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Shane Donnelly, PharmD

Renal Dosing for Commonly Used Oral Antibiotics

The kidneys are one of the most important organs responsible for eliminating substances from the body. Structural damage to the excretion mechanisms of the kidneys slows the filtration and elimination process down, allowing drug metabolites to stay in the body for longer periods of time. For some medications with inactive and harmless metabolites, this is not a relevant issue. However, for medications with active metabolites or medications that are not completely metabolized by the liver, this poses a potentially significant problem. The inability to efficiently eliminate active drug molecules puts patients at risk for harmful adverse effects. Antibiotics are particularly interesting in this regard. When dosed appropriately and efficiently eliminated by the body, side effect profiles are often mild and harmless. However, when dosed inappropriately in a patient with renal impairment, active drug molecules or metabolites can build up and may induce or exacerbate neurological, cardiac, or pulmonary comorbid conditions.

The table below provides a foundation for dosing common antibiotics in patients with renal impairment. It is important to utilize this table in the manner in which it was intended; purely as a reference point. Individualize treatment based on the patient and the indication that is being treated.

Renal Dosing Guide for Commonly Used Oral Antibiotics  
 
Antibiotic Renal-Dosing Special Considerations  
Amoxicillin (Amoxil) Amoxicillin + Clavulanate Potassium (Augmentin)

Severe Impairment (CKD Stage 4) give 250-500 mg amoxicillin q12h

End-Stage Disease (CKD Stage 5) give  250-500 mg amoxicillin q24h

All products containing

875 mg of Amoxicillin or extended-release formulations should be avoided in patients with severe impairment.

 
Azithromycin (Z-Pack, Zithromax) None. Use with caution. No specific renal dosing required in manufacturer's labeling.  
Cefaclor (Ceclor) None. Use with caution. No specific renal dosing required in manufacturer’s labeling.  
Cefuroxime (Ceftin)

Severe Impairment (CKD Stage 4) give the indicated dose q24h

End-Stage Disease (CKD Stage 5) give the indicated dose q48h

Alternatively, may dose at 15 mg/kg/dose q24h in patients with End-Stage Disease.  
Cephalexin (Keflex)

Moderate-Severe Impairment (CKD Stage 3-4) give 500 mg q8-12h

End-Stage Disease (CKD Stage 5) give 500 mg q12-24h

Cost-effective option for treating skin and soft tissue infections and may be used as an alternative agent for uncomplicated UTIs.  
Ciprofloxacin (Cipro)

Moderate Impairment (CKD Stage 3) give 250-500 mg q12h

Severe Impairment (CKD Stage 4) give 250-500 mg q18h

End-Stage Disease (CKD Stage 5) give 250-500 mg q24h

If using extended-release formulation, dose at 500 mg q24h with Severe Impairment.  
Clarithromycin (Biaxin) Severe Impairment (CKD Stage 4) decrease the dose by 50% Many drug interactions. May need to decrease dose with certain HIV medication.  
Clindamycin (Cleocin) None Potential alternative to penicillin due to allergy.  
Doxycycline Monohydrate (Vibramycin) None Potential safe alternative for community-acquired pneumonia or MRSA in patients with renal dysfunction.  
Erythromycin (Ery-Tab) None Medication can be used to induce gastric motility.  
Levofloxacin (Levaquin)

Moderate Impairment (CKD Stage 3) give 250 mg q24h +/- 500 mg loading dose (or) 750 mg q48h

Severe Impairment (CKD Stage 4) give 250-500 mg q48h +/- 500-750 mg loading dose

Dosing largely depends on indication. Utilize dose of that fits the suspected organism/infection.  
Metronidazole (Flagyl) None. Use with caution. Metabolites may accumulate in patients with End-Stage Renal Disease.  
Nitrofurantoin (Macrobid, Macrodantin) Moderate Impairment (CKD Stage 3) note that use is contraindicated Some literature1 suggests nitrofurantoin can be used safely in patients with a CrCl >40 mL/min for short-term treatment of uncomplicated UTI's (<1 week).  
Penicillin V Potassium (Pen VK) Use with caution. Excretion of penicillin is prolonged in patients with renal impairment.  
Sulfamethoxazole/ Trimethoprim (Bactrim, Septra)

Severe Impairment (CKD Stage 4) decrease the dose by 50%

End-Stage Disease (CKD Stage 5) note that use is not recommended

Dosing is highly dependent on indication.

*Per LexiComp, Wolters Kluwer Health 2
**Degree of Impairment and estimated Glomerular Filtration Rate: Moderate Impairment (CKD Stage 3): CrCl < 60 mL/min; Severe Impairment (CKD Stage 4): CrCl < 30 mL/min; End-Stage Disease (CKD Stage 5): CrCl < 15 mL/min

Age over 65 years old, hypertension, cardiovascular disease, diabetes, tobacco use, and obesity are all risk factors for developing chronic kidney disease 4. Many patients admitted to hospice have at least one of these risk factors. Awareness of the common signs of chronic kidney disease (known risk factors, consistent itching, changes in urine output, etc.4 can help the team to safely utilize medication.

Ultimately, the decision to treat and effectively dose antibiotics relies on the constant vigilance of the palliative care/hospice team. Awareness of the common dosing of antibiotics, the indications, and dosing for renal impairment can lead to better outcomes for patients who experience the uncomfortable reality of their diseases.


References:
1. Oplinger M and Andrews CO. “Drug Information Rounds: Nitrofurantoin Contraindication in Patients With a Creatinine Clearance Below 60 mL/min: Looking for the Evidence,” Ann Pharmacother, 2013, 47(1):106-11. 
2. LexiComp. Hudson, Ohio: Wolters Kluwer Health; c1978-2015. https://online.lexi.com/lco/action/home. 
3. The National Kidney Foundation. GFR. 2014. Available at: https://www.kidney.org/kidneydisease/siemens_hcp_gfr. 
4. Mayoclinic.org. Chronic kidney disease Risk factors - Mayo Clinic. 2015. Available at: http://www.mayoclinic.org/diseases-conditions/kidney-disease/basics/risk-factors/con-20026778.

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