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.
• 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 |
750 mg 2–3/week |
Triamterene |
I |
q12h |
q12h |
Avoid |
Avoid |
Avoid |
Tubocurarine |
D |
75% |
50% |
Avoid |
Unknown |
Unknown |
Vancomycin |
D, I |
500 mg |
500 mg |
500 mg |
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.