Appendix 12. Dose adjustments in renal insufficiency

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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)aCitation a.If possible use a calculator to avoid errors, e.g.:
https://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation
:
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 heightbCitation b.If possible use a calculator to avoid errors, e.g.:
https://www.mdcalc.com/ideal-body-weight-adjusted-body-weight
:
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 CrCl < 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)Citation a.Use with caution in case of severe renal insufficiency or dialysis (limited data).

No change

Lzd

No change

Cfz

No change

Cs(b)Citation b.Monitor carefully for signs of neurotoxicity.

250 mg once daily or 500 mg 3 times a  week

Dlm(c)Citation c.Use with caution in case of severe renal insufficiency or dialysis (limited data).

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(d)Citation d.Use with caution in case of severe renal insufficiency or dialysis (increased risk of nephrotoxicity and ototoxicity).

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

S(e)Citation e.Use with caution in case of severe renal insufficiency or dialysis (increased risk of nephrotoxicity and ototoxicity).

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

Eto/Pto

No change

PAS(f)Citation f.Avoid sodium salt formulations of PAS in patients with severe renal disease (risk of excessive sodium load).

4 g 2 times daily

Hh 

No information

Amx/Clv(g)Citation g.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.

No change

P

No change

Pa

No information

  • aUse with caution in case of severe renal insufficiency or dialysis (limited data).
  • bMonitor carefully for signs of neurotoxicity.
  • cUse with caution in case of severe renal insufficiency or dialysis (limited data).
  • dUse with caution in case of severe renal insufficiency or dialysis (increased risk of nephrotoxicity and ototoxicity).
  • eUse with caution in case of severe renal insufficiency or dialysis (increased risk of nephrotoxicity and ototoxicity).
  • fAvoid sodium salt formulations of PAS in patients with severe renal disease (risk of excessive sodium load).
  • gOn 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