| Drug | Hepatic Dysfunction | Renal Dysfunction |
| Bilirubin (mg/dL and μmol/L) | AST/SGOT (units/L) ALT/SGPT (units/L) | Percent Dosage/Dose Administered | Creatinine Clearance (CrCL) (mL/min) or Serum Creatinine (SCr) (mg/dL and μmol/L) | Percent Dosage/Dose Administered |
| Abiraterone acetate1 | Child-Pugh Class B (moderate hepatic impairment prior to starting treatment) | Reduce dose to 250 mg once daily | No Dosage Adjustments Necessary |
| Child-Pugh Class C (severe hepatic impairment prior to starting treatment) | Has not been studied in this population: avoid |
| Bilirubin >3 × ULN during treatment | ALT and/or AST >5 × ULN during treatment | Interrupt treatment. Restart 750 mg once daily after LFTs return to baseline or AST and ALT ≤2.5 × ULN and bilirubin <1.5 × ULN |
| Bilirubin >3 × ULN while receiving 750 mg once daily | ALT and/or AST >5 × ULN during treatment with 750 mg once daily | Interrupt treatment. Re-start 500 mg once daily after LFTs return to baseline or AST and ALT ≤2.5 × ULN and l bilirubin <1.5 × ULN |
| Bilirubin >3 × ULN while receiving 500 mg once daily | ALT and/or AST >5 × ULN during treatment with 500 mg once daily | Discontinue treatment |
| ado-Trastuzumab emtansine2 | Mild, moderate and severe hepatic impairment | No clinical trials have been conducted | Mild to moderate renal impairment (CrCL 30–90 mL/min [0.5–1.5 mL/s]) | No dosage adjustments necessary |
| Severe renal impairment (CrCL <30 mL/min [<0.5 mL/s]) | No clinical trials have been conducted |
| Afatinib | Child-Pugh Class C (severe hepatic impairment) | Limited data available. Monitor closely for toxicity | CrCL <30 mL/min | No data |
| CrCL 30–59 mL/min | Trough plasma concentration ⇧85% |
| CrCL 60–89 mL/min | Trough plasma concentration ⇧27% |
| CrCL >90 mL/min | No effect |
| Afatinib dimaleate3 | Mild to moderate hepatic impairment | No dosage adjustment necessary | CrCL 60–89 mL/min [1–1.48 mL/s] | No dosage adjustment necessary |
| Severe hepatic impairment | Monitor carefully and adjust dose if not tolerated | CrCL 30–59 mL/min [0.5–0.98 mL/s] CrCL <30 mL/min [<0.5 mL/s] | Monitor carefully and adjust dose if not tolerated |
| Aldesleukin4,5,6 | No dosage adjustments necessary | SCr>4.5 mg/dL (>398 μmol/L) | Hold or discontinue treatment. Resume when SCr <4 mg/dL (<354 μmol/L) |
| SCr ≥4.0 mg/dL (≥354 μmol/L) in presence of severe volume overload, acidosis, or hyperkalemia | Hold or discontinue treatment. Resume when SCr <4 mg/dL (<354 μmol/L) and fluid and electrolyte status are stable |
| Renal failure requiring dialysis >72 hours while receiving an earlier course of therapy | Treatment contraindicated |
| Persistent oliguria or urine output <10 mL/hour for 16–24 hours with rising serum creatinine | Withhold dose; may resume when urine output >10 mL/hour with serum creatinine decrease of >1.5 mg/dL (>133 μmol/L) or normalization |
| Alitretinoin7 | No dosage adjustments necessary | No dosage adjustments necessary |
| Alemtuzumab8 | No dosage adjustments necessary | No dosage adjustments necessary |
| Altretamine9 | No dosage adjustments necessary | No dosage adjustments necessary |
| Amifostine10 | No dosage adjustments necessary | No dosage adjustments necessary |
| Aminoglutethimide11 | No dosage adjustments necessary | No dosage adjustments necessary |
| Amsacrine12,13,14 | >2 mg/day (>34 μmol/L) | | Administer 60–75% of dosage | SCr 1.2–1.8 mg/dL (106–159 μmol/L) | Administer 75–100% of dosage |
| Severe hepatic impairment | Administer 50% of dosage | SCr 2–3 mg/dL, (177–265 μmol/L) | Administer 60–70% of dosage |
| Oliguric patients | Adjust dosage based on toxicity |
| Anagrelide HCl15 | Moderate hepatic impairment | Starting dose of 0.5 mg/day must be maintained for 1 week with cardiovascular monitoring. Do not increase dose more than 0.5 mg/day during any week. Measure liver function tests before and during treatment | No dosage adjustments necessary, but monitor renal function closely |
| Severe hepatic impairment | Do not administer |
| Anastrozole16 | Mild-to-moderate hepatic impairment | No dosage adjustments necessary | No dosage adjustments necessary |
| Severe hepatic impairment | No data available |
| Arsenic trioxide17 | Child-Pugh Class C (severe hepatic impairment) | Limited data available. Monitor closely for toxicity | CrCl <30 mL/min | Monitor closely; may require dosage reduction |
| Dialysis patients | Has not been studied |
| Axitinib18 | Mild hepatic impairment | No dosage adjustment necessary | Mild to severe renal impairment (CrCl 15 to <89 mL/min [0.25 to <1.48 mL/s]) | No dosage adjustment necessary |
| Moderate hepatic impairment | Reduce starting dosage |
| Severe hepatic impairment | Not recommended as it has not been studied | End stage renal disease (CrCL <15 mL/min [<0.25 mL/s]) | Use is not recommended as it has not been studied. Use only with caution |
| Azacitidine19 | Hepatic impairment | No data available. Monitor closely for toxicity | Elevations of BUN or SCr | Delay next cycle until values return to normal or baseline and reduce dosage by 50% |
| Asparaginase20 | Specific guidelines for dosage adjustments in hepatic impairment are not available; however, these patients may be at increased risk for toxicity. Evaluate hepatic enzymes and bilirubin pretreatment and periodically during treatment. Use caution in patients with a history of coagulopathy | Specific guidelines for dosage adjustments in renal impairment not available; it appears that no dosage adjustments are needed |
| Bendamustine HCl21 | Mild hepatic impairment | | Use with caution | CrCl 40–60 mL/min | Use with caution |
| 1.5–3 × ULN | AST or ALT 2.5–10 × ULN | Do not administer | CrCl <40 mL/min | Do not administer |
| >3 × ULN | | Do not administer | |
| Bevacizumab22 | No dosage adjustments necessary | No dosage adjustments necessary |
| Bexarotene23 | No specific studies have been conducted in patients with hepatic insufficiency. Less than 1% of a dose is excreted in the urine unchanged and there is in vitro evidence of extensive hepatic contribution to bexarotene elimination, thus hepatic impairment would be expected to lead to greatly decreased clearance. Use with great caution in this population | No formal studies have been conducted in patients with renal insufficiency. However, renal insufficiency may result in significant protein binding changes and may alter pharmacokinetics of bexarotene, so use caution |
| Bicalutamide24,25 | No adjustment required for mild, moderate, or severe hepatic impairment. Use caution with moderate-to-severe impairment. Consider periodic LFTs during long-term therapy. Discontinue if ALT >2 × ULN or jaundice develops | No dosage adjustment is necessary |
| Bleomycin sulfate26,27,28 | Not studied in patients with hepatic impairment; adjustment for hepatic impairment may be needed | Dosage recommendations using Cockcroft and Gault formula |
| CrCl >50 mL/min | Administer 100% of dosage |
| CrCl 40–49 mL/min | Administer 70% of dosage |
| CrCl 30–39 mL/min | Administer 60% of dosage |
| CrCl 20–29 mL/min | Administer 55% of dosage |
| CrCl 10–19 mL/min | Administer 45% of dosage |
| CrCl 5–9 mL/min | Administer 40% of dosage |
| |
| Continuous renal replacement therapy (CRRT) | Administer 75% of dose |
| Note: Terminal elimination half-life increases exponentially as the creatinine clearance decreases. Administration of nephrotoxic drugs with bleomycin may affect its renal clearance |
| Bosutinib29 | Mild, moderate and severe hepatic impairment | 200 mg/day | CrCL <30 mL/min [<0.5 mL/s] | 300 mg/day |
| Bortezomib30 | 1.5–3 × ULN | | Reduce dosage to 0.7 mg/m2 in the first cycle. Consider escalation to 1.0 mg/m2 or further reduction to 0.5 mg/m2 in subsequent cycles based on tolerability | No dosage adjustments necessary Note: Dialysis may reduce concentrations, so the drug should be administered postdialysis |
| Brentuximab vedotin31 | No dosage adjustments necessary | No dosage adjustments necessary |
| Buserelin acetate32 | No dosage adjustments necessary | No dosage adjustment necessary |
| Busulfan33 | Has not been administered in clinical studies to patients with hepatic impairment. Has extensive hepatic metabolism. Dosage adjustment may be necessary, although specific guidelines are not available | No data in patients with renal impairment. Renal excretion is <3% |
| Cabazitaxel34 | No hepatic impairment data available. Patients with total bilirubin >ULN and AST and/or ALT >1.5 × ULN were excluded from trials. Cabazitaxel is extensively metabolized by the liver and hepatic impairment is likely to increase cabazitaxel concentrations | CrCl <30 mL/min or end-stage renal disease | Use with caution |
| Cabozantinib S-malate35 | Moderate to severe hepatic impairment | Avoid | Mild to moderate renal impairment (CrCL 30–90 mL/min [0.5–1.5 mL/s]) | No dosage adjustment necessary |
| Severe renal impairment (CrCL <30 mL/min [<0.5 mL/s]) | Do not administer |
| Capecitabine36,37,39 | Mild-to-moderate hepatic dysfunction caused by liver metastases | No dosage adjustment necessary. Monitor carefully | CrCl 51–80 mL/min | No dosage adjustment necessary |
| CrCl 30–50 mL/min | Reduce dosage to 75% |
| Severe hepatic dysfunction | No data available | CrCl <30 mL/min | Do not administer |
| Carboplatin27,28,38,39 | No dosage adjustments necessary for initial therapy | Patients with CrCl values less than 60 mL/min are at increased risk of severe bone marrow suppression. Incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% with the tiered dosage modifications shown below [Note: Dose modification for impaired renal function is not necessary for carboplatin doses based on systemic exposure (AUC) calculations, such as the methods described by Calvert et al, Chatelut et al, and Bénezét et al] |
| CrCl 41–59 mL/min | 250 mg/m2 (Day 1) |
| CrCl 16–40 mL/min | 200 mg/m2 (Day 1) |
| CrCl ≤15 mL/min | No guidelines available |
| Hemodialysis | Administer 50% of dosage |
| Continuous ambulatory peritoneal dialysis (CAPD) | Administer 25% of dosage |
| Continuous renal replacement therapy (CRRT) | 200 mg/m2 |
| Carfilzomib40 | Bilirubin ≥2 × ULN | ALT/AST ≥3 × ULN | Not recommended as it has not been studied and these were exclusion criteria from trials | Mild, moderate and severe renal impairment | No dosage adjustment necessary |
| Hemodialysis | Administer after dialysis |
| Carmustine27,28 | Dosage adjustment may be necessary, but no specific guidelines are available | CrCl 46–60 mL/min | Administer 80% of dosage |
| CrCl 31–45 mL/min | Administer 75% of dosage |
| CrCl <30 mL/min | Consider alternative therapy |
| Cetuximab41 | No dosage adjustments necessary | No dosage adjustments necessary |
| Chlorambucil | Hepatic metabolism into active and inactive metabolites. Dosage adjustment may be needed in patients with hepatic impairment | CrCl 10–50 | Administer 75% of dosage |
| CrCl <10 mL/min | Administer 50% of dosage |
| Hemodialysis | Administer 50%; no supplemental dosing |
| Peritoneal dialysis | Administer 50%; no supplemental dosing |
| Cisplatin27,28 | No dosage adjustments necessary | CrCl 10–50 mL/min | Administer 75% of dosage |
| CrCl<10 mL/min | Administer 50% of dosage |
| Hemodialysis | Administer 50% of dosage post-dialysis |
| Peritoneal dialysis | Administer 50% of dosage |
| Continuous renal replacement therapy (CRRT) | Administer 75% of dosage |
| Cladribine42 | No specific dosage adjustment guidelines are available due to lack of data. Caution should be used in patients with hepatic impairment | Note: Clinicians have used the guidelines below. The manufacturer recommends repeat courses should not be given until SCr <1.5 mg/dL (<133 μmol/L) and/or BUN <25 (<8.9 mmol/L). No formal recommendation from FDA beyond use with caution |
| CrCl 10–50 mL/min | Adult: 75% of dosage |
| CrCl <10 mL/min | Adult: 50% of dosage |
| Clofarabine43 | Safety not established. Use with caution | Primary urinary excretion. Safety not established. Use with caution |
| Crizotinib44 | Data are insufficient to determine if dosage adjustments are necessary. Use with caution. As crizotinib is extensively metabolized in the liver, hepatic impairment is likely to increase plasma crizotinib concentrations | CrCl 30–90 mL/min | No dosage adjustments necessary |
| CrCl <30 mL/min | Starting dosage adjustments have not been determined; Use caution |
| End-stage renal disease | No data; use caution35 |
| Continuous ambulatory peritoneal dialysis (CAPD) | 75% of normal dosage |
| Continuous renal replacement therapy (CRRT) | No adjustment |
| Cytarabine 100–200 mg/m2 |
| No dosage adjustments necessary |
| Cytarabine14,28,46 | Dosage adjustments may be necessary, but no specific guidelines are available. Some clinicians have used the guidelines below. Transaminases (any elevation): administer 50% of dose; may increase subsequent doses in the absence of toxicities | High-dose Cytarabine 1000–3000 mg/m2 per dose |
| CrCl = 46–60 mL/min | Administer 60% of dosage |
| CrCl = 31–45 mL/min | Administer 50% of dosage |
| CrCl <30 mL/min | Consider use of alternative drug |
>2 mg/dL (>34 μmol/L) | Administer 50% of dosage. May increase subsequent dosages in the absence of toxicities | High-dose Cytarabine ≥2000 mg/m2 per dose |
| SCr 1.5–1.9 mg/dL (133–168 μmol/L) or an ↑ from baseline of 0.5–1.2 mg/dL (44–106 μmol/L) | Reduce dosage to 1000 mg/m2 per dose |
| SCr ≥2 mg/dL (≥176 μmol/L) or ↑ from baseline of >1.2 mg/dL (>106 μmol/L) | Reduce dosage to 100 mg/m2 per day as a continuous infusion |
| Cytarabine lipid complex (liposome)47 | No dosage adjustments necessary | No dosage adjustments necessary |
| Dabrafenib | Child-Pugh Class B-C (moderate to severe hepatic impairment) | Limited data available. Monitor closely for toxicity | Mild-moderate renal impairment | No dosage adjustment necessary |
| Severe renal impairment | Limited data available. Monitor closely for toxicity |
| Dabrafenib mesylate48 | Mild hepatic impairment | No dosage adjustments necessary | Mild to moderate renal impairment (CrCL 30–90 mL/min [0.5–1.5 mL/s]) | No dosage adjustments necessary |
| Moderate to severe hepatic impairment | No clinical trials have been conducted | Severe renal impairment (CrCL <30 mL/min [<0.5 mL/s]) | No clinical trials have been conducted |
| Dacarbazine49,50 | Dosage adjustments may be necessary but no specific guidelines are available | FDA-approved labeling does not contain dosage adjustment guidelines, but the following guidelines below have been used by some clinicians |
| CrCl 46–60 mL/min | Administer 80% of dosage |
| CrCl 31–45 mL/min | Administer 75% of dosage |
| CrCl <30 mL/min | Administer 70% of dosage |
| Dactinomycin51,52 | Dosage adjustment is unlikely to be necessary | No dosage adjustments necessary |
3 mg/dL (>51 μmol/L) | Administer 50% of dosage |
| Darbepoetin alfa53 | No dosage adjustments necessary | No dosage adjustments necessary |
| Dasatinib54 | No dosage adjustments necessary Note: After administering a 70-mg dose, compared to subjects with normal liver function, patients with moderate hepatic impairment (Child-Pugh Class B) had decreases in dose normalized Cmax and AUC of 47% and 8%, respectively; while patients with severe hepatic impairment (Child-Pugh Class C) had dose normalized Cmax decreased by 43% and AUC decreased by 28% compared to normal controls. These differences in Cmax and AUC are not clinically relevant | Currently no clinical studies on renal insufficiency. Less than 4% of dasatinib and its metabolites are excreted via the kidney |
| Daunorubicin HCl55 | 1.2–3.0 mg/dL (21–51 μmol/L) | Administer 75% of dosage | SCr >3 mg/dL (>265 μmol/L) | Administer 50% of dosage |
>3 mg/dL (>51 μmol/L) | Administer 50% of dosage |
>5 mg/dL (>85 μmol/L) | Hold therapy |
| Daunorubicin citrate Liposomal56 | 1.2–3.0 mg/dL (21–51 μmol/L) | Administer 75% of dosage | SCr >3 mg/dL (>265 μmol/L) | Administer 50% of dosage |
>3 mg/dL (>51 μmol/L) | Administer 50% of dosage |
| Decitabine57 | No data exists on the use of decitabine in patients with hepatic dysfunction; therefore, it should be used with caution. If bilirubin and/or ALT is >2 × ULN temporarily hold until resolution | No data exists on the use of decitabine in patients with renal dysfunction; therefore, it should be used with caution. If SCr >2 mg/dL (>177 μmol/L) temporarily withhold decitabine until resolution |
| Denosumab58 | No clinical trials have been conducted | CrCl <30 mL/min | Use with caution. No dosage adjustment |
| Denileukin diftitox59 | No dosage reductions necessary | No dosage reductions necessary |
| Dexrazoxane HCl60 | No dosage reductions necessary | CrCl <40 mL/min | Administer 50% of dosage |
| Docetaxel61,62,63,64,65,66 | >ULN | AST or ALT >1.5 × ULN and alkaline phosphatase >2.5 × ULN | Do not administer | No dosage reductions necessary Note: Not removed by hemodialysis; may be administered before or after hemodialysis |
| | AST or ALT 2.5–5 × ULN and alkaline phosphatase <2.5 × ULN | Administer 80% of dosage |
| | AST or ALT 1.5–5 × ULN and alkaline phosphatase >2.5–5 × ULN | Administer 80% of dosage |
| | AST or ALT >5 × ULN and/or alkaline phosphatase >5 × ULN | Do not administer |
| Doxorubicin HCl67,68,69 | 1.2–3 mg/dL (21–51 μmol/L) | | Administer 50% of dosage | No dosage reductions necessary |
3.1–5 mg/dL (51–85 μmol/L) | | Administer 25% of dosage |
>5 mg/dL (>85 μmol/L) | | Contraindicated |
| Doxorubicin HCl liposomal68,70 | 1.2–3 mg/dL (21–51 μmol/L) | | Administer 50% of dosage | No dosage reductions necessary |
3.1–5 mg/dL (51–85 μmol/L) | | Administer 25% of dosage |
>5 mg/dL (>85 μmol/L) | | Contraindicated |
| Enzalutamide71 | Mild to moderate hepatic impairment | No dosage adjustments necessary | Creatinine clearance 30 to ≤89 mL/min [0.5 to ≤1.48 mL/s]) | No dosage adjustment necessary |
| Severe hepatic impairment | No clinical trials have been conducted | CrCL <30 mL/min [<0.5 mL/s] | No clinical trials have been conducted |
| Epirubicin HCl39,72,73 | 1.2–3 mg/dL (21–51 μmol/L) | AST 2–4 × ULN | Administer 50% of dosage | CrCl <50 mL/min | No dosage adjustments necessary33 |
>3 mg/dL (>51 μmol/L) | AST >4 × ULN | Administer 25% of dosage | SCr >5 mg/dL (>442 μmol/L) | Dosage adjustment required; no specific guidelines |
| Severe hepatic impairment | Use is contraindicated | |
| Epoetin Alfa74 | No dosage adjustments necessary | No dosage adjustments necessary |
| Eribulin mesylate75 | Child-Pugh Class A (mild hepatic impairment) | Reduce dosage to 1.1 mg/m2 | CrCl >50 mL/min | No dosage adjustments necessary |
| Child-Pugh Class B (moderate hepatic impairment) | Reduce dosage to 0.7 mg/m2 | CrCl 30–50 mL/min | Reduce dosage to 1.1 mg/m2 |
| Child-Pugh Class C (severe hepatic impairment) | Use has not been studied | CrCl <30 mL/min | No clinical trials have been conducted |
| Erlotinib HCl76,77 | In vitro and in vivo data suggest erlotinib is cleared primarily by the liver. However, erlotinib exposure was similar in patients with moderately impaired hepatic function (Child-Pugh B) and patients with adequate hepatic function, including patients with primary liver cancer or hepatic metastases | No dosage adjustments necessary. Less than 9% of a single dose is excreted in the urine |
1–7 mg/dL (17–120 μmol/L) | AST >3 × ULN | Administer 50% dosage. Escalate dosage if tolerated |
| >3 × ULN | ALT or AST >5 × ULN | Use extreme caution if at baseline, or D/C therapy if already in progress |
| >ULN | Child-Pugh A, B, and C (mild, moderate, and severe hepatic impairment) | Monitor closely |
| Note: Erlotinib dosing should be interrupted or discontinued if changes in liver function are severe such as doubling of total bilirubin and/or tripling of transaminases in the setting of pretreatment values outside normal range |
| Estramustine phosphate sodium78 | No dosage adjustments necessary | No dosage adjustments necessary |
| Etoposide39,79,80 | 1.5–3.0 mg/dL (26–51 μmol/L) | SGOT >180 units/L | Administer 50% dosage | CrCl 10–50 mL/min | Administer 75% dosage |
| Note: Decreased albumin increases unbound drug concentration and increases hematologic toxic effects | CrCl <10 mL/min | Administer 50% dosage |
| Hemodialysis | Administer 50% dosage. No supplemental dosing needed |
| Continuous ambulatory peritoneal dialysis (CAPD) | Administer 50% dosage. No supplemental dosing needed |
| Continuous renal replacement therapy (CRRT) | Administer 75% dosage. No supplemental dosing needed |
| Etoposide phosphate45,80,81 | 1.5–3.0 mg/dL (26–51 μmol/L) | SGOT >180 units/L | Administer 50% dosage | CrCl 15–50 mL/min | Administer 75% dosage |
| CrCl <15 mL/min | Data are not available; consider further dose reductions |
| Everolimus82,83 | Child-Pugh Class A | No dosage adjustments necessary | No dosage adjustments necessary Renal transplants should have daily doses decreased to 5 mg |
| Child-Pugh Class B | Reduce the dose to 5 mg daily |
| Child-Pugh Class C | Data not available. Do not administer |
| Exemestane84 | No dosage adjustments necessary | No dosage adjustments necessary |
| Filgrastim85 | No dosage adjustments necessary | No dosage adjustments necessary |
| Floxuridine86 | 1.2 × ULN | Alkaline phosphatase 1.2 × ULN | Administer 80% of dosage | Dosage adjustment may be necessary. No specific guidelines are available |
| 1.5 × ULN | AST or ALT 3 × baseline or alkaline phosphatase 1.5 × ULN | Administer 50% of dosage |
| 2 × ULN | AST or ALT >3 × baseline or alkaline phosphatase 2 × ULN | No recommendations available38 |
| Fludarabine39,87 | Dosage adjustments may be necessary. No specific guidelines are available | CrCl 50–79 mL/min in adults | Administer 80% of IV dosage |
| CrCl 30–49 mL/min in adults | Administer 60–75% of IV dosage |
| CrCl <30 mL/min in adults | Administer 0–50% of IV dosage |
| CrCl 30–50 mL/min in children | Administer 80% of IV dosage |
| CrCl <30 mL/min in children | Do not administer |
| Hemodialysis | Administer IV dose after dialysis |
| Continuous ambulatory peritoneal dialysis (CAPD) | Administer 50% of IV dosage |
| Continuous renal replacement therapy (CRRT) | Administer 75% of IV dosage |
| CrCl 30–70 mL/min | Administer 80% of ORAL dosage Canadian PI: administer 50% of ORAL dosage |
| CrCl <30 mL/min | Administer 50% of ORAL dose Canadian PI: contraindicated |
| Fluorouracil39,45,88 | >5 mg/dL (>85 μmol/L) | Do not administer | Hemodialysis | Administer 50% dosage |
| Increased bilirubin: no relation to toxic effects; no adjustment needed74 |
| Fluoxymesterone89 | Severe hepatic impairment | Contraindicated | Severe renal impairment | Contraindicated |
| Flutamide90,91 | Severe hepatic impairment | Contraindicated | No dosage adjustments necessary |
| Fulvestrant92 | Child-Pugh Class A (mild hepatic impairment) | No dosage adjustments necessary | No dosage adjustments necessary |
| Child-Pugh Class B (moderate hepatic impairment) | Reduce maintenance and initial doses to 250 mg |
| Child-Pugh Class C (severe hepatic impairment) | Use has not been evaluated |
| Gefitinib93 | Moderate-to-severe impairment as a result of metastases | No dosage adjustments necessary | No dosage adjustments necessary |
| Gemcitabine HCl52,94,95 | | Elevated AST | No dosage adjustments necessary | No dosage adjustments necessary. Discontinue only if severe renal toxicity or hemolytic uremic syndrome (HUS) occur during treatment |
>5 mg/dL (>85 μmol/L) | | Reduce dosage by 20% |
| Gemtuzumab ozogamicin96 | Use extra caution when administering in patients with hepatic impairment | No dosage adjustments necessary |
| Goserelin acetate97 | No dosage adjustments necessary | No dosage adjustments necessary |
| Hydroxyurea45,98 | Moderate-to-severe hepatic impairment | Dosage adjustments may be necessary, but specific guidelines not available | CrCl <60 mL/min | Reduce initial dosage to 7.5 mg/kg/day. Titrate to response/avoidance of toxicity |
| CrCl 10–50 mL/min | Administer 50% dosage |
| CrCl <10 mL/min | Administer 20% dosage |
| Hemodialysis | Administer after dialysis. No supplemental dose necessary |
| Continuous renal replacement therapy (CRRT) | Administer 50% dosage |
| It is recommended to reduce the initial dose in sickle cell anemia |
| Ibritumomab tiuxetan99 | No dosage adjustments necessary | No dosage adjustments necessary |
| Ibrutinib | Metabolized in liver. Significant increases in exposure are expected with hepatic impairment. Insufficient data to recommend a dose in patients with baseline hepatic impairment | CrCL >25 mL/min | No dosage adjustment necessary |
| CrCL <25 mL/min or on dialysis | Limited data available. Monitor closely for toxicity |
| Idarubicin HCl39,45 | 1.5–3 mg/dL | AST/SGOT 60–180 units/L | Administer 75% dosage | CrCl 10–50 mL/min | Administer 75% dosage |
3–5 mg/dL (51–85 μmol/L) | AST/SGOT >180 units/L | Administer 50% dosage | CrCl <10 mL/min | Administer 50% dosage |
>5 mg/dL (>85 μmol/L) | | Do not administer | |
| Ifosfamide28,39,45,100 | Bilirubin >3 mg/dL (>85 μmol/L) | | Administer 25% of dosage | CrCl 46–60 mL/min | Administer 80% of dosage |
| Other dosage adjustments may be necessary, but no specific guidelines are available | CrCl 31–45 mL/min | Administer 75% of dosage |
| CrCl <30 mL/min | Administer 70% of dosage |
| Hemodialysis | No supplemental dose needed |
| Imatinib mesylate101,102 | >3–10 × ULN | | Administer 75% of dose | CrCl 40–59 mL/min | 600 mg = maximum recommended dose |
| CrCl 20–39 mL/min | Decrease starting dose by 50%. 400 mg = maximum recommended dose |
| CrCl <20 mL/min | Dose adjustment may be necessary, specific guidelines not available. Two patients with severe renal impairment tolerated 100 mg/day |
| Interferon alfa103 | No dosage adjustments necessary | No dosage adjustments necessary |
| Ipilimumab104 | No formal recommendation, but dosage adjustment seems unnecessary | No formal recommendation, but dosage adjustment seems unnecessary |
| Irinotecan HCl105,106,107,108 | 3-weekly irinotecan dosing (usual dose 350 mg/m2 every 3 weeks) | Use caution; not recommended for use in patients on dialysis |
| <1.5 × ULN | | 350 mg/m2 |
| 1.5–3 × ULN | | 200 mg/m2 |
| >3 × ULN | | Not recommended |
| Once weekly irinotecan dosing (usual dose 125 mg/m2 for 4 of 6 weeks) |
| 1.5–3 × ULN | AST/ALT ≤5 × ULN | 60 mg/m2 |
| 1.5–3 × ULN | AST/ALT 5.1–20 × ULN | 40 mg/m2 |
| 3.1–5 × ULN | AST/ALT ≤5 × ULN | 50 mg/m2 |
| ≤1.5 × ULN | AST/ALT 5.1–20 × ULN | 60 mg/m2 |
| Special Note: When administered in combination with other agents, or as a single-agent, a reduction in the starting dose by at least 1 level of irinotecan should be considered for patients known to be homozygous for the UGT1A1✫28 allele |
| Isotretinoin109 | Empiric dose reductions are recommended in patients with hepatitis or abnormal liver enzymes | No dosage adjustments necessary |
| Ixabepilone110 | ≤1 × ULN | AST and ALT ≤2.5 × ULN | No dosage adjustments necessary. If administering with capecitabine do not need a dosage adjustment | |
| ≤1.5 × ULN | AST and ALT 2.5–10 × ULN | Reduce dosage to 32 mg/m2 |
| 1.5–3 × ULN | AST and ALT ≤10 × ULN | Reduce dosage to 20 mg/m2 dosage in subsequent cycles may be escalated up to, but not exceed, 30 mg/m2 if tolerated | CrCl >30 mL/min | No dosage adjustment necessary |
| >3 × ULN | AST or ALT >10 × ULN | Do not administer | CrCl <50 mL/min | Combination therapy with capecitabine has not been studied |
| >1 × ULN | AST and ALT >2.5 × ULN | If administering with capecitabine, ixabepilone use is contraindicated | |
| Lapatinib111 | Child-Pugh Class C (severe hepatic impairment) | Dose reduction to 750 mg/day (HER2-positive metastatic breast cancer indication) or 1000 mg/day (hormone receptor-positive, HER 2-positive breast cancer indication) | Minimal renal elimination (<2%) Dosage adjustments may not be necessary |
| Lenalidomide112 | No dosage adjustments necessary | Dosage recommendations using Cockcroft and Gault formula |
| | Multiple Myeloma | MDS |
| CrCl 30–60 mL/min | 10 mg daily | 5 mg daily |
| CrCl <30 mL/min (not requiring dialysis) | 15 mg every 48 hours | 5 mg every 48 hours |
| CrCl <30 mL/min (requiring dialysis) | 5 mg daily after dialysis | 5 mg 3 × per week after dialysis |
| Leucovorin calcium113 | No dosage adjustments necessary | No dosage adjustments necessary |
| Leuprolide acetate114 | No dosage adjustments necessary | No dosage adjustments necessary |
| Letrozole115 | Child-Pugh Classes A and B (mild to moderate hepatic impairment) | No dose adjustments necessary | CrCl >10 mL/min | No dose adjustments necessary |
| Child-Pugh Class C (severe hepatic impairment) and cirrhosis | Reduce dose to 2.5 mg every other day |
| Lomustine39,45,116 | Dosage adjustments may be necessary, but no specific guidelines are available. Use caution in patients with hepatic dysfunction | CrCl 10–50 mL/min | Administer 75% dosage |
| CrCl <10 mL/min | Administer 25–50% dosage |
| Mechlorethamine HCl117 | No dosage adjustments necessary | No dosage adjustments necessary |
| Megestrol acetate118 | No dosage adjustments necessary | No dosage adjustments necessary |
| Melphalan or Melphalan HCl39,119,120 | No dosage adjustments necessary | CrCl 10–50 mL/min | Administer 75% dosage |
| CrCl <10 mL/min | Administer 50% dosage |
BUN ≥30 mg/dL (10.7 mmol/L) | Administer 50% dosage |
| Mercaptopurine39,121 | Dosage adjustment may be necessary, but no specific guidelines are available | CrCl <50 mL/min | Dose every 48 hours |
| Hemodialysis, continuous ambulatory peritoneal dialysis (CAPD), continuous renal replacement therapy (CRRT) | Administer every 48 hours |
| Mesna122 | Dosage adjustment may be necessary, but no specific guidelines are available | Dosage adjustment may be necessary, but no specific guidelines are available |
| Methotrexate39,45,52 | | | Children | Adult |
| CrCl 10–60 mL/min | Administer 50% dosage | Administer 50% dosage |
3.1–5.0 mg/dL (53–86 μmol/L) | ALT and AST >3 × ULN | Administer 75% dosage | CrCl <10 mL/min | Administer 30% dosage | Do not administer |
>5 mg/dL (>86 μmol/L) | Do not administer | Hemodialysis | Administer 30% dosage | Administer 50% dosage |
| | Continuous renal replacement therapy (CRRT) | Administer 50% dosage | Administer 50% dosage |
| Mitomycin39,123 | Dosage adjustment may be necessary, but no specific guidelines are available. Clearance is effected primarily by metabolism in the liver, but metabolism occurs in other tissues as well | CrCl <30 mL/min or SCr >1.7 mg/dL (>150 μmol/L) | Do not administer |
| Continuous ambulatory peritoneal dialysis (CAPD) | Administer 75% of dosage |
| Mitotane124 | Dosage adjustment may be necessary, but no specific guidelines are available. Monitoring serum levels is recommended | No dosage adjustments necessary |
| Mitoxantrone HCl125 | No laboratory measurement that allows for dose adjustment recommendations. Mitoxantrone is excreted in urine and feces as either unchanged drug or as inactive metabolites. Avoid in MS patients with hepatic impairment | No dosage adjustments necessary |
| Nelarabine126 | >3 × ULN | Monitor closely for toxicities | CrCl <50 mL/min | Monitor closely for toxicities |
| Nilotinib127 | Newly diagnosed Ph+ CML | Not studied in patients with serum creatinine >1.5 × ULN. Dosage adjustments for renal dysfunction may not be needed |
| Child-Pugh Class A, B, or C (mild, moderate or severe hepatic impairment) | 200 mg twice daily. Increase to 300 mg twice daily if tolerated |
| Resistant or intolerant Ph+ CML |
| Child-Pugh Class A or B (mild or moderate hepatic impairment) | 300 mg twice daily. Increase to 400 mg twice daily if tolerated |
| Child-Pugh Class C (severe hepatic impairment) | 200 mg twice daily; Increase to 300 mg twice daily and then further to 400 mg twice daily based on patient tolerability |
| During treatment |
| 3 × ULN | | Withhold treatment, monitor bilirubin; resume treatment at 400 mg once daily when bilirubin returns to ≤1.5 × ULN |
| | ALT or AST >5 × ULN | Withhold treatment, monitor transaminases; Resume treatment at 400 mg once daily when ALT or AST return to <2.5 × ULN |
| Nilutamide128 | Dosage adjustment may be necessary, but no specific guidelines are available | No dosage adjustments necessary |
| Severe hepatic impairment | Contraindicated |
| Jaundice during treatment | ALT >2 × ULN during treatment | Discontinue |
| Obinutuzumab | No data | CrCL <30 mL/min | No data |
| CrCL >30 mL/min | No effect on PK |
| Octreotide acetate129 | Established liver cirrhosis | Initial dose: 10 mg IM every 4 weeks. Titrate based upon response | Non–dialysis-dependent renal impairment | No dosage adjustments necessary |
| Dialysis-dependent renal impairment | Initial dose: 10 mg IM every 4 weeks. Titrate based upon response |
| Ofatumumab130 | No formal studies in patients with hepatic impairment have been conducted | No formal studies in patients with renal impairment have been conducted |
| Omacetaxine mepesuccinate131 | Hepatic impairment | No clinical trials have been conducted | Renal impairment | No clinical trials have been conducted |
| Oprelvekin132 | No dosage adjustments necessary | Dosage recommendations using Cockcroft and Gault formula |
| CrCl <30 mL/min | Administer 25 mcg/kg (50% of dosage for CrCl ≥30 mL/min), once daily for 10–21 days |
| Oxaliplatin133,134 | No dosage adjustments necessary | No formal recommendation for dose reduction. The AUC [0–48 hours] of platinum in patients with ClCr 50–80, 30–50, and <30mL/min increased by approximately 60, 140, and 190%, respectively, compared to patients with CrCl >80 mL/min. Consider omitting dose if CrCl <20 mL/min |
| Paclitaxel135,136 | 24-Hour infusion | No dosage adjustments necessary |
≤1.5 mg/dL (≤26 μmol/L) | AND | <2 × ULN | 135 mg/m2 |
≤1.5 mg/dL (≤26 μmol/L) | AND | 2–10 × ULN | 100 mg/m2 |
1.6–7.5 mg/dL (27–128 μmol/L) | AND | <10 × ULN | 50 mg/m2 |
>7.5 mg/dL (>128 μmol/L) | OR | ≥10 × ULN | Do not administer |
| 3-Hour infusion |
| ≤1.25 × ULN | AND | <10 × ULN | 175 mg/m2 |
| 1.26–2.0 × ULN | AND | <10 × ULN | 135 mg/m2 |
| 2.0–5.0 × ULN | AND | <10 × ULN | 90 mg/m2 |
| >5.0 × ULN | OR | ≥10 × ULN | Do not administer |
| Paclitaxel protein-bound particles137 | >ULN to ≤1.25 × ULN | AND | SGOT (AST) <10 × ULN | 260 mg/m2 | No dosage adjustments necessary |
| 1.26–2.0 × ULN | AND | SGOT (AST) <10 × ULN | 200 mg/m2 |
| 2.01–5.0 × ULN | AND | SGOT (AST) <10 × ULN | 130 mg/m2 |
| >5.0 × ULN | OR | SGOT (AST) >10 × ULN | Do not administer |
| Pamidronate disodium138 | Mild-to-moderate hepatic impairment | No dosage adjustments necessary | CrCl <30 mL/min or SCr >3 mg/dL (265 mmol/L) | Do not administer or administer with caution |
| Severe hepatic impairment | Not studied | Multiple myeloma: 90 mg over 4–6 hours unless renal impairment is preexisting then consider reduced initial dose |
| Panitumumab139 | No formal recommendation but dosage adjustment seems unnecessary | No formal recommendation but dosage adjustment seems unnecessary |
| Pazopanib HCl140,141 | Preexisting moderate dysfunction | Reduce to 200 mg once daily | No dosage adjustments necessary |
| Initial >3 × ULN | AND | Any ALT level | Do not administer |
| >2 times ULN | 3–8 × ULN during treatment | Continue treatment, monitor LFTs weekly until ALT G ≤1 or baseline |
| >8 × ULN during treatment | Interrupt treatment. Reinitiate when ALT G ≤1 or baseline at <400 mg/day |
| ALT >3 × ULN | Permanently discontinue. Monitor until resolution |
| Pegaspargase142 | No dosage adjustments necessary | No dosage adjustments necessary |
| Pegfilgrastim143 | No dosage adjustments seem to be necessary, but pharmacokinetic profiles in patients with hepatic insufficiency have not been assessed | No dosage adjustments necessary |
| Pemetrexed disodium144 | No dosage adjustments necessary | CrCl <80 mL/min | Use caution with concomitant NSAIDs |
| CrCl <45 mL/min | Insufficient data. Do not administer |
| Pentostatin145 | No dosage adjustments necessary | CrCl <60 mL/min | No recommendation but use caution |
| Pertuzumab146 | Mild, moderate and severe hepatic impairment | No clinical trials have been conducted | Creatinine clearance 30 to ≤90 mL/min [0.5 to ≤1.5 mL/s]) | No dosage adjustment necessary |
| CrCL <30 mL/min [<0.5 mL/s] | No clinical trials have been conducted |
| Plerixafor147 | No dosage adjustments necessary | CrCl >50 mL/min | No dosage adjustments necessary. 0.24 mg/kg; maximum dose: 40 mg/day |
| CrCl ≤50 mL/min | 0.16 mg/kg; maximum dose: 27 mg/day |
| Pomalidomide148 | Bilirubin >2 mg/dL [>34.2 μmol/L] | AST/SGOT >3 × ULN ALT/SGPT >3 × ULN | Avoid since patients with bilirubin >2 mg/dL [>34.2 μmol/L] and AST/ALT >3 × ULN were excluded from trials | SCr >3 mg/dL [>265 μmol/L] | Avoid since patients with SCr >3 mg/dL were excluded from trials |
| Ponatinib HCl149 | Moderate to severe hepatic impairment | Avoid unless benefits outweigh risks | Moderate to severe renal impairment (CrCL <60 mL/min [<1 mL/s]) | Avoid unless benefits outweigh risks |
| Pralatrexate150 | 1.5 mg/dL (26 μmol/L) | ALT or AST >2.5 × ULN | No clinical trials have been conducted | No formal recommendation, but dosage reduction may be necessary with moderate to severe renal function |
| Procarbazine HCl46 | Dosage adjustment may be necessary, no specific guidelines are available | CrCl ≤30 mL/min | Do not administer |
| Raloxifene HCl151 | Safety and efficacy have not been established in patients with hepatic impairment. Use with caution | Safety and efficacy have not been established in patients with moderate or severe renal impairment. Use with caution |
| Raltitrexed152 | No dosage adjustments necessary | CrCl 25–65 mL/min | Administer 50% dosage and increase dosage interval to 4 weeks |
| CrCl <25 mL/min | Do not administer |
| Regorafenib153 | Mild to moderate hepatic impairment | No dosage adjustments necessary | Mild renal impairment (CrCL 60–90 mL/min [1–1.5 mL/s]) | No dosage adjustment necessary |
| Severe hepatic impairment | Not recommended as it has not been studied | Moderate to severe renal impairment (CrCL <60 mL/min [<1 mL/s]) | Not recommended as it has not been studied |
| Rituximab154 | No dosage adjustments necessary | No dosage adjustments necessary |
| Romidepsin155 | Moderate-to-severe impairment | No formal recommendation, but dosage reduction may be necessary | End-stage renal disease | No formal recommendation, but dosage reduction may be necessary |
| Romiplostim156 | No clinical studies have been conducted in patients with hepatic impairment. Use caution in this population | No clinical studies have been conducted in patients with renal impairment. Use caution in this population |
| Sargramostim157 | No dosage adjustments necessary | No dosage adjustments necessary |
| Sipuleucel-T158 | No dosage adjustments seem to be necessary, but no pharmacokinetic profiles in patients with hepatic insufficiency have been assessed | No dosage adjustments seem to be necessary, but no pharmacokinetic profiles in patients with renal insufficiency have been assessed |
| Sorafenib tosylate159,160 | ≤1.5 × ULN | 400 mg BID | No dosage adjustments necessary if not on dialysis |
| 1.5–3 × ULN | 200 mg BID |
| 3–10 × ULN | Do not administer |
| Streptozocin39,161 | No dosage adjustments seem to be necessary, but follow liver function tests carefully | CrCl 10–50 mL/min | Administer 75% of dosage |
| CrCl <10 mL/min | Administer 50% of dosage |
| Note: Renal toxicity is dose related and cumulative; may be severe or fatal. Minimize adverse effects by basing dosage on clinical, renal, hematologic, and hepatic responses and tolerance of the patient |
| Sunitinib malate162 | Child-Pugh Class A or B (mild to moderate hepatic impairment) | No dosage adjustments necessary | No dosage adjustments necessary However, compared to subjects with normal renal function, the sunitinib exposure is 47% lower in subjects with ESRD on hemodialysis. Therefore, the subsequent dosages may be increased gradually up to 2-fold based on safety and tolerability |
| Child-Pugh Class C (severe hepatic impairment) | No information available |
| Tamoxifen citrate163 | No dosage adjustments necessary | No dosage adjustments necessary |
| Tegafur-uracil | Data not available | No dosage adjustments necessary |
| Temozolomide164 | No dosage adjustments necessary Use caution in patients with severe hepatic impairment | No dosage adjustments necessary Use caution in patients with severe renal impairment |
| Temsirolimus165 | 1–1.5 × ULN | AST >ULN but bilirubin ≤ULN | Reduce dose to 15 mg/week | No dosage adjustments necessary |
| >1.5 × ULN | Contraindicated |
| Teniposide166 | Dosage adjustments may be necessary in patient with significant hepatic impairment | Dosage adjustment may be necessary, but no specific guidelines are available |
| Thalidomide167 | No dosage adjustments necessary | No dosage adjustments necessary |
| Thioguanine168 | No formal recommendation but dosage adjustments are recommended in patient with hepatic impairment | No dosage adjustments necessary |
| Thiotepa169 | No formal recommendation, but dosage reduction may be necessary Monitor hepatic function tests | No formal recommendation, but dose reduction may be necessary Monitor renal function tests |
| Topotecan HCl170,171 | No dosage adjustments necessary | >40 mL/min | No dosage adjustment necessary |
| 20–39 mL/min | Reduce dosage to 0.75 mg/m2 |
| <10 mL/min | Insufficient data |
| Toremifene citrate172 | No dosage adjustments necessary | No dosage adjustments necessary |
| Tositumomab173 | No dosage adjustments necessary | No formal recommendation, but use with caution in presence of renal dysfunction |
| Trabectedin (ET-743)174 | Hepatic impairment may result in higher plasma concentrations but has not been sufficiently studied and is not recommended. Should not be used in patients with elevated bilirubin levels or clinically relevant liver disease such as hepatitis | CrCl <60 mL/min | Should not be used in combination with liposomal doxorubicin |
| CrCl <30 mL/min | Do not administer |
| Trametinib | Child-Pugh Class C (severe hepatic impairment) | Limited data available. Monitor closely for toxicity | Mild-moderate renal impairment | No dosage adjustment necessary |
| Severe renal impairment | Limited data available. Monitor closely for toxicity |
| Trametinib dimethyl sulfoxide175 | Mild to moderate hepatic impairment | No dosage adjustment necessary | Mild to moderate renal impairment (CrCL 30–90 mL/min [0.5–1.5 mL/s]) | No dosage adjustment necessary |
| Moderate to severe hepatic impairment | No clinical trials have been conducted | Severe renal impairment (CrCL <30 mL/min [<0.5 mL/s]) | No clinical trials have been conducted |
| Trastuzumab176 | No dosage adjustments necessary | No dosage adjustments necessary |
| Tretinoin45 | 3.1–5 mg/dL (53–86 μmol/L) | | ≤25 mg/m2 | CrCl ≤60 mL/min | ≤25 mg/m2 |
>5 mg/dL (>86 μmol/L) | | Do not administer |
| | 180 units/L | ≤25 mg/m2 |
| Trimetrexate glucuronate177 | No formal recommendation, but dosage adjustments may be necessary | No dosage adjustments necessary |
| Valrubicin178 | Dosage adjustments do not appear to be necessary, but no specific guidelines are available | Dosage adjustments do not appear to be necessary, but no specific guidelines are available |
| Vandetanib179 | Child-Pugh Classes B and C (moderate to severe hepatic impairment) | Data not available. Use is not recommended | CrCl <50 mL/min | Reduce starting dose to 200 mg |
| Vemurafenib180 | 1–3 × ULN | | No dosage adjustments necessary | CrCl 30–89 mL/min | No dosage adjustments necessary |
| >3 × ULN | | Need for dosage adjustments has not been determined | CrCl <29 mL/min | Need for dosage adjustments has not been determined |
| Vinblastine sulfate45 | 1.5–3 mg/dL (26–51 μmol/L) | AND | AST 60–180 units/L | Administer 50% dosage | No dosage adjustments necessary |
>3 mg/dL (>51 μmol/L) | | Administer 50% dosage |
>3 mg/dL (>51 μmol/L) | AND | AST >180 units/L | Do not administer |
| Vincristine sulfate45 | 1.5–3 mg/dL (26–51 μmol/L) | AND | AST 60–180 units/L | Administer 50% dosage | No dosage adjustments necessary |
>3 mg/dL (>51 μmol/L) | AND | AST >180 units/L | Do not administer |
| Vincristine sulfate liposome181 | Mild to moderate hepatic impairment | No clinical trials have been conducted but dosage adjustments likely not necessary | Mild, moderate and severe renal impairment | No clinical trials have been conducted |
| Severe hepatic impairment | Avoid unless benefits outweigh risks |
| Vinorelbine tartrate182,183 | 2.1–3 mg/dL (36–51 μmol/L) | | Administer 50% dosage | No dosage adjustments necessary |
3.1–5 mg/dL (53–85 μmol/L) | | Administer 25% dosage |
>5 mg/dL (>85 μmol/L) | | Do not administer |
| Diffuse liver metastases | | Administer 50% dosage |
| Vismodegib184 | Mild, moderate and severe hepatic impairment | No clinical trials have been conducted | Mild, moderate and severe renal impairment | No clinical trials have been conducted |
| Vorinostat 185,186 | 1.5–3 × ULN | Use is not recommended | No dosage adjustments necessary |
| >3 × ULN | Do not administer |
| ziv-Aflibercept187 | Mild to moderate hepatic impairment | No clinical trials have been conducted but dosage adjustments likely not necessary | Any renal impairment | No clinical trials have been conducted but dosage adjustments likely not necessary |
| Severe hepatic impairment | Avoid unless benefits outweigh risks |
| Zoledronic Acid188 | Data is not adequate to provide guidelines on dosage selection and adjustment or how to safely use zoledronic acid in patients with hepatic impairment | Dose recommendations using Cockcroft and Gault formula |
| CrCl >60 mL/min | 4 mg |
| CrCl 50–59 mL/min | 3.5 mg |
| CrCl 40–49 mL/min | 3.3 mg |
| CrCl 30–39 mL/min | 3 mg |
| CrCl <30 mL/min | Use not recommended |
| |
| Hypercalcemia of malignancy with SCr >4.5 mg/dL (>398 μmol/L) | Consider treatment only after considering risks vs. benefits. Use not recommended |
| Bone metastases with SCr >3.0 mg/dL (>265 μmol/L) | Use not recommended |