Tranexamic Acid Dosing in Chronic Kidney Disease
Tranexamic acid requires mandatory dose reduction in CKD patients based on serum creatinine levels, as the drug is 90% renally excreted and accumulation leads to serious neurotoxicity. 1
FDA-Approved Dose Adjustments by Renal Function
The FDA label provides explicit dosing reductions for patients with renal impairment 1:
- Serum creatinine 1.36-2.83 mg/dL (120-250 micromol/L): 10 mg/kg IV twice daily 1
- Serum creatinine 2.83-5.66 mg/dL (250-500 micromol/L): 10 mg/kg IV once daily 1
- Serum creatinine >5.66 mg/dL (>500 micromol/L): 10 mg/kg IV every 48 hours OR 5 mg/kg every 24 hours 1
These reductions apply to all indications, both perioperative and post-extraction maintenance dosing 1.
Clinical Rationale for Dose Reduction
Renal clearance is the primary elimination pathway for tranexamic acid, with approximately 90% excreted unchanged in urine within 24 hours. 2 Failure to adjust dosing in CKD leads to drug accumulation and severe complications 2, 3.
Toxicity Profile in CKD Patients
The most common and serious complication is neurotoxicity, manifesting as seizures 3, 4:
- Multiple case reports document seizures in CKD patients receiving standard doses without adjustment 3
- Risk factors include advanced age, underlying neurologic disease, chronic kidney disease, and high tranexamic acid doses 4
- All reported cases of neurotoxicity occurred when dosage was not adjusted for renal function 3
Other documented toxicities in CKD patients include 3:
- Retinal toxicity in hemodialysis patients 3
- Acute obstructive uropathy from blood clot retention (particularly in kidney transplant recipients) 3
- Ligneous conjunctivitis 3
Route-Specific Considerations
Intravenous Administration
- Standard infusion rate should not exceed 1 mL/minute to avoid hypotension 1
- For surgical procedures in CKD patients with good renal function (eGFR ≥60): 15 mg/kg bolus over 15 minutes followed by 7.5 mg/kg/hour maintenance infusion 5
- For CKD patients with poor renal function (eGFR <60): 15 mg/kg bolus over 15 minutes followed by 5 mg/kg/hour maintenance infusion 5
Oral Administration
- Oral tranexamic acid also requires dose adjustment in CKD 3, 6
- One peritoneal dialysis patient developed neurotoxicity after oral tranexamic acid without dose adjustment 3
- For severe hematuria in ADPKD with CKD stage IV: 1000 mg orally three times daily for one day, then once daily has been used successfully 7, though this exceeds FDA recommendations and should be adjusted per the FDA dosing table 1
Special Clinical Scenarios in CKD
Polycystic Kidney Disease with Hematuria
Tranexamic acid is particularly effective for intracystic bleeding in ADPKD, as local urokinase activation causes prolonged fibrinolysis 6, 7:
- Hematuria typically resolves within 2-5 days of treatment 6
- Can be used safely in ADPKD patients with preserved or impaired renal function when properly dose-adjusted 6, 7
- May prevent need for embolization or nephrectomy, thereby preserving renal function 6
Peritoneal Dialysis and Hemodialysis Patients
- Multiple cases of neurotoxicity reported in dialysis patients receiving unadjusted doses 3
- Use the most conservative dosing (10 mg/kg every 48 hours or 5 mg/kg every 24 hours) for patients with serum creatinine >5.66 mg/dL 1
Critical Safety Warnings
Absolute Contraindications
Tranexamic acid is contraindicated in 1:
Thromboembolic Risk
While thrombotic complications are rare in CKD patients 3, avoid concomitant use with pro-thrombotic agents including 1:
Route Administration Error
Tranexamic acid is for intravenous use only; intrathecal administration causes seizures and cardiac arrhythmias. 1
Monitoring Requirements
- Serial hemoglobin levels to assess bleeding control 6, 7
- Renal function monitoring (serum creatinine) to guide ongoing dose adjustments 1
- Neurologic assessment for early signs of neurotoxicity 3, 4
- All patients recovered without permanent disability when tranexamic acid was stopped promptly after toxicity recognition 3