Is montelukast (Singulair) associated with elevated Alanine Transaminase (ALT) and Aspartate Transaminase (AST) in a patient with a Fibrosis-4 (FIB-4) score of 1.6, indicating mild liver fibrosis?

From the Guidelines

Montelukast should be used with caution in patients with elevated liver enzymes, and the decision to continue or discontinue the medication should be based on a thorough evaluation of the potential benefits and risks, considering the patient's individual circumstances and the presence of other risk factors for liver disease, as recommended by the EASL clinical practice guidelines 1. Given the patient's FIB-4 score of 1.6, which is generally considered low risk for advanced liver fibrosis, the elevation in ALT and AST levels while taking montelukast warrants further investigation to determine the cause. The EASL guidelines suggest that non-invasive fibrosis tests, such as FIB-4, should be used for ruling out rather than diagnosing advanced fibrosis in low-prevalence populations, and that ALT, AST, and platelet count should be part of the routine investigations in primary care in patients with suspected liver disease 1. Some key points to consider in the management of this patient include:

• The potential for montelukast to cause liver enzyme elevations, although this is rare
• The need to investigate the cause of elevated liver enzymes, considering other potential factors such as alcohol use, other medications, viral hepatitis, or fatty liver disease
• The importance of balancing the therapeutic benefits of montelukast against the potential risk of liver injury
• The role of regular monitoring of liver function while continuing to take montelukast, especially if it's providing important benefits for asthma or allergic conditions, as recommended by the EASL guidelines 1. It is essential to note that the EASL guidelines emphasize the importance of applying non-invasive fibrosis tests to populations with risk factors for liver disease rather than unselected populations, to minimize the spectrum effect and ensure accurate diagnosis and management 1. In this case, the patient's elevated liver enzymes and FIB-4 score of 1.6 suggest the need for further evaluation and monitoring, rather than immediate discontinuation of montelukast, and the decision to continue or discontinue the medication should be made on a case-by-case basis, taking into account the patient's individual circumstances and the potential benefits and risks of the medication, as recommended by the EASL guidelines 1.

From the FDA Drug Label

The safety in patients 2 to 14 years of age with perennial allergic rhinitis is supported by the established safety in patients 2 to 14 years of age with seasonal allergic rhinitis In these two studies, the following events were reported with SINGULAIR with a frequency ≥1% and at an incidence greater than placebo, regardless of causality assessment: ... increased ALT.

Increased ALT and AST levels have been reported in patients taking montelukast, although the exact frequency is not specified in the provided text. Given the patient's FIB-4 score of 1.6, which is relatively low, and the presence of increased ALT and AST, it is unclear whether montelukast is causing the liver enzyme elevations. However, liver enzyme elevations have been reported in patients taking montelukast, and rare cases of cholestatic hepatitis, hepatocellular liver-injury, and mixed-pattern liver injury have also been reported 2. Therefore, caution should be exercised when using montelukast in patients with elevated liver enzymes, and monitoring of liver function tests may be necessary.

From the Research

Montelukast and Liver Enzymes

• Montelukast is a leukotriene receptor antagonist used in the treatment of asthma and other respiratory diseases.
• There is evidence to suggest that montelukast may have a protective effect on the liver, as shown in a study where it abrogated lipopolysaccharide-induced toxicity and oxidative stress in rat liver 3.
• In this study, montelukast decreased the markers of liver injury, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), after lipopolysaccharide challenge.
• However, the effect of montelukast on liver enzymes in humans is not well established, and more research is needed to fully understand its impact.

Fib-4 Score

• The Fib-4 score is a non-invasive test used to assess liver fibrosis.
• A Fib-4 score of 1.6 is considered to be within the normal range, indicating a low risk of liver fibrosis.
• There is no direct evidence to suggest that montelukast affects the Fib-4 score, and more research is needed to fully understand its impact on liver health.

Montelukast and Asthma

• Montelukast has been shown to be effective in reducing asthma exacerbations and improving quality of life in patients with asthma 4, 5, 6, 7.
• It works by blocking the action of leukotrienes, which are chemicals that can cause inflammation and constriction of the airways.
• Montelukast can be used as a monotherapy or in combination with other medications, such as inhaled corticosteroids, to treat asthma.