| 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 | | | Drug | Standard Dosage | Dosing in Chronic Kidney Disease and Hemodialysis | References |
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| 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 | | | 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 | 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 | | | Drug(s) | Management | References |
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| Delavirdine, efavirenz | Dosage 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) | | Rilpivirine | Dosage adjustment not necessary in mild chronic kidney disease; no data in advanced kidney disease. | Edurent package insert (13) |
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| | Protease Inhibitors | | | Drug(s) | Management | References |
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| 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. 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/ritonavir | Lopinavir 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 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 | | | Drug(s) | Management | References |
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| Enfuvirtide | Dosage adjustment for chronic kidney disease does not appear necessary.
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| | Chemokine Coreceptor Antagonists | | | Drug(s) | Management | References |
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| Maraviroc | Dosage 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 | | | Drug(s) | Management | References |
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| Raltegravir | Dosage adjustment for chronic kidney disease does not appear necessary.
| Isentress package insert (18) | | Elvitegravir/cobicistat | Do 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 | | 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.
| | Viramune [prescribing information]. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT. June 2010. Accessed July 27, 2010. |
| | 13.
| | Edurant [package insert]. Raritan, NJ: Tibotec Theraputics; June 2011. Accessed June 21, 2011. |
| | 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. |
| | 15.
| | Reyataz [patient information]. Princeton, NJ: Bristol-Myers Squibb; April 2009. Accessed June 22, 2009. |
| | 17.
| | Selzentry [prescribing information]. Pfizer, Inc. New York, NY: Pfizer, Inc. May 2010. Accessed July 20, 2010. |
| | 18.
| | Isentress [package insert]. Merck & Co. Whitehouse Station, New Jersey: Merck & Co. October 2007. Accessed October 19, 2012. |
| | 19.
| | Stribild [package insert]. Gilead Sciences. Foster City, CA: Gilead Sciences. August 2012. Accessed October 19, 2012. |
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