Clinical reference · Hepatic impairment drug dosing
Hepatic impairment drug dosing, the Child-Pugh dose adjustments in US labeling, and the drugs to avoid in liver disease
Liver disease changes prescribing less predictably than kidney disease. There is no single number like creatinine clearance that scales a dose: the liver loses metabolic capacity, synthetic function, albumin binding and portal first pass at different rates, and the patient with cirrhosis also carries a higher risk of bleeding, encephalopathy and renal failure that some drugs push over the edge. That is why US labeling uses the Child-Pugh class as the dosing input and states its rule class by class.
This page lists the drugs where that rule actually changes what you do, with the labeled statement for Child-Pugh A, B and C and the usual response, as a reference for licensed clinicians. Prescriber.io applies the same table to the regimen in front of you: enter the Child-Pugh class and every drug on the list with a labeled hepatic rule is flagged at the right level, with this row cited. You review, verify against the current labeling, and sign.
Press Run check for the interaction, contraindication, dosing and alternatives on this pair.
Not matched, so not checked: .
Nothing on this pair matched a row in the reference tables behind this check. That is not a clearance: it means these references do not name this combination.
Guideline-based alternatives
That was your demo check, run on the same references the desk uses. The desk adds renal dosing against an estimated clearance, hepatic review, unlimited checks, saved history and your sign-off on every card.
The on-page check covers five prescribing scenarios and never invents clinical output, so it will not produce a card for this pair.
The full Prescriber.io desk checks any regimen against interactions, contraindications, and renal or hepatic dosing, with cited sources for you to verify.
Interaction
Contraindication / allergy check
Dosing guidance (renal / hepatic)
Guideline-based alternatives
Decision support. You verify against official sources and sign.
Clinician in the loopDecision support for licensed clinicians. Prescriber.io does not diagnose or prescribe and is not a substitute for professional clinical judgment.
For licensed US clinicians
Decision-support: not autonomous prescribing
You review & sign off
In short
Hepatic dosing is set by Child-Pugh class, not by a single laboratory value. US labeling states a rule for many drugs at Child-Pugh A (mild), B (moderate) and C (severe): some need no change, some take a lower dose or a lower ceiling, and some are avoided or contraindicated. Rivaroxaban and edoxaban are avoided from class B, apixaban and ticagrelor in class C, duloxetine and ranolazine in any cirrhosis, while citalopram is capped at 20 mg a day and venlafaxine is halved. The table below gives the labeled statement by class for clinician review.
The list
Hepatic impairment drug dosing by Child-Pugh class
Drugs with a hepatic rule in US labeling, by Child-Pugh class. Reference for clinician review; statements vary by product, formulation and indication and must be confirmed in the current labeling.
| Drug or class | Drugs this row covers | Why liver function matters | What US labeling states by Child-Pugh class | What is usually done |
|---|---|---|---|---|
| Factor Xa inhibitors avoided from class B | Rivaroxaban, edoxaban | Hepatic metabolism and the coagulopathy of liver disease both raise exposure and bleeding risk | Class A: no adjustment. Rivaroxaban is avoided in class B and C and in any hepatic disease with coagulopathy; edoxaban is not recommended in class B and C | Choose a different anticoagulation strategy from class B onward, with the bleeding risk of the liver disease itself weighed |
| Apixaban | Apixaban | Partly hepatic clearance through CYP3A4, and cirrhosis adds its own bleeding risk | Class A: no adjustment. Class B: limited clinical experience, so use with caution. Class C: not recommended | Standard dosing in class A, a documented risk decision in class B, and an alternative in class C |
| Ticagrelor | Ticagrelor | Metabolized by hepatic CYP3A4, so exposure rises as hepatic function falls, with higher bleeding risk | Class A: no adjustment. Class B: consider the risks and benefits, as experience is limited. Class C: avoid | In severe impairment an antiplatelet with a different clearance route is usually considered |
| Warfarin | Warfarin | Reduced synthesis of clotting factors and slower warfarin metabolism both potentiate the response | Labeling warns that hepatic impairment can potentiate the response to warfarin; no class based dose is given | Lower starting dose and closer INR monitoring, remembering the baseline INR in cirrhosis does not reflect bleeding risk alone |
| Statins | Simvastatin, lovastatin, atorvastatin, rosuvastatin, pravastatin, pitavastatin | The liver is both the site of action and of metabolism, and statins raise aminotransferases in a minority of patients | Contraindicated in acute liver failure or decompensated cirrhosis; in compensated chronic liver disease they are used with monitoring | Usually continued in compensated disease for cardiovascular benefit; stopped in decompensated (class C) cirrhosis |
| Metformin | Metformin and metformin combination products | Impaired hepatic lactate clearance raises the risk of metformin associated lactic acidosis | Labeling states that metformin is not recommended in patients with hepatic impairment | Another agent is usually chosen; where metformin is continued in compensated disease, the decision and the lactic acidosis risk are documented |
| Sulfonylureas | Glyburide, glimepiride, glipizide | Hepatic metabolism falls and hepatic gluconeogenesis is impaired, so hypoglycemia is deeper and longer | Labeling calls for conservative initial and maintenance dosing in hepatic impairment | Start at the lowest dose and titrate slowly, or choose an agent with a lower hypoglycemia risk |
| Duloxetine | Duloxetine | Clearance falls sharply in cirrhosis and the drug itself is associated with hepatotoxicity | Avoid in patients with chronic liver disease or cirrhosis, at any Child-Pugh class | A different antidepressant or pain agent is chosen |
| Venlafaxine | Venlafaxine | Hepatic metabolism to desvenlafaxine slows, so exposure to both rises | Class A and B: reduce the total daily dose by 50 percent. Class C or cirrhosis: reduce by 50 percent or more, individualized | Halve the dose and titrate to response |
| Citalopram and escitalopram | Citalopram, escitalopram | Slower hepatic clearance raises exposure and the dose related QT effect | Hepatic impairment: citalopram maximum 20 mg a day; escitalopram 10 mg a day recommended | Use the lower ceiling, and check other QT prolonging drugs on the list |
| Sertraline | Sertraline | Extensive hepatic metabolism; exposure roughly triples in mild impairment | Class A: lower or less frequent dosing. Class B and C: not recommended | Lower dose in class A; another agent in class B and C |
| Paroxetine and fluoxetine | Paroxetine, fluoxetine | Hepatic CYP2D6 metabolism slows and the half life lengthens, fluoxetine most of all | Paroxetine in severe impairment: start at 10 mg a day, maximum 40 mg. Fluoxetine in cirrhosis: lower or less frequent dosing | Lower starting dose and slower titration |
| Diazepam and clonazepam | Diazepam, clonazepam | Hepatic oxidation slows, both accumulate with long half lives, and sedation can precipitate hepatic encephalopathy | Diazepam is contraindicated in severe hepatic insufficiency; clonazepam is contraindicated in significant liver disease | Lower doses from class B; not used in class C, where lorazepam or oxazepam, cleared by glucuronidation, are usually preferred if a benzodiazepine is needed |
| Alprazolam, triazolam and midazolam | Alprazolam, triazolam, midazolam | Hepatic CYP3A4 oxidation slows, the drugs accumulate, and sedation can precipitate hepatic encephalopathy | Alprazolam in advanced liver disease starts at 0.25 mg two or three times a day; triazolam and midazolam need lower doses and close monitoring in hepatic impairment | Lower doses from class B; in class C avoided, and lorazepam or oxazepam are usually preferred if a benzodiazepine is needed |
| Zolpidem and zaleplon | Zolpidem, zaleplon | Hepatic clearance falls and sedation can precipitate encephalopathy | Mild to moderate impairment: 5 mg. Severe impairment: avoid zolpidem, and zaleplon is not recommended | Lower dose in class A and B; another approach to sleep in class C |
| Eszopiclone | Eszopiclone | Exposure roughly doubles in severe hepatic impairment | Mild to moderate impairment: no adjustment. Severe impairment: start at 1 mg, maximum 2 mg | Lower ceiling in class C |
| Opioids | Morphine, tramadol, codeine, methadone, meperidine | Reduced first pass metabolism raises oral bioavailability, clearance falls, and sedation and constipation can precipitate encephalopathy | Tramadol immediate release in cirrhosis: 50 mg every 12 hours, and the extended release form is not recommended in severe impairment. The others: lower dose or longer interval with close monitoring | Lower doses and longer intervals from class A; meperidine and codeine are usually avoided in cirrhosis |
| Carvedilol | Carvedilol | Extensive first pass hepatic metabolism, so exposure rises several fold in cirrhosis | Contraindicated in severe hepatic impairment | In class C another beta blocker strategy is chosen; portal hypertension dosing in class A and B is a specialist decision |
| Non-dihydropyridine calcium channel blockers | Verapamil, diltiazem | High first pass hepatic metabolism; bioavailability and half life rise in cirrhosis | Verapamil in severe hepatic dysfunction: about 30 percent of the usual dose. Diltiazem: use with caution in hepatic impairment | Lower starting dose and monitoring of heart rate, PR interval and blood pressure |
| Ranolazine | Ranolazine | Exposure and the QT effect rise steeply in hepatic impairment | Contraindicated in liver cirrhosis, at any Child-Pugh class | A different antianginal is chosen |
| Ivabradine | Ivabradine | Metabolized by hepatic CYP3A4 | Class A: no adjustment. Class B: use with caution. Class C: contraindicated | Avoided in severe impairment |
| Finerenone | Finerenone | Hepatic CYP3A4 metabolism, so exposure rises and hyperkalemia risk with it | Class A: no adjustment. Class B: consider additional potassium monitoring. Class C: avoid | Extra potassium checks in class B; not used in class C |
| Tolvaptan | Tolvaptan | Associated with serious liver injury, and patients with liver disease are less able to recover from it | Avoid in patients with underlying liver disease, including cirrhosis | Another approach to hyponatremia is used |
| Spironolactone | Spironolactone | Fluid and electrolyte shifts in cirrhosis can precipitate hepatic encephalopathy | In cirrhosis labeling advises starting treatment in hospital and titrating slowly | Used routinely for ascites, with close monitoring of sodium, potassium and renal function |
| Oral ketoconazole | Ketoconazole tablets | Oral ketoconazole causes serious hepatotoxicity | Contraindicated in acute or chronic liver disease | Another antifungal is chosen |
| Voriconazole | Voriconazole | Hepatic metabolism with nonlinear kinetics, and a hepatotoxicity signal of its own | Class A and B: standard loading dose, then halve the maintenance dose. Class C: not studied, used only if the benefit outweighs the risk | Halved maintenance and level monitoring; in class C a documented risk decision |
| Methotrexate | Methotrexate | Direct hepatotoxicity with fibrosis on long exposure | Labeling for non-cancer indications lists alcoholic liver disease and other chronic liver disease as contraindications | Another agent for rheumatologic and dermatologic use; oncology use is a specialist decision |
| Colchicine | Colchicine | Hepatic CYP3A4 metabolism and biliary excretion; accumulation causes myelosuppression and neuromyopathy | Severe impairment: consider a dose reduction and do not repeat a flare course more often than every two weeks. With a P-gp or strong CYP3A4 inhibitor in hepatic impairment: contraindicated | Lower doses in severe disease and a check of the list for CYP3A4 and P-gp inhibitors |
| Sildenafil | Sildenafil | Hepatic CYP3A4 clearance falls and exposure rises in cirrhosis | For erectile dysfunction in hepatic impairment such as cirrhosis: start at 25 mg | Lower starting dose |
| Tadalafil and vardenafil | Tadalafil, vardenafil | Hepatic CYP3A4 clearance falls and exposure rises | Tadalafil: as needed at most 10 mg in mild to moderate impairment, not recommended in severe. Vardenafil: class B start at 5 mg, maximum 10 mg; not recommended in class C | Lower dose in class A and B; avoided in class C |
| NSAIDs in cirrhosis | Ibuprofen, naproxen, diclofenac, meloxicam, ketorolac, indomethacin | Cirrhosis makes renal perfusion prostaglandin dependent, so NSAIDs cause renal failure, diuretic resistance and variceal and gastrointestinal bleeding | Labeling advises caution in hepatic impairment; liver society guidance advises avoiding NSAIDs in cirrhosis with ascites | Acetaminophen at a reduced daily ceiling is the usual analgesic in cirrhosis |
| Celecoxib | Celecoxib | Hepatic CYP2C9 metabolism, with exposure roughly doubling in moderate impairment | Class A: no adjustment. Class B: reduce the dose by 50 percent. Class C: not recommended | Halved dose in class B; another analgesic in class C |
| Ondansetron | Ondansetron | Clearance falls to about a third in severe impairment | Class C: do not exceed 8 mg a day | A daily ceiling of 8 mg in severe impairment |
| Esomeprazole | Esomeprazole | Hepatic CYP2C19 and CYP3A4 metabolism slows in severe impairment | Class C: do not exceed 20 mg a day | A daily ceiling of 20 mg in severe impairment |
| Atomoxetine | Atomoxetine | Hepatic CYP2D6 metabolism; exposure doubles in class B and quadruples in class C | Class B: reduce to 50 percent of the usual dose. Class C: reduce to 25 percent | Dose reduced by class |
| Lurasidone | Lurasidone | Hepatic CYP3A4 metabolism, so exposure rises with impairment | Start at 20 mg a day. Class B: maximum 80 mg a day. Class C: maximum 40 mg a day | Lower ceiling by class |
| Quetiapine | Quetiapine | Extensive hepatic metabolism; clearance falls by about a quarter in hepatic impairment | Hepatic impairment: start at 25 mg a day and increase by 25 to 50 mg a day | Slower titration from a lower start |
| Galantamine | Galantamine | Hepatic metabolism, with clearance reduced in moderate impairment | Class B: do not exceed 16 mg a day. Class C: not recommended | Lower ceiling in class B; another agent in class C |
| Bosentan | Bosentan | Dose related aminotransferase elevations, with hepatic failure reported | Avoid in moderate or severe hepatic impairment; monthly aminotransferases on treatment | Another pulmonary hypertension agent from class B onward |
| Lomitapide | Lomitapide | Causes hepatic fat accumulation and aminotransferase elevations | Class A: maximum 40 mg a day. Class B and C: contraindicated | Lower ceiling in class A; not used from class B |
| Flibanserin | Flibanserin | Exposure rises several fold in hepatic impairment, with hypotension and syncope | Contraindicated in any degree of hepatic impairment | Not used |
| Naloxegol | Naloxegol | Hepatic CYP3A4 metabolism | Class A and B: no adjustment. Class C: avoid | Another agent for opioid induced constipation in class C |
| Dihydroergotamine | Dihydroergotamine | Hepatic metabolism, and vasoconstriction that impaired clearance prolongs | Contraindicated in severe hepatic impairment | Another acute migraine agent in class C |
| Eletriptan | Eletriptan | Hepatic CYP3A4 metabolism | Class A and B: no adjustment. Class C: not recommended | Another acute migraine agent in class C |
| Ubrogepant | Ubrogepant | Hepatic CYP3A4 metabolism; exposure doubles in severe impairment | Class C: 50 mg, with a second 50 mg dose if needed | Lower dose in severe impairment |
| Suzetrigine | Suzetrigine | Hepatic CYP3A metabolism, so exposure rises with impairment | Class A: no adjustment. Class B: reduced dosing regimen. Class C: avoid | Labeled lower regimen in class B; another analgesic in class C |
| Ibrutinib | Ibrutinib | Hepatic CYP3A4 metabolism; exposure rises several fold with impairment, with bleeding risk | Class A: 140 mg a day. Class B: 70 mg a day. Class C: avoid | Dose reduced by class, oncology decision |
| mTOR inhibitors | Everolimus, sirolimus | Hepatic CYP3A4 metabolism; exposure rises by class | Everolimus in oncology: class A 7.5 mg, class B 5 mg, class C 2.5 mg if the benefit outweighs the risk. Sirolimus: maintenance reduced by about a third in mild to moderate and by about half in severe | Dose reduced by class, guided by trough levels |
| Tacrolimus | Tacrolimus | Hepatic CYP3A4 metabolism, with a longer half life in severe impairment | Severe impairment (Child-Pugh score 10 or more) may need lower doses | Lower dose guided by close trough monitoring |
| Theophylline | Theophylline | Clearance falls by half or more in cirrhosis, with a narrow therapeutic index | Hepatic insufficiency: reduce the dose and monitor serum concentrations | Lower dose guided by levels |
| Hepatotoxic antituberculars | Isoniazid, rifampin | Both cause drug induced liver injury, and pre-existing disease lowers the reserve to absorb it | Isoniazid is contraindicated in acute liver disease; both are used with caution and liver tests in chronic liver disease | Specialist regimen choice and scheduled liver tests |
| Ergotamine | Ergotamine | Hepatic metabolism, and vasoconstriction that impaired clearance prolongs | Contraindicated in impaired hepatic function, at any class | Another acute migraine agent |
Class-level reference for licensed clinicians. Always verify against the current product labeling and your institutional references before prescribing.
How the Child-Pugh class sets a hepatic dose
The Child-Pugh score adds points for bilirubin, albumin, INR, ascites and encephalopathy. A score of 5 or 6 is class A, 7 to 9 is class B and 10 to 15 is class C. Drug manufacturers study pharmacokinetics in volunteers grouped by that class, which is why the dose statement in US labeling is written per class rather than per laboratory value.
Two limits follow from that. First, the class describes the liver, not the drug: a class A patient on a drug cleared almost entirely by glucuronidation may need nothing, while a class A patient on a high first pass drug may need a clear reduction. Second, many drugs were never studied in class C, and the labeling then says so rather than giving a dose. Both are reflected in the table above.
Which drugs are contraindicated in liver cirrhosis?
The labeled contraindications at any stage of cirrhosis are a short list: ranolazine, tolvaptan, flibanserin, oral ketoconazole and, for non-cancer use, methotrexate. Duloxetine is to be avoided in chronic liver disease or cirrhosis. From class B onward rivaroxaban, edoxaban, bosentan, lomitapide and sertraline join the list, and in class C apixaban, ticagrelor, carvedilol, ivabradine, finerenone and diazepam are added.
Everything else in the table is a dose or monitoring question. Statins are the best example of a drug stopped too often: they are contraindicated only in decompensated cirrhosis and acute liver failure, and in compensated disease they are usually continued.
Which painkiller and which sedative are safest in liver disease?
Acetaminophen at a reduced daily ceiling is the usual first choice for pain in cirrhosis, because NSAIDs threaten renal perfusion and cause bleeding. Opioids are used at lower doses and longer intervals, and constipation is treated actively because it can precipitate encephalopathy.
For sedation, the benzodiazepines cleared by glucuronidation, lorazepam and oxazepam, accumulate far less than diazepam, alprazolam or clonazepam. Any sedative still carries the encephalopathy risk, so the lowest effective dose applies throughout.
How Prescriber.io handles hepatic dosing at the point of care
On the desk the clinician records the Child-Pugh class alongside the regimen. Every drug on the list that has a labeled hepatic rule at that class is flagged at the matching level, avoid, adjust or review, with the row on this page cited under the flag so the statement can be read in full.
Drugs outside this table that depend on hepatic CYP3A4 are still flagged for review, with the CYP3A4 reference cited, so a recorded impairment never passes silently. You review, verify against the current labeling for the product and indication, and sign.
Questions clinicians ask
Hepatic impairment drug dosing, frequently asked questions
Keep going
Related clinical references and checkers
P-glycoprotein (P-gp) inhibitors
The inhibitor list by strength, the substrates that actually get people into trouble, and the inducers that push the other way.
Read the listSSRI drug interactions
The interactions that matter by agent: CYP2D6 and CYP2C19 inhibition, serotonin syndrome combinations, bleeding risk and the citalopram QT ceiling.
Read the listDrug interaction checker
Run the check on a real regimen instead of reading a list.
Open the checkerRenal dosing calculator
Dose adjustments for kidney function, surfaced in the same card.
See renal dosingChoosing a tool? Compare the options in our guide to the best clinical decision support software, or read which drug interaction checker clinicians pick in 2026.
Run the check on the patient in front of you
Interactions, contraindications, renal and hepatic dosing and guideline-based alternatives arrive in one card with sources cited. You review, verify against official sources, and sign.
Prescriber.io is a clinical reference and decision-support tool for licensed clinicians. It does not diagnose or prescribe autonomously and is not a substitute for professional clinical judgment. Always verify against official sources.