ASSOCIATION BETWEEN PYRAZINAMIDE-CONTAINING ANTI-TUBERCULOSIS REGIMENS AND THE INCIDENCE OF HEPATOTOXICITY: EVIDENCE-BASED CASE REPORT
Telly Kamelia 1 , Almira Divashti Adna 2

1 Division of Pulmonology and Critical Medicine, Department of Internal Medicine, Faculty of
Medicine, Universitas Indonesia, Cipto Mangunkusumo National General Hospital Jakarta,
Indonesia
2 Faculty of Medicine, Universitas Indonesia

ABSTRACT
Background: Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, remains a major global health burden. According to the WHO, approximately 9.6 million cases were reported in 2014, with 58% occurring in Southeast Asia, including Indonesia. Anti-tuberculosis treatment using Fixed-Dose Combination (FDC) regimens—comprising isoniazid, rifampicin, pyrazinamide, and ethambutol—is associated with several adverse effects, most notably hepatotoxicity.
Objective: To evaluate the impact of pyrazinamide-containing anti-tuberculosis regimens on
the incidence of hepatotoxicity in patients with tuberculosis.
Methods: A systematic literature search was conducted across three electronic databases:
PubMed, Cochrane Library, and Scopus. Selected studies underwent critical appraisal based
on the University of Oxford’s Centre for Evidence-Based Medicine (CEBM) guidelines.
Result: Two articles met the eligibility criteria for this report. Both studies compared two
patient groups—those receiving the RHZE regimen (with pyrazinamide) and those receiving
the RHE regimen (without pyrazinamide)—to monitor the incidence of hepatotoxicity during
the first two months of treatment.
Conclusion: The findings suggest that the inclusion of pyrazinamide (PZA) does not
significantly increase the incidence of hepatotoxicity in TB patients. A PZA dosage of 20-25
mg/kg/day was found to be within the safety limits for both adults and elderly patients.
Keywords: tuberculosis, drug-induced liver injury, hepatotoxicity, pyrazinamide