No formal studies have been conducted in patients with hepatic impairment so the pharmacokinetics of codeine in this patient population are unknown.

Start patients with hepatic disease with a lower than normal dosage of codeine or with longer dosing intervals and titrate slowly while monitoring for signs of hypoventilation, sedation, and hypotension. Although it is always prudent to use the smallest dose of acetaminophen for the shortest duration necessary, courses less than 2 weeks in length have been administered safely to adult patients with stable chronic liver disease. In addition, cytochrome P450 activity is not increased and glutathione stores are not depleted in hepatically impaired patients taking therapeutic doses, therefore toxic metabolite formation and accumulation is not altered. Though the half-life of acetaminophen may be prolonged, repeated dosing does not result in drug or metabolite accumulation. In patients with chronic hepatic disease, acetaminophen can be used safely in recommended doses and is often preferred to nonsteroidal anti-inflammatory drugs (NSAIDs) due to the absence of platelet impairment, gastrointestinal toxicity, and nephrotoxicity.

It is important to note that the risk of acetaminophen-induced hepatotoxicity is increased in patients with pre-existing hepatic disease (e.g., hepatitis), those who ingest alcohol (e.g., ethanol intoxication, alcoholism), those with chronic malnutrition, and those with severe hypovolemia. Advise patients receiving acetaminophen to carefully read OTC and prescription labels, to avoid excessive and/or duplicate medications, and to seek medical help immediately if more than 4 g/day of acetaminophen is ingested, even if they feel well. Use caution during the measurement of oral liquid dosage forms to minimize the risk of dosing errors that can result in accidental overdose. Most cases of liver injury are associated with the use of acetaminophen at doses exceeding 4 g/day and often involve the use of more than 1 acetaminophen-containing product. Accidental exposure, alcoholism, depression, ethanol intoxication, hepatic disease, hepatitis, hepatotoxicity, hypovolemia, malnutrition, opioid overdose, opioid use disorder, potential for overdose or poisoning, substance abuseДЄcetaminophen has the potential for overdose or poisoning causing hepatotoxicity and acute liver failure, at times resulting in liver transplantation and death.

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