Table 14-10: Dosing of Antiretroviral Agents in Renal Insufficiency and/or Hepatic Insufficiency
| Drug Name |
Usual Adult Dose |
Dosing for GFR > 50 mL/min |
Dosing for GFR 10-50 mL/min |
Dosing for
GFR <10 mL/min |
Dosing in Hemodialysis (HD) |
Dosing in Peritoneal dialysis (PD) |
| Zidovudine (Retrovir®; AZT) |
300 mg bid, or 200 mg tid |
300 mg bid |
300 mg bid |
300 mg qd |
300 mg qd |
300 mg qd, a very small amount removed in PD (no supplemental dose needed) (Gallicano, 1992) |
Extensive with significant first pass liver metabolism to GAZT. Excreted in urine as 14–18% unchanged drug and 60–74% GAZT. With GFR <20 mL/min half life is increased from 1.1–1.4 hr to 0.9 to 8 hours (with high inter patient variation). |
| Didanosine (Videx®; (Dideoxyinosine, ddI) |
Wt >60kg dose: 400 mg qd (tabs) or 500 mg qd (powder). Wt <60kg dose: 250 mg qd (tabs) or 334 mg qd (powder). Dose can also be taken in two divided doses |
Usual dose |
50% of usual dose |
25% of usual dose |
25% of usual dose qd, on days of dialysis give post dialysis. 30% removal after a 3-hours session (Knupp, 1996) |
25% of usual dose qd. Not removed with PD (Knupp, 1996) |
Metabolism not fully evaluated. 20–40% excreted unchanged in the urine. |
| Stavudine (Zerit®; d4T) |
Wt >60kg dose: 40 mg bid. Wt <60kg dose: 30 mg bid |
Wt >60kg dose: 40 mg bid. Wt <60kg dose: 30 mg bid |
Wt >60kg dose: 20 mg q12–24h. Wt <60kg dose: 15 mg q12–24 |
Wt >60kg dose: 20 mg q24h. Wt <60kg dose: 15 mg q24h |
Wt >60kg dose: 20 mg q24h. Wt <60kg dose: 15 mg q24h, on days of dialysis dose post dialysis. (Grasela, 2000) |
No data: Wt >60kg dose: 20 mg q24h. Wt <60kg dose: 15 mg q24h |
Some hepatic metabolism and degradation by pyrimidine pathway. 40% of drug excreted unchanged. |
| Zalcitabine (Hivid®; (Dideoxycytidine, ddC) |
0.75 mg tid |
0.75 mg tid |
0.75 mg bid |
0.75 mg qd |
No data: 0.75 mg qd, on days of dialysis dose post dialysis (likely to be dialysed out) |
No data: 0.75 mg qd, on days of dialysis dose post dialysis |
Insignificant liver metabolism. 62–75% excreted unchanged in the urine. 10% excreted unchanged in the feces. |
| Lamivudine (Epivir®; 3TC) |
150 mg bid or 300 mg qd |
150 mg bid |
150 mg qd |
150 mg x1 then 50 mg qd (some recommend 150 mg qd due to good safety profile and convenience) |
150 mg x 1 then 25–50 mg qd; Dose after HD |
50 mg qd; Limited data |
Intermittent hemodialysis does not warrant a further change in dose from that defined by CrCl (Johnson, 1996). |
| Emtricitabine (Emtriva®) (FTC) |
200 mg qd |
200 mg qd |
30–49 mL/min: 200 mg q 48hr. 15–29 mL/min: 200 mg q 72 hr. < 15 mL/min: 200 mg q 96 hr |
200 mg qd |
200 mg q 96 hr. (30% of dose removed with 3 hr. HD; on days of dialysis, dose post-HD) |
|
|
| Abacavir (Ziagen®) ABC |
300 mg bid or 600 mg qd |
300 mg bid |
300 mg bid |
300 mg bid |
Usual dose [In 4 patients undergoing HD or PD, the pharmacokinetics of abacavir were not altered (Thompson, 1998) |
Usual dose [In 4 patients undergoing HD or PD, the pharmacokinetics of abacavir were not altered (Thompson, 1998) |
Pharmacokinetics are unchanged in renal failure (Izzedine, 2001b). Animal studies: 12% unchanged Abacavir in the urine. Only 2% metabolized to carbovir. Consider ABC 200 bid with hepatic insufficiency. |
| Tenofovir (Viread®) |
300 mg qd |
300 mg qd
30–49 mL/min: 300 mg q48h. |
<30 mL/min: 300 mg
q72–96h |
300 mg q7days |
300 mg q 7 days following dialysis (54% removed with 4 hours high flux HD-healthy volunteer PK data) May require more if patient requires more than three 4-hour HD sessions. |
No data: Not recommended by manufacturer. Interval adjustment likely. |
Note: Dosing recommendations based on single dose PK data in healthy volunteer. HIV infected patients with Cr Clearance less than 60 mL/min were excluded from clinical trials. |
| Efavirenz (Sustiva®) |
600 mg qhs |
Usual dose** |
Usual dose likely** |
Usual dose likely** |
600 mg qhs, No significant removal with HD (Izzedine, 2000a) |
600 mg qhs, Not removed with PD (Gill, 2000) |
Data limited in renal failure. Extensive liver metabolism 14–34% excreted in urine as glucuronide metabolite and 16–61% excreted in stool. |
Nevirapine
Viramune®) |
200 mg qd x 14 days then 200 mg bid |
Usual dose |
Usual dose |
Usual dose |
Usual dose post-HD. Small amount removed (Izzedine, 2001a) |
Usual dose post dialysis. 16 mg removed in dialysate in a 24 hour period. |
Extensive liver metabolism to hydroxylated metabolites which are renally cleared. Less than 5% excreted unchanged in the urine. |
| Delavirdine (Rescriptor®) |
400 mg tid |
Usual dose** |
Usual dose likely** |
Usual dose likely** |
No data: Unlikely to be removed in dialysis due to high protein binding** |
No data: Unlikely to be removed in dialysis due to high protein binding** |
Extensive liver metabolism. |
| Nelfinavir (Viracept®) |
750 mg tid or 1250 mg bid |
Usual dose |
Usual dose |
Usual dose |
Usual dose. Removed with HD, MUST be given post-HD on days of dialysis (Izzedine, 2000a) |
Usual dose. Not removed with PD (Tillotson, 2000) |
Pharmacokinetics are unchanged in renal failure (Izzedine, 1999). Extensive liver metabolism to active oxidative metabolites. Major biliary excretion with less than 2% renal excretion. |
| Indinavir (Crixivan®) |
800 mg tid* or IDV 800/RTV 100–200 mg bid (increased incidence of kidney stones with RTV 200 mg–generally recommended only in pt also on EFV or NVP) |
Usual dose* |
Usual dose |
Usual dose |
Usual dose. Very small amount removed in dialysis (Izzedine, 2000b) |
No data: Usual dose likely** (Low probability of significant amount being removed in dialysis due to low protein binding) |
Pharmacokinetics are unchanged in renal failure (Izzedine, 2000b). Extensive liver metabolism to glucuronide and oxidative metabolites. Major biliary excretion with approximately 10% renal excretion. |
| Ritonavir (Norvir®) |
600 mg bid (High dose not well tolerated, dose may be lowered if used with another PI) |
Usual dose |
Usual dose |
Usual dose |
Small amount dialyzed out, dose post HD (Izzedine, 2001b) |
No data: Usual dose likely**, dose post dialysis on days of dialysis. (Unlikely to be removed in dialysis due to high protein binding, however due to low volume of distribution small amount possibly removed)** |
Pharmacokinetics are unchanged in renal failure (Izzedine, 2001b). Extensive liver metabolism to isopropylthiazole (active metabolites) and other inactive metabolite. Major biliary excretion with approximately 4–10% renal excretion. |
| Saquinavir (Invirase® (capsule); Fortovase® (soft gel capsule) |
Invirase 600* mg tid (not recommended as sole PI); Fortovase 1200 mg tid or INV 1000 mg/RTV 100 mg q12h. |
Usual dose |
Usual dose |
Usual dose |
Not dialyzed out (Izzedine, 2001b) |
No data: Usual dose likely** (Unlikely to be removed in dialysis due to high protein binding and large volume of distribution.) |
Pharmacokinetics are unchanged in renal failure (Izzedine, 2001b). Extensive first pass metabolism which accounts for saquinavir’s low bioavailability. Major biliary excretion with only 1–3% renal excretion. |
| Amprenavir (Agenarase®) |
1,200 mg bid* or APV 600 mg/RTV 100 mg q12h. |
Usual dose |
Usual dose likely |
Usual dose likely |
No data: Usual dose likely |
No data: Usual dose likely |
Impaired hepatic function moderate—consider dose reduction 450 mg bid; severe—300 mg bid. |
| LPV/RTV (Kaletra®) |
400/100 mg bid |
Usual dose |
Usual dose likely |
Usual dose likely |
Usual dose. Not removed with HD (Izzedine, 2001c) |
No data: Usual dose likely |
|
| Atazanavir (Reyataz®) |
400 mg qd* or ATV 300/RTV 100 qd. |
Usual dose |
Usual dose likely |
Usual dose likely |
Usual dose. Dose post-HD |
Usual dose likely |
ATV is not recommended in patients with severe hepatic insufficiency. ATV AUC increased by 45% with mild to moderate hepatic impairment. Consider decreasing ATV to 300 mg/day in subjects with mild to moderate hepatic impairment. Clinical data using the lower dose in hepatic insufficiency has not been assessed. |
| Fosamprenavir (Lexiva®) |
1400 mg* q12h or fAPV 700/100 RTV q12h. |
Usual dose |
Usual dose likely |
Usual dose likely |
No data. Usual dose likely. |
No data. Usual dose likely. |
|
| Enfuvirtide (Fuzeon®) |
90 mg SQ q12h |
Usual dose |
Usual dose likely |
Usual dose likely |
No data. Usual dose likely. |
No data. Usual dose likely. |
|