The effect of anti-tuberculosis drug pharmacokinetics on QTc prolongation.
Int J Antimicrob Agents
; 62(4): 106939, 2023 Oct.
Article
em En
| MEDLINE
| ID: mdl-37517627
ABSTRACT
BACKGROUND:
Implementation of newer anti-tuberculosis (TB) drugs may prolong the QT interval, increasing the risk of arrythmias and sudden cardiac death. The potential for cardiac adverse events has prompted recommendations for frequent cardiac monitoring during treatment. However, unknowns remain, including the association between drug concentrations and QT interval.METHODS:
An observational prospective cohort study design was used. Patients undergoing treatment for drug-resistant TB in Georgia were assessed. Serial blood samples were collected at 4-6 weeks for pharmacokinetics. Electrocardiograms were recommended to be performed monthly. A generalized estimating equation spline model was used to investigate (1) the effect difference between bedaquiline and delamanid, (2) the cumulative effect of number of anti-TB drugs, and (3) the relationship between serum drug concentrations on QTc interval.RESULTS:
Among 94 patients receiving either bedaquiline (n = 64) or delamanid (n = 30)-based treatment, most were male (82%), and the mean age was 39 years. The mean maximum QTc increase during the first six months was 37.5 ms (IQR 17.8-56.8). Bedaquiline- and delamanid-based regimens displayed similar increased mean QTc change from baseline during drug administration (P = 0.12). Increasing number of anti-TB drugs was associated with an increased QTc (P = 0.01), but participants trended back towards baseline after drug discontinuation (P = 0.25). A significant association between AUC, Cmin, Cmax, and increased QTc interval was found for bedaquiline (months 1-6) and levofloxacin (months 1-12).CONCLUSION:
Bedaquiline- and delamanid-based regimens and increasing number of QT prolonging agents led to modest increases in the QTc interval with minimal clinical effect.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome do QT Longo
/
Tuberculose Resistente a Múltiplos Medicamentos
/
Nitroimidazóis
Tipo de estudo:
Guideline
/
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Int J Antimicrob Agents
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Geórgia