Medication Dosing in Renal Impairment
For patients with impaired renal function, medication doses must be adjusted based on the degree of renal dysfunction, with frequency reduction rather than dose reduction being preferred for concentration-dependent antibiotics to maintain efficacy while preventing toxicity.
General Principles of Renal Dosing
Renal impairment affects drug pharmacokinetics in several ways:
- Decreased elimination of drugs excreted by the kidneys
- Accumulation of active metabolites
- Altered protein binding
- Changes in drug metabolism
- Potential for increased toxicity
Assessment of Renal Function
- Calculate creatinine clearance (CrCl) using the Cockroft-Gault formula
- Categorize renal function:
- Normal: CrCl >80 mL/min
- Moderate impairment: CrCl 30-80 mL/min
- Severe impairment: CrCl <30 mL/min
- End-stage renal disease (ESRD): Dialysis-dependent
Medication-Specific Dosing Adjustments
Antibiotics
Aminoglycosides (e.g., Streptomycin, Amikacin, Kanamycin)
- Normal dose: 15 mg/kg/day
- Adjustment for renal impairment: Maintain dose at 12-15 mg/kg but reduce frequency to 2-3 times weekly when CrCl <30 mL/min 1
- Rationale: Preserves concentration-dependent bactericidal effect while preventing toxicity
- Monitoring: Serum drug levels, audiometry, vestibular function, renal function
- Administration in dialysis: Give after dialysis to avoid premature removal 1
Capreomycin
- Normal dose: 15 mg/kg/day
- Adjustment: Reduce frequency to 12-15 mg/kg 2-3 times weekly when CrCl <30 mL/min 1
- Monitoring: Serum potassium, magnesium, renal function
First-line TB Drugs
- Isoniazid: No adjustment needed (300 mg daily or 900 mg 3 times/week) 1
- Rifampin: No adjustment needed (600 mg daily or 600 mg 3 times/week) 1
- Pyrazinamide: Change to 25-35 mg/kg 3 times/week (not daily) when CrCl <30 mL/min 1
- Ethambutol: Change to 20-25 mg/kg 3 times/week (not daily) when CrCl <30 mL/min 1
Fluoroquinolones
- Levofloxacin: 750-1000 mg 3 times/week (not daily) when CrCl <30 mL/min 1
- Moxifloxacin: No adjustment needed (400 mg once daily) 1
Anticoagulants
Low Molecular Weight Heparins
- Enoxaparin: Either contraindicated or dose adjustment required when CrCl <30 mL/min 1
- Fondaparinux: Contraindicated when CrCl <30 mL/min 1
Cardiovascular Medications
ACE Inhibitors
- Ramipril: Initial dose 1.25 mg daily when CrCl <30 mL/min; maximum 5 mg/day 1
- Monitor: Serum creatinine and potassium
Beta-Blockers
- Atenolol:
- CrCl 15-35 mL/min: Reduce to 50 mg/day (half dose)
- CrCl <15 mL/min: Reduce to 25 mg/day (quarter dose) 1
Antiplatelet Agents
Glycoprotein IIb/IIIa Inhibitors
- Tirofiban: Reduce to 50% of dose when CrCl <30 mL/min 1
- Eptifibatide:
- CrCl 30-50 mL/min: Reduce infusion to 1 mg/kg/min
- CrCl <30 mL/min: Contraindicated 1
- Abciximab: No specific dose adjustment, but careful evaluation of bleeding risk 1
Special Considerations
Dialysis Patients
- Administer medications after dialysis sessions to:
- Facilitate directly observed therapy
- Prevent premature drug removal 1
- Maintain full dose but adjust frequency for concentration-dependent antibiotics 1
Loading Doses
- Loading doses generally do not require adjustment based on renal function 1
- Important for antibiotics with low volume of distribution (e.g., vancomycin) to rapidly achieve therapeutic levels 1
Therapeutic Drug Monitoring
- Essential for drugs with narrow therapeutic indices
- Monitor serum concentrations for aminoglycosides, vancomycin, and other nephrotoxic drugs 1
Common Pitfalls to Avoid
Reducing dose instead of frequency for concentration-dependent antibiotics, which can lead to treatment failure 1
Failing to monitor for toxicity - nephrotoxic drugs require regular monitoring of renal function and drug levels 1
Ignoring drug interactions - some medications may have increased toxicity when combined in renally impaired patients
Not reassessing renal function - kidney function may fluctuate, requiring ongoing dose adjustments
Overlooking accumulation of metabolites - even if the parent drug doesn't require dose adjustment, metabolites may accumulate and cause toxicity 2
By following these principles and specific medication adjustments, clinicians can optimize drug therapy in patients with renal impairment, minimizing toxicity while maintaining efficacy.