug for ClCr
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 | | Nonnucleoside Reverse Transcriptase Inhibitors |  | Delavirdine, efavirenz, nevirapine Dosage adjustment for chronic kidney disease does not appear necessary. |
 | | Protease Inhibitors |  | 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. Atazanavir Although atazanavir is not cleared by hemodialysis, patients on hemodialysis have substantially lower plasma atazanavir concentrations compared with controls.(12, 13)
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.
Lopinavir/ritonavir Lopinavir and ritonavir also are not cleared by hemodialysis, but a recent study found that, in patients on hemodialysis, levels of both agents were lower than those of historical controls (Cmin was 44% lower).(14)
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.
Other PIs The 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 |  | Enfuvirtide Dosage adjustment for chronic kidney disease does not appear necessary. |
 | | Chemokine Coreceptor Antagonists |  | Maraviroc Dosage adjustment for chronic kidney disease does not appear necessary. |
 | | Integrase Inhibitors |  | Raltegravir Dosage adjustment for chronic kidney disease does not appear necessary. |
|  |  | References
 | | 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. |
 | | 8.
| | Personal communication with J. Flaherty. 2002. |
 | | 12.
| | Reyataz [patient information]. Princeton, NJ: Bristol-Myers Squibb; April 2009. Available at http://packageinserts.bms.com/pi/pi_reyataz.pdf. Accessed June 22, 2009. |
 | | 13.
| | 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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