What is the ideal dosing and timing of administration for Bedaquiline (BQT), Delamanid, and other drugs such as fluoroquinolones (e.g. Moxifloxacin) or aminoglycosides in a twice-daily regimen?

Optimal Dosing and Timing of BDQ, Delamanid, and Other Drugs in Twice-Daily MDR-TB Regimens

For patients with MDR/RR-TB, the BPaLM regimen (bedaquiline, pretomanid, linezolid 600 mg daily, and moxifloxacin) administered with bedaquiline 400 mg daily for 14 days followed by 200 mg three times weekly, pretomanid 200 mg daily, linezolid 600 mg daily, and moxifloxacin 400 mg daily for 6 months is the recommended dosing strategy. 1

Bedaquiline (BDQ) Dosing

• Loading phase: 400 mg once daily for 14 days
• Continuation phase: 200 mg three times weekly (e.g., Monday/Wednesday/Friday) for the remainder of treatment
• Timing: Can be taken with or without food, but absorption may be enhanced when taken with a meal

Delamanid Dosing

• Standard dose: 100 mg twice daily (12 hours apart)
• Duration: Typically for the full course of treatment (6 months)
• Timing: Should be taken with food to enhance absorption

Linezolid Dosing in BPaLM Regimen

• Dose: 600 mg once daily for 26 weeks
• Timing: Can be taken with or without food
• Note: Lower dose of 600 mg daily (rather than 1200 mg) is preferred as it maintains efficacy while significantly reducing adverse events 1, 2

Moxifloxacin Dosing

• Dose: 400 mg once daily
• Timing: Can be taken with or without food
• Administration: Should be taken at least 4 hours before or 8 hours after products containing magnesium, aluminum, iron, or zinc 3

Aminoglycosides (if included in regimen)

• Gentamicin: 5 mg/kg once daily IV/IM
• Amikacin: 15-20 mg/kg once daily IV/IM
• Timing: Once-daily dosing is preferred for efficacy and reduced toxicity 1, 4
• Duration: Typically limited to first 4-6 months of treatment 1

Special Considerations

QT Interval Monitoring

• Both bedaquiline and delamanid can prolong QT interval
• When used together, the effect is modest and not more than additive (mean increase of 20.7 ms) 5
• ECG monitoring should be performed at baseline and regularly during treatment
• Avoid concurrent use of other QT-prolonging medications when possible

Dose Adjustments After Interruptions

• For bedaquiline interruptions between weeks 3-72:
  • If interrupted for 1-6 weeks: Resume with 2-week loading dose of 200 mg once daily
  • If interrupted for >8 weeks: Resume with 2-week loading dose of 400 mg once daily 6

Drug Interactions

• Moxifloxacin should be taken at least 4 hours before or 8 hours after antacids, iron, zinc, or multivitamins 3
• If fluoroquinolone resistance is documented after starting BPaLM, moxifloxacin should be stopped, and the regimen continued as BPaL 1

Pediatric Considerations

For children (where applicable):

• Bedaquiline: For children >12 years and >30 kg: adult dose; for children >6 years and 15-30 kg: half the adult dose 1
• Delamanid: >35 kg: adult dose; 20-34 kg: 50 mg twice daily; 10-20 kg: 25 mg twice daily 1
• Moxifloxacin: For children 12-17 years ≥45 kg: 400 mg once daily; <45 kg: 4 mg/kg twice daily (max 200 mg/dose) 1

Common Pitfalls to Avoid

1. Inadequate loading dose: Failure to provide proper loading doses of bedaquiline can lead to suboptimal drug levels and potential treatment failure

2. Improper timing with food/supplements: Administering moxifloxacin with products containing divalent cations significantly reduces absorption

3. Excessive linezolid dosing: Using 1200 mg daily of linezolid instead of 600 mg significantly increases adverse events (myelosuppression 22% vs 2%, peripheral neuropathy 38% vs 24%) without substantial efficacy benefits 2

4. Inadequate monitoring: Failure to monitor for QT prolongation, myelosuppression, and peripheral neuropathy can lead to preventable adverse events

5. Inappropriate regimen modification: Stopping moxifloxacin without confirming fluoroquinolone resistance or failing to adjust bedaquiline dosing after interruptions

By following these evidence-based dosing recommendations, clinicians can optimize treatment outcomes while minimizing adverse events in patients receiving twice-daily MDR-TB regimens.