OVERVIEW ― We're getting questions about how to dose oral antibiotics with dialysis since medication labels and references may conflict or be murky.
KEY POINTS
- Recommend usual doses of antibiotics that aren't renally cleared including azithromycin, clindamycin, and doxycycline. But advise adjusting other antibiotics by reducing the dose, extending the interval or both. For instance, cephalexin may be dosed 250 mg BID instead of 500 mg BID or cefuroxime 500 mg every OTHER day instead of BID.
- Be aware of medications that can be given at usual doses, but just ONCE daily including amoxicillin, ciprofloxacin, or clarithromycin. For example, consider amoxicillin 250 to 500 mg DAILY instead of TID. Keep in mind, it takes longer to reach therapeutic blood levels if dosing intervals are extended. That's why a loading dose is used for some medications that need a high peak concentration to kill bacteria. Think of levofloxacin as an example. Suggest a 500 mg loading dose, then 250 mg every OTHER day instead of the usual 500 mg daily.
- Educate on proper dosing, especially with unusual regimens. Don't typically advise adding "replacement doses" even for highly dialyzed drugs, such as amoxicillin. Instead, tell hemodialysis patients to take antibiotic doses AFTER dialysis especially once-daily medications to limit drug removal. But explain that the timing of doses isn't a consideration with peritoneal dialysis since it doesn't remove medications very well.
- If patients are on a phosphate binder (calcium carbonate, etc), generally remind them to take their antibiotic 1 hour before or 3 hours after the binder. Many antimicrobial agents (see Table 1) are eliminated renally and require dosing adjustments in patients with chronic kidney disease; however, several commonly used agents do not require adjustments.
| Table (1). Antibiotic Dosing Requirements in Patients with Chronic Kidney Disease | ||||
|---|---|---|---|---|
| DRUG | USUAL DOSAGE | DOSAGE ADJUSTMENT (PERCENTAGE OF USUAL DOSAGE) BASED ON GFR (ML PER MINUTE PER 1.73 m2) | ||
| > 50 | 10 TO 50 | < 10 | ||
| Carbapenems | ||||
| Ertapenem (Invanz) | 1 g every 24 hours | 100% | 100% | 50% |
| Imipenem | 0.25 to 1 g every 6 hours | 100% | 50% | 25% |
| Meropenem (Meronem) |
1 to 2 g every 8 hours | 100% | 50% every 12 hours | 50% every 24 hours (GFR < 20) |
| Cephalosporins | ||||
| Cefaclor (Ceclor) | 250 to 500 mg every 8 hours | 100% | 50 to 100% | 50% |
| Cefadroxil (Duricef) | 0.5 to 1 g every 12 hours | 100% | Every 12 to 24 hours | Every 36 hours |
| Cefamandole (Mandol) | 0.5 to 1 g every 4 to 8 hours | Every 6 hours | Every 6 to 8 hours | Every 8 to 12 hours |
| Cefazolin (Ancef) | 0.25 to 2 g every 6 hours | Every 8 hours | Every 12 hours | 50% every 24 to 48 hours |
| Cefepime (Maxipime) | 0.25 to 2 g every 8 to 12 hours | 100% | 50 to 100% every 24 hours | 25 to 50% every 24 hours |
| Cefixime (Suprax) | 200 mg every 12 hours | 100% | 75% | 50% |
| Cefoperazone (Cefobid) | No adjustment needed | — | — | — |
| Cefotaxime (Claforan) | 1 to 2 g every 6 to 12 hours | Every 6 hours | Every 6 to 12 hours | Every 24 hours or 50% |
| Cefotetan (Cefotan) | 1 to 2 g every 12 hours | 100% | Every 24 hours | Every 48 hours |
| Cefoxitin (Mefoxin) | 1 to 2 g every 6 to 8 hours | Every 6 to 8 hours | Every 8 to 12 hours | Every 24 to 48 hours |
| Cefpodoxime (Vantin) | 100 to 400 mg every 12 hours | Every 12 hours | Every 24 hours | Every 24 hours |
| Cefprozil (Cefzil) | 250 to 500 mg every 12 hours | 100% | 50% every 12 hours | 50% every 12 hours |
| Ceftazidime (Fortaz) | 1 to 2 g every 8 hours | Every 8 to 12 hours | Every 12 to 24 hours | Every 24 to 48 hours |
| Ceftibuten (Cedax) | 400 mg every 24 hours | 100% | 25 to 50% | 25 to 50% |
| Ceftizoxime (Cefizox) | 1 to 2 g every 8 to 12 hours | Every 8 to 12 hours | Every 12 to 24 hours | Every 24 hours |
| Ceftriaxone (Rocephin) | No adjustment needed | — | — | — |
| Cefuroxime axetil (Ceftin) | No adjustment needed | — | — | — |
| Cefuroxime sodium (Zinacef) | 0.75 to 1.5 g every 8 hours | Every 8 hours | Every 8 to 12 hours | Every 12 hours |
| Cephalexin (Keflex) | 250 to 500 mg every 6 to 8 hours | Every 8 hours | Every 8 to 12 hours | Every 12 to 24 hours |
| Cephradine (Velosef) | 0.25 to 1 g every 6 to 12 hours | 100% | 50% | 25% |
| Macrolides | ||||
| Azithromycin (Zithromax) | No adjustment needed | — | — | — |
| Clarithromycin (Biaxin) | 250 to 500 mg every 12 hours (Biaxin); 1 g daily (Biaxin XL) | 100% | 50 to 100% | 50% |
| Dirithromycin | No adjustment needed | — | — | — |
| Erythromycin | No adjustment needed | — | — | — |
| Penicillins | ||||
| Amoxicillin | 250 to 500 mg every 8 hours | Every 8 hours | Every 8 to 12 hours | Every 24 hours |
| Ampicillin | 0.25 to 2 g every 6 hours | Every 6 hours | Every 6 to 12 hours | Every 12 to 24 hours |
| Ampicillin/sulbactam (Unasyn) | 1 to 2 g ampicillin and 0.5 to 1 g sulbactam every 6 to 8 hours | 100% (GFR ≥ 30) | Every 12 hours (GFR 15 to 29) | Every 24 hours (GFR 5 to 14) |
| Carbenicillin (Geocillin), 382-mg tablet | 1 or 2 tablets every 6 hours | Every 6 to 12 hours | Every 12 to 24 hours | Every 24 to 48 hours |
| Carbenicillin IV (not available in the United States) | 200 to 500 mg per kg per day, continuous infusion or in divided doses | Every 8 to 12 hours | Every 12 to 24 hours | Every 24 to 48 hours |
| Dicloxacillin (Dynapen) | No adjustment needed | — | — | — |
| Nafcillin | No adjustment needed | — | — | — |
| Penicillin G | 0.5 to 4 million U every 4 to 6 hours | 100% | 75% | 20 to 50% |
| Penicillin VK | No adjustment needed | — | — | — |
| Piperacillin | 3 to 4 g every 6 hours | Every 6 hours | Every 6 to 12 hours | Every 12 hours |
| Piperacillin/ tazobactam (Zosyn) |
3.375 to 4.5 g every 6 to 8 hours | 100% | 2.25 g every 6 hours; every 8 hours (GFR < 20) | 2.25 g every 8 hours |
| Ticarcillin | 3 g every 4 hours | 1 to 2 g every 4 hours | 1 to 2 g every 8 hours | 1 to 2 g every 12 hours |
| Ticarcillin/clavulanate (Timentin) | 3.1 g every 4 hours | 100% | Every 8 to 12 hours | 2 g every 12 hours |
| Quinolones | ||||
| Ciprofloxacin (Cipro) | 400 mg IV or 500 to 750 mg orally every 12 hours | 100% | 50 to 75% | 50% |
| Gatifloxacin | 400 mg every 24 hours | 100% | 400 mg initially, then 200 mg daily | 400 mg initially, then 200 mg daily |
| Gemifloxacin | 320 mg every 24 hours | 100% | 50 to 100% | 50% |
| Levofloxacin | 250 to 750 mg every 24 hours | 100% | 500 to 750 mg initial dose, then 250 to 750 mg every 24 to 48 hours | 500 mg initial dose, then 250 to 500 mg every 48 hours |
| Moxifloxacin (Avelox) | No adjustment needed | — | — | — |
| Norfloxacin | 400 mg every 12 hours | Every 12 hours | Every 12 to 24 hours | Avoid |
| Ofloxacin | 200 to 400 mg every 12 hours | 100% | 200 to 400 mg every 24 hours | 200 mg every 24 hours |
| Trovafloxacin |
No adjustment needed | — | — | — |
| Sulfas | ||||
| Sulfamethoxazole | 1 g every 8 to 12 hours | Every 12 hours | Every 18 hours | Every 24 hours |
| Sulfisoxazole | 1 to 2 g every 6 hours | Every 6 hours | Every 8 to 12 hours | Every 12 to 24 hours |
| Trimethoprim | 100 mg every 12 hours | Every 12 hours | Every 12 hours (GFR > 30); every 18 hours (GFR 10 to 30) | Every 24 hours |
| Tetracyclines | ||||
| Doxycycline (Vibramycin) | No adjustment needed | — | — | — |
| Tetracycline |
250 to 500 mg two to four times daily | Every 8 to 12 hours | Every 12 to 24 hours | Every 24 hours |
| Other | ||||
| Chloramphenicol | No adjustment needed | — | — | — |
| Clindamycin | No adjustment needed | — | — | — |
| Dalfopristin/ quinupristin |
No adjustment needed | — | — | — |
| Linezolid (Zyvox) | No adjustment needed | — | — | — |
| Nitrofurantoin | 500 to 1,000 mg every 6 hours | 100% | Avoid | Avoid |
| Telithromycin (Ketek) | No adjustment needed | — | — | — |
REFERENCES
-
Vilay, A.M. (2019). Antibiotic Dosing in Chronic Kidney Disease and End-Stage Renal Disease: A Focus on Contemporary Challenges. Advances in Chronic Kidney Disease, 26(1), pp.61–71. Available at: https://pubmed.ncbi.nlm.nih.gov/30876619
Smyth, B., Jones, C. and Saunders, J. (2016). Prescribing for patients on dialysis. Australian Prescriber, 39(1), pp.21–24. Available at: https://pubmed.ncbi.nlm.nih.gov/27041803
Matzke, G.R., Aronoff, and others (2011). Drug dosing consideration in patients with acute and chronic kidney disease—a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney International, 80(11), pp.1122–1137. Available at: https://pubmed.ncbi.nlm.nih.gov/21918498
Munar, M.Y., Munar, M.Y. and Harleen Signh (2013). Drug Dosing Adjustments in Patients with Chronic Kidney Disease. American Family Physician, [online] 75(10), pp.1487–1496. Available at: https://www.aafp.org/afp/2007/0515/p1487.html