Professional Documents
Culture Documents
Introduction
Anti TB medication
Management of common adverse reaction
Conclusion
Why do we need to treat?
Streptomycin
Ethambutol
Isoniazid
Rifampicin
Pyrazinamide
Regimen
Rationale for combination therapy
Flushing Arthralgia
Aminoglycoside
Acts at RNA level inhibiting protein synthesis
Injectable drug
Dosage: 15mg/kg/day (max: 1000mg/day)
Available vial: 1000mg/ml
Side effect of Streptomycin
Numbness Deafness
Tinnitus
Fixed dose combination
Combinations of multiple drugs in one tablet
AKuriT-4:
rifampicin 150mg + isoniazid 75mg + pyrazinamide 400mg + ethambutol 275mg
AKuriT-2
rifampicin 150mg + isoniazid 75mg
30-39 2 2
40-54 3 3
55-70 4 4
>70 5 5
Rimcure 3-FDC:
rifampicin 150mg + isoniazid 75mg + pyrazinamide 400mg
30-37 2
38-54 3
55-70 4
>70 5
Management of common adverse events
Epidemiology of anti TB adverse reaction
25
CLASSIFICATION OF ADR FOR ANTITB
Nausea
Troublesome but NOT Tiredness Treat
symptomatically
SERIOUS Pruritus WITHOUT
Minor rashes treatment
interruption
27
SYSTEMS MOST AFFECTED BY ANTITB DRUGS
Hepatobiliary
Skin
Gastrointestinal tract
Skeletal system
Renal
28
Cutaneous drug reaction
Types
Morbiliform rash
Erythema multiforme syndrome
Urticaria
Exfoliative dermatitis
Lichenoid eruption
Steven Johnson syndrome
Toxic epidermal necrolysis
Occurs within 2 months of initiation
Morbiliform eruption Erythema multiforme
Urticaria
Exfoliative dermatitis
Lichenoid eruption Steven Johnson syndrome
Toxic epidermal necrolysis
Cutaneous drug reaction
Pyrazinamide (MOST)
Drug-Induced
Algorithm
Severe Cutaneous ADRs
Questions?
FDC
Polypharmacy
Underlying hypersensitivity reaction
Carrier or active ingredient?
Severity of cutaneous reaction
Never start bridging therapy for cutaneous reaction
Management cutaneous drug reaction- Re challenge
Drugs Day Dose
Isoniazid 1 50mg
2 300mg
3 Full dose
Rifampicin 75mg
4
INH Full dose
300mg
5
Full dose
Full dose
6
Full dose
Pyrazinamide 250mg
7
RIF + INH Full dose
1000mg
8
Full dose
Full dose
9
Full dose
Ethambutol 100mg
10
RIF + INH + PZA Full dose
500mg
11
Full dose
Full dose
DAY 1 OF TB TREATMENT 12
Full dose
Girling DJ. Adverse effect of anti tuberculosis drugs. Drugs 1981;23. 56-74
Problems during re- challenge
Stop the last drug introduced
Continue with the other drugs that were well tolerated
Manage the rash
Once rash has subside, continue to challenge with the rest of the
drugs
If the drug in question is essential, it needs to be desensitised
Desensitisation should not be attempt in severe skin reaction
Cutaneous drug reaction
Desensitisation?
If the offending drugs are both isoniazid & rifampicin
If a suitable drug combination is available, it is not necessary to perform
desensitisation
It is done by careful administration of increasing doses of the drug under close
supervision
Attempted in HIV patients*
Complex Cutaneous ADRs requires specialists consultation
40
DRUG-INDUCED HEPATITIS
Alcoholism
Chronic viral hepatitis B & C Monitoring
infections At least for the first 2 - 4 weeks is recommended
among all patients with antiTB treatment as DIH
Pregnancy until 90 days usually occurs within the initial 2 months of
postpartum treatment.
HIV
Organ transplant recipients 2Blumberg
1Yew WW et al., Respirology, 2006
HM et al., Am J Respir Crit Care Med,412003
DRUG-INDUCED HEPATITIS
Restarting?
Depends on whether hepatotoxicity sets in during the initial or the
continuation phase of treatment & the amount of treatment received
prior to the onset of such toxicity.
42
DRUG-INDUCED
DRUG-INDUCED HEPATITIS
HEPATITIS (cont.)
When to Stop AntiTB?
Serum transaminase level reaches 3
x ULN for patients with symptoms
suggestive of hepatitis
Serum transaminase level reaches 5
x ULN for those without symptoms
Restarting
The patient can then be retreated with a
regimen containing fewer potentially
hepatotoxic drugs such as streptomycin,
ethambutol, isoniazid & fluoroquinolones.
43
DRUG-INDUCED HEPATITIS
Degree of
Rise in transaminases Symptoms Management
hepatotoxicity
After ALT has reduced to less than 2 times ULN and patient is
asymptomatic
Bridging therapy should be continued while patient is being
rechallenged
DRUG-INDUCED HEPATITIS Re challenge
Drug Day Dose
SEO Full dose
1
Rifampicin 75mg
Full dose
2
300mg
Full dose
3
Full dose
SEO+R Full dose
4
Isoniazid 50mg
Full dose
5
300mg
Full dose
6
Full dose
S EO+H+R Full dose
7
Pyrazinamide 250mg
Full dose
8
500mg
Full dose
9
Full dose
Day 1 of treatment SO E+H+R+Z 11 Full dose
DRUG-INDUCED HEPATITIS Alternative regimes
Use different
Acute renal failure SM, RIF
combination
NSAIDs
Gouty arthritis PZA
Colchicine
Conclusion