3364-133-100 Renal Dosing Adjustments

Name of Policy: Renal Dosing Adjustments

Policy Number: 3364-133-100 Department: Pharmacy Chair of Pharmacy and Therapeutics Approving Officer: Committee Chief Executive Officer Responsible Agent: Chief Pharmacy Officer Effective Date: 9/20/2019 Scope: University of Toledo Medical Center Initial Effective date 3/1/2014

New policy proposal x Minor/technical revision of existing policy Major revision of existing policy Reaffirmation of existing policy

(A) Principle Statement Credentialed pharmacists will automatically adjust doses of medications included in the approved list of medications for adult inpatients (> 18 years old).

(B) Procedure  Automatic dosing adjustments should not be done for patients receiving intermittent or continuous dialysis. If dosing adjustments are needed for these patients, pharmacists should communicate recommendations with nephrology fellow.  Automatic dosing adjustments should not be done if the physician indicates “do not adjust” in the comments section of the original order.  Automatic dosing adjustments should not be done for patients on long term suppression antimicrobials as home medications. The primary team should be contacted to suggest dosing adjustments in these patients.  Dosing adjustments should be based on estimated creatinine clearance using the Cockcroft-Gault equation. o Cockcroft-Gault equation: CrCl (ml/min)= (140-age)x(IBW) x 0.85 (for females only) 72xSCr  SCr= serum creatinine concentration in mg/dL  IBW= ideal body weight o IBW (males)= 50+(2.3 x inches > 5ft in height) o IBW (females= 45.5+(2.3 x inches > 5ft in height) o Use actual body weight if less than ideal body weight o Estimating renal function based on the Cockcroft-Gault equation requires serum creatinine to be at steady state and renal function to be stable. Acute and/or rapid fluctuations in renal function render the Cockcroft-Gault equation unreliable. o Estimating creatinine clearance using Cockcroft-Gault equation may also overestimate renal function in patients with decreased muscle mass. o The pharmacist should use their clinical judgment regarding these adjustments and communicate with physicians if clarification is needed.  When an automatic dosing adjustment is made, the pharmacist will discontinue the existing order, and enter a protocol order for the same drug with adjusted dosing. Orders for antimicrobial agents should be entered to reflect the remaining doses from the previous orders stop date.  Normal dosing and dose adjustments may be based on specific indications. The indication specific dosing listed is a guide and may vary depending on the drug reference used. The pharmacist must verify the indication for antimicrobial use and normal dose and/or dosing adjustment before making automatic changes.  All automatic dosing adjustments or recommendations should be documented in the “pharmacy interventions” system for follow up and tracking purposes. Section I: Medications That May Be Adjusted by a Credentialed Pharmacist Page | 2 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Acyclovir (IV) HSV suppression/prophylaxis: CRCL >50: Intermittent Hemodialysis: 3, 24, 19, 32, 51 2.5 mg/kg q8h No adjustment 2.5 – 5 mg/kg q24h * (5 mg q24h for meningoencephalitis and Use ABW for HSV Encephalitis: CRCL 25 – 49: varicella-zoster) dosing 10 mg/kg q8h x14-21 days Same dose q12h Peritoneal Dialysis: Use IBW if Mucocutaneous HSV: CRCL 10 – 24: 2.5 – 5 mg/kg q24h overweight  Esophagitis Same dose q24h (5 mg q24h for meningoencephalitis and (>130-190% IBW) 5 mg/kg q8h x7 days varicella-zoster)  Genital CRCL <10: Use AdjBW if 5 – 10mg/kg q8h x2 – 7 days 50% of usual dose q24h CRRT: obese (follow with oral therapy to  Loading Dose: (>190% IBW) 49 complete 10 days) None  Orolabial  Maintenance Dose: 5 mg/kg q8h 5 – 10 mg/kg q12 – 24h (10 mg q12h for Herpes Zoster (shingles): meningoencephalitis and varicella-  Immunocompromised zoster) 10 – 15 mg/kg q8h x7 days (10 – 14 days if HIV-infected) * To avoid HD removal, schedule Varicella (chickenpox) in HIV: administration time after dialysis on dialysis  Immunocompromised days 10 – 15 mg/kg q8h x7-10 days (10 – 14 days if retinal involvement)

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 3

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Acyclovir (PO) HSV suppression/prophylaxis: CRCL >25: Intermittent Hemodialysis: 1, 16, 24, 32, 51 400 mg q12h No adjustment  If usual dose is 800 mg five time daily: Genital HSV: CRCL 10 – 24: 400 mg load now, then 200 mg  Initial episode  If the usual dose is 800 mg five times daily: q12h maintenance, plus an 400 mg q8h x7 – 10 days 800 q8h additional 400 mg dose  Recurrence  All other indications: immediately after each HD session 400 mg q8h or No adjustment  All other indications: 800 mg q12h x5 days 200 mg q12h  Chronic Suppression CRCL <10: 400 mg q12h  If the usual dose is 800 mg five times daily: Peritoneal Dialysis: 800 mg q12h 600 – 800 mg q24h Orolabial HSV:  All other indications:  HIV-Infected 200 mg q12h CRRT: 400 mg q8h x5 – 10 days Insufficient Data  Immunocompromised 400 mg five times daily x5 days  Chronic Suppression 400 mg q12h

Herpes Zoster (shingles): 800 mg five times daily x7 – 10 day

Varicella (chickenpox):  Immunocompetent 800 mg q6h x5 days  Recurrence 800 mg five times daily x5 – 7 days

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 4

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Amantadine (PO) Drug-Induced Extrapyramidal CRCL >50: Intermittent Hemodialysis: 3, 14, 17, 24 Symptoms: No adjustment 200 mg every 7 days 100 mg q12h (MDD: 300 mg) CRCL 30 – 49: Peritoneal Dialysis: Parkinson Disease: 200 mg on day 1, then 100 mg q24h 200 mg every 7 days 100 mg q12h (MDD: 400 mg) * CRCL 15 – 29: CRRT: *Patients receiving other anti-Parkinson 200 mg on day 1, then 100 mg q48h  Loading Dose: medications or having serious None concomitant illnesses should be started CRCL <15:  Maintenance Dose: at 100 mg q24h (MDD 200 mg) 200 mg every 7 days 100 mg q24 – 48h

Traumatic Brain Injury:

100 mg q12h (MDD: 400 mg)

Amoxicillin (PO) Streptococcal Pharyngitis (Group A): CRCL >30: Intermittent Hemodialysis: 3, 10, 24, 28, 34, 38, 43, 45 IR: 500 mg q12h or 1 g q24h x10 days No adjustment 250 – 500 mg q24h *

Rhinosinusitis, Otitis Media, CRCL 10 – 29: * Peritoneal Dialysis: Cystitis (uncomplicated), SSTI: 500 mg q12h 250 – 500 mg q12h IR: 500 mg q8h or 875 mg q12h CRCL <10: * CRRT: CAP: 500 mg q24h Insufficient Data IR: 1 g q8h in combination with a macrolide or doxycycline x5 days * Use of 875 mg IR tablets is not recommended * To avoid HD removal, schedule administration time after dialysis on dialysis H. pylori Infection: days IR: 1 g q12h in combination IR: 1 g q8h*

*for high-dose dual therapy regimen

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 5

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Amoxicillin/ UTI (uncomplicated): CRCL >30: Intermittent Hemodialysis: Clavulanate IR: 500 mg q12h No adjustment 250 – 500 mg q24h (PO) (with a supplemental dose being given 3, 16, 24, 28, 43 SSTI, UTI (complicated), Rhino- CRCL 10 – 29: * both during and after HD) sinusitis, Otitis Media, Lower 500 mg q12h Respiratory Tract Infections: Peritoneal Dialysis: IR: 875 mg q12h or 500 mg q8h CRCL <10: * 250 – 500 mg q24h 500 mg q24h CAP: CRRT: XR: 2,000 mg q12h in combination *Use of 875 mg IR tablets and any XR tablets is not Insufficient Data with a macrolide or doxycycline recommended in CrCl <30 x5-10 days

Ampicillin (IV) Standard Dose CRCL >50: Intermittent Hemodialysis: 3, 5, 19, 24, 48 (GI, GU, URI): No adjustment 1 – 2 g q12 – 24h * 1 – 2 g q 4 – 6h CRCL 30 – 49: Peritoneal Dialysis: High Dose Same dose q6 – 8h 250 mg q12h (Bacteremia, Meningitis, Endocarditis): CRCL 10 – 29: CRRT:

2 g q4 – 6h Same dose q8 – 12h  Loading Dose: 2 g CRCL <10:  Maintenance Dose: Same dose q12h 1 – 2 g q6 – 8h

* To avoid HD removal, schedule administration time after dialysis on dialysis days

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 6 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Ampicillin (PO) Standard Dose CRCL >50: Intermittent Hemodialysis: 24 (GI, GU, URI): No adjustment Insufficient Data 500 mg q6h CRCL 30 – 49: Peritoneal Dialysis:

Same dose q6 – 8h Insufficient Data

CRCL 10 – 29: CRRT: Same dose q8 – 12h Insufficient Data

CRCL <10: Same dose q12h

Ampicillin/ SSTI, URI: CRCL >50: Intermittent Hemodialysis: Sulbactam (IV) 1.5 – 3 g q6 – 8h No adjustment Same dose q12 – 24h 5, 19, 24, 29, 47, 51 Bacteremia, Endocarditis, GI, GU, CRCL 30 – 49: Peritoneal Dialysis: PID: Same dose q8h Insufficient Data 3 g q6h

CRCL 15 – 29: CRRT:

Same dose q12h  Loading Dose 3 g CRCL 5 – 14:  Maintenance Dose: Same dose q24h 1.5 – 3 g q6 – 8h

Apixaban (PO) VTE Treatment: Non-Valvular Atrial Fibrillation: Intermittent Hemodialysis: 24 10 mg q12h x7days, then 5 mg q12h If patient meets 2 of 3 below criteria, adjust dose to Same as for non-HD patients 2.5 mg q12h: Non-Valvular Atrial Fibrillation: Peritoneal Dialysis: 5 mg q12h 1) SCr > 1.5 Insufficient Data 2) Age >80 VTE Prophylaxis: 3) Body weight <60 kg CRRT: 2.5 mg q12h after >6 months of initial Insufficient Data treatment therapy All other indications: No adjustment provided, not studied in patients with: TKA/THA DVT Prophylaxis: CRCL <25 for VTE prophylaxis 2.5 mg q12h for up to 35 days CRCL <30 for THA/TKA VTE prophylaxis

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 7 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Aztreonam (IV) Cystitis: CRCL >30: Intermittent Hemodialysis: 3, 19, 24, 47 1 g q8h No adjustment Same initial dose, then 25% of the usual dose at the same interval for Moderately severe systemic CRCL 10 – 29: maintenance * infections Same initial dose, then 50% of the usual dose at the (SSTI, Intra-abdominal Infection, same interval for maintenance Peritoneal Dialysis: CAP, etc.): Same initial dose, then 25% of the usual 1 – 2 g q8h CRCL <10: dose at the same interval for Same initial dose, then 25% of the usual dose at the maintenance Severe systemic or life-threatening same interval for maintenance infections (or infections potentially CRRT: or actually involving P. aeruginosa):  Loading Dose: 2 g q6 – 8h 2 g  Maintenance Dose: 1 g q8h or 2 g q12h

* For severe systemic or life-threatening infections, give an additional 12.5% of the usual dose after each HD session in addition to the above dose adjustment

Cefazolin (IV) Prophylaxis: CRCL >35: Intermittent Hemodialysis: 5, 6, 19, 24, 29, 44, 47 1 g q8h No adjustment  Q24h Dosing 1 g q24h Standard Dose CRCL 11 – 34:  With HD MWF Dosing (Cystitis, PNA, Osteomyelitis, Same dose q12h 2 g on MW and 3 g on F Bacteremia, Endocarditis):  With HD TThS Dosing 2 g q8h CRCL <10: 2 g on TTh and 3 g on S 1 g 24h Peritoneal Dialysis: 500 mg q12h

CRRT:  Loading Dose: 2 g  Maintenance Dose: 1 – 2 g q8h

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 8 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis

Cefepime (IV) Standard Dose CRCL Recommended Regimen Intermittent Hemodialysis: 9, 22, 24, 29, 31, 35, 48 (mild/moderate infections):  Q24h Dosing >60 1 g q8h 2 g q8h 1 g q8h 1 g q24h (normal dose) (normal dose)

Bacteremia, Meningitis, Febrile 30-59 1 g q12h 1 g q8h  With HD Dosing Neutropenia, Endocarditis, 2 g on HD days HAP/VAP, SSTI, (or infections 11-29 1 g q24h 1 g q12h potentially or actually involving P. Peritoneal Dialysis: aeruginosa): Usual dose q48h <11 1 g q24h 1 g q24h 2 g q8h CRRT:  Loading Dose: Extended-infusion (EI): CRCL >50: 2 g 2 g q8h over 3 hours No adjustment  Maintenance Dose:

2 g q8h CRCL 30 – 49:

1 g q8h over 3 hours

CRCL <30: See standard dosing above, EI not required

Cefixime (PO) UTI, URI: CRCL >50: Intermittent Hemodialysis: 24 400 mg q24h or 200 mg q12h No adjustment 200 mg q24h *

Gonorrhea: * CRCL 30 – 49: Peritoneal Dialysis:  Uncomplicated 300 mg q24h 200 mg q24h 400 mg x1  Disseminated CRCL 10 – 29: CRRT: 400 mg q12h 200 mg q24h Insufficient data

*Only if ceftriaxone is not an option * To avoid HD removal, schedule administration time after dialysis on dialysis days

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 9 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Cefoxitin (IV) SSTI (uncomplicated), Urinary or CRCL >50: Intermittent Hemodialysis: 24, 51 Lower Respiratory Tract Infections: No adjustment Dose for CRCL plus additional 1 – 2 g 1 g q6 – 8h after each dialysis session CRCL 30 – 49: Moderately Severe or Severe 1 – 2 g q8h Peritoneal Dialysis: Infections Insufficient Data (Intra-abdominal Infection): CRCL 10 – 29: 2 g q6 – 8h 1 – 2 g q12h CRRT: Insufficient Data PID: CRCL <10: 2 g q6h (with doxycycline) 1 g q24h

Cephalexin (PO) AOM: CRCL >50: Intermittent Hemodialysis: 3, 24 250 mg q6h No adjustment 500 mg q12h

Streptococcal Pharyngitis, Cystitis CRCL 30 – 49: Peritoneal Dialysis: (uncomplicated): 500 mg q6h 500 mg q12h 500 mg q12h CRCL 15 – 29: CRRT: SSTI: 500 mg q8h Insufficient Data 500 mg q6h CRCL <15: 500 mg q12h

Ciprofloxacin Standard Dose CRCL >30: Intermittent Hemodialysis: (IV) (Anthrax [non-systemic], Bite No adjustment 400 mg q24h * 5, 6, 16, 19, 20, 24, 26, 36, 43, Wound, Intra-abdominal Infection, 47, 48 IE, Osteomyelitis, Diabetic Foot CRCL 10 – 29: Peritoneal Dialysis: Infection, PJI, Prostatitis, SBP, Septic 400 mg q24h or 400 mg q12h 400 mg q24h Arthritis, SSTI, Cystitis (complicated): 400 mg q12h CRCL <10: CRRT: 400 mg q24h  Loading Dose: High Dose None (Anthrax [systemic], PNA,  Maintenance Dose: Meningitis, and any systemic 400 mg q12 – 24h infection potentially or actually * To avoid HD removal, schedule involving P. aeruginosa): administration time after dialysis on dialysis 400 mg q8h days Policy 3364-133-100 (Renal Dosing Adjustments) Page | 10 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Ciprofloxacin Prophylaxis/Chronic Suppression: CRCL >50: Intermittent Hemodialysis: (PO) 500 mg q12h No adjustment 500 mg q24h * 5, 6, 16, 19, 20, 24, 26, 36, 43, 47, 48 Anthrax (non-systemic), Diabetic CRCL 30 – 49: Peritoneal Dialysis: Foot Infection, Intra-abdominal 500 mg q12h 250 mg q24h Infection, IE, Prostatitis, SBP, SSTI, Cystitis (complicated): CRCL 10 – 29: CRRT: 500 mg q12h 500 mg q24h Insufficient Data

Bite Wound, Osteomyelitis, Septic CRCL <10: * To avoid HD removal, schedule Arthritis: 250 mg q24h administration time after dialysis on dialysis 500-750 mg q12h days

PNA, PJI, SSTI, and any systemic infection potentially or actually involving P. aeruginosa: 750 mg q8 – 12h

Clarithromycin URI, H. pylori, MAC (treatment and CRCL >50: Intermittent Hemodialysis: (PO) prophylaxis), SSTI: No Adjustment 500 mg q24h * 3, 24, 32, 11, 500 mg q12h CRCL 30 – 49: Peritoneal Dialysis: No adjustment Insufficient Data

CRCL <30: CRRT: Same dose q24h Insufficient Data

* To avoid HD removal, schedule administration time after dialysis on dialysis days

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 11 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Dabigatran (PO) VTE Treatment, VTE Prophylaxis: VTE Treatment/Prophylaxis: Intermittent Hemodialysis: 24 Following x5 days of parenteral  No adjustment recommendations provided Insufficient Data anticoagulation:  If CRCL <50 and patient receiving a P-gp 150 mg q12h inhibitor, then avoid coadministration Peritoneal Dialysis:  CRCL <30, not studied Insufficient Data Non-Valvular Atrial Fibrillation: 150 mg q12h or 110 mg q12h* Non-Valvular Atrial Fibrillation: CRRT:  CRCL 30 – 50, adjust to 75 mg q12h if patient Insufficient Data *110 mg = for high risk of bleed receiving dronedarone or ketoconazole (off-label)  CRCL 15 – 30, adjust to 75 mg q12h unless patient receiving concomitant P-gp inhibitor, TKA/THA DVT Prophylaxis: then avoid use 220 mg q24h for up to 35 days  CRCL <15, not studied

DVT Prophylaxis for THA/TKA:  If CRCL <50 and is receiving concomitant P-gp inhibitor, then avoid coadministration  CRCL <30, not studied

Enoxaparin (SQ) DVT Prophylaxis: CRCL >30: Intermittent Hemodialysis: 24 40 mg q24h or 30 mg q12h No adjustment Insufficient Data

VTE Treatment: CRCL <30: Peritoneal Dialysis: 1 mg/kg q12h or 1.5 mg/kg q24h*  Prophylaxis: Insufficient Data 30 mg q24h *Do not use 1.5 mg/kg for outpatient  Treatment: CRRT: use, STEMI/NSTEMI or bridging for 1 mg/kg q24h Insufficient Data mechanical heart valves

Famotidine Duodenal/Gastric Ulcer, GERD, CRCL >50: Intermittent Hemodialysis: (IV/PO) Heartburn, SUP: No Adjustment Insufficient Data 24, 46 20 mg q12h CRCL <50: Peritoneal Dialysis: NSAID-Induced Ulcer Prophylaxis:  GI Hyper-secretory Disorder: Insufficient Data 40 mg q12h Avoid Use  All Other Indications: CRRT: GI Hyper-Secretory Disorder: 20 mg q24h or 40 mg q48h Insufficient Data 20 mg q6h Policy 3364-133-100 (Renal Dosing Adjustments) Page | 12 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Fluconazole Vulvovaginitis: CRCL >30: Intermittent Hemodialysis: (IV/PO)  Uncomplicated: No adjustment 100-200 mg q24h or 3, 24, 33, 47, 51 150 mg x1 dose post-HD three times weekly or  Complicated CRCL <30: * 6 mg/kg post-HD three times weekly 150 mg q72h x2 – 3 doses 50% of usual dose q24h (or 3 mg/kg/day based on ABW) Peritoneal Dialysis: Oropharyngeal Candidiasis: 50% of usual dose q24h 200 mg load on day 1 then, *Doses for vulvovaginitis do not require adjustments. 100 – 200 mg q24h Do not reduce loading doses for other indications. CRRT:  Loading Dose: Esophageal Candidiasis: 400 – 800 mg 400 mg load on day 1 then,  Maintenance Dose: 200 – 400 mg q24h 400 – 800 mg q24h

Cystitis: 200 mg q24h

Candidemia, Invasive Candidiasis: 800 mg load on day 1 then, 400 mg q24h (or 12 mg/kg x 1, then 6 mg/kg/day based on ABW) *

*Note: doses up to 1200 mg/day have been reported

Fondaparinux VTE Prophylaxis: CRCL >50: Intermittent Hemodialysis: (SQ) 2.5 mg q24h No adjustment Insufficient Data 13, 24 VTE Treatment: CRCL 30 – 49: Peritoneal Dialysis: <50 kg: 5 mg q24h 50% of usual dose q24h Insufficient Data 50-100 kg: 7.5 mg q24h >100 kg: 10 mg q24h CRCL <30: CRRT: Contraindicated Insufficient Data

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 13 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Gemfibrozil (PO) Hyperlipidemia, CRCL >60: Intermittent Hemodialysis: 12, 24 Hypertriglyceridemia: No adjustment Insufficient Data 600 mg q12h CRCL 10 – 59: Peritoneal Dialysis: 50% of dose q12h Insufficient Data

CRCL <10: CRRT: Contraindicated Insufficient Data

Ketorolac (IV) Pain Management: The specific degree of renal impairment where use is Intermittent Hemodialysis: 24 30 mg q6h (MDD: 120 mg) permitted is not defined in the product labeling; Insufficient Data however, use is contraindicated in patients with advanced renal impairment or those at risk for renal Peritoneal Dialysis: failure due to volume depletion. Insufficient Data

CRRT: Insufficient Data

Ketorolac (PO) Pain Management: The specific degree of renal impairment where use is Intermittent Hemodialysis: 24 20 mg x1, then 10 mg q4-6h permitted is not defined in the product labeling; Insufficient Data (MDD: 40 mg) however, use is contraindicated in patients with advanced renal impairment or those at risk for renal Peritoneal Dialysis: failure due to volume depletion. Insufficient Data

CRRT: Insufficient Data

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 14 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Levofloxacin GI/GU, H. pylori, COPD Exacerbation, CRCL >50: Intermittent Hemodialysis: (IV/PO) Neutropenia Prophylaxis: No adjustment  If usual dose is 500 mg: 2, 3, 16, 24, 43, 47 500 mg q24h 500 mg load, then 250 mg q48h CRCL 20 – 49:  If usual dose is 750 mg: Rhinosinusitis:  If usual dose is 500 mg: 750 mg load, then 500 mg q48h 500 – 750 mg q24h 500 mg load, then 250 q24h  If usual dose is 750 mg: Peritoneal Dialysis: Cystitis, Pyelonephritis, SSTI, CAP, 750 mg q48h  If usual dose is 500 mg: Intra-abdominal Infection, and any 500 mg load, then 250 mg q48h systemic infection potentially or CRCL 10 – 19:  If usual dose is 750 mg: actually involving P. aeruginosa:  If usual dose is 500 mg: 750 mg load, then 500 mg q48h 750 mg q24h 500 mg load, then 250 q48h  If usual dose is 750 mg: CRRT: 750 mg load, then 500 mg q48h  Loading Dose: 500 – 750 mg  Maintenance Dose: 250 – 750 mg q24h

Metoclopramide Gastroparesis: CRCL >40: Intermittent Hemodialysis: (IV) 5 – 10 mg q6 – 12h (MDD: 30 mg) No adjustment Insufficient Data 8, 24, 30 GERD: CRCL <40: Peritoneal Dialysis: 5 – 10 mg q6 – 8h 50% of the usual dose at same interval Insufficient Data

Nausea/Vomiting: CRRT: 10 mg q4 – 6h Insufficient Data

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 15 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Metoclopramide Gastroparesis: CRCL <61: Intermittent Hemodialysis: (PO) 5 – 10 mg q6 – 12h (MDD: 40 mg)  For Gastroparesis only:  For GERD: 8, 24, 30 5 mg q6h (MDD: 20 mg/day) 5 mg q6h or 10 mg q12h GERD:  For Gastroparesis: 5 – 10 mg q6 – 8h CRCL <40: 5 mg q12h  For all other indications:  For Nausea: Nausea/Vomiting: 50% of the usual dose at same interval Insufficient Data 10 mg q4 – 6h Peritoneal Dialysis:  For GERD: 5 mg q6h or 10 mg q12h  For Gastroparesis: 5 mg q12h  For Nausea: Insufficient Data

CRRT: Insufficient Data

Meropenem (IV) SSTI, Intra-abdominal Infection, CRCL Recommended Regimen Intermittent Hemodialysis: 3, 24, 29, 31, 41, 43, 47, 48 PNA, Bacteremia: >50 500 mg q6h 1 g q8h 2 g q8h EI  For Meningitis or MDR organisms: 500 mg q6h (usual dose) (usual (usual (usual 1 g q24h dose) dose) dose)  All other indications: Febrile Neutropenia: 26-49 500 mg q8h 1 g 2 g q12h 1 g q8h 500 mg q24h 1 g q8h q12h Peritoneal Dialysis: Meningitis: 10-25 500 mg q12h 500 mg 1 g q12h 1 g q12h Same dose q24h 2 g q8h q12h CRRT: Extended-Infusion (EI) Dosing: <10 500 mg q24h 500 mg 1 g q24h 1 g q24h *  Loading Dose: 2 g q8h over 3 hours q24h 1 g  Maintenance Dose: 500 mg q6 – 8h or 1 g q8 – 12h

* Extended infusion not required

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 16 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Oseltamivir (PO) Treatment: CRCL >30: Intermittent Hemodialysis: 18, 22, 24 75 mg q12h x5 days No adjustment  Treatment: 30 mg load, then 30 mg after each Prophylaxis: CRCL 11 – 29: dialysis session 75 mg q24h x7 days  Treatment:  Prophylaxis: 75 mg q24h 30 mg load, then 30 mg dose after  Prophylaxis: every other dialysis session 75 mg q48h Peritoneal Dialysis: CRCL <11:  Treatment: Use not recommended 30 mg once, immediately after an exchange  Prophylaxis: 30 mg once immediately after an exchange, then 30 mg dose once weekly (or twice weekly if significant residual renal function) for 7-day duration

CRRT: Same as for CRCL >30

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 17 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Penicillin G (IV) Endocarditis (S. Viridans or S. bovis): CRCL >50: Intermittent Hemodialysis: 3, 5, 19, 24, 43  Native valve and MIC <0.12 No adjustment Administer usual dose as load, then: mcg/mL:  Mild/Mod Infection: 12 – 18 million units in divided CRCL 30 – 49: 2 million units q8h doses q4h (i.e. 2 million units  If usual dose is 2 million units q4h:  Severe Infection: q4h) 2 million units q6h 4 million units q8h  All other types:  If usual dose is 4 million units q4h: 24 million units in divided doses No adjustment Peritoneal Dialysis: q4 – 6h (i.e. 4 million units q4h) Dose for CRCL < 10 CRCL 10 – 29:  If usual dose is 2 million units q4h: CRRT: Streptococcal Skin Infection: 2 million units q8h  Loading Dose: 2 – 4 million units q4 – 6h  If usual dose is 4 million units q4h: 4 million units 4 million units q6h  Maintenance Dose: Group A Streptococcus Invasive 2 – 4 million units q4 – 6h Infection: CRCL <10: 3 – 4 million units q4h  If usual dose is 2 million units q4h: 2 million units q8h  If usual dose is 4 million units q4h: 4 million units q8h

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 18 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Piperacillin/ (Preferred) Extended Infusion Dosing CRCL >20: * Intermittent Hemodialysis: Tazobactam (IV) All Indications: * No adjustment 3.375 g q12h 24, 27, 34, 37 3.375 g q8h CRCL <20: * Peritoneal Dialysis: *Give a 4.5 g loading dose over 30 3.375 g q12h Insufficient Data minutes, especially when rapid attainment of therapeutic drug *Maintenance dose should be scheduled 4 hours post CRRT: concentrations is necessary (e.g. sepsis) loading dose, or 8 hours post loading dose if CRCL is <20 3.375 g q8h

Non-Extended-Infusion Dosing: CRCL >30: Intermittent Hemodialysis: 4.5 g q6h No adjustment 2.25 g q8-12h (0.75 g supplemental dose after HD if CRCL 10 – 29: next schedule dose is not after HD) 4.5 g q8h Peritoneal Dialysis: CRCL <10: 2.25 g q8-12h 4.5 g q12h CRRT: 4.5 g q8h

Ranitidine (PO) Stress Ulcer Prophylaxis: CRCL >50: Intermittent Hemodialysis: 4, 23, 24, 39 150 mg q12h No Adjustment Same dose q24h

GERD: CRCL <50: Peritoneal Dialysis: 75 – 150 mg q12h Same dose q24h Same dose q24h

CRRT: Insufficient Data

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 19 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Rivaroxaban VTE Treatment: Non-Valvular Atrial Fibrillation: Intermittent Hemodialysis: (PO) 15 mg q12 x21 days, then 20 mg  CRCL >50, no adjustment required Insufficient Data 24 q24h  CRCL 15 – 49, 15 mg q24h  CRCL <15, not studied Peritoneal Dialysis: VTE Prophylaxis: Insufficient Data 20 mg q24h VTE Treatment/Prophylaxis:  CRCL >30, no adjustment required CRRT: THA/TKA VTE Prophylaxis:  CRCL <30, avoid use Insufficient Data 10 mg q24h x10 – 35 days VTE Prophylaxis in THA/TKA: Non-Valvular Atrial Fibrillation:  CRCL >50, no adjustment required 20 mg q24h  CRCL 30 – 49, use with caution  CRCL <30, avoid use

Sitagliptin (PO) Diabetes Mellitus, Type 2: CRCL >50: Intermittent Hemodialysis: 24 100 mg q24h No Adjustment 25 mg q24h

CRCL 30 - 49: Peritoneal Dialysis: 50 mg q24h 25 mg q24h

CRCL <30: CRRT: 25 mg q24h Insufficient Data

Tramadol (PO) Acute/Chronic Pain: CRCL >30: Intermittent Hemodialysis: 24 25-100 mg q4-6h No Adjustment Same dose q12 (MDD: 400 mg) (MDD: 200 mg) CRCL <30: Same dose q12h Peritoneal Dialysis: (MDD: 200 mg) Insufficient Data

CRRT: Insufficient Data

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 20 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Trimethoprim/ PCP Pneumonia (treatment) or other PCP Pneumonia (treatment): Intermittent Hemodialysis: Sulfamethoxazole severe respiratory/CNS infections  CRCL 30 – 50, no adjustment  For PCP (treatment): (IV) (i.e. Stenotrophomons, nocardia):  CRCL 10 – 29, 5 mg/kg q12h 5 mg/kg q24h 15, 19, 24, 32 15 – 20 mg/kg in 3 – 4 divided doses  CRCL <10, 5 mg/kg q24h  For Other Indications: 2.5 – 5 mg/kg q24h *Dosing is based Severe Cystitis: All Other Indications: on trimethoprim 2.5 mg/kg q12h  CRCL 30 – 50, no adjustment Peritoneal Dialysis: component using  CRCL 10 – 29, 2.5 – 5 mg/kg q12h  Trimethoprim Component: ideal body weight SSTI:  CRCL <10, avoid use* Dose for CRCL < 10

5 mg/kg q12h  Sulfamethoxazole Component: *If necessary, 2.5 – 5 mg/kg q24h 1 g q24h max

CRRT:  Loading Dose: None  Maintenance Dose: 2.5 – 10 mg/kg q12h (10 mg/kg for PCP)

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 21 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Trimethoprim/ PCP Pneumonia (treatment) or other PCP Pneumonia (treatment): Intermittent Hemodialysis: Sulfamethoxazole severe respiratory/CNS infections  CRCL 30 – 50, no adjustment  For PCP (treatment): (PO) (i.e. Stenotrophomons, nocardia):  CRCL 10 – 29, 320 mg (2 DS or 5 mg/kg) q12h 320 mg (2 DS or 5 mg/kg) q24h 15, 16, 19, 24, 32, 43, 50 15 – 20 mg/kg in 3 divided doses or  CRCL <10 320 mg (2 DS or 5 mg/kg) q24h  For PCP (prophylaxis): 320 mg q8h 160 mg (1 DS or 2.5 mg/kg) thrice *Dosing is based PCP Pneumonia (prophylaxis): weekly on trimethoprim PCP Pneumonia (prophylaxis):  CRCL 30 – 50, no adjustment  For Other Indications: component using 160 mg q24h (1 DS q24h) * or  CRCL 10 – 29, 160 mg (1 DS or 2.5 mg/kg) 160 mg (1 DS or 2.5 mg/kg) q24h ideal body weight 80 mg q24h (1 SS q24h) or thrice weekly

160 mg thrice weekly (1 DS thrice  CRCL <10, 160 mg (1 DS or 2.5 mg/kg) thrice Peritoneal Dialysis:

weekly) weekly  Trimethoprim Component:

Dose for CRCL < 10 Lower Respiratory Tract Infections: All Other Indications:  Sulfamethoxazole Component: 160 mg (1 DS) q12h  CRCL 30 – 50, no adjustment 1 g q24h max  CRCL 10 – 29, 160 mg (1 DS or 2.5 mg/kg) Cystitis (uncomplicated): q12h CRRT: 160 mg (1 DS) q12h  CRCL <10, avoid use*  Loading Dose:

None SSTI: *If necessary, 160 mg (1 DS or 2.5 mg/kg) q24h  Maintenance Dose: 160 – 320 mg (1 – 2 DS) q12h 2.5 – 10 mg/kg q12h (10 mg/kg for PCP) *Preferred if patient also requires toxoplasmosis prophylaxis

Policy 3364-133-100 (Renal Dosing Adjustments) Page | 22 Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Valacyclovir Herpes Zoster (shingles): Herpes Zoster (shingles): Intermittent Hemodialysis: (PO) 1 g q8h x7 days  CRCL 30 – 50, 1 g q12h Dose for CRCL <10 24, 32, 51 (7 – 14 days if immunocompromised)  CRCL 10 – 29, 1 g q24h  CRCL <10, mg q24h Peritoneal Dialysis: Genital Herpes Dose for CRCL <10 (initial episode): Genital Herpes: (unless significant residual renal 1 g q12h x7 – 10 days  Initial Episode: function remains, then adjust for (5 – 10 days if immunocompromised) CRCL 30 – 50, no adjustment CRCL <30) CRCL 10 – 29, 1 g q24h Genital Herpes CRCL <10, 500 mg q24h CRRT: (recurrent episode):  Recurrent Episode (Immunocompetent): Insufficient Data  If Immunocompetent: CRCL 30 – 50, no adjustment 500 mg q12h x 3 days or CRCL <30, 500 mg q24h 1 g q24 x 5 days  Recurrent Episode (Immunocompromised):  If Immunocompromised: CRCL 30 – 50, no adjustment 1 g q12h x 5-10 days CRCL 10 – 29, 1 gm q24h CRCL <10, 500 mg q24h Genital Herpes  Suppressive Therapy: (suppressive therapy): CRCL 30 – 50, no adjustment  If Immunocompetent: CRCL <30: If usual dose 500 mg q24h, then 500 mg or 1 g q24h * adjust to 500 mg q48h, otherwise:  If Immunocompromised: 500 mg q24h 500 mg q12h Herpes Labialis: Herpes Labialis  CRCL 30 – 50, 1 g q12h x1 day (immunocompetent):  CRCL 10 – 29, 500 mg q12h x1 day 2 g q12h x1 day  CRCL <10, 500 mg as single dose

*1 g dose more effective for patients experiencing >9 recurrences per year

IHD Drug Dosing: Assumes regular thrice weekly sessions.

PD Dosing: Dosing provided is for the IV administration route, not for intraperitoneal.

CRRT Drug Dosing: Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate), and considerations for drug-resistant organisms. The presented doses are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment. Section II: Drug References Page | 23 1. Almond MK, Fan S, Dhillon S, et al. Avoiding neurotoxicity in patients with chronic renal failure undergoing haemodialysis. Nephron. 1995. 2. Amsden GW, Baird IM, Simon S, et al. Efficacy and safety of azithromycin vs levofloxacin in the outpatient treatment of acute bacterial exacerbations of chronic bronchitis. Chest. 2003. 3. Aronoff G, Bennett W, Berns J, et al. Drug prescribing in renal failure. 2007. 4. ASHP therapeutic guidelines on stress ulcer prophylaxis. Am J Health Syst Pharm. 1999. 5. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015. 6. Berbari EF, Kanj SS, Kowalski TJ, et al. Clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis. 2015. 7. Brede CM, Shoskes DA. The etiology and management of acute prostatitis. Nat Rev Urol. 2011. 8. Camilleri M, Parkman HP, Shafi MA, et al. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013. 9. Chaijamorn W, Charoensareerat T, Srisawat N, et al. Cefepime dosing regimens in critically ill patients receiving continuous renal replacement therapy: a Monte Carlo simulation study. 2018. 10. Chey WD, Leontiadis GI, Howden CW, et al. Clinical guideline: treatment of Helicobacter pylori infection . Am J Gastroenterol. 2017. 11. Chow AW, Benninger MS, Brook I, et al. Clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012. 12. Davidson MH, Armanu A, McKenney JM, et al. Safety considerations with fibrate therapy. Am J Cardiol. 2007. 13. Garcia DA, Baglin TP, Weitz JI, et al. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis. Chest. 2012. 14. Giacino JT, Whyte J, Bagiella E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012 15. Golightly LK, Teitelbaum I, Kiser TH, et al. Renal Pharmacotherapy. 2013. 16. Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the Management of Chronic Kidney Disease in HIV-Infected Patients. Clin Infect Dis. 2005. 17. Hammond FM, Bickett AK, Norton JH, et al. Effectiveness of amantadine hydrochloride in the reduction of chronic traumatic brain injury irritability and aggression. J Head Trauma Rehabil. 2014 18. He G, Massarella J, Ward P. Clinical Pharmacokinetics of the prodrug oseltamivir and its active metabolite ro 64-0802. Clin Pharmacokinet. 1999. 19. Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacother J Hum Pharmacol Drug Ther. 2009 20. Hendricks KA, Wright ME, Shadomy SV, et al. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis. 2014. 21. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia. Clin Infect Dis. 2016. 22. Kamal MA, Lien KY, Robson R, et al. Investigating clinically adequate concentrations of oseltamivir carboxylate in end-stage renal disease patients undergoing hemodialysis using a population pharmacokinetic approach. Antimicrob Agents Chemother. 2015. 23. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux. Am J Gastroenterol. 2013. 24. Lexicomp Online. http://online.lexi.com. Last Accessed on 2019 May 10. 25. Lim WS, Baudouin SV, George RC, et al. BTS guidelines for the management of community acquired pneumonia in adults. Thorax. 2009. 26. Lipsky BA, Berendt AR, Cornia PB, et al; Clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012. 27. Lodise TP Jr, Lomaestro B, Drusano GL. Piperacillin-tazobactam for pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin Infect Dis. 2007. 28. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious diseases society of america/american thoracic society consensus guidelines on the management of community- acquired pneumonia in adults. Clin Infect Dis. 2007. 29. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection. Clin Inf Dis. 2009. 30. Moayyedi PM, Lacy BE, Andrews CN, et al.. ACG and CAG clinical guideline: management of dyspepsia. Am J Gastroenterol. 2017. 31. NCCN. Prevention and treatment of cancer-related infections. 2017. Accessed 15 Feb 201 Policy 3364-133-100 (Renal Dosing Adjustments) Page | 24

32. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2018. Accessed 15 Feb 2019. 33. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis. Clin Infect Dis. 2016. 34. Patel N, Scheetz MH, Drusano GL, et al. Identification of optimal renal dosage adjustments for traditional and extended-infusion piperacillin-tazobactam dosing regimens in hospitalized patients. Antimicrob Agents Chemother. 2010. 35. Perez KK, Hughes DW, Maxwell PR, et al. Cefepime for gram-negative bacteremia in long-term hemodialysis: a single-center experience. Am J Kidney Dis. 2012. 36. Runyon BA. Management of adult patients with ascites due to cirrhosis. Hepatology. 2012. 37. Shea KM, Cheatham SC, Smith DW, et al. Comparative pharmacodynamics of intermittent and prolonged infusions of piperacillin/tazobactam using monte carlo simulations and steady-state pharmacokinetic data from hospitalized patients. Ann Pharmacother. 2009. 38. Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis. Clin Infect Dis. 2012. 39. Sica DA, Comstock T, Harford A, et al. Eur J Clin Pharmacol. 1987. 40. Sionitis KC, Zhang X, Eckard A, et al. Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the Unites States. Circulation. 2018. 41. Solomkin JS, Mazuski JE, Bradley JS, et al.; Diagnosis and management of complicated Intra-abdominal Infection in adults and children. Clin Infect Dis. 2010. 42. Stathoulopoulou F, Almond MK, Dhillon S, et al. Clinical pharmacokinetics of oral acyclovir in patients on continuoiius ambulatory peritoneal dialysis. Nephron. 1996. 43. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections. Clin Infect Dis. 2014. 44. Stryjewski ME, Szchech LA, Benjamin DK Jr, et al. Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible staphylococcus aureus bacteremia. Clin Inf Dis. 2007. 45. Swaminathan S, Alangaden GJ. Treatment of resistant enterococcal urinary tract infections. Curr Infect Dis Rep. 2010. 46. Taha AS, Hudson N, Hawkey CJ, et al. Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs. N Engl J Med 1996. 47. Trotman RL, Williamson JC, Shoemaker DM, et al. Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy. Clin Infect Dis. 2005. 48. Tunkel AR, Hasbun R, Bhimraj A, et al. Clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. 2017. 49. Turner RB, Cumpston A, Sweet M, et al. Prospective, controlled study of acyclovir pharmacokinetics in obese patients. Antimicrob Agents Chemother. 2016. 50. Vestbo J, Hurd SS, Agusti AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013. Workowski KA, Bolan GA, et al. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2 Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 25 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Amikacin (IV) Dosing per pharmacokinetics

Amphotericin B 0.5 – 1.5 mg/kg q24h Not renally eliminated but may consider reduction in Poorly dialyzed; no supplemental dose or deoxycholate total daily dose by 50% if renal dysfunction due to dosage adjustment necessary (IV) the drug Amphotericin B 3 – 5 mg/kg q24h Not renally eliminated but may consider reduction in Poorly dialyzed; no supplemental dose or liposomal (IV) total daily dose to reduce risk of further dosage adjustment necessary nephrotoxicity Atovaquone PCP treatment: No renal dose adjustment (PO) 750 mg q12h

PCP prophylaxis: 1500 mg q24h

Azithromycin 500mg q24h No renal dose adjustment (IV) Azithromycin URI: No renal dose adjustment (PO) 500 mg q24h x3 days or 500 mg x1 then 250mg q24h x4 days

MAC prophylaxis: 1200 mg once weekly or 600 mg twice weekly

Chlamydia trachomatis: 1 g x 1

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 26 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Cefotaxime (IV) SSTI (uncomplicated), Cystitis CRCL >20: Intermittent Hemodialysis: (uncomplicated): No adjustment 1 – 2 g q24h * 1 g q12h CRCL <20: Peritoneal Dialysis: CAP: 50% of usual dose at same interval 1 g q24h 1 – 2 g q8h CRRT: Septic Arthritis:  Loading Dose: 1 – 2 g q8h None  Maintenance Dose: Intra-abdominal: 1 – 2 g q6 – 8h 1-2 g q6-8h * To avoid HD removal, schedule administration Sepsis, Bacteremia, HAP/VAP: time after dialysis on dialysis days 2 g q6-8h

Meningitis: 2 g q4-6h

Cefotetan (IV) SSTI (mild to moderate): CRCL >30: Intermittent Hemodialysis: 1 g q12h No adjustment Give 25% of the usual dose q24h on NON-HD days, and 50% of the dose on HD days Cystitis: CRCL 10 – 29: 1-2 g q12h 50% of dose at same interval Peritoneal Dialysis: 1 g q24h PID SSTI (severe): CRCL <10: 2 g q12h 25% of dose at same interval CRRT: Same dose q24h Life-threatening Infections: 3 g q12h

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 27 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Cefpodoxime URI, SSTI, UTI: CRCL >50: Intermittent Hemodialysis: (PO) 100 – 400 mg q12h No adjustments Same dose after HD on HD days

CRCL 30 – 49: Peritoneal Dialysis: No adjustment Same dose q24h

CRCL 10 – 29: CRRT: Same dose q24h Insufficient Data

CRCL <10: Same dose q24h

Ceftaroline (IV) SSTI, CAP: CRCL >50: Intermittent Hemodialysis: 600 mg q12h No adjustments Dose for CRCL <10

MRSA Bacteremia, Endocarditis: CRCL 30 – 49: Peritoneal Dialysis: 600 mg q8h 400 mg at same interval Insufficient Data

CRCL 10 – 29: CRRT: 300 mg at same interval Insufficient Data

CRCL <10:  If usual dose is 600 mg q12h: 200 mg q12h  If usual dose is 600 mg q8h: 400 mg q12h

Ceftriaxone (IV) Standard Dose: No renal dose adjustment 1 g q24h

Obesity, Deep-seated Infections: 2 g q24h Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 28 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Meningitis, Endocarditis: 2 g q12h

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 29 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Cefuroxime (IV) Cystitis (uncomplicated), SSTI, PNA CRCL >20: Intermittent Hemodialysis: (uncomplicated): No adjustment Dose for CRCL and administer an additional 750 mg q8h recommended dose at the end of HD CRCL 10 – 19: Intra-abdominal, Bone and Joint Same dose q12h Peritoneal Dialysis: Infections: Same dose q24h 1.5 g q8h CRCL <10: Same dose q24h CRRT: Life-threatening Infections: 1 g q12h 1.5 g q6h

Cefuroxime (PO) Streptococcal Pharyngitis, Cystitis CRCL >30: Intermittent Hemodialysis: 3, 24 (uncomplicated): No adjustment Dose for CRCL and administer an additional 250 mg q12h recommended dose at the end of HD CRCL 10 - 29: COPD Exacerbation: Same dose q24h Peritoneal Dialysis: 250 – 500 mg q12h No Data CRCL <10: Lyme Disease, AOM, CAP: Same dose q48h CRRT: 500 mg q12h Insufficient Data

Cidofovir (IV) Consult Infectious Diseases Physician or Pharmacist

Clindamycin (IV) All Indications: No renal dose adjustment 600 – 900 mg q8h

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 30 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Clindamycin All Indications: No renal dose adjustment (PO) 300 – 450 mg q6h

Colistin (IV) Loading Dose: CRCL >70: Intermittent Hemodialysis: Cssavgtarget*x 2.0 x IBW (kg) No adjustment Same Cssavgtarget goal of 2.5 mcg/mL (max dose 300 mg CBA**) Q12h dosing is suggested. CRCL 10 – 69: Maintenance Dose: Same dose q8 – 12h  Dosing Cssavgtarget x ([1.5 x CRCL] + 30) Each 30 mg of colistin divided 2-3 times per day CRCL <10: administered equals Same dose q12h Cssavgtarget 1.0 mcg/mL, * Cssavgtarget is typically 2.5 mcg/mL therefore, total daily dose should be 75 mg ** Dosing is in colistin base activity (CBA)  Give Supplemental Dose on HD-Days Supplemental dose equals 30% of the daily maintenance dose. Supplemental dose should be added onto one of the two doses for the day and administered directly after dialysis session

Peritoneal Dialysis: Insufficient Data

CRRT: Same Cssavgtarget goal of 2.5 mcg/mL Q8 – 12h dosing is suggested.

 Dosing Each 192 mg of colistin administered equals Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 31 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Cssavgtarget 1.0 mcg/mL, therefore, total daily dose should be 480 mg

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 32 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Daptomycin (IV) See Daptomycin Dosing and Batch Printing Policy

Dicloxacillin SSTI: No renal dose adjustment (PO) 500 mg q6h

Doxycycline SSTI, URI: No renal dose adjustment (IV/PO) 100 mg q12h

Ertapenem (IV) Intra-abdominal Infection, SSTI: CRCL >30: Intermittent Hemodialysis: 1 g q24h No Adjustment 500 mg q24h; supplemental dose of 150 mg is required if dose is given within 6 CRCL 10 – 29: hours of HD 500 mg q24h Peritoneal Dialysis: CRCL <10: 500 mg q24h 500 mg q24h CRRT: 1 g q24h

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 33 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Ethambutol (PO) Tuberculosis: CRCL >10: Intermittent Hemodialysis: 15 – 25 mg/kg (max 2.5 gm) q24h No adjustment Same dose q48h * based on IBW CRCL <10: Peritoneal Dialysis: 40 – 55 kg: 800 mg Same dose q48h Same dose q48h 56 – 75 kg: 1,200 mg 76 – 90 kg: 1,600 mg CRRT: Same dose q24h

* To avoid HD removal, schedule administration time after dialysis on dialysis days

Flucytosine (PO) Cryptococcal meningitis: CRCL >50: Intermittent Hemodialysis: 12.5 – 37.5 mg/kg q6h based on ideal No adjustment Same dose q48-72h * body weight (50 – 150 mg/kg/day divided q6h) CRCL 30 – 49: Peritoneal Dialysis: Same dose q12h 0.5 – 1 gm/day *Note: Monitoring of serum flucytosine concentrations (2 hours after CRCL 10 – 29: CRRT: administration of a dose after 3 – 5 Same dose q24h Same dose q12h days of treatment) should be considered to achieve a therapeutic CRCL <10: * To avoid HD removal, schedule administration range of 30 – 80 mcg/mL Same dose q48h time after dialysis on dialysis days (concentrations over 100 mcg/mL are associated with bone marrow toxicity and hepatotoxicity)

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 34 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Foscarnet (IV) HSV Induction: For patients with CRCL <70, consult infectious diseases physician or pharmacist 40 mg/kg q8h

HSV Maintenance: 40 mg/kg q12h

CMV Induction: 90 mg/kg q12h

CMV Maintenance: 90 mg/kg q24h

Fosfomycin (PO) UTI: No renal dose adjustments 3 g sachet x 1 dose

Complicated UTI: 3 g sachet q2-3 days x3 doses

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 35 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Ganciclovir (IV) Induction: CRCL >70: Intermittent Hemodialysis: 5 mg/kg q12h No adjustment 1.25 mg/kg thrice weekly after HD *

CRCL 50 – 69: Peritoneal Dialysis: 2.5 mg/kg q12h 1.25 mg/kg q48h

CRCL 30 – 49: CRRT: 2.5 mg/kg q24h 2.5 mg/kg q12-24h

CRCL 10 – 29: * To avoid HD removal, schedule administration 1.25 mg/kg q24h time after dialysis on dialysis days

CRCL <10: 1.25 mg/kg q48h

Maintenance: CRCL >70: Intermittent Hemodialysis: 5 mg/kg q24h No adjustment 0.625 mg/kg thrice weekly after HD *

CRCL 50 – 69: Peritoneal Dialysis: 2.5 mg/kg q24h 0.625 mg/kg q48h

CRCL 30 – 49: CRRT: 1.25 mg/kg q24h 1.25 – 2.5 mg/kg q24h

CRCL 10 – 29: * To avoid HD removal, schedule administration 0.625 mg/kg q24h time after dialysis on dialysis days

CRCL <10: 0.625 mg/kg q48h

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 36 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Gentamicin (IV) Dosing per pharmacokinetics

Isoniazid (PO) Tuberculosis: No renal dose adjustment 5 mg/kg (max 300 mg) q24h *

*Supplement with 50 – 100 mg pyridoxine daily to prevent neurotoxicity

Itraconazole Fungal infections: No renal dose adjustment (PO) 200 – 400 mg q12h – 24h

Ketoconazole Fungal infections: No renal dose adjustment (PO) 200 – 400 mg q24h

Prostate cancer, Cushing syndrome: 200-400 mg q8h-12h

Linezolid IV/PO SSTI, PNA: No renal dose adjustment 600 mg q12h

Metronidazole Bacterial Vaginosis, PID, No renal dose adjustment IV/PO Trichomoniasis: 500 mg q12h x7-14 days

Intra-abdominal Infection, SSTI, All Other Indications: 500 mg q8h Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 37 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Moxifloxacin URI, SSTI, Intra-abdominal Infection: No renal dose adjustment IV/PO 400 mg q24h

Nafcillin IV All indications: No renal dose adjustment 2 g q4h

Nitrofurantoin UTI prophylaxis: No renal dose adjustment PO 50-100 mg q24h at bedtime Use not recommended in age >65 years or CRCL <30

UTI treatment:  Using Macrodantin 50-100 mg q6h x7 days  Using Macrobid 100 mg q12h x7 days

Penicillin V (PO) URI, SSTI: No renal dose adjustments; use caution in renal impairment (excretion is prolonged) 500 mg q6h Consider: 500mg q8h if CRCL 10-30; 500 mg q12h if CRCl <10

Pentamidine PCP Pneumonia: No renal dose adjustments (IV) 4 mg/kg q24h Consider: 4 mg/kg q 24 – 36h if CRCL <10

Pentamidine PCP Prophylaxis: No renal dose adjustment (Inhaled) 300 mg q4 weeks

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 38 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Posaconazole Aspergillus/Candida No renal dose adjustment (PO) (Prophylaxis and Treatment):  DR tablets 300 mg q12h x2 doses then 300 mg q24h  Suspension 200 mg q8h (may consider 200 mg q6h or 400 mg q12h for treatment of aspergillosis or other fungal infections)

Oropharyngeal Candidiasis:  Suspension 100 mg q12h x 2 doses then 100 mg q24h; up to 400 mg q12h for cases refractory to fluconazole

Posaconazole All Indications: No renal dose adjustment (IV) 300 mg q12h x 2 doses then 300 mg q24h

Pyrazinamide Tuberculosis: No renal dose adjustment Intermittent Hemodialysis: (PO) Once daily dosing 25-30 mg/kg thrice weekly after HD * Dose based on IBW Peritoneal Dialysis: 40 – 55 kg: 1,000 mg No adjustment 56 – 75 kg: 1,500 mg 76 – 90 kg: 2,000 mg CRRT: No adjustment

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 39 *Requires communication to medical team with recommendation (not part of auto-adjustment policy) * To avoid HD removal, schedule administration time after dialysis on dialysis days

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 40 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Pyrimethamine PCP or Toxoplasmosis Prophylaxis: No renal dose adjustment (PO) 50 – 75 mg once weekly (in combination with dapsone and leucovorin) or 25 mg once weekly (in combination with atovaquone and leucovorin)

Toxoplasmosis Treatment: 200 mg x1 then 50 mg (if < 60kg) or 75 mg (if > 60 kg) q24h (in combination with sulfadiazine and leucovorin)

Rifabutin (PO) Tuberculosis: No renal dose adjustment 5 mg/kg (typically 300 mg) q24h

Rifampin (PO) Mycobacterial infections: CRCL >10: Intermittent Hemodialysis: 10 mg/kg (typically 600 mg) q24h No adjustment 600 mg q24h or 600 mg thrice weekly after HD * Maximum dose: CRCL <10: 600 mg q12h 600 mg q24h Peritoneal Dialysis: (doses may range from 300 mg q8h 600 mg q24h to 300 – 600 mg q12h) CRRT: No adjustment

* To avoid HD removal, schedule administration time after dialysis on dialysis days

Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 41 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Rifapentine (PO) Tuberculosis (initial): No renal dose adjustment 10 – 20 mg/kg (600 mg) twice weekly x2 months

Tuberculosis (maintenance): 10 – 20 mg/kg (600 mg) once weekly x4 months

Rimantidine Treatment: CRCL >30: Intermittent Hemodialysis: (PO) 100 mg q12h x5 – 7 days No adjustment Insufficient Data

Prophylaxis: CRCL 10 – 29: Peritoneal Dialysis: 100 mg q12h x7 days after last known 100 mg q24h Insufficient Data exposure CRCL <10: CRRT: 100 mg q24h Insufficient Data

Tigecycline (IV) All indications: No renal dose adjustment 100 mg x1 then 50 mg q12h Adjust for liver dysfunction (Child-Pugh 7-9): 100 mg x1 then 25 mg q12h

Tobramycin (IV) Dosing per pharmacokinetics

Tobramycin PNA: No renal dose adjustment (Inhaled) 300 mg q12h

Vancomycin (IV) Dosing per pharmacokinetics Section III: Recommended Renal Dosing of Select Antimicrobial Agents Page | 42 *Requires communication to medical team with recommendation (not part of auto-adjustment policy)

Drug Standard Dosing Adjustment in Renal Impairment Adjustment in Dialysis Vancomycin C. difficile (nonsevere): No renal dose adjustment (PO) 125 mg q6h

C. difficile (fulminant): 500 mg q6h

Voriconazole All indications: No renal dose adjustment; due to potential for accumulation of intravenous beta-cyclodextrin (IV) 6 mg/kg q12h x2 doses, then 4 mg/kg vehicle, avoid in patients with renal dysfunction q12h (based on ideal or adjusted body weight) Therapeutic drug monitoring is suggested; goal is a steady state trough of 2 – 5 mcg/mL

Voriconazole All indications: No renal dose adjustment (PO) 200 mg q12h, may increase to 300 mg q12h if inadequate response or Therapeutic drug monitoring is suggested; goal is a steady state trough of 2 – 5 mcg/mL based on trough concentrations

Policy 3364-133-100 (Renal Dosing Adjustments)

Approved by: Review/Revision Date: 4/1/2018 9/1/2019 /s/ 09/24/2019 Russell Smith Pharm D, MBA, BCPS Date Chief Pharmacy Officer

/s/______09/27/2019_ Daniel Barbee MBA, BSN, RN, FACHE Date Chief Executive Officer

/s/ 09/24/2019 Dr. Heather Klepacz, MD Date Chair Pharmacy and Therapeutics Committee

Review/Revision Completed By: Pharmacy

Next Review Date: 9/1/2022 Policies Superseded by This Policy: It is the responsibility of the reader to verify with the responsible agent that this is the most current version of the policy.