1 Constructing a regimen Session 5

USAID TB CARE II PROJECT Principles of designing an MDR-TB treatment regimen Include at least four second-line anti-TB drugs likely to be effective as well as pyrazinamide during the intensive phase. More than four second-line anti-TB drugs is recommended if the effectiveness of some of the drugs is uncertain. The continuation phase should contain at least three second-line anti-TB drugs (pyrazinamide should also be continued in the continuation phase if extensive lung damage is present). More than three second-line anti- TB drugs is recommended if the effectiveness of some of the drugs is uncertain. Include a fluoroquinolone—a higher generation fluoroquinolone (levofloxacin or moxifloxacin) is strongly preferred. Ethambutol can be included but is not counted as a core drug in the regimen. Consider drug resistance data (of individual or region) and patient treatment history when designing a regimen.

USAID TB CARE II PROJECT Duration of therapy The intensive phase should be at least 8 months and at least 4 months past conversion (whichever is longer). Total duration of treatment should be at least 20 months and at least 18 months past conversion.

USAID TB CARE II PROJECT Constructing the regimen — Group 1 Include pyrazinamide Pyrazinamide should be included whenever the strain is susceptible or if susceptibility is unknown. DST to ethambutol is not very reliable and even if the strain is testing susceptible to ethambutol it should not be counted as a core effective drug against MDR-TB strains. INH (H) RIF (R) EMB (E) PZA (Z) First-line

USAID TB CARE II PROJECT Constructing the regimen — Group 2 Include an injectable for the intensive phase Cross resistance between KM and AMK is considered complete There is cross resistance of CM with KM and AMK All injectables must be given IM or IV (not absorbed when given orally) Streptomycin is considered a first-line drug by the WHO INH (H) RIF (R) EMB (E) PZA (Z) First-line SM KM AMK CM Injectable Second-line

USAID TB CARE II PROJECT Constructing the regimen — Group 3 Include a fluoroquinolone Highly effective Minimal side effects It is recommended to use a higher generation fluoroquinolone (levofloxacin or moxifloxacin) INH (H) RIF (R) EMB (E) PZA (Z) First-line SM KM AMK CM Injectable OFX LFX MFX Quinolone Second-line

USAID TB CARE II PROJECT Constructing the regimen — Group 4 Complete the regimen with Group 4 drugs (aiming to have four or five second-line drugs — five if you are worried about second-line resistance) Side effects are common ETO/PTO may be the most effective Group 4 drugs If INH A mutation is responsible for the isoniazid resistance, there may be cross-resistance with ETO/PTO INH (H) RIF (R) EMB (E) PZA (Z) First-line SM KM AMK CM Injectable OFX LFX MFX Quinolone ETO or PTO CS PAS Other 2 nd -line Second-line

USAID TB CARE II PROJECT Constructing the regimen — Group 5 Group 5 drugs are used in cases of extensive resistance such as XDR-TB Minimal clinical evidence of efficacy Use two or three agents from Group 5 when it has been determined that a regimen of at least four effective drugs from Groups 2 to 4 are not available. INH (H) RIF (R) EMB (E) PZA (Z) First-line Second-line Third-line SM KM AMK CM Injectable OFX LFX MFX Quinolone ETO or PTO CS PAS Other 2 nd -line Other agents Amx/Clv Clofazimine High dose H Linezolid

USAID TB CARE II PROJECT Standardized regimens for communities with little or no second-line anti-TB drug resistance. A common standardized regimen when very little resistance to second-line drugs exists in the population is: Z-Km-Lfx-Eto-Cs INH (H) RIF (R) EMB (E) PZA (Z) First-line Second-line Third-line SM KM AMK CM Injectable OFX LFX MFX Quinolone ETO/PTO CS PAS Other 2 nd -line Other agents Amx/Clv Clofazimine High dose H Linezolid

USAID TB CARE II PROJECT Standardized regimens for communities with little or no second-line anti-TB drug resistance. A common standardized regimen when significant amounts of resistance to second-line drugs exists in the population is: Z-Km-Lfx-Eto-Cs-PAS INH (H) RIF (R) EMB (E) PZA (Z) First-line Second-line Third-line Other agents Amx/Clv Clofazimine High dose H Linezolid SM KM AMK CM Injectable OFX LFX MFX Quinolone ETO/PTO CS PAS Other 2 nd -line

USAID TB CARE II PROJECT Adjusting standardized regimens Standardized therapies need to be adjusted in: Pregnancy Liver disease Chronic kidney disease MDR-TB contacts History of treatment with second-line drugs