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)
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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)
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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 |
Mpm | 750 mg every 12 hours for CrCl 20-40 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.
| 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 |