Diazepam

General Toxicity Notes
May cause excessive sedation and encephalopathy in ESRD.
Excreted Unchanged %
<1
Half-Life (Normalesrd) Hours
30-56/37
Plasma Protein Binding %
98
Volume Of Distribution L/Kg
0.8-1.4
Dose For Normal Renal Function
2-10 mg q6-24h
Adjustment For Renal Failure Method
D
Adjustment For Renal Failure Gfr, Ml/Min >50 [Recommended Level]
100% (see notes) [A]
Adjustment For Renal Failure Gfr, Ml/Min 10-50 [Recommended Level]
100% (see notes) [A]
Adjustment For Renal Failure Gfr, Ml/Min <10 [Recommended Level]
100% (see notes) [A]
Supplement For Dialysis [Recommendation Level]: Ihd
IHD: None, [D]
Supplement For Dialysis [Recommendation Level]: Pd
PD: None, [D]
Supplement For Dialysis [Recommendation Level]: Crrt
CRRT: Dose for GFR 10-50, [D]
References
Gaudreault P, Guay J, Thivierge RL, Verdy I. Benzodiazepine poisoning. Clinical and pharmacological considerations and treatment. Drug Saf. 1991; 6: 247-65. [PMID: 1888441] / Greenblatt DJ. Benzodiazepine hypnotics: sorting the pharmacokinetic facts. J Clin Psychiatry. 1991; 52 Suppl: 4-10. [PMID: 1680125] / Greenblatt DJ. Pharmacokinetics and pharmacodynamics. Hosp Pract (Off Ed). 1990; 25 Suppl 2: 9-15; discussion 16-8. [PMID: 2114417] / Greenblatt DJ, Harmatz JS, Friedman H, Locniskar A, Shader RI. A large-sample study of diazepam pharmacokinetics. Ther Drug Monit. 1989; 11: 652-7. [PMID: 2512694] / Ochs HR, Greenblatt DJ, Kaschell HJ, Klehr U, Divoll M, Abernethy DR. Diazepam kinetics in patients with renal insufficiency or hyperthyroidism. Br J Clin Pharmacol. 1981; 12: 829-32. [PMID: 7340884] / Treiman DM. Pharmacokinetics and clinical use of benzodiazepines in the management of status epilepticus. Epilepsia. 1989; 30 Suppl 2: S4-10. [PMID: 2670537] / Vanholder R, Van Landschoot N, De Smet R, Schoots A, Ringoir S. Drug protein binding in chronic renal failure: evaluation of nine drugs. Kidney Int. 1988; 33: 996-1004. [PMID: 3392889]
Toxicity Notes
Active metabolites, desmethyldiazepam and oxazepam, may accumulate in renal failure. Reduce dose if given longer than a few days. Protein binding decreases in uremia.