What medications are contraindicated in patients with liver failure?

Medications Contraindicated in Liver Failure

Several medications are absolutely contraindicated in patients with liver failure due to their potential to worsen outcomes, increase mortality, and reduce quality of life. 1, 2, 3

Absolutely Contraindicated Medications

• Pyrazinamide is contraindicated in persons with severe hepatic damage due to risk of further hepatotoxicity 2
• Valproic acid should not be administered to patients with hepatic disease or significant hepatic dysfunction 3
• Benzodiazepines should be avoided in patients with liver failure due to their deleterious effects on encephalopathy 4
• Metoclopramide and other psychotropic drugs should be avoided as they can worsen hepatic encephalopathy 5
• Nephrotoxic drugs including NSAIDs should be avoided in patients with liver failure to prevent further renal injury 5, 1
• Dexmedetomidine should be used with extreme caution as its metabolism is exclusively hepatic 4

Medications Requiring Dose Adjustment or Caution

• Drugs with first-pass metabolism require reduction in oral dosages due to altered drug disposition in liver failure 6
• High clearance drugs need adjustment in both loading and maintenance dosages 6
• Low clearance drugs require maintenance dose adjustment 6
• Opioids such as morphine, oxycodone, and tramadol require lower doses and longer administration intervals due to decreased clearance in moderate to severe hepatic impairment 7
• ACE inhibitors should be used with extreme caution as they can counteract the enhanced activity of the renin-angiotensin system in advanced liver disease, leading to excessive hypotension 8

Safer Alternatives

• Propofol is the preferred sedative agent for patients with acute liver failure due to its favorable pharmacokinetic profile and minimal impact on hepatic encephalopathy 4
• Phenylpiperidine opioids such as fentanyl, sufentanil, and remifentanil have pharmacokinetics that appear to be relatively unaffected in hepatic disease 7
• Acetaminophen can be used safely at reduced doses (maximum 2 grams daily) in patients with non-alcoholic liver disease for short-term use 9, 7
• Crystalloid fluids are recommended as first choice for fluid expansion in patients with liver failure 5
• Norepinephrine is recommended for refractory hypotension in patients with liver failure 5

Special Considerations

• Coagulation factors should only be administered in cases of active bleeding, not prophylactically 5
• N-acetylcysteine should be administered systematically regardless of suspected etiology in patients with liver failure 1
• Empirical broad-spectrum antibiotics should be administered to patients with worsening hepatic encephalopathy or signs of SIRS 5, 1

Monitoring Recommendations

• Blood glucose should be monitored at least every 2 hours in patients with liver failure to prevent hypoglycemia 5, 1
• Serum sodium levels should be maintained between 140-145 mmol/L to prevent cerebral edema 5, 1
• Frequent mental status checks are more valuable than ammonia measurements for monitoring disease progression 10
• Drug levels should be measured when possible, especially for medications with narrow therapeutic windows 6

Common Pitfalls to Avoid

• Assuming that all drugs in a class have similar hepatic metabolism profiles - even drugs sharing the same metabolic pathway may have different dispositions in liver disease 8
• Relying solely on standard dosing guidelines without considering the degree of hepatic impairment 6
• Failing to recognize that patients with liver failure may have increased sensitivity to standard doses of medications, particularly psychoactive agents 8
• Overlooking the potential for drug-induced hepatotoxicity to be poorly tolerated in patients with pre-existing liver disease 6

Remember that medication management in liver failure requires careful consideration of altered pharmacokinetics, increased sensitivity to adverse effects, and the potential for medications to worsen hepatic function or precipitate complications.