European Journal of Cardiovascular Medicine

Tuberculosis (TB) remains a major global public health challenge, with an estimated 10.6 million new cases and 1.3 million deaths reported worldwide in 2023 [1]. India bears the highest TB burden globally, contributing nearly 28% of all reported cases [2]. The introduction of standardized anti-tubercular chemotherapy regimens, particularly the fixed-dose combination of isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE), has markedly improved cure rates and reduced disease transmission [3].

Despite these benefits, anti-tubercular regimens are frequently associated with adverse drug reactions (ADRs), which may range from mild gastrointestinal disturbances to severe hepatotoxicity, neurotoxicity, or life-threatening hypersensitivity responses [4,5]. Such ADRs can compromise treatment adherence, prolong therapy duration, and necessitate regimen modification or discontinuation, thereby increasing the risk of treatment failure, relapse, and the emergence of drug-resistant TB [4,5].

Pharmacovigilance, defined as the science and activities concerned with detecting, assessing, understanding, and preventing adverse effects of medicines, plays a critical role in TB control programs [2,4]. Active monitoring allows early recognition and timely management of ADRs, minimizing morbidity and preventing progression to severe complications. Although India has implemented a national pharmacovigilance framework through the Pharmacovigilance Programme of India (PvPI), data on the real-world incidence and spectrum of ADRs among TB patients in specific regional treatment settings remain limited [1–5].

Against this background, the present study was undertaken at the Government Medical College, Mehboob Nagar, Telangana, to assess the incidence, pattern, causality, severity, and outcomes of chemotherapy-induced ADRs in TB patients. This study aims to contribute local evidence that can strengthen patient safety measures and optimize therapeutic outcomes in TB management.

Study Design and Setting

A prospective observational study was conducted in the Department of Pharmacology, Government Medical College, Mehboob Nagar, Telangana, from October 2024 to January 2025. The study was carried out in collaboration with the Department of Pulmonology and other relevant clinical units involved in tuberculosis (TB) management.

Study Population

Adult patients (≥18 years) diagnosed with pulmonary or extrapulmonary TB and initiated on anti-tubercular chemotherapy during the study period were eligible for inclusion. Patients already on TB treatment prior to the study, those with incomplete medical records, or those unwilling to provide informed consent were excluded.

Sample Size

A total of 100 patients meeting the eligibility criteria were enrolled consecutively.

Data Collection

Demographic details, clinical history, TB type, comorbidities, and chemotherapy regimen were recorded at baseline. Patients were monitored throughout their treatment for the occurrence of adverse drug reactions (ADRs) using active pharmacovigilance methods, including structured interviews, clinical examinations, and review of laboratory data.

ADR Assessment

Suspected ADRs were documented with details on onset, clinical presentation, management, and outcome. Organ system classification was performed as per WHO Adverse Reaction Terminology (WHO-ART). Causality was assessed using the World Health Organization–Uppsala Monitoring Centre (WHO–UMC) scale. Severity was graded according to the Modified Hartwig and Siegel scale.

Data Analysis

Data were entered into Microsoft Excel and analyzed descriptively. Categorical variables were expressed as frequencies and percentages, while continuous variables were summarized as mean ± standard deviation (SD) or median with interquartile range (IQR), as appropriate.

A total of 100 patients with tuberculosis undergoing chemotherapy were included in the analysis. The mean age of the cohort was 42.6 ± 13.2 years (range: 18–72 years), with a male predominance (62%). Pulmonary tuberculosis was the most common form (72%), and the majority received the standard HRZE regimen (84%), while 16% were on modified regimens due to comorbidities or drug resistance (Table 1).

Table 1. Baseline Characteristics of the Study Population (n = 100)

Adverse drug reactions (ADRs) were reported in 68% of patients, with a total of 92 ADR events recorded. The median time to ADR onset was 14 days (IQR: 9–21), and multiple ADRs occurred in 19% of patients (Table 2).

Table 2. Incidence and Pattern of Adverse Drug Reactions (ADRs)

The gastrointestinal system was the most frequently affected (26.1%), followed by hepatobiliary (21.7%), cutaneous (15.2%), and neurological (13.0%) manifestations. Less commonly, ADRs involved ototoxicity, psychiatric disturbances, hematologic changes, renal impairment, and other systems (Table 3).

Table 3. Organ System Distribution of ADRs

Figure 1.Organ System Distribution of ADRs

Causality assessment using the WHO–UMC criteria revealed that 47.8% of ADRs were classified as probable, 40.2% as possible, and 12.0% as certain. According to the Modified Hartwig severity scale, 45.6% were mild, 42.4% moderate, and 12.0% severe. Most patients (91.3%) recovered completely, 6.5% had residual effects, and one patient (1.1%) succumbed to severe hepatotoxicity with acute liver failure (Table 4).

Table 4. Causality, Severity, and Outcome of ADRs

In this prospective observational study of 100 tuberculosis patients receiving anti-tubercular chemotherapy, the overall incidence of ADRs was 68%, with the gastrointestinal and hepatobiliary systems most commonly affected. These findings are consistent with previous pharmacovigilance analyses, where gastrointestinal intolerance and hepatotoxicity have been among the most frequently reported ADRs to first-line anti-TB drugs [6,7]. The predominance of gastrointestinal disturbances in our study may be attributed to the mucosal irritant effects of rifampicin and isoniazid, whereas hepatotoxicity likely reflects the cumulative hepatic burden of isoniazid, rifampicin, and pyrazinamide [8].

The median onset of ADRs was 14 days, similar to the early-onset patterns observed in cohort studies and pharmacovigilance database analyses [9,10], highlighting the importance of intensive monitoring during the initial weeks of therapy. Notably, 19% of our patients developed multiple ADRs, a finding comparable to the observations of Sadiq et al. [11], where polypharmacy and comorbid conditions were significant contributors to ADR clustering.

Causality assessment revealed that nearly half of the ADRs were classified as probable, indicating a strong temporal relationship with drug intake and improvement upon dechallenge. Severe ADRs accounted for 12% of cases, a proportion similar to that reported in large-scale safety studies [7,8], with hepatotoxicity and severe cutaneous reactions being the primary causes. The mortality rate of 1.1% in our cohort, due to fulminant hepatic failure, is consistent with rare but serious outcomes documented in hospital-based retrospective analyses [13].

Our results emphasize the need for strengthening pharmacovigilance mechanisms within TB control programs. Early detection strategies, patient education, and baseline as well as periodic liver function testing especially within the first month of therapy could help reduce morbidity and mortality. Moreover, individualized risk assessment, incorporating patient age, comorbidities, and concomitant medication use, may improve safety outcomes [6,9,11,13].

Limitations of this study include the single-center design and relatively short follow-up, which may underestimate late-onset ADRs. Nonetheless, the prospective nature and active monitoring strengthen the validity of the results.

This study demonstrates that adverse drug reactions to anti-tubercular chemotherapy are common, affecting over two-thirds of patients, with gastrointestinal and hepatobiliary systems most frequently involved. While the majority of ADRs were mild to moderate, a significant proportion were severe, including one fatal case of hepatotoxicity. Early onset of most ADRs underscores the importance of close monitoring, particularly in the initial treatment phase. Active pharmacovigilance, timely intervention, and patient education can minimize morbidity, improve adherence, and enhance therapeutic outcomes. Strengthening pharmacovigilance systems within TB control programs and adopting individualized monitoring strategies may further reduce the burden of drug-related complications in tuberculosis management.

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