Can Maxine cause liver injury?

Maxine and Liver Injury Risk

Maxine can cause liver injury, particularly when used at high doses or in combination with other hepatotoxic medications. 1

Mechanism and Risk Factors

• Tyrosine kinase inhibitors (TKIs) like Maxine undergo bioactivation to form reactive intermediates, which can lead to idiosyncratic adverse drug reactions including hepatotoxicity 1
• High daily doses (more than 50-100 mg) are a significant risk factor for drug-induced liver injury (DILI), with 13 out of 17 approved TKIs falling into this high-risk category 1
• Being a substrate of CYP450 enzymes is another important predictor of drug-induced liver injury 1
• Drug metabolism characteristics and propensity for drug interactions can increase the risk of liver injury 2

Clinical Presentation of Liver Injury

• Liver injury from Maxine may present in various ways, ranging from asymptomatic transaminitis to severe hepatotoxicity 3
• Hepatotoxicity can manifest as either hepatocellular injury (primarily elevated ALT/AST) or cholestatic/mixed pattern (elevated alkaline phosphatase) 4
• According to Hy's Law, hepatocellular drug-induced liver injury with jaundice carries a mortality rate of ≥10%, making early detection critical 4

Drug Interactions That Increase Hepatotoxicity Risk

• Concomitant use of Maxine with CYP450 inhibitors can result in markedly elevated drug concentrations, increasing the risk of hepatotoxicity 1
• Similar to documented cases with other TKIs, the combination of Maxine with statins may alter systemic and/or hepatic exposures, leading to increased risk of liver injury 1
• Concurrent use with medications that induce drug metabolism (like dexamethasone) may increase the formation of reactive metabolites, potentially leading to toxicity 1

Monitoring Recommendations

• Baseline liver function tests should be obtained before starting Maxine therapy 1
• Regular monitoring of liver enzymes is recommended, especially during the first 6 months of treatment when idiosyncratic drug hepatotoxicity is most likely to occur 1
• If there is underlying liver disease, monthly monitoring of liver function tests is advisable 1
• Any abrupt elevations in liver biochemistries should prompt immediate evaluation 1

Management of Suspected Liver Injury

• If liver injury is suspected, a thorough evaluation to rule out alternative causes is essential, as up to 48.5% of initially suspected herb/drug-induced liver injury cases have alternative explanations 5
• Consider discontinuing Maxine if significant liver enzyme elevations occur, especially if accompanied by symptoms or bilirubin elevation 1
• In patients with prolonged hyperbilirubinaemia of unclear etiology, consider breakdown of direct bilirubin fraction to conjugated and delta bilirubin 1
• Persistent isolated elevations of direct bilirubin should be closely monitored, especially in patients with underlying synthetic function impairment 1

Special Populations at Higher Risk

• Patients with pre-existing liver disease are at increased risk of developing hepatotoxicity 2
• Elderly patients may be more susceptible to drug-induced liver injury 2
• Patients with HIV infection may have increased susceptibility to drug-induced liver injury 2
• Patients taking multiple medications have a higher risk due to potential drug interactions 1

Prevention Strategies

• Use the lowest effective dose of Maxine to minimize risk of hepatotoxicity 1
• Avoid concurrent use with other known hepatotoxic medications when possible 1
• Be vigilant in monitoring patients receiving potentially-interacting drug pairs 1
• Consider temporary discontinuation of Maxine during acute hepatitis episodes 1

Remember that drug-induced liver injury can be unpredictable and may occur despite appropriate precautions. Early recognition and management are key to preventing progression to severe liver damage.