Pharmacokinetic and pharmacodynamic considerations of antimicrobial drug therapy in cancer patients with kidney dysfunction

Table 1 Proposals for adjustment of an anti-infective drug dose to the estimated kidney function or to intermittent hemodialysis and continuous hemofiltration

Drug	Half life		Loadingdose	Normal kidney function		Kidney impairment		Failure (GFR ≤5 mL/min) and hemodialysis			Hemofiltration (2 L/h) and continuous dialysis
	(h)			(GFR = 100 mL/min)		(GFR about 30 mL/min)		Off dialysis day Dfail		DHD = Dfail + Dsup
	Normal	Failure	Dstart (mg)	Maintenancedose (mg)	Dose interval (h)	Maintenancedose (mg)	Dose interval (h)	Maintenancedose (mg)	Dose interval (h)	Post dialysis DHD (mg)	Maintenancedose (mg)	Dose interval (h)
Abacavir (po)	1.5	2.1	600	600	12	600	12	600	12
Aciclovir	2.5	25	750	750	8	500	12	500	24	750	750	24
Adefovir (po)	1.6	160	10	10	24	10	48	10	168	10
Albendazole (po)	8	8	400	400	12	400	12	400	12
Amantadine (iv)	13	600	200	200	8	200	72	200	168	200	200	72
(po)	20	610	100	100	12	100	72	100	168	100
Amikacin	2	40	Norm/Failure	1500	24	500	24	250	24	750	750	24
			1500/750
Amoxicillin (po)	1.2	12	1000	1000	8	1000	12	500	12	1000
Amoxicillin + Clavulanic acid	1.2 + 1.2	12 + 4.3	500 + 125	500 + 125	8	500 + 125	12	500 + 125	12	500 + 125	500 + 125	12
			875 + 125	875 + 125	8	875 + 125	12	500 + 125	12
Amphotericin B	24 (360)	35 (360)	70	70	24	70	24	50	24	50	50	24
Amphotericin B liposomal	24/92	24/160	200	200	24	200	48	200	24	200	200	24
Ampicillin	1	13	2000	2000	8	2000	12	1000	12	2000	2000	12
+ Sulbactam	+ 1	+ 6.6	+ 1000	+ 1000	8	+ 1000	12	+ 500	12	+ 1000	+ 1000	12
Amprenavir	8	8	1200	1200	12	1200	12	1200	12
Anidulafungin	26	26	200	100	24	100	24	100	24	100	100	24
Artesunate	0.5			180
Atazanavir (po)	9			300	24
Atovaquone (po)	63	63	750	750	12
Atovaquone +	63	63	250 + 100	250 + 100	24	250 + 100	24	250 + 100	24
Proguanil (po)	14	23
Azidothymidine	1	1.9 (52)	200	200	8	100	8	100	8	200	200	24
Azithromycin	39	40	1000	500	24	500	24	500	24	500	-	-
Brivudin (po)	14 (144)		125	125	24 for 7 d
Caspofungin	10	10	70	50	24	50	24	50	24	50	50	24
Cefaclor (po)	0.7	3	1000	1000	8	1000	12	1000	12	1000
Cefazolin	2.2	34	2000	2000	8	2000	12	500	12	1500	1000	12
Cefotaxime	1.2	7 (10)	2000	2000	8	2000	12	1000	12	2000	2000	12
Cefotiam	1	8	2000	2000	8	2000	12	1000	12	2000	2000	12
Ceftaroline fosamil	2.7	6	600	600	12	600	12	600	12	600	600	12
Ceftobiprol-medocaril	3.3	11	1000	1000	8	1000	12	500	12	1000	1000	12
Ceftazidime	2.1	25	2000	2000	8	2000	12	1000	24	2000	1000	12
Ceftriaxone	8	15	2000	2000	24	2000	24	2000	24	2000	2000	24
Cefuroxime (iv)	1.1	18	1500	1500	8	1500	12	750	24	1500	750	12
(po)			500	500	8	500	12	500	24
Chinin = Quinine	13	15	600	600	12	600	12	600	12	600	600	12
Chloramphenicol	2.5	7	1000	1000	8	1000	8	1000	12	1000	1000	12
Chloroquine	48/212	300	250 mg/8 h	150	8	75	24
Cidofovir	3.4	45	375 mg/168 h	375	336 h = 14 d	70	336 = 14 d	35	336 = 14 d	70	140	336 = 14 d
Ciprofloxacin (iv)	4.4	10	400	400	12	400	12	400	24	400	400	12
(po)			500	500
Clarithromycin	6.8	17	500	500	12	500	12	500	24
Clindamycin	3	3	900	600	6 - 8	600	6 - 8	600	6 - 8	600	600	6 - 8
Colistin colistimethate Na	3 (9)	24 (11)	480 - 720	240	8	240	12	240	24	240	320	12
			= 7 Mio IE	= 3 Mio IE		= 3 Mio IE		= 3 Mio IE		= 3 Mio IE	= 4 Mio IE
Colistin (po)	3	16	160 mg	2 Mio IE	12
			= 2 Mio IE
Co-trimoxazole	11/10	31/28	160/800	160/800	12	160/800	24	160/800	24	160/800	160/800	12
Dalbavancin	336		1000	500	168
Dapsone (po)	24	31	200	200	24	200	24	200	24	200
Daptomycin	8	33	500	500	24	500	48	500	48	500	350	24
				6-10 mg/kg		6-10 mg/kg		6-10 mg/kg		6-10 mg/kg
Darunavir (po)	8			600	12
Delavirdine	5.8			400	8
Didanosine (po)	1.4	4.5	200	200	12	200	12	200	24
Doripenem	1	8	1000	1000	8	1000	8	1000	12	1000	1000	8
Doxycycline	15	23	200	100	24	100	24	100	24	100	100	24
Efavirenz (po)	46.8	47	600	600	24	600	24	600	24
Emtricitabine (po)	8.7	36	200	200	24	200	24	200	72
Enfuvirtide	30			90	12
Entecavir (po)	24 (138)	67 (384)	1.0	1.0	24	0.5	48	0.5	72	0.5
Ertapenem	4.1	14.4	1000	1000	24	1000	24	1000	24	1000	1000	24
Erythromycin	2.3	5	1000	1000	8	1000	12	1000	12	1000	1000	8
Ethambutol	3.1	9.6	1600	1600	24	1200	24	1000	48	1600	1600	24
			20 mg/kg
Famciclovir (po)	2.2	14	250	250	12	250	12	250	24
Flucloxacillin	0.8	3	2000	2000	8	2000	8	2000	8	2000	2000	8
Fluconazole	25	110	800 or 400	800	24	400	24	400	48	400	800	24
Flucytosine	4	150	2500	2500	6	2500	12	2500	48	2500	1250	24
Fosamprenavir	19			700	12
Foscarnet	4.5	100	6000	6000	12	3000	24	3000	72	4000	3000	24
				4000	8
Fosfomycin (iv)	1.5	20	5000	5000	8	5000	24	2500	24	5000	5000	12
(po)			3000	single dose
Ganciclovir	4.2	60	500	500	12	500	24	300	24	400	200	12
			5 mg/kg KG
Gentamicin	2	48	Norm/Fail	240	24	120	24	40	24	120	120	24
			240/120					0	48	320 before HD
Hydroxy-chloroquine	400			200	8
Imipenem/	0.9/	3.3/	1000	1000	8	1000	12	500	12	1000	1000	12
+ Cilastatin	0.9	13.8
Indinavir (po)	1.8	2.1	800	800	8	800	8	800	8
Isoniazid	1/3.3	5/12	300	300	24	300	24	300	24	300	300	24
Itraconazole (po)	16	25	200	200	24	200	24	200	24	200
Ketoconazole (po)	3	2	200	200	12	200	12	200	12	200
Lamivudine (po)	6.2	21	150	150	12	150	24	100	24	150
Levofloxacin	7.3	35	750	500	12	500	24	250	24	500	500	12
Linezolid	4.9	6.9	600	600	12	600	12	600	12	600	600	12
Lopinavir/Ritonavir	7/3.7	7/6.3	400 + 100	400 + 100	12	400 + 100	12	400 + 100	12
Maraviroc (po)	36	36	300	300	12	300	12	300	12
Mebendazole (po)	5		2 x 500	1000	8
Mefloquine (po)	336	340	250	250	168	250	168	250	168
Meropenem	1	9.7	1000	1000	8	1000	12	1000	12	1000	1000	12
Metronidazole (iv)	10	11 (34)	500	500	8	500	12	500	12	500	500	12
(po)			400	400		400		400
Micafungin	13	14	100	100	24	100	24	100	24	100
Miconazole	24	24	1200	1200	24	1200	24	1200	24	1200
Moxifloxacin	12	15	400	400	24	400	24	400	24	400	400	24
Nelfinavir (po)	4.5	4	750	750	8	750	8	750	8
Nitrofurantoin (po)	1.0	1.2	100	100	8
Nevirapine (po)	28	22	200/24	200	12	200	12	200	12
Oritavancin	336		1200
Oseltamivir (po)	7	(80)	75	75	12	30	24	75	72	75
Paromomycin	2	40		500	8	500	24	500	48
Penicillin G =	0.5	10	10 mega	10 mega	8	10 mega	12	5 mega	12	5 mega	5 mega	8
Benzylpenicillin
Penicillin V (po)	0.6	4.1	1 mega	1 mega	8	1 mega	8	1 mega	12
Pentamidine (iv) (inhaled)	60	96	300	300	24	300	24	300	24
			600	600	24
			300	300	4 wk
Piperacillin	1.1	4	4000	4000	8	4000	12	4000	12	4000	4000	12
+ Sulbactam	1	8	500	500	8	500	12	500	12	500	500	12
Piperacillin	1.1	4	4000	4000	8	4000	12	4000	12	4000	4000	12
+ Tazobactam	1	8	500	500	8	500	12	500	12	500	500	12
Posaconazole (po)	24	29	2 x 300	300	24	300	24	300	24
Primaquine (po)	6.3	6.4	30	30	24	30	24	30	24
Proguanil (po)	14	23		200	24
Propicillin (po)	1		700 = 1 mega	700	8
Prothionamide (po)	1.5		1000	1000	24	500	24	250	24	500	?	?
Pyrazinamide (po)	9.1	19	2000	2000	24	2000	24	2000	48	2000	-	-
Pyrimethamine	92	80	75	50	24	50	24	50	24
Pyrvinium embonate	?	?	50	Single dosing
Quinine	13	15	600	600	12	600	12	600	12	600	600	12
Raltegravir (po)	5.5	2.5	400	400	12	400	12	400	12
Ribavirin aerosol	44	26	6000	6000	12	6000	12	6000	12	6000	6000	12
Ribavirin (po)	4/250	24/672	600	600	12	400	24	200	24	400	400	72
(iv)			1000	1000	8	500	12	500	48	500	500	48
Rifabutin (po)	25	37	600	600	24	600	24	300	24
Rifabutin +	25	37	600	600	24	600	24	300	24
Clarithromycin	6.8	17	300	300	24	300	24	300	24
Rifampicin (iv)	4.5	4.5	600	600	24	600	24	600	24	600	600	24
(po)			450	450	12	450	12	450	12
Rifaximin (po)	intestine	unch	400	400	12	400	12	400	12
Ritonavir (po)	3.7	6.3	600	600	12	600	12	600	12
Roxithromycin	12	15	300	300	24	300	24	300	24	-	-	-
Saquinavir (po)	7	13	2 x 500	1000	12	1000	12	600	12
Stavudine (po)	1.5	6.0	40	40	12	40	12	40	12	40
Sofosbuvir	1 (18)	(25)	400	400	24	400	24	300	24	400
Streptomycin	2.6	100	1000	1000	24	500	48	250	72	250	500	24
Teicoplanin	52	348	3 x (800/24)	1200	24	400	24	400	48	800	400	24
Telavancin	7.3	25	750	750	24	500	24	250	24	500	750	24
Telbivudine (po)	22		600	600	24
Tenofovir (po)	14	28	245	245	24	245	24	245	48	245
Terbinafine (po)	16	16	250	250	24	250	24	250	24
Tetracycline (po)	8.9	83	500	500	8
Tigecycline	40	47	100	50	12	50	12	50	12	50	50	12
Tipranavir (iv)	2.8	2.8	500	500	12
+ Ritonavir (po)	3.7	6.3	+ 200	+ 200
Tobramycin	2	48	Norm/Fail	240	24	120	24	40	24	120	120	24
			240/120
Trimethoprim (iv) (po)	11	31	200	150	12	150	24	150	24	-	-	-
			100	100	24	100	24
Trimethoprim +	11	31	160	160	12	160	24	160	24	160	160	12
Sulfamethoxazole	10	28	+ 800	+ 800	12	+ 800	24	+ 800	24	+ 800	+ 800	12
Trimethoprim +	11	31	400	400	8	320	12	400	24	400	400	12
Sulfamethoxazole	10	28	+ 2000	+ 2000	8	+ 1600	12	+ 2000	24	+ 2000	+ 2000	12
(Pneumocystis)
Valacyclovir (po)	2.5	25	1000	1000	8	1000	12	500	24	1000
Valganciclovir (po)	3.0	68	900	900	12	450	24	450	72	900
Vancomycin	6	150	1000	1000	12	1000	24	500	72	1000	1000	24
Voriconazole	8	12	2 x 400/24	200	12	200	12	200	12	200	200	12
Zalcitabine (po)	1.8	11	0.75	0.75	8	0.75	12	0.75	24
Zanamivir	2.5	13.7	10	10	12	10	12	10	12		10	24
Zidovudine	1	1.9 (52)	200	200	8	100	8	100	8	200	200	12

Drugs are listed in alphabetical order and the parameter values for the drug (or active metabolite) are taken from our NEPharm database. If the individual GFR is not exactly 100 mL/min, or 30 mL/min, or 5 mL/min, the dose could be estimated by interpolation between the stated proposals. GFR: Glomerular filtration rate.