Help manage dose adjustments in liver disease
As a hospital pharmacist, you should Be ready with strategies to adjust medication doses in patients with liver impairment since medication labels often lack clear recommendations. For more information, see note on "Prescribing medications in patients with liver cirrhosis". Most medications don't need dose adjustments until liver function is at least 90% impaired such as in patients with decompensated cirrhosis who have jaundice or variceal bleeding. But it's harder to quantify liver impairment than kidney impairment.
Liver enzymes (ALT, AST) are just markers of hepatic injury, NOT how well the liver is functioning. In fact, these labs (ALT, AST) may be normal in a patient with advanced cirrhosis. Continue to think of elevated liver enzymes as a flag to evaluate if liver injury is due to a medication or supplement (statins, etc). On the other hand, lean more on markers of liver function, such as albumin, bilirubin, or INR (prothrombin time) to guide medication adjustments.
For patients with cirrhosis, expect to hear more about the Child-Pugh score (see Table 1) which estimates the degree of liver impairment. It uses labs (albumin, bilirubin, INR) and severity of ascites and encephalopathy to assign a score of 5 to 15. This correlates to Child-Pugh class A, B, or C (least to most severe). For examples, for instance, ondansetron (Zofran) labelling advises a maximum of 8 mg/day for patients with moderate to severe hepatic impairment which can be extrapolated to Child-Pugh class B and C. And limit esomeprazole (Nexium) to 20 mg/day or bupropion SR to 150 mg every other day for those with severe impairment or Child-Pugh class C.
| Table (1). Child‐Pugh–Turcotte classification | ||
|---|---|---|
| Assessment | Degree of abnormality | Score |
| Encephalopathy | None | 1 |
| Moderate | 2 | |
| Severe | 3 | |
| Ascites | Absent | 1 |
| Slight | 2 | |
| Moderate | 3 | |
| Bilirubin (mg/dL) | <2 | 1 |
| 2.1–3 | 2 | |
| >3 | 3 | |
| Albumin (g/dL) | >3.5 | 1 |
| 2.8–3.5 | 2 | |
| <2.8 | 3 | |
| Prothrombin time (s > control) | 0–3.9 | 1 |
| 4.0–6.0 | 2 | |
| >6.0 | 3 | |
| Total score group severity | 5–6 A Mild = MELD 1–10 | |
| 7–9 B Moderate = MELD 11–20 | ||
| 10–15 C Severe = MELD >20 | ||
Follow dose recommendations per labelling if they exist. Otherwise, recommend starting low and going slow especially with medications highly metabolized in the liver, such as fluoxetine or propranolol. These can accumulate and increase side effects.
Also be alert for highly protein-bound drugs, such as phenytoin or warfarin since low albumin levels may increase med effects. Keep in mind, liver failure and kidney failure often go hand in hand. Continue to adjust doses based on renal function if needed.
REFERENCES
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Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis - a practical guide. Aliment Pharmacol Ther. 2013 Jun;37(12):1132-56. Available at: https://pubmed.ncbi.nlm.nih.gov/23638982
Weersink RA, Bouma M, Burger DM, Drenth JPH, Harkes-Idzinga SF, Hunfeld NGM, Metselaar HJ, Monster-Simons MH, Taxis K, Borgsteede SD. Evidence-Based Recommendations to Improve the Safe Use of Drugs in Patients with Liver Cirrhosis. Drug Saf. 2018 Jun;41(6):603-613. Available at: https://pubmed.ncbi.nlm.nih.gov/29330714
Weersink RA, Burger DM, Hayward KL, Taxis K, Drenth JPH, Borgsteede SD. Safe use of medication in patients with cirrhosis: pharmacokinetic and pharmacodynamic considerations. Expert Opin Drug Metab Toxicol. 2020 Jan;16(1):45-57. Available at: https://pubmed.ncbi.nlm.nih.gov/31810397
