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Table 6. Dosing Recommendations for Drugs Used to Treat or Prevent Opportunistic Infections that Require Dosage Adjustment in Adults With Renal Insufficiency

Individuals with reduced renal function are at risk of drug accumulation and concentration-dependent toxicities when taking medications that are primarily excreted by the kidneys. The dosage adjustment recommendations in Table 6 are based on estimates of renal function using either creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR). Although both methods are commonly used to determine dosage adjustments, it is important to note that CrCl and eGFR are not interchangeable and may yield differing results.

Renal clearance, though critical, is only one of several pharmacokinetic parameters that influence disposition of drugs that are primarily excreted by the kidneys. Other factors, such as alterations in volume of distribution or reduction in oral absorption, can also impact drug concentrations. For instance, although reduced renal clearance may necessitate a dose reduction to prevent drug accumulation, increased volume of distribution or impaired oral absorption might require a dose increase to achieve therapeutic concentrations.

Therapeutic drug monitoring (TDM), if available and appropriate, allows the clinician to make informed, individualized decisions in complicated scenarios, leading to dose adjustments that are more precise than those based on estimated CrCl or eGFR. When TDM is desired, clinicians should contact their clinical laboratory to determine assay availability and turnaround time for their institution. Drugs in this table that are used for the prevention or treatment of opportunistic infections and that are known to have assays (for clinical and/or research purposes) available within the United States and typically in Europe include the following:

  • Acyclovir
  • Amikacin
  • Ciprofloxacin
  • Clarithromycin
  • Cycloserine
  • Emtricitabine
  • Ethambutol
  • Ethionamide
  • Famciclovir
  • Fluconazole
  • Flucytosine
  • Ganciclovir
  • Levofloxacin
  • Posaconazole
  • Pyrazinamide
  • Quinine
  • Rifabutin
  • Tenofovir
  • Trimethoprim
  • Valacyclovir
  • Voriconazole
    

Note: The dosing recommendations provided for people on hemodialysis (HD) specifically apply to those receiving intermittent HD several times weekly. Guidance for other forms of renal replacement therapy (RRT), such as peritoneal dialysis or continuous RRT, is beyond the scope of these guidelines. Given the complexities of drug dosing in people receiving other forms of RRT, clinicians should consult specialists and consider TDM to ensure optimal management.

Drug(s)Usual DoseDosage Adjustment in Renal Insufficiency
CrCl^ or eGFR# (mL/min)Dose

Acyclovir

For IV acyclovir, administer IV fluid hydration to reduce the risk of nephrotoxicity.

IV Dose for Serious HSV Infections

  • 5 mg/kg IV every 8 hours

IV Dose for Serious VZV Infections or HSV Encephalitis

  • 10 mg/kg IV every 8 hours
26–50100% of dose IV every 12 hours
10–25100% of dose IV every 24 hours
<10 or HD

50% of dose IV every 24 hours

For people on HD, administer dose after HD on dialysis days.

PO Dose for Herpes Zoster: 800 mg PO five times per day10–25800 mg PO every 8 hours
<10 or HD

800 mg PO every 12 hours

For people on HD, administer dose after HD on dialysis days.

Amikacin

Administer IV fluid hydration to reduce the risk of nephrotoxicity.

For Mycobacterial Infections:

  • 15 mg/kg IV per day
  • Target peak concentration 35–‍45 mcg/mL; target trough concentration <5 mcg/mL

or

  • 25 mg/kg three times per week
  • Target peak concentration 65–‍80 mcg/mL; target trough concentration <5 mcg/mL

<60 or HD

Use with caution in people with renal insufficiency and ototoxicity.

Perform TDM to adjust dose and interval as needed to attain target concentrations. Doses likely needed only 2–3 times per week. Consider consulting local pharmacokinetic dosing services if available.

For people on HD, administer dose after HD on dialysis days.

Cidofovir

Administer IV fluid hydration and oral probenecid to reduce the risk of nephrotoxicity (see Table 2 for dosing instructions).

5 mg/kg IV on Day 0, repeat 5 mg/kg IV dose on Day 7, then 5 mg/kg IV every 2 weeks

Pretreatment SCr >1.5 mg/dL

or

CrCl <55 mL/min

or

Urine protein ≥100 mg/dL (≥2+ proteinuria)

Cidofovir is not recommended unless benefits outweigh risks. See “Pharmacokinetics of cidofovir in renal insufficiency and in continuous ambulatory peritoneal dialysis or high-flux hemodialysis” for recommendations on renal dose adjustments.
If SCr increases by 0.3–0.4 mg/dL above baseline

Decrease to 3 mg/kg IV per dose.

 

If SCr increases by ≥0.5 mg/dL above baseline

or

≥3+ proteinuria

Discontinue therapy.
Ciprofloxacin

500–750 mg PO every 12 hours

or

400 mg IV every 8–12 hours

 

30–50

 

500–750 mg PO every 12 hours

or

400 mg IV every 12 hours

<30

250–500 mg PO every 24 hours

or

400 mg IV every 24 hours

HD

250–500 mg PO every 24 hours

or

200–400 mg IV every 24 hours; administer dose after HD on dialysis days.

Clarithromycin500 mg PO every 12 hours30–60Usual dose unless used with an HIV PI or with COBI, then reduce dose by 50% (or consider using azithromycin as alternative).
<30 or HD

250 mg PO twice daily

or

500 mg PO once daily

If used with an HIV PI or COBI, reduce dose by 75% (or consider using azithromycin as alternative).

Cycloserine

10–15 mg/kg/day PO in two divided doses (maximum 1,000 mg/day); start at 250 mg once daily and increase dose per tolerability.

Target peak concentration 20–35 mcg/mL

30–80Usual dose; consider TDM and monitor for toxicities.
<30 or HD

250 mg once daily or 500 mg three times per week

Perform TDM and adjust dose accordingly. Monitor for toxicities.

Use with caution in people with ESRD who are not on dialysis.

Emtricitabinea
(FTC)

Note: Please refer to Appendix B in the Adult and Adolescent Antiretroviral Guidelines for dosing recommendations for ARV FDC products containing FTC.

One 200 mg capsule PO once daily

or

240 mg solution PO once daily

CrCl^ or eGFR# (mL/min)Oral CapsulesOral Solution

15–29

(see footnoteb)

200 mg every 72 hours80 mg every 24 hours
<15200 mg every 96 hours60 mg every 24 hours
HD (administer dose after HD on dialysis days)No dose adjustment necessary.No dose adjustment necessary.

Emtricitabine/
Tenofovir Alafenamide (FTC/TAF)

(FDC Trade Name: Descovy)

Note: Please refer to Appendix B in the Adult and Adolescent Antiretroviral Guidelines for dosing recommendations for other ARV FDC products containing FTC/TAF.

One tablet (FTC 200 mg/TAF 25 mg) PO once daily15–29

Coformulated tablet is not recommended.

See footnoteb for more information.

<15Coformulated tablet is not recommended.
HDOne tablet daily; on dialysis days, administer dose after HD.

Emtricitabine/
Tenofovir Disoproxil Fumarate (FTC/TDF)

(FDC Trade Name: Truvada)

Note: Please refer to Appendix B in the Adult and Adolescent Antiretroviral Guidelines for dosing recommendations for other ARV FDC products containing FTC/TDF.

One tablet (FTC 200 mg/TDF 300 mg) PO once daily

 

<30 or HD

Do not use coformulated tablet.

Use formulation for each component drug and adjust dose according to recommendations for the individual drugs.

Entecavir

Usual Dose: 0.5 mg PO once daily

For Treatment of 3TC-Refractory HBV or for Decompensated Liver Disease: 1 mg PO once daily

 

CrCl^ or eGFR# (mL/min)Usual Renal Dose Adjustment3TC-Refractory or Decompensated Liver Disease
30 to <50
  • 0.25 mg PO once daily, or
  • 0.5 mg PO every 48 hours
  • 0.5 mg PO once daily, or
  • 1 mg PO every 48 hours
10 to <30
  • 0.15 mg PO once daily, or
  • 0.5 mg PO every 72 hours
  • 0.3 mg PO once daily, or
  • 1 mg PO every 72 hours
<10 or HD (for people on HD, administer dose after HD on dialysis days.)
  • 0.05 mg PO once daily, or
  • 0.5 mg PO once every 7 days
  • 0.1 mg PO once daily, or
  • 1 mg PO once every 7 days
Ethambutol

For MAI: 15 mg/kg PO daily

For MTB: 15–25 mg/kg PO daily

(See the Mycobacterium tuberculosis section for additional MTB dosing recommendations.)

<30 or HD

 

 

 

 

For MAI: 15 mg/kg PO three times weekly

For MTB: 15–25 mg/kg PO three times weekly

For people on HD, administer dose after HD.

Perform TDM to guide optimal dosing.

 

Ethionamide

15–20 mg/kg PO daily

(usually 250–500 mg PO once or twice daily)

<30 or HD

250–500 mg PO once daily

Consider TDM.

Famciclovir

For Herpes Zoster: 500 mg PO every 8 hours

For HSV: 500 mg PO every 12 hours

40–59500 mg PO every 12 hours
20–39500 mg PO every 24 hours
<20250 mg PO every 24 hours
HD250 mg PO only on HD days, administer dose after HD
Fluconazole200–1,200 mg PO or IV every 24 hours (dose and route of administration depends on type of OI)≤50Administer 100% of the indication-specific initial dose, then adjust maintenance doses to 50% of dose every 24 hours.
HDAdminister 100% of the indication-specific initial dose, then adjust maintenance doses to full dose three times per week after HD.
Flucytosine

25 mg/kg PO every 6 hours

TDM is recommended to guide optimal dosing (target peak serum concentration 2 hours after dose: 25–‍100 mcg/mL). If TDM is not possible, monitor CBC twice weekly.

21–4025 mg/kg PO every 12 hours
10–2025 mg/kg PO every 24 hours
<1025 mg/kg PO every 48 hours
HD

25–50 mg/kg PO every 48–72 hours; administer dose after HD.

 

Foscarnet

Administer IV fluid hydration to reduce the risk of nephrotoxicity.

Induction Therapy for CMV Infection: 180 mg/kg/day IV in two divided doses

Maintenance Therapy for CMV Infection or for Treatment of HSV Infections: 90–120 mg/kg IV once daily

Dosage adjustment needed according to calculated CrCl/kg; consult product label for dosing table.Dosage adjustment needed according to calculated CrCl/kg; consult product label for dosing table.
Ganciclovir

Induction Therapy: 5 mg/kg IV every 12 hours

 

50–692.5 mg/kg IV every 12 hours
25–492.5 mg/kg IV every 24 hours
10–241.25 mg/kg IV every 24 hours
<10 or HD

1.25 mg/kg IV three times per week

For people on HD, administer dose after HD.

Maintenance Therapy: 5 mg/kg IV every 24 hours

 

50–692.5 mg/kg IV every 24 hours
25–491.25 mg/kg IV every 24 hours
10–240.625 mg/kg IV every 24 hours
<10 or HD

0.625 mg/kg IV three times per week.

For people on HD, administer dose after HD.

Lamivudine (3TC)

Note: Please refer to Appendix B in the Adult and Adolescent Antiretroviral Guidelines for dosing recommendations for other ARV FDC products containing 3TC.

300 mg PO every 24 hours

See footnoted for more information on alternative dosing.

CrCl^ or eGFR# (mL/min)Epivir LabelcAlternative Dose
15–29150 mg PO once, then 100 mg PO every 24 hours100–150 mg every 24 hours
5–14150 mg PO once, then 50 mg PO every 24 hours100–150 mg every 24 hours
<5 or HD (for people on HD, administer dose after HD on dialysis days)50 mg PO once, then 25 mg PO every 24 hours100–150 mg every 24 hours

Lamivudine/
Tenofovir Disoproxil Fumarate (3TC/TDF)

(FDC Trade Name: Cimduo)

Note: Please refer to Appendix B in the Adult and Adolescent Antiretroviral Guidelines for dosing recommendations for other ARV FDC products containing 3TC/TDF.

One tablet (3TC 300 mg/TDF 300 mg) PO once daily

 

<50 or HD

Coformulated tablet is not recommended.

 

Levofloxacin

500 mg (low dose) or 750–1,000 mg (high dose) IV or PO daily

Dose can be adjusted based on serum concentrations

CrCl^ or eGFR# (mL/min)Low DoseHigh Dose
20–49500 mg once, then 250 mg every 24 hours, IV or PO750 mg every 48 hours IV or PO
<20 or HD (for people on HD, administer dose after HD on dialysis days)500 mg once, then 250 mg every 48 hours, IV or PO750 mg once, then 500 mg every 48 hours, IV or PO
Paromomycin500 mg PO every 6 hours<10 or HDMinimal systemic absorption. No dosage adjustment necessary but monitor for worsening renal function and ototoxicity in people with ESRD.
Penicillin G (Potassium
or Sodium)

Neurosyphilis, Ocular Syphilis, or Otosyphilis

  • 3–4 million units IV every 4 hours, or
  • 18–24 million units IV daily as continuous infusion
10–502–3 million units IV every 4 hours or 12–18 million units IV as continuous infusion
<102 million units IV every 4–6 hours or 8–12 million units IV as continuous infusion
HD2 million units IV every 4–6 hours or 8 million units IV as continuous infusion
Pentamidine

4 mg/kg IV every 24 hours

May reduce dose to 3 mg/kg IV daily in the event of toxicities.

<10 or HD4 mg/kg IV every 48 hours
Posaconazole

IV: 300 mg twice daily on Day 1; then 300 mg once daily

Delayed-Release Tablet: 300 mg (three 100 mg delayed-release tablets) PO once daily

Oral Suspension: 400 mg PO twice daily

 

<50 or HD

The manufacturer recommends that IV posaconazole be avoided because of potential toxicity due to accumulation of SBECD (vehicle of IV product), unless benefits outweigh risks. An observational study did not find worsening in renal function in people with CrCl <50 ml/min given SBECD.

Switch people with CrCl <50 mL/min to oral posaconazole when feasible.

No dosage adjustment of oral dose in people with renal insufficiency. Higher variability in serum concentrations observed in people with CrCl <20 mL/min.

Perform posaconazole TDM (target trough concentration >1.25 mcg/mL for treatment).

PyrazinamideSee the Mycobacterium tuberculosis section for weight-based dosing guidelines.<30 or HD

25–35 mg/kg/dose three times per week

For people on HD, administer dose after HD.

Perform TDM to guide optimal dosing.

Quinine Sulfate650 mg salt (524 mg base) PO every 8 hours<10 or HD650 mg once, then 325 mg PO every 12 hours
Rifabutin

5 mg/kg PO daily (usually 300 mg PO daily)

See the Mycobacterium tuberculosis section and Drug–Drug Interactions in the Adult and Adolescent Antiretroviral Guidelines for dosage adjustment based on interactions with ARVs.

<30Perform rifabutin TDM. If rifabutin-associated neutropenia is suspected, consider 50% of dose once daily.
Streptomycin

15 mg/kg IM or IV every 24 hours

or

25 mg/kg IM or IV three times per week

Use with caution in people with renal insufficiency.

TDM is no longer available. Consider an alternative aminoglycoside, as clinically appropriate.

If used: 15 mg/kg two to three times weekly. Administer dose after HD.

Sulfadiazine

Administer oral or IV fluid hydration to reduce the risk for nephrotoxicity.

1,000–1,500 mg PO every 6 hours (1,500 mg every 6 hours for people >60 kg)

≤50 or HD

 

No data. Use alternative anti-toxoplasma therapy.

 

Tecovirimat

IV:

35 to <120 kg

  • 200 mg every 12 hours

≥120 kg

  • 300 mg every 12 hours
30–89

No dosage adjustment necessary.

Use with caution because of potential accumulation of hydroxypropyl-β-cyclodextrin.

<30

Contraindicated because of potential accumulation of hydroxypropyl-β-cyclodextrin.

Note: IV formulation may be considered in people with CrCl <30 only if drug absorption via enteral administration is expected to be problematic based on an individual risk–benefit assessment in consultation with CDC. In these circumstances, use with caution and monitor renal function continuously. Switch to the oral formulation as soon as possible.

PO:

40 to <120 kg

  • 600 mg every 12 hours

≥120 kg

  • 600 mg every 8 hours
Any eGFRNo dosage adjustment necessary.

Tenofovir Alafenamide (TAF)

Note: Please refer to Appendix B in the Adult and Adolescent Antiretroviral Guidelines for dosing recommendations for other ARV FDC products containing TAF.

25 mg PO daily

<15

 

Not recommended

 

HDNo dosage adjustment necessary. Administer dose after HD on dialysis days.

Tenofovir Disoproxil Fumarate (TDF)

Note: Please refer to Appendix B in the Adult and Adolescent Antiretroviral Guidelines for dosing recommendations for other ARV FDC products containing TDF.

300 mg PO daily30–49300 mg PO every 48 hours (consider switching to TAF for treatment of HBV)
10–29300 mg PO every 72–96 hours (consider switching to alternative agent for treatment of HBV)
<10Not recommended
HD300 mg PO once weekly; administer dose after dialysis.

Trimethoprim/
Sulfamethoxazole (TMP-SMX)

Encourage oral hydration when using oral TMP-SMX.

For PCP Treatment:

  • 5 mg/kg (of TMP component) IV every 6–‍8 hours, or
  • Two TMP-SMX DS tablets PO every 8 hours

 

15–305 mg/kg (TMP) IV every 12 hours, or two TMP-SMX DS tablets PO every 12 hours
<155 mg/kg (TMP) IV every 24 hours, or one TMP-SMX DS tablet PO every 12 hours (or two TMP-SMX DS tablets every 24 hours)
HD

5 mg/kg (TMP) IV every 24 hours, or two TMP-SMX DS tablets PO daily; on dialysis days, administer dose after HD.

Consider TDM to optimize therapy (target TMP concentrations: 5–8 mcg/mL).

For PCP Prophylaxis:

  • One TMP-SMX DS tablet PO daily,
  • One TMP-SMX DS tablet PO three times per week, or
  • One TMP-SMX SS tablet PO daily
15–30Reduce dose by 50% (e.g., 1 SS tablet PO daily).
<15 or HD

Reduce dose by 50% or use alternative agent.

For people on HD, administer dose after HD on dialysis days.

For TE Treatment: 5 mg/kg (TMP component) IV or PO every 12 hours

 

15–305 mg/kg (TMP component) IV or PO every 24 hours
<15 or HD

5 mg/kg (TMP component) IV or PO every 24 hours or use alternative agent.

For people on HD, administer dose after HD on dialysis days).

For TE Chronic Maintenance Therapy:

  • One TMP-SMX DS tablet twice daily, or
  • One TMP-SMX DS tablet daily
15–30Reduce dose by 50%.
<15 or HD

Reduce dose by 50% or use alternative agent.

For people on HD, administer dose after HD on dialysis days).

For Toxoplasmosis Primary Prophylaxis: One TMP-SMX DS tablet PO daily15–30Reduce dose by 50%.
<15 or HD

Reduce dose by 50% or use alternative agent.

For people on HD, administer dose after HD on dialysis days.

Valacyclovir

Encourage oral fluid hydration to reduce the risk for nephrotoxicity.

For Herpes Zoster: 1 g PO three times daily30–491 g PO every 12 hours
10–291 g PO every 24 hours
<10 or HD

500 mg PO every 24 hours

For people on HD, administer dose after HD on dialysis days).

For HSV Treatment: 1 g PO twice daily

For HSV Chronic Suppressive Therapy: 500 mg PO twice daily

30–49No dosage adjustment necessary.
10–29

For Treatment: 1 g PO every 24 hours

For Suppressive Therapy: 500 mg PO every 24 hours

<10 or HD

500 mg PO every 24 hours

For people on HD, administer dose after HD on dialysis days).

Valganciclovir

Encourage oral fluid hydration to reduce the risk for nephrotoxicity.

Induction Therapy: 900 mg PO twice daily

Maintenance Therapy: 900 mg PO once daily

CrCl^ or eGFR# (mL/min)InductionMaintenance
40–59450 mg PO twice daily450 mg PO daily
26–39450 mg PO daily450 mg PO every 48 hours
10–25450 mg PO every 48 hours450 mg PO twice weekly
<10 or HD (for people on HD, administer dose after HD on dialysis days)

Not recommended

Use IV ganciclovir.

May consider:

  • 200 mg (oral powder for solution) PO three times per week

If oral powder formulation is not available, consider:

  • 450 mg (tablet) PO three times weekly

Not recommended

Use IV ganciclovir.

May consider:

  • 100 mg (oral powder for solution) PO three times per week

If oral powder formulation is not available, consider:

  • 450 mg (tablet) PO twice weekly
Voriconazole

6 mg/kg IV every 12 hours for two doses, then 4 mg/kg IV every 12 hours

or

200–300 mg PO every 12 hours

 

<50 or HD

IV voriconazole is not recommended by the manufacturer for CrCl <50 ml/min because of potential toxicity from accumulation of SBECD (vehicle of IV product). Observational studies did not find worsening in renal function in people with CrCl <50 ml/min.

Switch people with CrCl <50 ml/min or on HD to oral voriconazole when feasible. No need for dosage adjustment when the oral dose is used.

Perform TDM to adjust dose.

a The prescribing information for emtricitabine (Emtriva) recommends adjusting doses for people with CrCl 30–49 mL/min and for people on hemodialysis. However, the prescribing information for certain FDC products that contain emtricitabine (including Descovy, Biktarvy, Genvoya, and Odefsey) recommends that the standard dose (emtricitabine 200 mg) can be given once daily in these individuals (for people on HD, administer dose after HD on dialysis days). The recommendations in this table incorporate the dosing guidance from the FDC products.

b To allow people to remain on certain TAF-containing FDC products, some clinicians may use full-dose, daily emtricitabine in people with CrCl 15–29 mL/min who are not on HD. For more information, see the Adult and Adolescent Antiretroviral Guidelines.

c The prescribing information for lamivudine (Epivir) recommends dosage adjustment from 300 mg once daily to 150 mg once daily for people with CrCl 30–49 mL/min. However, the prescribing information for certain FDC products that contain lamivudine (including Dovato and Triumeq) recommends no dose adjustment for CrCl 30–49 mL/min. The recommendations in this table incorporate the dosing guidance from the FDC products.

d Clinicians may consider using the nearest available lamivudine tablet strength (100 mg or 150 mg) to avoid the need for 3TC oral solution, thereby simplifying regimens and facilitating adherence. Some clinicians may use full-dose 3TC to allow people to remain on certain FDC antiretroviral products. For more information, see the Adult and Adolescent Antiretroviral Guidelines.

^ CrCl based on the Cockroft-Gault formula can be determined using this CrCl calculator. Please refer to the drug’s prescribing information and to the National Institute of Diabetes and Digestive and Kidney Diseases Determining Drug Dosing in Adults with Chronic Kidney Disease page for a discussion on using CrCl based on the Cockcroft-Gault equation versus eGFR.

# eGFR based on the 2021 CKD-EPI equation can be determined using this eGFR calculator. Please refer to the drug’s prescribing information and to the National Institute of Diabetes and Digestive and Kidney Diseases Determining Drug Dosing in Adults With Chronic Kidney Disease page for a discussion on using CrCl based on the Cockcroft-Gault equation versus eGFR.

Key: 3TC = lamivudine; ARV = antiretroviral; CBC = complete blood count; CDC = Centers for Disease Control and Prevention; CMV = cytomegalovirus; COBI = cobicistat; CrCl = creatinine clearance; DS = double strength; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; FDC = fixed-dose combination; FTC = emtricitabine; HBV = hepatitis B virus; HD = hemodialysis; HSV = herpes simplex virus; IM = intramuscular; IV = intravenous; MAI = Mycobacterium avium intracellulare; MTB = Mycobacterium tuberculosis; OI = opportunistic infection; PCP = Pneumocystis pneumonia; PI = protease inhibitor; PO = orally; SCr = serum creatinine; SBECD = sulfobutylether cyclodextrin; SS = single strength; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TDM = therapeutic drug monitoring; TE = Toxoplasma gondii encephalitis TMP-SMX = trimethoprim-sulfamethoxazole; VZV = varicella zoster virus

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