EFFECTIVENESS AND PHARMCOKINETICS OF FIRST-LINE ANTI TUBERCULOSIS DRUGS IN CHILDREN: A SYSTEMATIC REVIEW

Authors

  • M. Hadi Faculty of Medicine, University of Malahayati, Indonesia

DOI:

https://doi.org/10.53555/nnmhs.v9i7.1752

Keywords:

Anti-tuberculosis drugs, Effectiveness, Pharmacokinetics, and Pediatrics

Abstract

Background: The optimal doses of first-line drugs for treating drug-susceptible tuberculosis in children and adolescents are still uncertain.

Aim: The purpose of this study was to determine whether children treated with recommended or increased doses of first-line drugs achieve successful outcomes and adequate pharmacokinetic (PK) exposures.

Methods: A systematic search strategy was conducted across several electronic reference databases (PubMed, Cochrane Library, Google Scholar) and included articles published between 2010–2023. Duplicate publications, review articles, editorials, and incomplete articles were excluded.

Results: Database searches identified a total of 59.123 articles. Of these, 300 articles passed the screening process, resulting in 47 articles for full-text assessment. Among them, 28 articles did not evaluate the outcome of interest. Hence, we found 19 appropriate studies included.

Conclusion: The outcomes are highly variable. Children have lower drug exposures than adults. Rifampicin exposure is inadequate for younger infants and/or those with HIV. For optimal administration, standardisation of pharmacokinetic paediatric studies and individual patient data analysis with safety assessment are required.

References

1. World Health Organization. WHO operational handbook on tuberculosis. Module 4: treatment: drug-susceptible tuberculosis treatment. 2022.

2. World Health Organization. Global tuberculosis report. 2020. Available from:https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdf

3. Drobac PC, Shin SS, Huamani P, Atwood S, Furin J, Franke MF, et al. Risk factors for in-hospital mortality among children with tuberculosis: The 25-year experience in Peru. Pediatrics. 2012;130(2).

4. Swaminathan S, Pasipanodya JG, Ramachandran G, Kumar AKH, Srivastava S, Deshpande D, et al. Drug Concentration Thresholds Predictive of Therapy Failure and Death in Children with Tuberculosis: Bread Crumb Trails in Random Forests. Clin Infect Dis. 2016;63.

5. Pasipanodya JG, McIlleron H, Burger A, Wash PA, Smith P, Gumbo T. Serum drug concentrations predictive of pulmonary tuberculosis outcomes. J Infect Dis. 2013;208(9).

6. World Health Organization. Implementing the end TB strategy: the essentials. Geneva, Switzerland: World Health Organization. 2015.

7. World Health Organization. Technical report on the pharmacokinetics and pharmacodynamics (PK/PD) of medicines used in the treatment of drug-resistant tuberculosis. Geneva, Switzerland: World Health Organization. 2018. Available from: https://apps.who.int/iris/handle/10665/260440

8. European Medicines Agency. Joint evaluation of regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999. 2022. Available from: https://health.ec.europa.eu/system/files/2020-08/orphanregulation_eval_swd_2020-163_part-1_0.pdf.

9. US Food and Drug Administration. General clinical pharmacology considerations for pediatric studies for drugs and biological products. 2022. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegu%0AlatoryInformation/Guidances/UCM425885.pdf.

10. Barbour AM, Fossler MJ, Barrett J. Practical considerations for dose selection in pediatric patients to ensure target exposure requirements. Vol. 16, AAPS Journal. 2014.

11. Antwi S, Yang H, Enimil A, Sarfo AM, Gillani FS, Ansong D, et al. Pharmacokinetics of the first-line antituberculosis drugs in Ghanaian children with tuberculosis with or without HIV coinfection. Antimicrob Agents Chemother. 2017;61(2).

12. Justine M, Yeconia A, Nicodemu I, Augustino D, Gratz J, Mduma E, et al. Pharmacokinetics of First-Line Drugs among Children with Tuberculosis in Rural Tanzania. J Pediatric Infect Dis Soc. 2019;9(1):14–20.

13. Ramachandran G, Kumar AKH, Bhavani PK, Kannan T, Kumar SR, Gangadevi NP, et al. Pharmacokinetics of first-line antituberculosis drugs in HIV-infected children with tuberculosis treated with intermittent regimens in India. Antimicrob Agents Chemother. 2015;59(2):1162–7.

14. Ramachandran G, Hemanth Kumar AK, Bhavani PK, Poorana Gangadevi N, Sekar L, Vijayasekaran D, et al. Age, nutritional status and INH acetylator status affect pharmacokinetics of anti-tuberculosis drugs in children. Int J Tuberc Lung Dis. 2013;17(6):800–6.

15. Arya A, Roy V, Lomash A, Kapoor S, Khanna A, Rangari G. Rifampicin pharmacokinetics in children under the Revised National Tuberculosis Control Programme, India, 2009. Int J Tuberc Lung Dis. 2015;19(4):440–5.

16. Rangari GM, Roy V, Sethi GR, Mishra TK, Khanna A. Blood levels of isoniazid in Indian children with tuberculosis. Indian J Tuberc. 2015;62(2):80–5.

17. Garcia-Prats AJ, Svensson EM, Winckler J, Draper HR, Fairlie L, Van Der Laan LE, et al. Pharmacokinetics and safety of high-dose rifampicin in children with TB: The Opti-Rif trial. J Antimicrob Chemother. 2021;76(12):3237–46.

18. Ranjalkar J, Mathew SK, Verghese VP, Bose A, Rose W, Gupta D, et al. Isoniazid and rifampicin concentrations in children with tuberculosis with either a daily or intermittent regimen: implications for the revised RNTCP 2012 doses in India. Int J Antimicrob Agents. 2018;51(5).

19. Mukherjee A, Velpandian T, Singla M, Kanhiya K, Kabra SK, Lodha R. Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in Indian children. BMC Infect Dis. 2015;15(1).

20. Radtke KK, Hibma JE, Hesseling AC, Savic RM. Pragmatic global dosing recommendations for the 3-month, once-weekly rifapentine and isoniazid preventive TB regimen in children. Vol. 57, The European respiratory journal. 2021.

21. Bekker A, Schaaf HS, Draper HR, Van Ser Laan L, Murray S, Wiesner L, et al. Pharmacokinetics of rifampin, isoniazid, pyrazinamide, and ethambutol in infants dosed according to revised whorecommended treatment guidelines. Antimicrob Agents Chemother. 2016;60(4):2171–9.

22. Panjasawatwong N, Wattanakul T, Hoglund RM, Bang ND, Pouplin T, Nosoongnoen W, et al. Population pharmacokinetic properties of antituberculosis drugs in Vietnamese children with tuberculous meningitis. Antimicrob Agents Chemother. 2021;65(1).

23. Thee S, Seddon JA, Donald PR, Seifart HI, Werely CJ, Hesseling AC, et al. Pharmacokinetics of isoniazid, rifampin,and pyrazinamide in children younger than two years of age with tuberculosis: Evidence for implementation of revised World Health Organization recommendations. Antimicrob Agents Chemother. 2011;55(12):5560–7.

24. Roy V, Sahni P, Gupta P, Sethi GR, Khanna A. Blood levels of pyrazinamide in children at doses administered under the revised national tuberculosis control program. Indian Pediatr. 2012;49(9).

25. Mlotha R, Waterhouse D, Dzinjalamala F, Ardrey A, Molyneux E, Davies GR, et al. Pharmacokinetics of anti-TB drugs in Malawian children: reconsidering the role of ethambutol. J Antimicrob Chemother. 2014;70(6):1798–803.

26. Hiruy H, Rogers Z, Mbowane C, Adamson J, Ngotho L, Karim F, et al. Subtherapeutic concentrations of first-line anti-TB drugs in South African children treated according to current guidelines: The PHATISA study. J Antimicrob Chemother. 2014;70(4):1115–23.

27. Mukherjee A, Velpandian T, Singla M, Kanhiya K, Kabra SK, Lodha R. Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in HIV-infected Indian children. Int J Tuberc Lung Dis. 2016;20(5).

28. Dayal R, Singh Y, Agarwal D, Kumar M, Swaminathan S, Ramachandran G, et al. Pharmacokinetic study of isoniazid and pyrazinamide in children: Impact of age and nutritional status. Arch Dis Child. 2018;103(12):1150–4.

29. Shah I, Jadhao N, Mali N, Deshpande S, Gogtay N, Thatte U. Pharmacokinetics of isoniazid in Indian children with tuberculosis on daily treatment. Int J Tuberc Lung Dis. 2019;23(1).

30. Wobudeya E, Chabala C, Hesseling AC, Mave V, Hissar S, Turkova A, et al. LB-2056-24 Shorter treatment for minimal tuberculosis in children: main findings from the SHINE trial. Int J Tuberc Lung Dis. 2020;24(10).

31. Nansumba M, Kumbakumba E, Orikiriza P, Bastard M, Mwanga JA, Boum Y, et al. Treatment outcomes and tolerability of the revised WHO anti-tuberculosis drug dosages for children. Int J Tuberc Lung Dis. 2018;22(2).

32. Adebisi YA, Ibrahim K, Lucero-Prisno DE, Ekpenyong A, Micheal AI, Chinemelum IG, et al. Prevalence and Socio-economic Impacts of Malnutrition Among Children in Uganda. Nutr Metab Insights. 2019;12.

33. Swaminathan S, Hemalatha R, Pandey A, Kassebaum NJ, Laxmaiah A, Longvah T, et al. The burden of child and maternal malnutrition and trends in its indicators in the states of India: the Global Burden of Disease Study 1990–2017. Lancet Child Adolesc Heal. 2019;3(12).

34. Guiastrennec B, Ramachandran G, Karlsson MO, Kumar AKH, Bhavani PK, Gangadevi NP, et al. Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications. Clin Pharmacol Ther. 2018;104(4).

35. Svensson EM, Yngman G, Denti P, McIlleron H, Kjellsson MC, Karlsson MO. Evidence-Based Design of Fixed-Dose Combinations: Principles and Application to Pediatric Anti-Tuberculosis Therapy. Clin Pharmacokinet. 2018;57(5).

36. Stott KE, Pertinez H, Sturkenboom MGG, Boeree MJ, Aarnoutse R, Ramachandran G, et al. Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: A systematic review and meta-analysis. J Antimicrob Chemother. 2018;73(9).

37. Hong BL, D’Cunha R, Li P, Al-Shaer MH, Alghamdi WA, An G, et al. A Systematic Review and Meta-analysis of Isoniazid Pharmacokinetics in Healthy Volunteers and Patients with Tuberculosis. Clin Ther. 2020;42(11).

38. McIlleron H, Chirehwa MT. Current research toward optimizing dosing of first-line antituberculosis treatment. Vol. 17, Expert Review of Anti-Infective Therapy. 2019.

39. Azuma J, Ohno M, Kubota R, Yokota S, Nagai T, Tsuyuguchi K, et al. NAT2 genotype guided regimen reduces isoniazid-induced liver injury and early treatment failure in the 6-month four-drug standard treatment of tuberculosis: A randomized controlled trial for pharmacogenetics-based therapy. Eur J Clin Pharmacol. 2013;69(5).

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Published

2023-07-05

How to Cite

M. Hadi. (2023). EFFECTIVENESS AND PHARMCOKINETICS OF FIRST-LINE ANTI TUBERCULOSIS DRUGS IN CHILDREN: A SYSTEMATIC REVIEW. Journal of Advanced Research in Medical and Health Science (ISSN 2208-2425), 9(7), 31-36. https://doi.org/10.53555/nnmhs.v9i7.1752