ANTI TUBERCULAR &

ANTILEPROTIC DRUGS
Dr. Yogeeta S C Walke
Assistant Professor
Tuberculosis
• Chronic granulomatous disease

• Causative organism is Mycobacterium tuberculosis

• In 2012 the Government of India has declared TB to be a

notifiable disease

• Free treatment is provided to all TB pts

• 1997 The Revised National Tuberculosis Control

Programme was launched (RNTCP)
Tuberculosis

• India is the highest contributor with 2.3 million cases

• About 1000 people die from TB every day in India.

• India has a large load of HIV infected subjects

• especially vulnerable to severe forms of tubercular/ MAC infection.

• Emergence of ‘multidrug resistant’ (MDR) TB or

Extensive drug resistant (XDR) TB
• Presumptive pulmonary TB
• Refers to a person with any of the symptoms and signs suggestive
of TB including
• cough>2 weeks
• fever >2weeks
• significant weight loss
• Haemoptysis
• any abnormality in chest radiograph

• Note: in addition, contacts of microbiologically confirmed TB patients, PLHIV,

diabetics, malnourished, cancer patients, patients on immune-suppressants or
steroid should be regularly screened for sign and symptoms of TB
Challenges in treatment…..
• Tubercle bacilli grow slowly, dividing only once in 1-2 days
even in the most favourable circumstances such as in an open
cavitary, pulmonary lesion

• In less favourable circumstances , such as closed, caseous,

the bacteria become metabolically dormant & may persist
(persisters) for many years

• Tubercle bacilli remain viable & multiply even when ingested by

macrophages

• The caseation & fibrosis tend to block the blood vessels supplying
the necrotic area making penetration of drugs difficult
 New case
• A TB patient who has never
had treatment for TB or has
taken anti-TB drugs for less
than one month
Previously treated patients have received
one month or more ATD in the past
• Previously declared as successfully
Recurrent treated (cured/treatment completed)
TB case and who is subsequently found to be
microbiologically confirmed TB case

• Those who have previously been

Treatment treated for TB and whose treatment
after failure failed at the end of their most recent
course of treatment

• Previously treated for TB for one

month or more and who was
Treatment declared lost to follow-up in their
after loss to most recent course of treatment and
follow-up subsequently found microbiologically
confirmed TB cases.
• Classification on the basis of drug
resistance
• Biological specimen • Biological specimen • Biological specimen is resistant
is resistant to one is resistant to more to both INH and rifampicin with
first-line anti-TB than one first-line or without resistance other first-
drug only anti-TB drug, other line ATD, based on results from
than both INH and a quality assured laboratory
rifampicin
Mono
Poly resistance
resistance Multi-drug resistance
(PDR)
(MR) (MDR)

• Resistance to rifampicin detected by • MDR TB case whose biological

phenotypic or genotypic methods with specimen was resistant to a
or without resistant to other ATD fluoroquinolone (FQ) and a second-
excluding INH. line injectable ATD from a quality
assured laboratory.
case
as MDR
Extensive drug resistance
Rifampicin resistance (RR) Treated
(XDR)
Multi-drug resistance (MDR)

• Biological specimen is resistant to both

INH and Rifampicin

with or without resistance to other first-line ATD,

based on results from a quality assured laboratory

Extensive drug resistance (XDR)

• MDR TB case whose biological specimen was resistant to

Fluoroquinolone (FQ)

Second-line injectable ATD

from a quality assured laboratory.

Antitubercular Drugs
First line Second Line

• High efficacy • Low efficacy

• Low toxicity • High toxicity

• Used Routinely • Reserve drugs

First line drugs
• Isoniazid (H)

• Rifampicin (R)

• Pyrazinamide (Z)

• Ethambutol (E)

• Streptomycin (S)
Second line drugs

Fluoroquinolones
• Ofloxacin (Ofx)
• Levofloxacin (Lfx)
• Moxifloxacin (Mfx)
• Ciprofloxacin (Cfx)

Injectable drugs
• Kanamycin (Km)
• Amikacin (Am)
• Capreomycin (Cm)
Second line drugs

• Ethionamide (Eto),

• Prothionamide (Pto)

• Cycloserine (Cs),

• Terizidone (Trd)

• Para-aminosalicylic acid (PAS)

• Rifabutin,

• Thiacetazone (Thz)
Isoniazid (Isonicotinic acid hydrazide,H)
• Excellent antitubercular drug

• Essential component of all anti TB regimens

• Tuberculocidal
Isoniazid (Isonicotinic acid hydrazide,H)
• Fast multiplying organisms are rapidly killed

• Kills the bacilli inside the macrophages

• Does not eliminate the persisters

• Poor sterilising activity as it fails to kill all viable organism

Isoniazid (Isonicotinic acid hydrazide,H)
• It is more effective than other drugs in preventing drug
resistance to other drugs

• It is well tolerated, cheap & safe even in pregnancy

• Equally active in acidic or alkaline medium

Isoniazid (Isonicotinic acid hydrazide,H)
MOA
• INH is a prodrug

• It is activated by mycobacterial catalase peroxidase to an

active compound, which inhibits the synthesis of mycolic

acid, a unique constituent of the mycobacterial cell wall

Isoniazid (Isonicotinic acid hydrazide,H)
Pharmacokinetics
• Completely absorbed orally & penetrates all body tissues,
tubercular cavities, placenta & meningitis

• It is extensively metabolised in the liver, most important

pathway being N acetylation

• The rate of INH acetylation shows genetic variation, there

are either
Fast acetylators 30-40% indians t1/2 of INH 1 hour
Slow acetylators 60-70% indians t1/2 of INH 3 hour
Isoniazid (Isonicotinic acid hydrazide,H)
• INH induced peripheral neuritis is more common in slow
acetylators

• Hepatotoxicity is more common in fast acetylators

Drug Interactions
• Aluminium hydroxide inhibits INH absorption

• INH inhibits the metabolism of phenytoin, carbamazepine

diazepam

• PAS inhibits INH metabolism

Adverse Effects
1. Peripheral neuritis is most important adverse effect

• Due to interference with production of the active

coenzyme pyridoxal phosphate from pyridoxine, and its
increased excretion in urine

• Pyridoxine given prophylactically (10 mg/day) prevents

the neurotoxicity

• INH induced peripheral neuritis is more common in slow

acetylators
Adverse Effects
2. Hepatotoxicity
• Rare in children more common in older people (>50)
& in alcoholics

• Metabolite of INH may have a role to play

• Hepatotoxicity is more common in fast acetylators

3. Rash, fever, lethargy

Rifampin (Rifampicin)/(R)
• Semisynthetic derivative of rifamycin B obtained from
Streptomyces mediterranei.

• Effective against tuberculosis and leprosy

• Effective against many gram-positive and gram-negative

bacteria

• Against TB bacilli, it is as efficacious as INH and better

than all other drugs.
Rifampin (Rifampicin)/(R)
• Bactericidal action covers all subpopulations of TB bacilli,
but acts best on slowly or intermittently dividing ones
(spurters).

• Both extra- and intracellular organisms are affected.

• The only drug which acts on the persisters

• It has good sterilizing and resistance preventing actions.

MoA –

• Interrupts RNA synthesis

• Inhibits mycobacterial DNA-dependent RNA

polymerase

• Selective toxicity – mammalian RNA polymerase

does not avidly bind rifampin.
Pharmacokinetics

• Well absorbed orally, (bioavailability ~ 70%)

• Food decreases absorption; to be taken on empty stomach.

• Widely distributed in the body: penetrates intracellularly

• Metabolized in liver

• Excreted mainly in bile.

• Undergoes enterohepatic circulation.

• t½ is 2–5 hours
Drug Interactions

• Rifampin is a microsomal enzyme inducer

• It enhances its own metabolism.

• Enhances metabolism of many other drugs including

warfarin, oral contraceptives, corticosteroids, HIV
protease inhibitors, theophylline, ketoconazole, phenytoin

• Contraceptive failures have occurred.

Adverse effects

• Hepatitis is the major adverse effect

• Occurs in pts with preexisting liver disease & is dose

related

• Development of jaundice requires discontinuation of the

drug- then it is reversible
Adverse effects

• Cutaneous syndrome: flushing, pruritus + rash (especially

on face and scalp), redness and watering of eyes.

• Flu syndrome: with chills, fever, headache, malaise and

bone pain.

• Abdominal syndrome: nausea, vomiting, abdominal

cramps with or without diarrhoea

• Respiratory syndrome
• Urine and secretions may become orange-red
Other uses
• Leprosy

• Prophylaxis of meningococcal & H influenzae meningitis &

carrier state

• Combination of doxycycline & rifampin is the first line

therapy in Brucellosis
Pyrazinamide (Z)
• Weakly tuberculocidal
• More active in acidic medium.
• More lethal to intracellularly located bacilli and to those at
sites showing an inflammatory response
• Highly effective during the first 2 months of therapy when
inflammatory changes are present.
• Good ‘sterilizing’ activity.
• Its inclusion has enabled duration of treatment to be
shortened and risk of relapse to be reduced.
MoA – Pyrazinamide (Z)

• Prodrug

• Converted inside the mycobacterial cell into an active

metabolite pyrazinoic acid

• This metabolite gets accumulated in acidic medium and

inhibits mycolic acid synthesis

• Pyrazinoic acid also appears to disrupt mycobacterial cell

membrane and its transport function.
Pharmacokinetics of Pyrazinamide (Z)

• Absorbed orally, widely distributed

• Good penetration in CSF 

highly useful in meningeal TB;

• Extensively metabolized in liver

• Excreted in urine

• Plasma t½ is 6–10 hours.

Adverse Effects of Pyrazinamide (Z)

• Hepatotoxicity

• Hyperuricaemia due to inhibition of uric acid secretion in

kidney: gout can occur.

• Arthralgia, flushing, rashes, fever

• Hyperglycaemia & Loss of Diabetes control:

repeated blood glucose monitoring is needed in diabetics.
Ethambutol (E)
• Selectively tuberculostatic

• Active against MAC as well as some other mycobacteria,

but not other types of bacteria.

• Fast multiplying bacilli are more susceptible.

• Has been found to hasten the rate of sputum conversion

• Prevents development of resistance  primary purpose of

using it
Ethambutol (E) MoA

• Inhibits arabinosyl transferases involved in

arabinogalactan synthesis

• Thus interferes with mycolic acid incorporation in

mycobacterial cell wall.
Ethambutol (E) Pharmacokinetics

• 75% of an oral dose is absorbed

• Distributed widely, but penetrates meninges incompletely
and is temporarily stored in RBCs.
• Less than 50% metabolized.
• Plasma t½ is ~4 hrs.
• Excreted in urine
• Caution is required in use in patients with renal disease
Ethambutol (E) Adverse Effects
• Loss of visual acuity/colour vision, optic neuritis
Patients should be instructed to stop the drug at the first
indication of visual impairment.

• Nausea, rashes, fever

• Peripheral neuritis

• Hyperuricemia due to interference with urate excretion.

Streptomycin (S)
• The first clinically useful antitubercular drug.

• It is tuberculocidal, but less effective than INH or rifampin

• Acts only on extracellular bacilli (because of poor

penetration into cells).

• Penetrates tubercular cavities, but does not cross the

CSF

• Poor action in acidic medium.

Streptomycin (S) MoA

• Streptomycin binds to 30S ribosomes in the mycobacterial

cell

• Freezes initiation of protein synthesis

• peptides of abnormal lengths are produced.

• Secondary changes in the integrity of bacterial cell

membrane occur

• Bacteria become more permeable; ions, amino acids and

even proteins leak out followed by cell death.
Streptomycin (S) Pharmacokinetics

• Highly ionized, neither absorbed nor destroyed in the g.i.t.

• Absorption from injection site in muscles is rapid: peak

plasma levels are attained in 30–60 minutes.

• Distributed only extracellularly.

• High concentrations are present in inner ear  ototoxicity

• Concentrations in CSF and aqueous humour are

nontherapeutic even in the presence of inflammation
Streptomycin (S) Pharmacokinetics

• Not metabolized

• Excreted unchanged in urine

• The plasma t½ ranges between 2–4 hours,

• The t½ is prolonged and accumulation occurs

in patients with renal insufficiency
Streptomycin (S)
Adverse Effects
• Ototoxicity
• Nephrotoxicity
• Hypersensitivity reactions

• Because of need for i.m. injections and adverse effects,

use is restricted to a maximum of 2 months.

• Labelled as a ‘supplemental’ 1st line drug.

Second line drugs
• These are less effective and/or less well tolerated anti-TB
drugs

Used only in case

• Mycobacteria are resistant to one or more first line drugs

• When these are not tolerated/are contraindicated.

Kanamycin (Km), Amikacin (Am)

• These are tuberculocidal aminoglycoside antibiotics

•
• Very similar in antitubercular activity, pharmacokinetic
properties and adverse effects to Streptomycin.

• Many Streptomycin resistant and MDR strains of

M.tuberculosis remain sensitive to them.

• One of these is usually included in the regimen for MDR-

TB during the intensive phase
Fluoroquinolones (FQs)

• Well tolerated alternatives to 1st line anti-TB drugs.

• Moxifloxacin is the most active FQ against M.tuberculosis,

• Primary indication is for treatment of drug resistant TB

• A key component of all regimens for MDR-TB, except

when bacilli are found to be resistance to them.
Ethionamide (Eto)

• Anti-TB drug of moderate efficacy

• Mechanism of action is similar to INH

• Tolerability poor; frequent adverse effects are — anorexia,

nausea, vomiting, salivation, metallic taste, epigastric
discomfort, hepatitis, peripheral neuritis, behavioural
changes, rashes, impotence, menstrual disturbances and
goiter on prolonged use.
Para-amino salicylic acid (PAS)

• PAS is related to sulfonamides

• Acts by the same mechanism, i.e. inhibition of folate
synthase of M.tuberculosis.
• Tuberculostatic and one of the least active drugs
• Does not add to the efficacy of more active drugs given
with it
• Only delays development of resistance
• Used only in resistant TB
Rifabutin

• Related to Rifampin in structure and mechanism of action

• Less active against M.tuberculosis and more active

against MAC

• Primary indication – prophylaxis and treatment of MAC

infection in HIV-AIDS patients
 Bedaquiline
• New anti-TB drug

• MoA – Blocks Mycobacterial ATP Synthase, an enzyme

essential for the supply of energy to the mycobacteria

• Very long t1/2 – 5.5 months

• Essential component of treatment of MDR-TB and XDR-TB

• A/Es – Headache, increased liver enzymes, Qtc

prolongation
Goals of Anti-Tubercular Therapy

Kill dividing bacilli

• Drugs with early bactericidal action rapidly reduce
bacillary load
• Achieves quick sputum negativity  patient is non-
contagious  transmission of TB is interrupted.
• Quick symptom relief.
Kill persisting bacilli
• To effect cure and prevent relapse.
• This depends on sterilizing capacity of the drug.
Prevent emergence of resistance
• So that the bacilli remain susceptible to the drugs
Treatment groups for therapy
Treatment Groups Type of Patient
Microbiologically confirmed TB
case
(Definitive)
New
Clinically diagnosed TB case
(Probable)

Recurrent TB

Treatment after failure

Previously Treated Treatment after loss to

followup

Other previously treated

patient
Regimens
• New RNTCP 2016 guidelines

• Daily DOTS
(Directly Observed Treatment Short Course)

• Frequency of Dosage: DAILY (7 day/week)

• 4 weeks per month, i.e.: 28 doses

• FDCs (Fixed Dose Combinations)

First line drugs
• Isoniazid (H)

• Rifampicin (R)

• Pyrazinamide (Z)

• Ethambutol (E)

• Streptomycin (S)
 Treatment Regimen

Treatment
Regimen (in months)
Group
New 2HRZE (IP) + 4HRE (CP)
(Red) 6 months

2HRZES (IP)
+
Previously
1HRZE (IP)
Treated
+
(Green)
5HRE (CP)
8 months

IP – Intensive Phase CP – Continuation Phase

 Drug Recommended Daily dose

Isoniazid (H) 5 mg/kg (4–6 mg/kg) daily

Rifampin (R) 10 mg/kg (8–12 mg/kg) daily

Pyrazinamide (Z) 25 mg/kg (20–30 mg/kg) daily

Ethambutol (E) 15 mg/kg (15–20 mg/kg) daily

Streptomycin (S) 15 mg/kg (12–18 mg/kg) daily

 Number Of Tablets

Continuation Inj. Streptomycin

Intensive Phase
Phase (Intensive Phase
Weight Band Only)

HRZE HRE
75/150/400/275
75/150/275 mg in gms
mg

25 – 39 kg 2 2 0.5
40 – 54 kg 3 3 0.75
55 – 69 kg 4 4 1
≥ 70 kg 5 5 1
Multidrug –resistant TB
• Resistance to first line drugs

• Complex multiple 2nd line drug regimens which are longer

more expensive & more toxic

• As per WHO India has the highest no. of MDR-TB cases

in South East Asia
Standard RNTCP regimen for MDR TB
• Intensive phase • Continuation phase
6-9 months 18 months
1. Kanamycin 1. Levofloxacin
2. Levofloxacin 2. Ethionamide
3. Ethionamide 3. Cycloserine
4. Cycloserine 4. Ethambutol
5. Pyrazinamide
6. Ethambutol

Pyridoxine 100 mg
Tuberculosis in pregnant women
• Standard 6 month ( 2HRZE + 4HRE)

• Streptomycin is contraindicated since it is ototoxic to

foetus

• All pregnant women being treated with INH should receive

pyridoxine 10 mg/day
Read

• Management of patients with ADRs to anti TB drugs

• TB in AIDS patienst
Leprosy
• Leprosy takes its name from Greek word Lepros which
means ‘scaly man’

• Gerhard Hansen a Norwegian physician discovered

Mycobacterium leprae in 1873

• Social stigma was associated with leprosy which was a

main barrier to self reporting and early treatment

• Leprosy was equated with an untouchable status which

persists long after the disease was cured creating life long
prospects of divorce, eviction & ostracism
Baba Amte
• “I took up leprosy work not to help anyone,

but to overcome that fear in my life.

That it worked out good for others was a by-

product .

But the fact is I did it to overcome fear”

• Baba Amte founded an Ashram Anandwan in 1952 in
•
Maharashtra for leprosy patients & the disabled from

downtrodden sections of society

Leprosy
• Caused by Mycobacterium leprae

• One of the oldest disease known to mankind

• Primarily affects skin, mucus membrane & peripheral nerves

• 1982: Govt of India Launched NLEP & introduced MDT

• MDT was provided to all PHCs free of cost

• India achieved elimination of leprosy (prevalence rate < 1

case per 10,000 population) in Dec. 2005

• Still, 12,000 new cases a year seen (Not Eradicated)

Classification of Anti-Leprotic drugs

1. Sulfone – Dapsone (DDS)

2. Phenazine derivative – Clofazimine

3. Antitubercular drugs – Rifampin, Ethionamide

4. Other antibiotics – Ofloxacin, Moxifloxacin

Minocycline, Clarithromycin
Dapsone (DDS)
• Diamino Diphenyl Sulfone (DDS)

• Simplest, oldest, cheapest

• Most active, most commonly used

• Leprostatic at very low concentrations

MOA- Dapsone (DDS)

• Chemically related to sulfonamides

• Same mechanism of action

• Inhibition of PABA incorporation into folic acid by folate

synthase.
Pharmacokinetics -Dapsone (DDS)
• Completely absorbed after oral administration

• Widely distributed in the body

• Penetration in CSF is poor.

• Concentrated in skin (especially lepromatous skin),

muscle, liver and kidney.

• Acetylated as well as glucuronide and sulfate conjugated

in liver.
Pharmacokinetics- Dapsone (DDS)
• Metabolites are excreted in bile and reabsorbed from
intestine

• Ultimate excretion occurs mostly in urine.

• Plasma t½ of dapsone > 24 hrs.

• Elimination takes 1–2 weeks or longer.

• The drug is cumulative due to retention in tissues and

enterohepatic circulation.
Adverse Effects- Dapsone (DDS)
• Mild haemolytic anaemia
(Patients with G-6-PD deficiency are more susceptible)

• Gastric intolerance

• Methaemoglobinaemia

• Allergic rashes, fixed drug eruption, phototoxicity

• Hepatitis & Agranulocytosis are rare

Adverse Effects- Dapsone (DDS)
• Sulfone syndrome

Reaction which develops 4–6 weeks after starting dapsone

treatment

consists of fever, malaise, lymph node enlargement,

desquamation of skin, jaundice and anaemia.

Contraindications- Dapsone (DDS)

• Patients with severe anaemia (Hb < 7 g/dl)

• G-6-PD deficiency

• Patients showing hypersensitivity reactions.

Other use of Dapsone
• I n combination with pyrimethamine, dapsone can be

used for chloroquine resistant malaria,

toxoplasmosis and

P. Jirovecii infection
Clofazimine (CLO)
A dye with leprostatic & anti-inflammatory properties

• Clinical response is slower than that to dapsone,

•
• Dapsone–resistant M. leprae respond to clofazimine.

• Component of multidrug therapy (MDT) of leprosy.

• Valuable in lepra reaction.

• Component of MDT for MAC infection.

MoA –Clofazimine (CLO)

• Interference with template function of DNA in M.leprae

• Alteration of membrane stucture and its transport function.

• Disruption of mitochondrial electron transport chain

Pharmacokinetics-Clofazimine (CLO)
• Orally active (40–70% absorbed).

• Accumulates in macrophages and gets deposited in many

tissues including subcutaneous fat, as needle-shaped

crystals.

• Entry in CSF is poor.

• The t½ is 70 days (intermittent therapy is possible)

Adverse Effects- Clofazimine (CLO)
• Reddish-black discolouration of skin, especially on
exposed parts.

• Discolouration of hair and body secretions

• Nausea, anorexia, abdominal pain, weight loss

• Enteritis with intermittent loose stools

Rifampin (R)
• Most potent cidal drug for M.leprae

• Rapidly renders leprosy patients noncontagious.

• Included in the MDT of leprosy

• Shortens the duration of treatment, and no resistance

develops.

• Remains effective in leprosy even if given once a month

Rifampin (R)
• Should not be given to patients with hepatic or
renal dysfunction

• Should not be given during ‘erythema nodosum leprosum’

(ENL) and ‘reversal reaction’ in leprosy patients,

• Can release large quantities of mycobacterial antigens by

inducing rapid bacillary killing.
4. Other antibiotics
Ofloxacin

Moxifloxacin

Minocycline

Clarithromycin
Ofloxacin
• Cidal to M. leprae

• Can be used as an alternative regimen in case rifampicin

cannot be used or to shorten the duration of treatment &
reduce the chances of drug resistance

Safety during long term treatment is not well documented

Moxifloxacin
• Most potent FQ against M. leprae
Minocycline
• Because of high lipophilicity , this tetracycline penetrates
into M. leprae & is active against them

• Antileprotic activity is less marked as compared to

rifampicin but greater than clarithromycin

• A good clinical response in terms of relief of lepromatous

symptoms has also been reported

• Vertigo is the serious long term complication

Clarithromycin
• Only macrolide antibiotic with significant activity against
M. leprae

• A synergistic action with clarithromycin has been

demonstrated
Classification of Leprosy
• Ridley and Jopling (1966) Classification
Lepromatous (LL)

Borderline lepromatous (BL) MBL

Borderline (BB)

Borderline tuberculoid (BT)

PBL
Tuberculoid (TT)
 WHO Classification of Leprosy
Paucibacillary (PB)
• 1-5 skin lesions
• No nerve/only one nerve involvement, + 1–5 skin lesions.
• Skin smear negative at all sites
• It includes TT & BT types

Multibacillary (MB)
• 6 or more skin lesions
• > 1 nerve involved irrespective of number of skin lesions
• Skin smear positive at any one site
• It includes LL, BL & BB
Multi Drug Therapy (MDT) of leprosy
• Regimen of choice for all cases of leprosy.

Advantages
• Effective in cases with primary dapsone resistance.

• Prevents emergence of dapsone resistance.

• Affords quick symptom relief and renders

• MBL cases noncontagious within few days.

• Reduces total duration of therapy.

 Multibacillary Paucibacillary

600 mg once a month 600 mg once a month

Rifampin supervised supervised

100 mg daily 100 mg daily

Dapsone self administered self administered
300 mg once a month
supervised

Clofazimine and –

50 mg daily
self administered

Duration 12 months 6 months

Reactions in leprosy
1. Lepra reaction Type 2
Occurs in LL
• Possibly Arthus type

• Usually coincides with institution of chemotherapy and/ or

intercurrent infection.

• Due to release of antigens from the killed bacilli

• May be mild, severe or life-threatening, i.e.

Erythema Nodosum Leprosum (ENL).
 Lepra reaction Type 2

• Abrupt onset

• Existing lesions enlarge, become red, swollen and painful

• Several new lesions may appear.

• Malaise, fever and other constitutional symptoms

Treatment of Lepra reactionType 2

1. Clofazimine (200 mg daily) is effective

(anti-inflammatory property)

In severe cases
• Temporary discontinuation of Dapsone

2. Prednisolone 40–60 mg/day

Started immediately and continued till the reaction subsides.
Then tapered over 2–3 months.

3. Thalidomide
Thalidomide
• Anti-inflammatory, cytokine (TNF alpha, ILs, interferon)
modulating drug with anxiolytic, antiemetic property.

Thalidomide can be used in ENL as an alternative to

prednisolone.
Dose:100–300 mg OD at bed time

It was introduced in 1958 for morning sickness was found

to be highly teratogenic and withdrawn in 1961

• It has been reintroduced for ENL & multiple myeloma

 Lepra reaction Type 1
Reversal reaction

• Seen in TT and BL cases

• Manifestation of delayed hypersensitivity to M. leprae antigens.

•
• Cutaneous ulceration, multiple nerve involvement with swollen,
painful and tender nerves, occur suddenly even after completion
of therapy.

• Treated with clofazimine or corticosteroids in the same way as

ENL.

• Thalidomide is ineffective.
Thank You