Dosing of penicillin, antistaphylococcal penicillins, and broad-spectrum penicillins in adult patients with dose adjustments for kidney impairment

Drug	CrCl (mL/minute)	Usual adult dose	Frequency
Penicillin
Penicillin V potassium (oral)	No adjustment necessary^[1]; excretion may be delayed in severe kidney impairment	250 to 500 mg orally	Every 6 to 12 hours
Penicillin V potassium (oral)	iHD*^[1]	250 to 500 mg orally	Every 6 to 12 hours*
Penicillin G (IV)^¶	≥15 (non-uremic)	2 to 5 million units IV	Every 4 to 6 hours (or total daily dose as a 24-hour continuous infusion)
	10 to <15 (uremic)	Loading dose: 2 to 5 million units IV once Maintenance dose: 1 to 2.5 million units IV	Every 4 to 5 hours (maintenance dose)
	<10	Loading dose: 2 to 5 million units IV once Maintenance dose: 1 to 2.5 million units IV	Every 8 to 10 hours (maintenance dose)
	iHD*^[1]	Loading dose: 2 to 5 million units IV once Maintenance dose: 0.5 to 2.5 million units IV	Every 4 to 6 hours (maintenance dose)*
	CVVHD (1 to 2 L/hour)^[2]	Loading dose: 4 million units IV once Maintenance dose: 2 to 3 million units IV	Every 4 to 6 hours (maintenance dose)
Penicillin G procaine^Δ (intermediate-acting IM suspension)	No specific adjustment available; excretion may be delayed in severe kidney impairment	600,000 to 2.4 million units IM	Every 24 hours (or divided every 12 hours)
Penicillin G benzathine and penicillin G procaine^Δ (mixture of intermediate- and long-acting IM suspension)	No specific adjustment available; excretion may be delayed in severe kidney impairment	1.2 to 2.4 million units IM	Single dose or repeated after 2 to 3 days
Penicillin G benzathine^Δ (long-acting intramuscular suspension)	No specific adjustment available; excretion may be delayed in severe kidney impairment	1.2 to 2.4 million units IM	Single dose or repeated weekly
Antistaphylococcal penicillins
Cloxacillin (oral)^◊	No adjustment necessary	250 to 500 mg^◊	Every 6 hours
Cloxacillin (IV)^◊	No adjustment necessary	2 g IV^◊	Every 4 to 6 hours
Dicloxacillin (oral)	No adjustment necessary	250 to 500 mg orally	Oral: Every 6 hours
Dicloxacillin (IV)^◊	No adjustment necessary	1 to 2 g IV^◊	Every 4 to 6 hours
Nafcillin (IV)	No adjustment necessary	1 to 2 g IV	Every 4 to 6 hours (or total daily dose as a 24-hour continuous infusion)
Oxacillin (IV)	No adjustment necessary; caution in end stage kidney disease^§	1 to 2 g IV	Every 4 hours
Second-generation penicillins (aminopenicillins)
Amoxicillin (oral, immediate-release)	>30	500 mg to 1 g orally	Every 8 to 12 hours
	10 to 30	250 mg to 1 g orally	Every 12 hours
	<10	250 to 500 mg orally	Every 12 to 24 hours
	iHD*	250 to 500 mg orally	Every 12 to 24 hours*
	PD	250 to 500 mg orally	Every 12 hours
Ampicillin (IV)	≥50	1 to 2 g IV	Every 4 to 6 hours
	30 to <50	1 to 2 g IV	Every 6 to 8 hours
	15 to <30	1 to 2 g IV	Every 8 to 12 hours
	<15	1 to 2 g IV	Every 12 to 24 hours
	iHD*	1 to 2 g IV	Every 12 to 24 hours*
	PD	1 to 2 g IV	Every 12 to 24 hours
	CVVHD^[2,3]	1 to 2 g IV	Every 6 to 12 hours
Ampicillin (oral)^[2]	≥50	250 to 500 mg orally	Every 6 hours
	10 to <50	250 to 500 mg orally	Every 6 to 12 hours
	<10	250 to 500 mg orally	Every 12 to 16 hours
	iHD*	250 to 500 mg orally	Every 12 to 24 hours; supplemental dose after each dialysis session*
	PD	250 mg orally	Every 12 hours
Other broad-spectrum penicillin
Piperacillin (IV)^◊¥	≥40	3 to 4 g IV	Every 4 to 6 hours
	20 to 40	4 g IV	Every 8 hours
	<20	4 g IV	Every 12 hours
	iHD*	2 g IV	Every 8 hours; 1 g supplemental dose after each dialysis session*
	PD	4 g IV	Every 12 hours
	CRRT^[1]	4 g IV	Every 8 hours

This table lists doses of penicillin antibiotics, with suggested dosing adjustments for kidney impairment. The first dose listed for each agent represents the suggested dose range for normal kidney function. For specific dosing recommendations, refer to related disease treatment topics(s) and Lexicomp drug monograph.
Kidney function is evaluated based on estimated CrCl using the Cockcroft-Gault equation. A calculator for estimating CrCl based on the Cockcroft-Gault equation is available in UpToDate. Combinations of penicillins with beta-lactamase inhibitors (eg, amoxicillin-clavulanate, piperacillin-tazobactam) are reviewed separately; refer to separate topic review and table of combination beta-lactamase inhibitors, carbapenems, and monobactams.

CrCl: creatinine clearance; CVVHD: continuous veno-venous hemodialysis; CRRT: continuous renal replacement therapy; iHD: intermittent hemodialysis; PD: peritoneal dialysis.

* Based on three times weekly dialysis sessions of 3 to 4 hours each; on dialysis days administer dose after dialysis. A loading dose or supplemental dose following dialysis may be warranted for some antibiotics depending on clinical scenario; refer to Lexicomp monograph for detail.

¶ Alternative suggested adjustment for kidney impairment: GFR >50 mL/min: No adjustment; GFR 10 to 50 mL/min: 75% of indication-specific dose; GFR <10 mL/min: 20 to 50% of indication-specific dose.^[1]

Δ Suspension formulations of penicillin are for intramuscular use only and must not be administered intravenously.

◊ Not available in the United States but may be available elsewhere.

§ For those with CrCl <10 mL/minute, on iHD, or on PD, monitor for signs of accumulation (eg, neurotoxicity) or consider alternatives.

¥ Dosing for severe infections; lower and/or less frequent dosing recommended in milder infections. For dosing of the combination piperacillin-tazobactam product available in the United States, refer to separate table in UpToDate and Lexicomp monograph.

References:

Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed, American College of Physicians 2007.
Golightly LK, Teitelbaum I, Kiser TH, et al, eds. Renal Pharmacotherapy: Dosage Adjustment of Medications Eliminated by the Kidneys, Springer 2013.
Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy 2009; 29:562.

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Dosing of penicillin, antistaphylococcal penicillins, and broad-spectrum penicillins in adult patients with dose adjustments for kidney impairment