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Frequency of adverse reactions to first- and second-line anti-tuberculosis chemotherapy in a Korean cohort.

ABSTRACT: OBJECTIVE:To determine the frequency of and risk factors for major adverse drug reactions (MADRs) associated with anti-tuberculosis treatment at a tuberculosis (TB) referral hospital in the Republic of Korea. METHODS:Data from an ongoing natural history cohort study were analyzed for permanent regimen changes due to adverse drug reactions and confirmed by chart review. RESULTS:Among 655 subjects, there were 132 MADRs in 112 (17%) subjects. The most common MADRs were gastrointestinal (n = 53), musculoskeletal (n = 22), psychiatric (n = 10), visual (n = 9) and peripheral neuropathic (n = 8). MADRs were more frequent in subjects being treated with second-line regimens (16%) compared to first-line regimens (2.5%). Drugs frequently associated with MADRs were amikacin (3/10, 30%), linezolid (8/29, 28%), para-aminosalicylic acid (47/192, 24%), pyrazinamide (31/528, 5.8%), macrolides (2/44, 4.5%) and cycloserine (12/272, 4.4%). Fluoroquinolones accounted for a single MADR (1/377, 0.003%), despite widespread usage. In multivariate analysis, infection with multi- or extensively drug-resistant disease and previous history of anti-tuberculosis treatment were risk factors for MADR, with adjusted hazard ratios of respectively 2.2 (P = 0.02) and 1.6 (P = 0.04). CONCLUSION:MADRs are common during anti-tuberculosis chemotherapy in this population, occurring in more than one in six subjects. New and less toxic agents to treat drug-resistant TB are urgently needed.

SUBMITTER: Carroll MW

PROVIDER: S-EPMC6379909 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Frequency of adverse reactions to first- and second-line anti-tuberculosis chemotherapy in a Korean cohort.

Carroll M W MW Lee M M Cai Y Y Hallahan C W CW Shaw P A PA Min J H JH Goldfeder L C LC Alekseyev V V Grinkrug S S Kang H S HS Hwang S S Park H-M HM Kang E E Lee S-Y SY Jin B B Park H-E HE Min S S Park S K SK Jeon D S DS Via L E LE Barry C E CE

The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 20120508 7

<h4>Objective</h4>To determine the frequency of and risk factors for major adverse drug reactions (MADRs) associated with anti-tuberculosis treatment at a tuberculosis (TB) referral hospital in the Republic of Korea.<h4>Methods</h4>Data from an ongoing natural history cohort study were analyzed for permanent regimen changes due to adverse drug reactions and confirmed by chart review.<h4>Results</h4>Among 655 subjects, there were 132 MADRs in 112 (17%) subjects. The most common MADRs were gastro ...[more]

PMID: 22584241

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Project description:BackgroundFurther work is required to understand the intrapulmonary pharmacokinetics of first-line anti-tuberculosis drugs. This study aimed to describe the plasma and intrapulmonary pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol, and explore relationships with clinical treatment outcomes in patients with pulmonary tuberculosis.MethodsMalawian adults with a first presentation of microbiologically-confirmed pulmonary tuberculosis received standard 6-month first-line therapy. Plasma and intrapulmonary samples were collected 8 and 16 weeks into treatment and drug concentrations measured in plasma, lung/airway epithelial lining fluid, and alveolar cells. Population pharmacokinetic modelling generated estimates of drug exposure (Cmax and AUC) from individual-level post-hoc Bayesian estimates of plasma and intrapulmonary pharmacokinetics.ResultsOne-hundred-and-fifty-seven patients (58% HIV co-infected) participated. Despite standard weight-based dosing, peak plasma concentrations of first-line drugs were below therapeutic drug monitoring targets. Rifampicin concentrations were low in all three compartments. Isoniazid, pyrazinamide, and ethambutol achieved higher concentrations in epithelial lining fluid and alveolar cells than plasma. Isoniazid and pyrazinamide concentrations were 14.6 (95% CI: 11.2-18.0) and 49.8-fold (95% CI: 34.2-65.3) higher in lining fluid than plasma respectively. Ethambutol concentrations were highest in alveolar cells (alveolar cells:plasma ratio 15.0, 95% CI 11.4-18.6). Plasma or intrapulmonary pharmacokinetics did not predict clinical treatment response.ConclusionsWe report differential drug concentrations between plasma and the lung. While plasma concentrations were below therapeutic monitoring targets, accumulation of drugs at the site of disease may explain the success of the first-line regimen. The low rifampicin concentrations observed in all compartments lend strong support for ongoing clinical trials of high-dose rifampicin regimens.

Dataset Information

Frequency of adverse reactions to first- and second-line anti-tuberculosis chemotherapy in a Korean cohort.

Publications

Frequency of adverse reactions to first- and second-line anti-tuberculosis chemotherapy in a Korean cohort.

Similar Datasets

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