Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

Abstract

The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life.

Isoniazid: A Review of Characteristics, Properties and Analytical Methods

“…In addition, the drug is also used in combination with rifampicin in soft capsules at two different concentrations: 100 mg C 150 mg and 200 mg C 300 mg, respectively. Both pharmaceutical forms, tablets and capsules are provided free of charge by the federal government, given the importance of the effective control of TB (BRASIL, 2011;Daher et al, 2015a). Around the world, isoniazid is marketed with the following brand names: Cotinazin (Pfizer); Dinacrin (Winthrop); Ditubin (Schering); Hycozid (Takeda); Iscotin (Daiichi); Isobicina (Maggioni); Isocid (CID); Isolyn (Abbott); Isonex (Dumex); Isonizida (Bial); Isozid (Fatol); Laniazid (Lannett); Mybasan (Antigen); Neoteben (Bayer); Nicizina (Pfizer); Niconyl (Parke-Davis); Nicotibina (Lapetit); Nydrazid (Bristol-Myers Squibb); Pycazide (Smith & Nephew); Pyricidin (Nepera); Rimifon (Roche); Tibinide (Ferrosan); Tubilysin (Orion) (Global Alliance for TB Drug Development, 2008).…”

Access and adherence to isoniazid preventive therapy and occurrence of active TB in a cohort of people living with HIV: a retrospective cohort study in Sao Paulo, Brazil

“…However, 11.7% of our patients missed the TST measurement appointment, revealing potential pitfalls in the cascade of latent TB diagnosis and treatment. Strategies to further improve access and adherence to PTI have been explored by several authors, including shorter duration regimens, use of digital technologies to improve adherence and retention in care, use of simplified treatment regimens or use of regimens with better tolerance [36][37][38] . In addition, access to PTI could be improved with the implementation of the interferon-γ release assay testing in settings with scarcity of TST or whenever an additional visit to the clinic to assess the TST result is not feasible 39 .…”

Protocol for pragmatic randomized clinical trial to evaluate the completion of treatment of latent Mycobacterium tuberculosis infection with Isoniazid in the 300 mg formulation

“…In Brazil, Isoniazid is widely used in the 100 mg tablet formulation [ 5 , 8 ]. A clinical trial conducted in Brazil showed bioequivalence of Isoniazid 300 mg with 3 tablets in the 100 mg formulation [ 10 ]. Isoniazid 300 mg has been available in Brazil’s National List of Essential Medicines since 2018 and has been used in the treatment of LTBI in patients with HIV/AIDS.…”