Medications Requiring Renal Dosage Adjustments

Chronic kidney disease (CKD) and renal dysfunction can alter medications’ renal elimination and lead to subtherapeutic or supratherapeutic drug concentrations, which may decrease efficacy or increase toxicity.

Using the Cockroft-Gault equation or the Modification of Diet in Renal Disease (MDRD) to estimate creatinine clearance (CrCl) helps provide the appropriate dosage of renally-excreted medications.¹ Because elderly patients tend to have poor renal function, it’s important to take CrCl into consideration when dosing medications that follow renal elimination.

Renal damage can alter clearance of active drug metabolites, potentially causing accumulation.² Altered renal function can also affect dosing intervals of renally-eliminated medications.

The following medications require renal dosage adjustments^3,4:

• Allopurinol (Zyloprim)
• Lithium (Lithobid)
• Acyclovir (Valtrex)
• Amantadine (Symmetrel)
• Fexofenadine (Allegra)
• Gabapentin (Neurontin)
• Metoclopramide (Reglan)
• Ranitidine (Zantac)
• Rivaroxaban (Xarelto)
• Fesoterodine (Toviaz)

*List isn’t conclusive of all renally-dosed medications

Some common antimicrobials requiring renal dosing include³:

• Cephalexin (Keflex)
• Amoxicillin (Amoxil)
• Cefuroxime (Ceftin)
• Ciprofloxacin (Cipro)
• Clarithromycin (Biaxin)
• Levofloxacin (Levaquin)
• Nitrofurantoin (Macrobid)
• Piperacillin/Tazobactam (Zosyn)
• Tetracycline (Sumycin)
• Trimethoprim/Sulfamethoxazole (Bactrim)

*List isn’t conclusive of all renally-dosed medications

Roughly half of adults 30 to 64 years old are expected to develop CKD in their lifetime.⁵ In patients with a glomerular filtration rate (GFR) <60 mL/min/1.73m², MDRD is considered superior to the Cockroft-Gault equation in estimating GFR to help determine dosing adjustments.¹

CKD patients will require dosage adjustments for certain medications, including antihypertensives, hypoglycemic agents, analgesics, statins. Staging of CKD is dependent on the patient’s GFR results.

Diuretics

Thiazide diuretics are considered first-line treatment for patients with uncomplicated hypertension and CKD (only if S_cr <2.5 mg/dL or CrCl >30 mL/min). Loop diuretics are also commonly used to treat uncomplicated hypertension in CKD patients, but potassium-sparing diuretics should be avoided because the mechanism through which they work (excreting extra fluids and retaining potassium) is detrimental to the health of these patients.¹

Antihypertensives

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are first-line antihypertensives used in patients with type 1 or 2 diabetes and early CKD.¹ Beta-blockers that are hydrophilic (including atenolol, bisoprolol, and nadolol) require dosing adjustments in CKD patients.

Hypoglycemic Agents

A renally-excreted hypoglycemic agent like metformin isn’t recommended if S_cr is >1.5 mg/dL in men or >1.4 mg/dL in women. It’s important to monitor CKD patients on metformin closely for lactic acidosis development. Sulfonylureas like chlorpropamide and glyburide should be avoided in patients with stage 3 to 5 CKD,¹ as their use increases hypoglycemia risk.

Analgesics

Metabolites of morphine, tramadol, and codeine can accumulate in CKD patients, leading to respiratory adverse effects. Dosage reduction is recommended for morphine and codeine in patients with CrCl <50 mL/min. Metabolite accumulation can lead to supratherapeutic concentrations and cause severe harm. Dosing intervals for opioids may need to be modified in CKD patients.

Statins

Statin therapy for dyslipidemia is commonly used in CKD patients. Atorvastatin and pravastatin have no dose adjustment recommendation in these patients,⁶ but rosuvastatin, simvastatin, and lovastatin do have dose adjustment recommendations dependent on CKD severity. Fluvastatin should be used with caution in CKD patients.

Taking renal function into consideration when necessary can help ensure optimal therapy. Considering CrCl and GFR may prevent unnecessary adverse effects from medications that require renal dosage adjustments.

References

1. Munar MY, et al. Drug dosing adjustments in patients with chronic kidney disease. American Academy of Fam Physicians. aafp.org/afp/2007/0515/p1487.pdf. Accessed August 10, 2016.

2. Doogue MP, et al. Drug dosing in renal disease. Clin Biochem. 2011;32:69-73.

3. Renal dosing - database. GlobalRPh. globalrph.com/index_renal.htm. Accessed August 13, 2016.

4. Renal dosage adjustment guidelines for antimicrobials. Nebraska Medicine. nebraskamed.com/app_files/pdf/careers/education-programs/asp/antimicrobial-renal-dosing-guidelines.pdf. Updated March 2013. Accessed August 10, 2016.

5. CDC. Chronic kidney disease (CKD) surveillance system. nccd.cdc.gov/ckd/. Updated June 23, 2016. Accessed August 13, 2016.

6. Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. National Kidney Foundation. kidney.org/professionals/KDOQI/guideline_diabetes. Accessed August 13, 2016.