Leprosy Treatment: Daily Doses Should Be Given First
In leprosy treatment, daily doses of dapsone (and clofazimine when indicated) should be initiated first and continued throughout the entire treatment course, with monthly rifampicin doses added as supervised therapy—not given as the initial or sole treatment. 1, 2
Standard Treatment Approach
Multibacillary Leprosy (Lepromatous and Borderline-Lepromatous)
The WHO-recommended multidrug therapy requires:
- Daily dapsone 100 mg (started immediately and continued without interruption) 2
- Daily clofazimine 50-100 mg (started simultaneously with dapsone) 1
- Monthly rifampicin 600 mg (given under supervision, added to the daily regimen) 3, 4
The daily medications form the backbone of therapy and must be maintained continuously for 12 months (previously 24 months), while the monthly rifampicin provides intensive bactericidal activity under direct observation 4. Daily dapsone should never be interrupted to accommodate monthly dosing schedules 2.
Paucibacillary Leprosy (Tuberculoid and Indeterminate)
Treatment consists of:
- Daily dapsone 100 mg (continuous throughout treatment) 2
- Monthly rifampicin 600 mg (supervised, for 6 months) 2, 4
The daily dapsone continues for an additional 6 months after completing rifampicin, then for 3 more years for tuberculoid/indeterminate disease or 5 years for borderline tuberculoid disease 2.
Clinical Rationale for Daily-First Approach
The daily-first strategy prevents secondary dapsone resistance, which was the primary reason WHO and the USPHS at Carville recommended that dapsone be maintained at full daily dosage without interruption when combined with other anti-leprosy drugs 2. Historical data from the 1980s demonstrated that once-monthly rifampicin (1200 mg) combined with daily dapsone (100 mg) produced rapid bacteriological regression within one week, with moderate to marked clinical improvement in all patients 5, 3.
Network meta-analysis of 70 years of leprosy treatment data confirms that single-drug regimens are insufficient, and multidrug therapy with continuous daily dosing is more effective than intermittent schedules 6. The combination of daily dapsone plus monthly supervised rifampicin costs approximately one-tenth of daily rifampicin regimens while maintaining equivalent therapeutic efficacy 3.
Critical Implementation Details
Dosing Schedule
- Adults receive dapsone 100 mg daily (children receive proportionally smaller doses) 2
- Rifampicin 600 mg is given monthly under supervision (can be increased to 1200 mg monthly in some protocols) 5, 3
- All medications should be administered together when given on the same day—split dosing should be avoided 2
Monitoring Requirements
Before initiating daily dapsone:
- Screen for G6PD deficiency due to hemolytic anemia risk 1
- Obtain baseline complete blood count and liver function tests 1
During treatment:
- Monitor for dapsone adverse effects (hemolysis, methemoglobinemia, nausea) with regular CBC and LFTs 1, 2
- Perform baseline ECG and QT interval monitoring when using clofazimine 1
- Assess clinical response by 4-6 weeks (lesion flattening expected) 1
Common Pitfalls to Avoid
Do not start with monthly rifampicin alone or give it before establishing daily therapy—this increases resistance risk and reduces treatment efficacy 2, 6. The daily medications must be initiated first and maintained continuously.
Do not discontinue daily dapsone during leprosy reactions (type 1 reversal reactions or type 2 erythema nodosum leprosum)—these require anti-inflammatory management but continuation of multidrug therapy 1. Reactions are not treatment failure.
Do not reduce dapsone dosage below 100 mg daily in adults unless adjusting for proven dapsone resistance or severe adverse effects requiring alternative regimens 2. The full 100 mg daily dose is necessary to prevent resistance emergence.
Special Considerations for Pregnancy
Treatment should continue during pregnancy as benefits outweigh risks, with close monitoring required 1. Daily dosing remains the standard approach in pregnant patients.