Prescribing Medications in Patients With Cirrhosis
Prescribing Medications in Patients With Cirrhosis
The safe use of medications in patients with CLD is an ongoing challenge for prescribers and patients alike. This becomes especially true in patients with cirrhosis, in whom significant changes can occur in the metabolism and handling of various agents, specifically those medications which undergo first-pass metabolism or are metabolised by the CYP3A enzymatic pathway. The presence of portosystemic shunts, including TIPS, may lead to increased bioavailability of drugs leading to QTc prolongation in cirrhotics, which may precipitate potentially fatal ventricular arrhythmias.
Very few drugs have been shown to have their hepatotoxicity potential enhanced by CLD with or without cirrhosis; nearly all of these involve antituberculosis agents given in the setting of chronic hepatitis B or C and among HIV/AIDS patients. Statins, in particular, appear to be beneficial in chronic hepatitis C and other causes of cirrhosis and may prevent progression to HCC.
Lower doses are recommended for the use of several drugs in cirrhosis, although in many cases, the rationale for this is based mostly on reduced clearance mechanisms rather than any known excess risk of hepatotoxicity or other adverse PD effects. NSAIDs, in general, should be used cautiously (or not at all) in cirrhotics due to their risk of precipitating renal failure and inducing or worsening GI bleeding. Nevertheless, OTCAs are widely prescribed, although they do not appear to increase the risk of hospitalisation. Paracetamol (acetaminophen) is safe in patients with CLD, including cirrhosis when used in small (2–3 g or less/day) doses for short durations, and is recommended as first-line treatment of visceral or musculoskeletal pain. Most narcotics and BZDs are best avoided as their half-lives can be prolonged in cirrhosis and may precipitate or worsen encephalopathy. Propofol (without BZDs or narcotics) is well tolerated among cirrhotic patients undergoing endoscopic procedures and isoflurane is a preferred inhalational anaesthetic for cirrhotics undergoing liver transplant. Many patients with CLD use herbal remedies, and clinicians need to be mindful that some can be hepatotoxic, making it essential to obtain a complete drug use history, including all prescription and OTC medicines and supplements.
Proton pump inhibitors and other acid-suppressive agents have been linked to a greater risk of SBP in cirrhotics and should be used with caution or avoided entirely. When required, shorter duration therapy should be considered, along with the use of prophylactic antibiotics to prevent bacteremia in patients with variceal or other GI bleeding undergoing endoscopy or other invasive procedures. Antibiotics are also recommended to prevent recurrent SBP in patients who have been successfully treated for a prior episode; whether or not this will reduce the risk of SBP from acid-suppressive agents has not been formally studied, but is likely a prudent recommendation.
Conclusions
The safe use of medications in patients with CLD is an ongoing challenge for prescribers and patients alike. This becomes especially true in patients with cirrhosis, in whom significant changes can occur in the metabolism and handling of various agents, specifically those medications which undergo first-pass metabolism or are metabolised by the CYP3A enzymatic pathway. The presence of portosystemic shunts, including TIPS, may lead to increased bioavailability of drugs leading to QTc prolongation in cirrhotics, which may precipitate potentially fatal ventricular arrhythmias.
Very few drugs have been shown to have their hepatotoxicity potential enhanced by CLD with or without cirrhosis; nearly all of these involve antituberculosis agents given in the setting of chronic hepatitis B or C and among HIV/AIDS patients. Statins, in particular, appear to be beneficial in chronic hepatitis C and other causes of cirrhosis and may prevent progression to HCC.
Lower doses are recommended for the use of several drugs in cirrhosis, although in many cases, the rationale for this is based mostly on reduced clearance mechanisms rather than any known excess risk of hepatotoxicity or other adverse PD effects. NSAIDs, in general, should be used cautiously (or not at all) in cirrhotics due to their risk of precipitating renal failure and inducing or worsening GI bleeding. Nevertheless, OTCAs are widely prescribed, although they do not appear to increase the risk of hospitalisation. Paracetamol (acetaminophen) is safe in patients with CLD, including cirrhosis when used in small (2–3 g or less/day) doses for short durations, and is recommended as first-line treatment of visceral or musculoskeletal pain. Most narcotics and BZDs are best avoided as their half-lives can be prolonged in cirrhosis and may precipitate or worsen encephalopathy. Propofol (without BZDs or narcotics) is well tolerated among cirrhotic patients undergoing endoscopic procedures and isoflurane is a preferred inhalational anaesthetic for cirrhotics undergoing liver transplant. Many patients with CLD use herbal remedies, and clinicians need to be mindful that some can be hepatotoxic, making it essential to obtain a complete drug use history, including all prescription and OTC medicines and supplements.
Proton pump inhibitors and other acid-suppressive agents have been linked to a greater risk of SBP in cirrhotics and should be used with caution or avoided entirely. When required, shorter duration therapy should be considered, along with the use of prophylactic antibiotics to prevent bacteremia in patients with variceal or other GI bleeding undergoing endoscopy or other invasive procedures. Antibiotics are also recommended to prevent recurrent SBP in patients who have been successfully treated for a prior episode; whether or not this will reduce the risk of SBP from acid-suppressive agents has not been formally studied, but is likely a prudent recommendation.
