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Tuesday, April 28, 2020

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

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.

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
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 17th 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

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