What medication should be prescribed immediately to a leprosy patient experiencing a severe hypersensitivity reaction to rifampicin (antibiotic)?

Immediate Management of Severe Rifampicin Hypersensitivity in Leprosy

For a leprosy patient experiencing a severe hypersensitivity reaction to rifampicin, immediately discontinue rifampicin and administer systemic corticosteroids (prednisolone 1 mg/kg daily) while providing supportive care for any hemodynamic instability, hemolysis, or renal complications. 1

Immediate Actions Required

Discontinue Rifampicin Immediately

• Stop all rifampicin administration at once - severe hypersensitivity reactions to rifampicin can progress rapidly to life-threatening complications including shock, intravascular hemolysis, and acute renal failure 1
• These reactions are mediated by immune complexes with anti-rifampicin antibodies followed by complement binding 1

Initiate Corticosteroid Therapy

• Start prednisolone at 1 mg/kg daily as the primary treatment for severe hypersensitivity reactions 2
• Corticosteroids are specifically indicated to suppress hypersensitivity reactions to antituberculosis drugs, including rifampicin 3
• Continue corticosteroid therapy until clinical improvement is evident, typically requiring several weeks of treatment 2

Provide Supportive Care Based on Severity

• Monitor for hemodynamic instability - if shock develops, provide IV fluid resuscitation and hemodynamic support 1
• Assess for intravascular hemolysis - check hemoglobin, haptoglobin, and LDH; severe cases may require blood transfusion 1
• Monitor renal function closely - acute renal failure may develop and require hemodialysis in severe cases 1
• Obtain baseline liver function tests - hepatotoxicity can occur with rifampicin reactions 3

Critical Clinical Context

Risk Factors for Severe Reactions

• Intermittent rifampicin dosing (such as monthly WHO/MDT regimen) carries higher risk than daily dosing 1
• Prior rifampicin exposure followed by re-challenge increases risk of serious complications including hypotension, hemolysis, and acute renal failure 1
• Multibacillary leprosy cases have higher incidence of adverse effects 1
• Most severe reactions occur within the first 6 doses of intermittent regimens 1

Alternative Treatment Strategy

• Continue dapsone and clofazimine from the WHO multibacillary regimen while rifampicin is discontinued 4
• Consider adding prothionamide 250 mg daily as a substitute for rifampicin once the acute reaction resolves 5
• Do not attempt rifampicin desensitization - the risk of recurrent severe reactions is too high 1

Monitoring During Recovery

Clinical Parameters

• Daily assessment of vital signs, particularly blood pressure and temperature 1
• Monitor for resolution of fever, rash, and any systemic symptoms 4
• Assess for development of eosinophilia which may indicate DRESS syndrome 4

Laboratory Monitoring

• Serial complete blood counts to monitor for hemolysis and recovery 1
• Daily renal function tests (creatinine, BUN) until stable 1
• Liver function tests every 2-3 days initially, then weekly 4
• Bilirubin levels if jaundice develops 4

Corticosteroid Tapering Strategy

• Maintain initial prednisolone dose (1 mg/kg daily) for 4 weeks or until complete clinical improvement 2
• Begin tapering only after all acute symptoms have resolved and laboratory values are normalizing 2
• Taper gradually over 12 weeks to prevent rebound reactions 2

Common Pitfalls to Avoid

• Never rechallenge with rifampicin after a severe hypersensitivity reaction - the risk of recurrent life-threatening complications is unacceptably high 1
• Do not delay corticosteroid initiation while awaiting laboratory confirmation - clinical suspicion alone warrants immediate treatment 2
• Avoid premature corticosteroid tapering - reactions can persist or worsen if steroids are reduced too quickly 2
• Do not assume all reactions are Type 1 reversal reactions - rifampicin hypersensitivity presents differently and requires different management 2, 1