Details of Replacement Sequence of Drugs in Longer Oral M/XDR-TB Regimen

Replacement of component(s) drug(s) is required in conditions like adverse drug reaction, poor tolerance, contraindication and resistance detected on baseline Liquid Culture (LC) Drug Susceptibility Testing (DST). 

The replacement sequence of drugs is prepared according to their efficacy, no demonstrable resistance, prior use, side-effect profile and background resistance to replacement drug in the country.

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In case of the need for replacement of any of the component(s) in the longer oral Multi (M)/ Extensively Drug-resistant TB (XDR-TB) regimen, the following broad principles apply:​

• The regimen should preferably be fully oral. However, in certain circumstances, injectables may have to be used.​
• At least 4-5 drugs are to be used in the initial 6 to 8 months and at least 3-4 drugs in the last 12 months. ​
• Replacement sequence of Group C drugs for longer oral M/XDR-TB regimen was recommended in the order of – Delamanid (Dlm), Amikacin (Am), Pyrazinamide (Z), Ethionamide (Eto), P-aminosalicylic acid (PAS), Ethambutol (E), Penems.​​​​
• The combined use of Bedaquiline (Bdq) and Dlm in the regimen is recommended in whom an appropriate regimen cannot be designed using all 5 drugs from Group A and B.​
• Dlm and Am will not be initiated in the final 12 months of treatment.​
• The duration of new drugs (Bdq or Dlm) is limited to 6 months. Extension beyond 6 months to be considered in patients with whom an effective regimen cannot be otherwise designed
• Imipenem-Cilastatin (Imp-Cln) will only be used as a last resort.
• In individual patients for whom the design of an effective regimen is not possible as per recommendations, BPaL regimen (Bedaquiline, Pretomanid, Linezolid regimen) can be considered as a last resort under prevailing ethical standards.​

To modify the regimen, the Nodal and District Drug-resistant TB Centre (N/DDR-TBC) physician must review DST and patient profile and then suitable regimen to be designed based on the replacement sequence table given in the Programmatic Management of Drug-resistant TB (PMDT) guideline.

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Resources

• Guidelines for Programmatic Management of Drug-resistant Tuberculosis in India, March 2021.
• WHO Consolidated Guidelines on Tuberculosis: Module 4 – Treatment: Drug-resistant TB Treatment, 2020.

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