All oral longer regimen full details from this pdf only with replacement sequence also
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I now have all the data needed. Let me compile the comprehensive answer based purely on these two PMDT files.
18–20 Month Longer Oral M/XDR-TB Regimen — Full Details
(Source: PMDT Guidelines March 2025 & PMDT 2021)
1. Indications (Who Gets This Regimen?)
Used for MDR/RR-TB patients who are:
- Excluded from the shorter oral Bdq-containing MDR/RR-TB regimen, including XDR-TB patients
- Those with FQ resistance detected (Pre-XDR or XDR-TB)
- Those with H resistance due to both KatG AND InhA mutations
- Patients switching from the shorter regimen due to additional resistance, intolerance, non-availability, or emergence of exclusion criteria
- Patients switched from shorter regimen if they are found positive at month 3/6
2. Standard Regimen
Bdq (6 months or longer) + (18–20 months) Lfx + Lzd# + Cfz + Cs
# Lzd dose tapered to 300 mg after the initial 6–8 months of treatment (based on bacteriological response at month 4/5 culture)
- Duration: 18–20 months (no separate intensive/continuation phase)
- Pre-XDR/XDR-TB: 20 months
- Pyridoxine given to all patients throughout (as per weight band)
3. Drug Groups for Composing the Regimen
| Group | Drugs |
|---|---|
| Group A | Levofloxacin (Lfx), Bedaquiline (Bdq), Linezolid (Lzd) |
| Group B | Clofazimine (Cfz), Cycloserine (Cs) |
| Group C (add if A+B insufficient) | Dlm → Am → Z → Eto → PAS → E → Penems (Imp-Cln/Mpm) |
Composition Rules:
- Start with all 5 drugs (Group A + B); continue with 4 drugs beyond 6–9 months for operational ease
- Include all 3 Group A agents + at least 1 Group B agent = minimum 4 effective drugs at start; minimum 3 drugs if Bdq stopped
- If only 1–2 Group A agents usable → both Group B agents must be included
- If Groups A+B insufficient → add Group C drugs in the sequence above
4. Drug Dosages (Adults, by Weight Band)
| Drug | 16–29 kg | 30–45 kg | 46–70 kg | >70 kg |
|---|---|---|---|---|
| Levofloxacin (Lfx) | 250 mg | 750 mg | 1000 mg | 1000 mg |
| Moxifloxacin (Mfx) | 200 mg | 400 mg | 400 mg | 400 mg |
| High-dose Mfx (Mfxh) | 400 mg | 600 mg | 800 mg | 800 mg |
| Bedaquiline (Bdq) | Wk 0–2: 400 mg daily; Wk 3–24: 200 mg 3×/week | ← same across all bands → | ||
| Clofazimine (Cfz) | 50 mg | 100 mg | 100 mg | 200 mg |
| Cycloserine (Cs) | 250 mg | 500 mg | 750 mg | 1000 mg |
| Linezolid (Lzd) | 300 mg | 600 mg | 600 mg | 600 mg |
| Delamanid (Dlm) | 50 mg BD (6–11 yr) / 100 mg BD (≥12 yr) for 24 wks | |||
| Amikacin (Am) | 500 mg | 750 mg | 750 mg | 1000 mg |
| Pyrazinamide (Z) | 750 mg | 1250 mg | 1750 mg | 2000 mg |
| Ethionamide (Eto) | 375 mg | 500 mg | 750 mg | 1000 mg |
| Na-PAS (60% w/v) | 10 gm | 14 gm | 16 gm | 22 gm |
| Ethambutol (E) | 400 mg | 800 mg | 1200 mg | 1600 mg |
| Pyridoxine (Pdx) | 50 mg | 100 mg | 100 mg | 100 mg |
For adults >60 years: SLI (Am) dose reduced to 10 mg/kg (max 750 mg). Cs/Eto/PAS/Mpm can be given in divided doses if intolerant.
5. Bdq Extension Rules
Bdq extended beyond 6 months when an effective regimen cannot otherwise be designed — specifically when only 2 of 5 drugs from Group A & B are available AND adequate Group C drugs unavailable due to high background resistance, non-availability, or unreliable DST.
6. Lzd Dose Tapering Protocol
| Situation | Action |
|---|---|
| Culture negative at month 4/5 (available by end of month 6) | Taper Lzd to 300 mg from month 6 onwards |
| Culture positive at month 5 or 4 | Extend Lzd 600 mg by 1 month (up to max month 8) |
| Month 8 culture also positive | Send for FL/SL-LPA + C&DST; reassess for regimen modification |
| Maximum treatment duration | 20 months |
Minimum 8 months of treatment before declaring treatment failed if no culture conversion.
7. Replacement Sequence (2025 PMDT)
The March 2025 guidelines provide this core regimen for the longer oral regimen:
(6–9m) Bdq + (18–20m) Lfx + Lzd# + Cfz + Cs
8. Full Replacement Sequence Tables (2021 PMDT — Still Applicable)
Principles:
- Drugs replaced per: efficacy, no demonstrable resistance, prior use, side-effect profile, national background resistance (NDRS)
- Initial 6–8 months: at least 4–5 drugs
- Final 12 months: at least 3–4 drugs from Group A & B
- Group C replacement order: Dlm → Am → Z → Eto → PAS → E → Penems
- Dlm and Am NOT started in final 12 months
- Imp-Cln: last resort only (requires PICC line)
Replacement Table 1 — 1 Group A or 1 Group B drug unavailable
| Sr. | Drugs Replaced | Gr A | Gr B | Gr C | Final Regimen |
|---|---|---|---|---|---|
| 1 | None$ | 3 | 2 | – | 6–8m: Lfx, Bdq, Lzd, Cfz, Cs / 12m: Lfx, Lzd, Cfz, Cs |
| 2 | 1 Group A drug | 2 | 2 | 1 | No FQ → 6–8m: Bdq, Lzd, Cfz, Cs, Dlm / 12m: Lzd, Cfz, Cs |
| No Bdq → 6–8m: Lfx*, Lzd, Cfz, Cs, Dlm / 12m: Lfx*, Lzd, Cfz | |||||
| No Lzd → 6–8m: Lfx*, Bdq, Cfz, Cs, Dlm / 12m: Lfx*, Cfz, Cs | |||||
| 3 | 1 Group B drug | 3 | 1 | 1 | No Cfz → 6–8m: Lfx*, Bdq, Lzd, Cs, Dlm / 12m: Lfx*, Lzd, Cs |
| No Cs → 6–8m: Lfx*, Bdq, Lzd, Cfz, Dlm / 12m: Lfx*, Lzd, Cfz |
$No replacement required if any one drug is dropped in the last 12 months.
*If Lfx can't be used → use Mfxh if SL-LPA pattern suggests, continue if Mfx(1.0) sensitive on LC-DST.
Replacement Table 2 — 1 Group A + 1 Group B, or 2 Group A drugs unavailable
| Sr. | Drugs Replaced | Gr A | Gr B | Gr C | Final Regimen |
|---|---|---|---|---|---|
| 4 | 1 Gr A + 1 Gr B | 2 | 1 | 2 | No FQ & Cfz → 6–8m: Bdq, Lzd, Cs, Dlm, Am# / 12m: Lzd, Cs, Z#, Eto# |
| No FQ & Cs → 6–8m: Bdq, Lzd, Cfz, Dlm, Am# / 12m: Lzd, Cfz, Z#, Eto# | |||||
| No Bdq & Cfz → 6–8m: Lfx*, Lzd, Cs, Dlm, Am# / 12m: Lfx*, Lzd, Cs | |||||
| No Bdq & Cs → 6–8m: Lfx*, Lzd, Cfz, Dlm, Am# / 12m: Lfx*, Lzd, Cfz | |||||
| No Lzd & Cfz → 6–8m: Lfx*, Bdq, Cs, Dlm, Am# / 12m: Lfx*, Cs, Z#, Eto# | |||||
| No Lzd & Cs → 6–8m: Lfx*, Bdq, Cfz, Dlm, Am# / 12m: Lfx*, Cfz, Z#, Eto# | |||||
| 5 | 2 Group A drugs | 1 | 2 | 2 | No FQ & Bdq → 6–8m: Lzd, Cfz, Cs, Dlm, Am# / 12m: Lzd, Cfz, Cs, Z# |
| No FQ & Lzd → 6–8m: Bdq, Cfz, Cs, Dlm, Am# / 12m: Cfz, Cs, Z#, Eto# | |||||
| No Bdq & Lzd → 6–8m: Lfx*, Cfz, Cs, Dlm, Am# / 12m: Lfx*, Cfz, Cs, Z# |
Replacement Table 3 — Both Group B, or 3+ from A+B drugs unavailable
| Sr. | Drugs Replaced | Gr A | Gr B | Gr C | Final Regimen |
|---|---|---|---|---|---|
| 6 | Both Group B drugs | 3 | 0 | 2 | No Cfz & Cs → 6–8m: Lfx*, Bdq, Lzd, Dlm, Am# / 12m: Lfx*, Lzd, Z#, Eto# |
| 7 | 3+ from Group A & B | Remaining | — | 3 or more | Use remaining Gr A+B + 3–5 Gr C drugs (sequence#) for ≥5–6 effective drugs. If Bdq+Dlm both usable: combined use with ≥4–5 drugs or extended use till conversion. If Bdq+Lzd both usable: consider BPaL as last resort. |
# Group C sequence: Dlm → Am# → Z# → Eto# → PAS → E → Imp-Cln/Mpm (if sensitive on LPA or LC-DST; InhA mutation → Eto resistance). Dlm & Am NOT introduced after initial 8 months; in later phase use Z#, Eto#, PAS, E only.
9. Follow-up Monitoring
| Assessment | Frequency |
|---|---|
| Clinical review (weight, BMI, adherence, ADRs) | Monthly |
| CBC (Hb, platelets), ECG | Day 15, 30, then monthly till month 6; more if clinically indicated |
| Visual acuity & colour vision | Week 9, 13, 26; more if indicated |
| Smear + culture | Monthly from month 2 onwards |
| DST (NAAT MTB/XDR or FL/SL-LPA + LC-DST) | If culture +ve at end of month 4/end of Rx/as indicated |
| Chest X-ray + LFT | Month 3, end of treatment, as indicated |
| Serum electrolytes (Na, K, Mg, Ca) | If QTcF prolongation occurs |
| Specialist consultation (ophthalmology, neurology) | As clinically indicated |
| Surgical evaluation | After culture conversion |
| Long-term post-treatment follow-up | 6, 12, 18, 24 months after completion (Clinical + CXR + Smear + C&DST if symptomatic) |
10. Special Situations
| Situation | Modification |
|---|---|
| Children <14 years | Eligible; Bdq replaced by Dlm |
| Children <5 years (Bdq not approved) | Bdq replaced by Am + Z + Eto in initial phase |
| Pregnancy | Regimen: 18–20m Lfx, Bdq (6m or longer), Lzd, Cfz, Cs. Modify if drug intolerated. Eto may be used after 32 weeks' gestation. Am in post-partum only (not in final 12 months). Z, E, PAS in order for replacements. |
| PLHIV | Avoid efavirenz (reduces Bdq/Pa exposure); use DTG. Caution with ritonavir (↑Bdq exposure). Avoid zidovudine (cross-toxicity with Lzd). |
| Renal impairment | Dose/interval adjustment for E, FQ, Cs, PAS. Severe impairment → discontinue Am; monitor closely. |
| Pre-existing liver disease | R, H, Z, PAS, Eto, Bdq are hepatotoxic; monitor strictly. |
| CNS/TB Meningitis | Good BBB penetration: FQs, Lzd, Eto, Cs, Imp-Cln, Hh, Z. Poor penetration: Cfz, Bdq, Dlm, PAS, E. Prefer Mpm over Imp-Cln for TB meningitis/children. |
| Seizure disorders | Avoid Cs if uncontrolled seizures; give Pyridoxine with Cs. Eto and FQ also associated with seizures. |
11. Treatment Failure Declaration
- Patient not converted after minimum 8 months → declare treatment failed
- If culture +ve at month 8 → FL/SL-LPA + C&DST + reassess regimen modification
- Maximum total treatment: 20 months (no extensions beyond this)
Key abbreviations: Bdq = Bedaquiline | Lfx = Levofloxacin | Lzd = Linezolid | Cfz = Clofazimine | Cs = Cycloserine | Mfxh = High-dose Moxifloxacin | Dlm = Delamanid | Am = Amikacin | Z = Pyrazinamide | Eto = Ethionamide | PAS = Para-aminosalicylic acid | E = Ethambutol | Imp-Cln = Imipenem-Cilastatin | Mpm = Meropenem
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