In all adults preparing to begin isoniazid treatment, the clinician should order baseline measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, alkaline phosphatase, serum creatinine, and platelet count. Regular monitoring of hepatic and renal function during treatment is not necessary unless the patient has abnormal baseline levels or is at increased risk for hepatotoxicity (alcohol abuse, hepatitis B or C infection, etc.). For those patients, serum transaminases should be measured again two to four weeks after treatment initiation.[1]

In patients with pulmonary tuberculosis, monthly sputum specimens are necessary (until there are two consecutive negative cultures) to assess response to treatment.

Isoniazid is metabolized primarily by the liver, by acetylation of N-acetyl transferase 2 (NAT2). Three metabolites have implications that correlate with the liver injury associated with the drug: acetyl hydrazine (AcHz), hydrazine (Hz), and a metabolite from the bioactivation of isoniazid itself. There is considerable variation in acetylation rate and elimination half-life from individual to individual, which is not accounted for by dose and concentration, and this appears to contribute to risk for hepatotoxicity as well as the other adverse effects associated with isoniazid.[8]

Mild liver injury will occur in up to 20% of patients taking isoniazid. Clinical manifestations of hepatotoxicity include fever, fatigue, nausea, and vomiting. However, most patients experiencing isoniazid-induced liver injury are asymptomatic. Usually, it is detected only by measuring increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which may rise to as high as five times the normal limit. In a process called “adaptation,” the hepatic markers will return to normal in most of these patients even with continued administration of the drug. About 1% of patients will experience severe liver injury, and isoniazid therapy should stop immediately.  Reintroduction of isoniazid in these cases is contraindicated as it can cause rapid symptom onset, and fatal hepatitis during isoniazid treatment is associated with continued use after symptoms of hepatitis present.[9] Serious isoniazid-induced liver injury is associated with the older age of the patient, in addition to concurrent treatment with rifampin, which induces CYP metabolism. Incidence is also higher in slow acetylators and this links with higher serum levels of both isoniazid and the AcHz metabolite. Additional risk factors include preexisting liver disease, a history of heavy alcohol use, and being in the postpartum period. More recently identified risk factors include polymorphisms in glutathione S-transferase, CYP2E1, TNF-alpha, and others.[8]

Most patients recover entirely from isoniazid hepatotoxicity after discontinuation, although full regression takes weeks.[10]

Providers treating TB patients with INH must be cognizant of the patient's baseline liver function and the hepatotoxic risks associated with INH. Although estimates of fatal hepatitis associated with INH treatment are only 0.023%, these cases correlate with continued administration despite symptoms of hepatitis during treatment.[1]

Tuberculosis is a disease with widespread and high-burden effects, both for the individual patient and for communities.  Appropriate treatment is crucial for curing the sick patient, as well as for limiting the spread of TB and preventing drug resistance. Therefore, a provider treating TB has a responsibility not only to prescribe the appropriate treatment regimen but also to ensure adequate adherence to and completion of treatment.[1]

A growing concern is INH-resistant strains of TB, and it appears that these may serve as precursors to multi-drug resistant strains. Thus, providers should monitor patient progress to rapidly detect those who are not responding to INH treatment and, therefore, may harbor a resistant strain. INH-resistant strains require an altered regimen and increased efforts to prevent disease transmission.[11][12]

Public health departments typically provide TB treatment, and they frequently collaborate with other entities such as private providers, community health centers, shelters, and others to ensure completion of treatment. A patient-centered approach should serve to tailor a treatment plan specific to each patient's needs to provide the best opportunity for treatment completion. This approach often involves social workers and case managers in addition to medical professionals, and communication and coordination of services are essential. One means by which to maximize adherence is direct observation of therapy (DOT), which is providing the medications directly to the patient and watching as he/she swallows them. This approach has become the preferred method of drug administration in TB. DOT provides a close connection to the healthcare system and allows for early identification of nonadherence and adverse effects of treatment or the worsening of the patient's condition.[1]