Appendix 7d: Renal Impairment

Dosing considerations in renal impairment

The number of patients with chronic kidney disease (CKD) and reduced renal function have been inexorably increasing. Reduced renal function may need adjustment in drug therapy as kidney plays a major role in the pharmacokinetics of a large number of drugs.

• Renal insufficiency frequently alters drug distribution volume. Edema and ascites increase the apparent volume of distribution of highly water-soluble or protein-bound drugs. Usual doses of such drugs given to edematous patients result in inadequate, low plasma levels.

• The alteration of plasma protein binding in patients with renal insufficiency is an important factor affecting both efficacy and toxicity. In patients with uremia the unbound fraction of several acidic drugs is substantially increased which may lead to serious toxicity.

• Although renal insufficiency is thought to affect primarily the renal elimination of drugs or metabolites, renal failure substantially affects drug biotransformation. Uremia slows the rate of reduction and hydrolysis reactions.

• Many active or toxic metabolites are produced during drug metabolism. Many of these metabolites depend on the kidneys for their removal from the body. The accumulation of active metabolites can explain in part the high incidence of ADRs seen in renal failure.

A few points should be kept in mind while prescribing;

• Renal function declines with age so that by the age of 80 it is half that in healthy young subjects.

• It is advisable to determine renal function not only before but also during the period of treatment and adjust the maintenance dose as necessary.

• One should try to keep drug prescription to minimum.

• Nephrotoxic drugs should, if possible, be avoided in all patients with renal disease because the nephrotoxicity is more likely to be serious.

• One should stay alert for unexpected ADRs.

The recommendations in the table below are meant only as a guide and do not imply efficacy or safety of a recommended dose in an individual patient.

A loading dose equivalent to the usual dose in patients with normal renal function should be considered for drugs with a particularly long half-life.

The table below gives the common drugs where in renal impairment dose adjustment is required.

When the dose method (D) is suggested, the percentage of the dose for normal renal function is given and when the interval method (I) is suggested, the actual dose interval is provided.

Drug

Dose Method

GFR >50 (ml/ min)

GFR 10-50 ml/min)

GFR <10(ml/min)

CAPD

HD

Acetaminophen

I

q4h

q6h

q8h

Dose as GFR < 10

Dose as GFR < 10

Acetazolamide

I

q6h

q12h

Avoid

No data

No data

Acetylsalicyclic Acid

I

Q4h

Q4-6h

Avoid

As normal GFR

As normal GFR dose post HD

Acyclovir

D, I

5 mg/kg q8h

5 mg/kg q12-24h

2.5 mg/kg q24h

Dose as GFR < 10

Dose as GFR < 10 dose post HD

Allopurinol

D

75%

50%

33%

Dose as GFR < 10

Dose as GFR < 10

Amikacin

D, I

60–90% q12h

30–70% q12–18h

20–30% q24–48h

15–20 mg /L/day

5 mg/kg post HD

Amiloride

D

100%

50%

Avoid

NA

NA

Aminophylline

D

100%

200–400 mg q12h

200–300 mg q12h

Dose as GFR < 10

Dose as GFR < 10

Amphotericin B

I

q24h

q24h

q24-36h

Dose as GFR < 10

Dose as GFR < 10

Ampicillin

I

q6h

q6–12h

q12-24h

Dose as GFR < 10

Dose as GFR < 10

Cefazolin

I

q8h

q12h

q24–48h

0.5 g q12h

0.5–1.0 g post HD

Cefixime

D

100%

75%

50%

200 mg q24h

200 mg q24h dose post HD

Cefotaxime

I

100% q8h

100% q8h

50% q8–12h

1 g q24h

Dose as GFR < 10 dose post HD

Chloroquine

D

100%

100%

50%

Dose as GFR < 10

Dose as GFR < 10

Ciprofloxacin

D

100%

50-75%

50%

250 mg q8h

250 mg q12h

Cisplatin

D

100%

75%

50%

Dose as GFR < 10

Dose as GFR < 10

Cyclophosphamide

D

100%

75-100%

50-75%

Dose as GFR < 10

Dose as GFR < 10

Dapsone

 

100%

100%

50%

Dose as GFR < 10

Dose as GFR < 10

Didanosine

I

100%

50%

25%

Dose as GFR < 10

Dose as GFR < 10

Digoxin

D, I

100% q24h

25–75% q36h

10–25% q48h

Dose as GFR < 10

Dose as GFR < 10

Enalapril

D

100%

75-100%

50-75%

Dose as GFR < 10

Dose as GFR < 10

Erythromycin

D

100%

100%

50-75%

Dose as GFR < 10

Dose as GFR < 10

Ethambutol

I

q24h

q24-36h

q48h

Dose as GFR < 10

Dose as GFR < 10 dose post HD

Etoposide

D

100%

75%

50%

Dose as GFR < 10

Dose as GFR < 10

Fentanyl

D

100%

75%

50%

Dose as GFR < 10

Dose as GFR < 10

Fluconazole

D

100%

100%

50%

Dose as GFR < 10

Dose as GFR < 10 dose post HD

Gentamicin

D, I

60–90% q8–12h

30–70% q12h

20–30% q24–72h

3–4 mg/L/day

Dose as GFR < 10 dose post HD

Isoniazid

D

100%

100%

75%

Dose as GFR < 10

Dose as GFR < 10 dose post HD

Lamivudine

D, I

100%

50–150 mg qd

25 mg qd

Dose as GFR < 10

Dose as GFR < 10 dose post HD

Metformin

D

50%

Avoid

Avoid

Avoid

Avoid

Metoclopramide

D

100%

75%

50%

Dose as GFR < 10

Dose as GFR < 10

Penicillin G

D

100%

75%

20-50%

Dose as GFR < 10

Dose as GFR < 10

Pyrazinamide

D

100%

As normal GFR

As normal GFR

As normal GFR

As normal GFR

Quinine

I

q8h

q8-12h

q24h

Dose as GFR < 10

Dose as GFR < 10 dose post HD

Streptomycin

I

q24h

q24–72h

q72h

20–40 mg
/L/day

750 mg 2–3/week

Triamterene

I

q12h

q12h

Avoid

Avoid

Avoid

Tubocurarine

D

75%

50%

Avoid

Unknown

Unknown

Vancomycin

D, I

500 mg
q6-12h

500 mg
q12-48h

500 mg
q48-96h

Dose as GFR < 10

Dose as GFR < 10

Zidovudine (AZT)

D, I

100% q8h

100% q8h

50% q12h

Dose as GFR < 10

Dose as GFR < 10

HD: Hemodialysis; CAPD: Chronic Ambulatory Peritoneal Dialysis.