Appendix 12. Dose adjustments in renal insufficiency

Update: January 2022

12.1 Normal values for creatinine clearance (CrCl)

Women: 88 to 128 ml/minute
Men: 97 to 137 ml/minute

12.2 Estimation of CrCl (Cockcroft-Gault method)

12.2.1 If serum creatinine is in µmol/litre

    Weight (kg) x (140 – age) x (constant)
––––––––––––––––––––––––––––––––––
          Serum creatinine (µmol/litre)

The constant = 1.04 for women and 1.23 for men

12.2.2 If serum creatinine is in mg/dl

       Weight (kg) x (140 – age)
––––––––––––––––––––––––––
   72 x serum creatinine (mg/dl)

For women, the result must be multiplied by 0.85.

Example (calculation with serum creatinine in µmol/litre)1 :
A woman on cycloserine (Cs), 50 kg, 46 years, serum creatinine = 212 µmol/litre
Step 1 - Calculate the CrCl:
50 x (140 – 46) x 1.04 = 4,888
4,888 ÷ 212 = 23.1
For this patient, the CrCl is 23.1 ml/minute
Step 2 - CrCl is < 30 ml/minute, administer 250 mg of Cs once daily or 500 mg 3 times a week.
Step 3 - Adjust each drug as required according to the table below.

12.2.3 Overweight and obese patients

For overweight (BMI > 25) or obese (BMI > 30) patients, use the ideal body weight (IBW) rather than the actual body weight to avoid overestimation of the CrCl. 

The IBW is calculated using the patient’s height2 :
IBW women (kg) = 45.4 + 0.89 (height in cm – 152.4)
IBW men (kg) = 49.9 + 0.89 (height in cm – 152.4)

Example:
A woman, weight 70 kg, height 160 cm (BMI = 27.3, i.e. overweight)
45.4 + 0.89 (160 – 152.4) = 45.4 + 0.89 (7.6) = 45.4 + 6.76 = 52.2
For this patient, the IBW is 52 kg.

12.3 Dosing of TB drugs in renal insufficiency

Drugs

Dose and frequency if Clcr < 30 ml/min

H

No change

R

No change

Z

25 mg/kg 3 times a week (not daily)

E

15-25 mg/kg 3 times a week (not daily)

Rfb

No change

Mfx

No change

Lfx

750-1000 mg 3 times a week (not daily)

Bdq(a)

No change

Lzd

No change

Cfz

No change

Cs(b)

250 mg once daily or 500 mg 3 times a  week

Dlm(a)

No change

Ipm/Cln

750 mg every 12 hours for CrCl 20-40 ml/min
500 mg every 12 hours for CrCl < 20 ml/min

Mpm

750 mg every 12 hours for CrCl 20-40 ml/min
500 mg every 12 hours for CrCl < 20 ml/min

Am(c)

12-15 mg/kg 2 or 3 times a week (not daily)

S(c)

12-15 mg/kg 2 or 3 times a week (not daily)

Eto/Pto

No change

PAS(d)

4 g 2 times daily

Hh 

No information

Amx/Clv(e)

No change

P

No change

Pa

No information

(a) Use with caution in case of severe renal insufficiency or dialysis (limited data).
(b) Monitor carefully for signs of neurotoxicity.
(c) Use with caution in case of severe renal insufficiency or dialysis (increased risk of nephrotoxicity and ototoxicity).
(d) Avoid sodium salt formulations of PAS in patients with renal disease (risk of excessive sodium load).
(e) On a case-by-case basis, consider once daily dosing (e.g. 500/125 mg every 24 hours) for patients with CrCl < 10 ml/minute.



Footnotes
Ref Notes
1 If possible use a calculator to avoid errors, e.g.: https://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation
2 If possible use a calculator to avoid errors, e.g.: https://www.mdcalc.com/ideal-body-weight-adjusted-body-weight