Growing prevalence of liver disease and its impact on medication dosing
In direct patient care, we know the probability of encountering a patient with a hepatic insufficiency is growing dramatically:
- According to the World Health Organization, liver disease rates have increased significantly over the past few years. It now is the 11th leading cause of the death worldwide.
- It’s also become the fifth leading cause of death in the United Kingdom.
- Liver disease is the ninth leading cause of death overall and the second leading cause of mortality among all digestive diseases in the United States (US).
- Liver cirrhosis or irreversible liver damage continues to go unrecognized and impacts nearly 10% of the global population.
So, why does this matter?
The liver is sometimes affectionately referred to by medical professionals as the “garbage can of the body.” It's able to filters substances that come into a patient’s system, removing toxins and processing the substance in the most effective way.
That includes the vital role of drug metabolism.
The liver is responsible for the metabolism and bioconversion of many drugs our patients are taking. If the liver is unable to do its job, the drugs we choose may not become active to treat the patient’s condition or they may accumulate and cause side effects or toxicity in the patient, leaving the patient vulnerable to unpredictable outcomes unless the dose is carefully selected and titrated based on their individual liver function.
Why dosing for liver disease requires expertise
The challenge we encounter when trying to identify an appropriate drug dose for patients with liver impairment begins with the complexities of understanding liver dysfunction in the first place. Liver function tests such as AST (aspartate aminotransferase) and ALT (alanine transaminase) do not translate into a direct or definitive result that indicates a liver function level. They are usually grouped with a panel of tests to contribute to a wider picture of liver health and symptoms.
To help inform a patient’s safe medication dosing adjustment concurrent with liver disease, healthcare providers must look at several patient factors:
- Identify the patient’s Child-Turcotte-Pugh or MELD score.
- Identify hepatic biomarkers of synthetic functions such as international normalized ratio (INR), coagulation parameters, or protein synthesis.
- Translate that into what you think their liver function is in order to adjust their medications.
These adjustments required for safe treatment and made by experience, expertise, and best practice are not available in the package insert most of the time, and they likely require a substantial evaluation of the existing literature about the drug’s pharmacokinetics and dynamics and how they change with liver insufficiency. This can be very time-consuming and potentially delay getting the appropriate recommended dose to a patient.
Evidence-based approach to dosing in liver impairment
Dosing recommendations in liver impairment are often missing because pre-marketing studies are not performed on patients with liver impairment, and post-marketing studies are also not required to include patients with any liver conditions. In the US, the FDA warns that despite extensive efforts, no single measure or group of measures has gained widespread clinical use to allow estimation in a given patient of how hepatic impairment will affect the pharmacokinetics or dynamics of a given drug it has approved.
This is often why frontline clinicians are stuck making “educated guesses” about what to do with patients with liver impairment.
It is challenging for busy providers and pharmacists to navigate the available data and literature to simulate the best recommendation or guardrail for individual drugs and evaluate what the risks are of using that drug in a patient with liver insufficiency.
Dosing recommendations for hepatic impairment
Based on feedback from users that ranked this challenge as one of the most important to address, the UpToDate® Lexidrug™ referential drug solution is working to fill in those gaps to provide dosing recommendations for patients who have liver impairment. Our rigorous review process includes a team of four senior clinical experts, which includes two pharmacists and two hepatologists, along with 10 clinicians practicing at the bedside who sift through and synthesize the available literature to provide expert recommendations for using drugs in patients with liver insufficiency where there were not recommendations before.
These recommendations are made based on the broad evaluation of the available literature, including the pharmacokinetics and dynamics of the medication and documented use of the medication in a patient with liver insufficiency. When there is no use data in this group, the experts provide a dosing recommendation based on years of clinical experience as well as their expert knowledge of the pharmacokinetics and dynamics of the drug and how that could be impacted by liver insufficiency.
We also try to dispel some of the inferences that are commonly held about certain medications.
Improving safe and effective use of medications in liver patients
October is National Liver Awareness Month in the US, a time to recognize the importance of liver health and proper care for those who are experiencing symptoms of liver cancers, cirrhosis, and diseases. While the bulk of attention is on the direct effects of liver dysfunction, we cannot forget that hepatic insufficiency can affect medications for a variety of comorbidities, including cardiology and psychiatry treatments. Expert recommendations are available to support decision-making at various stages of the patient’s journey, including:
- Initiation of a medication.
- Identifying the best course of action if liver function worsens.
- How to adjust during an acute event like hospitalization.
Having actionable recommendations and resources to fill in information where labels are lacking can be an essential support to clinicians seeking appropriate dose adjustments for patients with liver impairment.
