Can I give Artemether-Lumefantrine (AL) to a patient with elevated liver enzymes and hyperbilirubinemia?

Administration of Artemether-Lumefantrine in Patients with Elevated Liver Enzymes

Artemether-Lumefantrine (AL) should not be administered to patients with liver enzymes elevated to twice the upper limit of normal and bilirubin of 15 mg/dL due to the risk of worsening hepatotoxicity.

Assessment of Liver Function and Antimalarial Therapy

Liver function is a critical consideration when selecting antimalarial therapy. The current clinical scenario presents a patient with:

• Liver enzymes elevated to 2 times normal
• Bilirubin level of 15 mg/dL

Contraindications Based on Liver Function

The consensus guidelines for drug-induced liver injury (DILI) provide clear recommendations regarding medication use in patients with liver dysfunction:

• Patients with elevated liver enzymes and hyperbilirubinemia are at increased risk for drug-induced liver injury 1
• Medications should be interrupted when ALT ≥3× ULN if total bilirubin ≥2× baseline 1
• Persistent isolated elevations of direct bilirubin in patients with cholestatic liver disease should be closely monitored, as this may be a sign of DILI 1

Artemether-Lumefantrine and Hepatic Effects

Artemether-Lumefantrine has known effects on liver function:

• AL therapy can cause asymptomatic liver enzyme abnormalities in the first days of treatment 2
• The artemether component undergoes first-pass metabolism in the liver 3
• Patients treated with artemether-based therapy show a higher proportion of significant liver enzyme abnormalities (42% vs. 5%) compared to quinine-doxycycline 2

Alternative Treatment Options

For patients with elevated liver enzymes and hyperbilirubinemia, alternative antimalarial regimens should be considered:

1. Atovaquone-proguanil: Recommended as a second-line drug for the treatment of uncomplicated P. falciparum malaria when ACTs are contraindicated 1

2. Quinine sulphate with doxycycline or clindamycin: Can be used as an alternative treatment option 1

Monitoring Recommendations

If treatment with antimalarials is absolutely necessary despite liver dysfunction:

• Monitor liver function tests every 2-5 days initially 4
• Watch for signs of worsening liver function (increasing bilirubin, prolonged INR, encephalopathy)
• Consider vitamin K supplementation if INR is prolonged 1

Important Considerations and Pitfalls

• Hy's law pattern (ALT >3× ULN and bilirubin >2× ULN without cholestasis) suggests high risk of severe DILI 4
• Medication exposure levels: In patients with liver dysfunction, drug levels may be higher due to impaired metabolism 1
• Concomitant medications: Review all medications for potential hepatotoxic effects or interactions 4
• Underlying liver disease: The presence of underlying liver disease significantly increases the risk of drug-induced hepatotoxicity 1

Conclusion for Clinical Practice

The current patient with liver enzymes elevated to twice normal and bilirubin of 15 mg/dL already shows evidence of significant liver dysfunction. Adding Artemether-Lumefantrine, which has known hepatic effects, poses an unacceptable risk of worsening liver injury. Alternative antimalarial regimens should be selected based on the patient's clinical condition, malaria species, and severity of infection.