ROLE OF CLOFAZIMINE IN

MANAGEMENT OF REACTIONS IN
LEPROSY : A BRIEF OVERVIEW

Journal Reading
ABSTRACT
Clofazimine is a synthetic dye that has been used in the treatment of
leprosy since many years. Its role in the treatment of lepra reactions was
subsequently recognized. When the dose of 300 mg/day is used, it doubles
the serum concentration of the drug and supposedly exerts potent anti-
neutrophilic effect and inhibits of prostaglandins. Our personal experience
with high dosages of clofazimine in type II lepra reactions and review of the
literature suggests that clofazimine has been extremely useful in providing
good and satisfactory results in leprosy patients suffering from these
embarrassing conditions. The antiinflammatory effect of clofazimine is
greatly useful in managing recurrent and chronic type II reactions with its
steroid-sparing effect and providing an alternate and in expensive option.
INTRODUCTION
Clofazimine has been in use in the treatment of leprosy since 1962
A clinical trial with clofazimine for the management of multibacillary
leprosy patients was found to be effective as reported
Although its role in the management of type I reaction is not documented
adequately, Pfaltzgraf (1989) [2] has referred to its role in controlling type
I reaction too.
ABOUT CLOFAZIMINE
This synthetic riminophenazine dye has been used in the treatment of
leprosy for over five decades
Browne and Hogerzeil[3] showed the clinical and bacteriological
improvement in lepromatous patients with its use
The drug has a mild bactericidal action against Mycobacterium leprae the
effect being slightly less than dapsone
The drug possibly acts by blocking the template function of DNA.
The advantage with clofazimine is the antiinflammatory action and its
resultant efficacy in type II reactions
 300 mg dose results in double the concentration.
The drug passes into various organs and is stored as needlelike crystals
preferentially in macrophages and cells of the reticuloendothelial system.
accumulation within the macrophages inhibition of the multiplication of
intracellular M. leprae.
A Large quantity of the drug accumulates in the skin, subcutaneous fat,
liver, lungs, adrenals, kidneys, lymph nodes, and gastrointestinal tract.
accumulation in the tissues discoloration of the organs and the skin.
 The drug is slowly excreted from the body and usually takes 612 months
on an average.
Hence, it takes quite long for patients to regain their normal coloration.
The accumulation of clofazimine in the macrophages possibly interferes
with the capacity of macrophage to process and present antigens thereby
preventing their mobilization and activation, interleukin 2 release.
the basis of the monthly loading dose of clofazimine 300 mg given in adults
along with the pulse dose of rifampicin in the World Health Organization
(WHO) standard multidru.g therapy in multibacillary leprosy is based on
this principle
 The clinical response with 50100 mg daily dose of clofazimine is slow.
Clofazimine is indicated in patients with type II reactions although its
antiinflammatory action is very slow.
Clofazimine has a special role in the prevention and management of
patients with chronic erythema nodosum leprosum (ENL) reactions
REVIEW OF LITERATURE
In an earlier study by Ganapati and Dongre,[1] wherein they investigated
the role of clofazimine in the treatment of 25 cases of reactive states of
lepromatous and borderline leprosy and seven lepromatous patients not
responding to dapsone, corticosteroids which had to be given for the
control of reactions could be withdrawn and dapsone therapy reintroduced
during the period of administration of clofazimine.
In this study, 20 patients who were subjects of repeated reactions mostly of
the pustular type who could not be managed by the usual antireactive
drugs and who invariably required corticosteroid therapy were selected.
At the time of inclusion in the trial, all the patients were in a state of
moderate to severe reactions associated with fever, lymphadenitis,
neuritis, proteinuria, etc. Most of them were already on maximum doses of
1520 mg of prednisolone daily.
 While introducing clofazimine, the corticosteroids were continued, but it
was possible to tail down their dose gradually over a period of 34 weeks.
In all patients, clofazimine was started with a dose of 300 mg daily and
continued for varying periods after the withdrawal of steroids, depending
upon the control of severity of the reaction.
15 out of the 20 patients, the drug was given for periods ranging from 6
weeks to 30 weeks.
In 4 cases was extended up to 4283 weeks, since these were somewhat
refractory and could not be controlled with the general prefixed schedule of
therapy.
it was and is unfortunate that this useful compound was not so widely
employed, because of lack of availability and perhaps also the high cost
 This study summarizes the clinical experience with clofazimine in the
treatment of patients predominantly in reactive states of leprosy as well as
a few lepromatous patients who had persistent lesions in spite of regular
treatment with maximum doses of dapsone.
In a doubleblind controlled trial by Hastings et al.[6] in 24 lepromatous
leprosy patients in reaction showed that clofazimine (Lamprene) controlled
symptoms of ENL reaction in lepromatous leprosy better than prednisolone.
Clofazimine also appeared to be significantly superior in preventing
recurrence once the reaction had been controlled.
Red/black hyperpigmentation was seen among practically all patients on
clofazimine. No other sideeffects or deleterious systemic effects were
observed.
 In a doubleblind study by Katoch et al.[7] Three hundred PB patients (smear negative,
indeterminate, tuberculoid, and borderline tuberculoid) were randomly allotted to two
regimens :
the control subjects (150 patients) receiving the standard WHO multidrug regimen of six
doses of once a month rifampicin with daily dapsone therapy for 6 months,

the study group (150 patients) receiving 50 mg of clofazimine daily for 6 months in
addition to the WHO regimen.
In 7.5% of patients on clofaziminecontaining regimen, lesions showed persisting activity
at the time of stoppage of therapy compared with 16% on the control regimen. This
activity subsided spontaneously, more rapidly, in the study group (80% compared with
30% in the control group) in 6 months. Two patients in the control group and one patient
in the study group developed a late reaction. There were no relapses in the study group,
whereas, two patients relapsed in the control group during a followup of 2.53.5 years.
 In a study by Pai et al.,[8] wherein the investigation on type I reaction in 82
patients, who had recurrent and chronic reactions (no response to
prednisolone) and then treated with clofazimine (300 mg daily) for
minimum 6 months
it was observed that in 67 (81.7%) out of 82 patients, the severity and
frequency of such episodes of reactions was well controlled. Clinical
improvement was also observed in 82% of patients with type I reaction and
81% of 51 patients with type II reaction responded well.
This alternate interventional drug or a secondary line of drug like
clofazimine not only helps in the management of recurrent type II
reactions, but also helps to wean off patients dependent on steroids and
also preempts them from steroid adverse effects while acting as a steroid
sparing agent.
ADVERSE EFFECT
The brownish red discolouration secondary to deposition of clofazimine in
the skin is fairly common. It is more marked on sunexposed areas
including face.
In patients with reactions receiving a higher dose of 200300 mg for long
periods of time the effects are due to clofazimine deposition in RE cells of
various organs. In women, this may result rarely in abdominal problems like
pain and/or diarrhea which in turn may lead to malabsorption
Clinical laboratory testing in the search for any toxicity secondary to the
drug Statistically significant changes toward abnormality were found in
fasting blood sugar and total serum bilirubin.
on the evidence to date, its advantages outweigh its disadvantages in
those leprosy patients for whom it is indicated.
CONCLUSION
clofazimine seems to be a useful drug not only as an antibacterial drug but
also as an alternate intervention for management of type II ENL reaction in
leprosy.
In fact, its role in the management of type I reaction or persistent lesions or
lesions on the face has also been underestimated and perhaps has not
been properly understood.
clofazimine has been extremely useful in providing good and satisfactory
results in leprosy patients suffering from these embarrassing conditions.
The antiinflammatory effect of clofazimine is greatly useful in managing
recurrent and chronic type II reactions with steroidsparing effect.