Tranexamic Acid & Renal Dose Adjustment

l   Tranexamic acid is excreted mainly in the urine as unchanged drug.

l   Urinary excretion via glomerular filtration is the main route of elimination.

l   Plasma concentrations increase in patients with renal failure.

l   Dose of tranexamic acid should be reduced in renal impairment because of the risk of accumulation.

l   Following administration of a single IV injection, urinary excretion declines as renal function decreases.

A) Adult (Injection) 

Indication	Dose Adjustment	Reference
Tooth extraction in patients with hemophilia	Serum creatinine (mcmol/L) Dose 120.2-250.2 Maintenance dose of 10 mg/kg/dose twice daily 250.2-500.4 Maintenance dose of 10 mg/kg/dose once daily >500.4 Maintenance dose of 10 mg/kg/dose every 48 hours or 5 mg/kg/dose once daily	Lexicomp & Medscape [1&2]
Cardiac Surgery	Serum creatinine (mcmol/L) Dose 141.5-291.2 Reduce maintenance infusion to 1.5 mg/kg/hour (25% reduction from 2 mg/kg/hour) 291.2-583.4 Reduce maintenance infusion to 1 mg/kg/hour (50% reduction from 2 mg/kg/hour) >583.4 Reduce maintenance infusion to 0.5 mg/kg/hour (75% reduction from 2 mg/kg/hour)	Lexicomp [1]
	eGFR (mL/min/1.73m2) Loading Prime Infusion 60-89 15 mg/kg 0.6 mg/kg 3.75 mg/kg/h 30- 59 15 mg/kg 0.6 mg/kg 2.5 mg/kg/h < 29 15 mg/kg 0.6 mg/kg 1.25 mg/kg/h	https://globalrph.com/dilution/tranexamic-acid/  [4]
Total Knee/ Hip  Arthoplasty	eGFR (mL/min/1.73m2) Dosage adjustment 60-89 Administration of 15 mg/kg tranexamic acid immediately prior to tourniquet release followed by a repeat bolus of 11.25 mg/kg at 8 hourly intervals after the initial dose. The last bolus dose is to be administered 16 hours after the initial dose. 30-59 Administration of 15 mg/kg tranexamic acid immediately prior to tourniquet release followed by a repeat bolus of 8.4 mg/kg at 8 hourly intervals after the initial dose. The last bolus dose is to be administered 16 hours after the initial dose. <29 Administration of 15 mg/kg tranexamic acid immediately prior to tourniquet release followed by a repeat bolus of 6.3 mg/kg at 8 hourly intervals after the initial dose. The last bolus dose is to be administered 16 hours after the initial dose.	https://globalrph.com/dilution/tranexamic-acid/  [4]
Other indication	Serum Creatinine (mcmol/L) Dose 120 to 249 10mg/kg BD 250 to 500 10mg/kg OD  > 500 5mg/kg OD	EMC, MIMS Malaysia & Drugs.com [ 3, 7, 9 ]
	Creatinine Clearance (GFR) mL/min Dose 50 to 80 Administer 50% of normal dose or 10 mg/kg twice daily 10 to 50 Administer 25% of normal dose or 10 mg/kg/day Less than 10 Administer 10% of normal dose or 10 mg/kg/dose every 48 hours	RQH Health [6]
	Creatinine Clearance (GFR) mL/min Dose 20–50 10mg/kg BD 10–20 10mg/kg OD-BD Less than 10 5mg/kg OD-BD CAPD /HD / HD F/High flux Unknown dialysability. Dose as in GFR <10 mL/min CAV/VVHD Unknown dialysability. Dose as in GFR = 10–20 mL/min Note: Most other more updated references use q24-48 h when serum creatinine is > 250 mcmol/L, in general.	The Renal Drug Handbook Third Edition 2007 [8]

B) Adult (Oral)

Indication	Dose Adjustment	Reference
Other Indication	Lysteda: Serum creatinine level (mcmol/L) Dose 120 to 250 1,300 mg twice daily (2,600 mg/day) for up to 5 days 250 to 500 1,300 mg once daily for up to 5 days ≥500 650 mg once daily for up to 5 days	Lexicomp [1]
	Cyklokapron [Canadian product]: Serum creatinine level (mcmol/L) Dose 120 to 250 15 mg/kg twice daily 250 to 500 15 mg/kg every 24 hours ≥500 15 mg/kg every 48 hours	Lexicomp [1]
	GFR (mL/min) Dose 30–60 Begin with 1-1.5 g BD-TDS (SCr = 120-249 mcmol/L : 15 mg/kg BD) 10–30 Begin with 1-1.5 g OD (SCr = 250-500 mcmol/L : 15 mg/kg OD) < 10 or Dialysis Begin with 500-1000 mg OD (SCr = >500 mcmol/L : 7.5 mg/kg OD ; post-dialysis if dialysis patient)	The Renal Drug Reference Guide 2007 [5]
	Creatinine Clearance (GFR) mL/min Dose 20–50 25 mg/kg 12 hourly 10–20 25 mg/kg 12–24 hourly Less than 10 12.5 mg/kg 12–24 hourly CAPD /HD / HD F/High flux Unknown dialysability. Dose as in GFR <10 mL/min CAV/VVHD Unknown dialysability.  Dose as in GFR = 10–20 mL/min Note: Most other more updated references use q24-48 h when serum creatinine is > 250 mcmol/L, in general.	The Renal Drug Handbook Third Edition 2007 [8]
	Serum creatinine level (mcmol/L) Dose 120-249 15 mg/kg bid 250-500 15 mg/kg daily Severe Contraindicated	MIMS Malaysia [7]
Treatment of cyclic heavy menstrual bleeding	Serum creatinine level (mcmol/L) Dose 123.8 – 247.5 1300 mg orally two times a day for a maximum of 5 days during menstruation 247.5 –503.9 1300 mg orally once a day for a maximum of 5 days during menstruation. >503.9 650 mg orally once a day for a maximum of 5 days during menstruation.	Drugs.com [9]

C) Peadiatric  (Injection)

Indication	Dose Adjustment	Reference
Tooth extraction in patients with hemophilia	Serum creatinine (mcmol/L) Dose 120.2 – 250.2 Maintenance dose of 10 mg/kg/dose twice daily 250.2 – 500.3   Maintenance dose of 10 mg/kg/dose once daily >500.3 Maintenance dose of 10 mg/kg/dose every 48 hours or 5 mg/kg/dose once daily	Lexicomp [1]
Other Indication	Avoid in severe impairment. Dose adjustments Reduce dose in mild to moderate impairment.	BNF for Children 2019-2020 [10]
	10-15 mg/kg (adult 0.5-1 g) TDS	Frank Shann (2017-2020)

D) Peadiatric  (Oral )

Indication	Dose Adjustment	Reference
Menorrhagia (Female Children ≥12 years )	Serum creatinine (mcmol/L) Dose 123.8 – 247.5 1,300 mg twice daily (2,600 mg/day) for up to 5 days 247.5 – 503.9 1,300 mg once daily for up to 5 days >503.9 650 mg once daily for up to 5 days	Lexicomp [1]
Other Indication	Avoid in severe impairment. Dose adjustments Reduce dose in mild to moderate impairment.	BNF for Children 2019-2020 [10]
	15-25 mg/kg (adult 1-1.5 g) TDS  for ≤ 5 days	Frank Shann (2017-2020)

Remarks

* To convert mmol/l to mg/dl, multiply by 0.0113.

* To convert mg/dl to mmol/l, multiply by 88.4.

Reference :

1.       Tranexamic Acid , Lexicomp

2.       Tranexamic Acid , Medscape

3.       Tranexamic Acid , EMC Retrieved from https://www.medicines.org.uk/emc/product/1220/smpc

4.       Tranexamic Acid , Globalrph Retrieved from https://globalrph.com/dilution/tranexamic-acid/

5.       The Renal Drug Reference Guide, First Edition 2007

6.       Tranexamic Acid, RQH Health Retrieved from http://www.rqhealth.ca/service-lines/master/files/8991002_8_Tranexamic-acid-IV-Monograph.pdf

7.       Tranexamic Acid , MIMS Retrieved from https://www.mims.com/malaysia/drug/info/tranexamic%20acid/?type=brief&mtype=generic#RenalImpairment

8.       The Renal Drug Handbook Third Edition 2007

9.       Tranexamic Acid , Drugs.com https://www.drugs.com/dosage/tranexamic-acid.html

10.     BNF for Children 2019-2020

11.     Frank Shann 17^th Edition (2017-2020)

12.     Appendix C: Tables, conversions and abbreviations Nephrology Dialysis Transplantation Retrieved from Nephrol Dial Transplant (2004) 19 [Suppl 2]: ii42–ii43 DOI: 10.1093/ndt/gfh1030

[All references are accessed on 7 Apr 2020]

Prepared by N. Nabiha
Edited by J. Ho