Determinants of adverse reactions to first-line antitubercular medicines: a prospective cohort study

Djochie et al. Journal of Pharmaceutical Policy and Practice https://doi.org/10.1186/s40545-023-00577-6 (2023) 16:70 Journal of Pharmaceutical Policy and Practice Open Access RESEARCH Determinants of adverse reactions to first‑line antitubercular medicines: a prospective cohort study Richard Delali Agbeko Djochie1 , Berko Panyin Anto1*   and Mercy Naa Aduele Opare‑Addo1    Abstract Background The success of tuberculosis treatment relies on patients adhering to their medication regimen con‑ sistently. However, adherence levels tend to decrease among patients who experience adverse drug reactions to antitubercular medications, leading to suboptimal treatment outcomes. Hence, this study aimed to examine the types, incidence rates, and severity of adverse reactions caused by first-line antitubercular drugs. Additionally, it aimed to identify factors associated with the development of these reactions. By doing so, the study aimed to facilitate the provision of personalized and effective treatment to patients, ultimately improving treatment outcomes. Methods Newly diagnosed patients with active tuberculosis were monitored from the start of their treatment until the completion of therapy. Any adverse reactions to anti-TB drugs that they encountered were carefully recorded. The collected data were analyzed using appropriate statistical methods such as analysis of variance, Chi-squared test, Fisher’s exact test, and independent t-tests. Logistic regression was employed to assess the association between adverse drug reactions and various socio-demographic and clinical factors of the patients, using odds ratios as a measure of association. Results Among the 378 patients included in the study, 181 individuals (47.9%) reported experiencing at least one adverse drug reaction, with an incidence rate of 1.75 events per 100-person months. The majority of these reactions occurred during the intensive phase of treatment. The gastrointestinal tract was the most commonly affected system, followed by the nervous system and skin. Patients aged over 45 years (OR = 1.55, 95% CI 1.01–2.39, p = 0.046) and those with extrapulmonary tuberculosis (OR = 2.41, 95% CI 1.03–5.64) were more likely to develop gastrointestinal reactions. Female gender was a significant predictor of both skin (OR = 1.78, 95% CI 1.05–3.02, p = 0.032) and nervous system (OR = 1.65, 95% CI 1.07–2.55, p = 0.024) reactions. Additionally, alcohol use and HIV infection were identified as independent predictors of adverse drug reactions affecting all three systems. Conclusion Significant risk factors for developing antitubercular drug adverse reactions include alcohol consump‑ tion, cigarette smoking, being HIV positive, female gender and extrapulmonary tuberculosis. Keywords Antitubercular drugs, Adverse drug reactions, Pharmacovigilance, Ghana *Correspondence: Berko Panyin Anto ; 1 Department of Pharmacy Practice, Faculty of Pharmacy and Pharmaceutical Sciences Kwame Nkrumah University of Science and Technology, Kumasi Private Mailbag, Kumasi, Ghana Background Tuberculosis (TB) remains a significant public health concern worldwide, particularly in developing countries with limited healthcare resources. It is the leading cause of death among individuals living with HIV/AIDS [1], with a rapid progression of the disease in this population [2]. Antibiotic chemotherapy is the fundamental © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Djochie et al. Journal of Pharmaceutical Policy and Practice (2023) 16:70 approach to combat TB, and successful treatment outcomes rely on patients maintaining high levels of adherence to their anti-TB medications. In Ghana, the treatment of TB aligns with the World Health Organization’s (WHO) recommendations, utilizing a combination of rifampicin, isoniazid, pyrazinamide, and ethambutol. The dosages are calculated based on the patient’s weight during the initial 2 months (intensive phase), followed by a continuation phase of rifampicin and isoniazid for an additional 4 months. Most patients undergoing this treatment regimen achieve sputum sterility within 2 weeks, thereby reducing the risk of transmitting the infection in their communities. The tuberculosis treatment success rate in Ghana has shown improvement over the years, increasing from 50% in 2000 to 84% in 2012 [3]. Aligned with the WHO’s End TB Strategy, the Ministry of Health in Ghana aimed to further enhance the treatment success rate to 91% for all forms of TB by 2020. However, as of the end of 2022, the treatment success rate remained at 84% [4]. Nonadherence to treatment is a significant contributing factor to unsuccessful TB treatment outcomes, with approximately half of TB patients failing to complete their treatment. This leads to prolonged infectiousness, relapse, and an increased risk of mortality [5]. In Ghana, studies have indicated treatment adherence rates ranging from 62 to 63% [6, 7], and these studies have revealed that patients who experience adverse drug reactions or have concerns about medication side effects are less likely to adhere to their treatment plans [7–9]. These adverse drug reactions play a major role in nonadherence and can result in significant complications, the development of multi-drug resistant TB, relapse, and even death [10, 11]. Adverse reactions to antitubercular drugs are a prevalent issue during tuberculosis (TB) treatment, contributing to treatment failure, increased morbidity, and mortality. Nevertheless, there is a lack of research investigating the factors that contribute to these adverse reactions among TB patients in Ghana. This study aims to contribute to the existing knowledge by exploring the sociodemographic and clinical determinants of adverse reactions to antitubercular drugs among TB patients in Ghana, a lower-middle-income country. The study findings will assist policymakers in developing a management algorithm for tuberculosis adverse drug reactions (ADRs) (...truncated)