4. Incidence
⦿ Affects 6-30% of all patients (Jick H)
⦿ ADR is 4th-6th leading cause of death (Brown
SD et, al)
⦿ 3-8% hospital admissions are due to ADR
⦿ Approximately 2% of adverse cutaneous
reactions are severe and few are fatal
⦿ Antimicrobials and anti-epileptics account for
>75% of ADR
5. Risk factors for ADR
⦿ Genetic Susceptibility
⦿ Drug formulation (chemical properties and
molecular weight), dose and duration of its
use
⦿ Increased age (> 65 yrs)
⦿ Number of concomitant Drug use
⦿ Women
⦿ Inter-current illnesses (Auto-immune and
viral infections)
⦿ Immune compromised status
6. Approach to ADR patient
Evaluation should begin with:
1. Take detail drug history including h/o prior
allergies
2. Exclude other etiologies: (viral, bacterial,
nutritional or metabolic)
3. Evaluate temporal relationship between drug
intake and the onset of clinical symptoms
4. Drug interactions should also be noted because
these can sometimes precipitate a drug rash
7. Clinical Impression
Based on:
⦿ Morphology of the cutaneous eruption:
exanthematous, urticarial, blistering or pustular.
⦿ Extracutaneous (systemic) signs (e.g., malaise,
fever, hypotension, tachycardia,
lymphadenopathy, synovitis, dyspnoea, etc.)
Note: Presence of extracutaneous signs may aid in distinguishing benign
cutaneous drug eruptions from potentially severe systemic drug
eruptions
8. Laboratory/Diagnostic Tests
⦿ Complete blood count
⦿ Liver and renal function tests
⦿ Drug levels
⦿ Enzymes and metabolites
⦿ Skin biopsy
⦿ Prick or scratch test
⦿ Patch test
⦿ Culture (bacterial, viral, fungal)
Note: Eosinophil counts more than 1000 cells/mm 3 indicate a serious
drug-induced cutaneous eruption
9. Principle of Management of ADR
⦿ The ultimate goal is always to discontinue the
offending medication if possible
⦿ Non essential medications should best be
avoided
⦿ Ensure that any substituted drugs are not
pharmacologically and/or chemically related to
the suspect drug
10. Principle of Mgt…
Decision to continue the drug is influenced by
the following factors:
⦿Severity and probable course of the
reaction
⦿Disease for which the drug was prescribed
⦿Ease or difficulty with which the reaction
can be managed
⦿Availability of chemically unrelated drugs
with similar pharmacologic properties
⦿Risk/benefit ratio of such drug
11.
12. SIDE EFFECTS of Anti-TB drugs
COMMON DRUG ADVERSE EFFECTS RARE ADVERSE EFFECTS
Isoniazid Peripheral neuropathy, hepatitis Convulsions, pellagra, joint pains
agranulocytosis, lupoid
reactions, skin rash
Rifampicin GI Intolerance, Hepatitis ARF, Shock, TCP, Rash, Flu like
syndrome
Pyrazinamide Joint pain, Hepatitis GII, Rash, Sideroblastic anemia
Ethambutol Optic Neuritis Rash, Peripheral Neuropathy, Jt
pain
Streptomycin Aauditory and vestibular Skin Rash
nerve damage, renal damage
13. Incidence of serious side effects by type and drug. Shaded columns isoniazid; cross-
hatched columns, rifampin; open columns, pyrazinamide; dotted columns, ethambutol.
(Yee, Valiquette, Pelletier, et al.: Side Effects of TB Therapy)
14. Management of ADR to Anti-TB Drugs
Cutaneous Features:
A. Therapy for exanthematous eruption:
⦿ Antihistamines
⦿ Soothing agents
⦿ Mild topical steroids
⦿ Moisturizing lotions for desquamative phase.
B. Severe reactions (SJS,TEN & hypersensitivity
reactions)
⦿ Stop the drug. Needs Hospital admission
⦿ TEN best managed preferably in a burn unit with special
attention to fluid/electrolyte balance & secondary
infection
⦿ Systemic corticosteroids
⦿ IVIG has been proved to improve outcomes for TEN
patients
15. Management of Hepatitis
Most anti-TB drugs Isoniazide, Rifampicin
and pyrazinamide and rarely Ethambutol
can damage the liver.
Rule out other possible causes before
deciding that the hepatitis is drug-induced.
16. If anti-TB drug induced
hepatitis
⦿ Stop anti-TB drugs. Wait until the jaundice
resolves. Re-start the same anti-TB drugs.
⦿ If jaundice returns, and the patient had not
completed the intensive phase, give 2
months of streptomycin, isoniazide &
ethambutol followed by 10 months of
isoniazide & ethambutol.
⦿ If the patient has completed the intensive
phase, give isoniazide and ethambutol until
he/she receives a total of 8 month’s
treatment.
17. Management of…
ADVERSE EFFECTS DRUG PROBABLY
RESPONSIBLE MANAGEMENT
Minor All Continue anti-TB drugs
Skin Rash All Antihistamines,
Moisturizer topical steroid
Anorexia, nausea .......................rifampicin ................... give tablets as last
abdominal pain thing at night
joint pains .................................pyrazinamide .............. Aspirin/NSAID
burning sensation in feet ..........isoniazide ...................... pyridoxine 10
mg/day
orange/red urine .......................rifampicin ................... Reassurance
18. Major A/E
⦿ Gen. itching/ Skin rash thiacetazone stop anti-TB drugs
streptomycin
⦿ Deafness .............................streptomycin ................ stop streptomycin,
give ethambutol instead
⦿ Dizziness ............................streptomycin ................ stop streptomycin, use
(vertigo and nystagmus) ethambutol instead
⦿ Jaundice most anti-TB drugs stop all anti-TB drugs
until
other causes excluded, jaundice resolves
⦿ Nausea/Vomiting most anti-TB drugs .... stop anti-TB drugs, urgent
(suspect drug-induced liver function tests
pre-icteric hepatitis)
⦿ visual impairment .....................ethambutol .................. stop ethambutol
⦿ Generalised rash, including ......rifampicin ................... stop rifampicin
shock and purpura
19. When to stop AntiTB drugs?
⦿ For minor drug side-effects, explain the situation, offer symptomatic
treatment, and encourage him/her to continue treatment.
⦿ For a major reaction (severe cutaneous and or systemic reaction),
stop the suspected drug(s) responsible at once.
⦿ A patient who develops one of the following reactions must never
receive that drug again:
REACTION DRUG RESPONSIBLE
⦿ hearing loss or disturbed balance ................................. streptomycin
⦿ visual disturbance (poor vision and color perception)....ethambutol
⦿ renal failure, shock, or thrombocytopenia..................... rifampicin
20. Second line Anti-TB drugs
⦿ Para amino salicylic acid
⦿ Floroquinolones
⦿ Aminoglycosides
⦿ Prothionamide/Ethionamide
⦿ Cycloserine
21. AE of PAS
⦿ GI disturbance & general skin or other
hypersensitivity reaction including hepatic
dysfunction.
⦿ Hypokalamia may occur.
⦿ Prolonged administration in large doses may
produce hypothyroidism and goitre
Precautions
PAS is best avoided in renal failure as it may
make acidosis worse.
22. AE of Floroquinolones
GI disturbance or central nervous system effect
(dizziness, headache, mood changes)
Precautions:
Should not be used in pregnant women and
growing children.
Because of drug interaction, the following
drugs should be avoided: antacids, iron, zinc
and sucralfate.
23. AE of Aminoglycosides
Ototoxicity, deafness or vertigo may occur.
Reversible nephrotoxicity may occur.
Precautions:
In patients with impaired renal function.
This drug should not be used in
pregnant women except as a last resort.
24. Prothionamide/Ethionami
de
Epigastric discomfort: anorexia, nausea, metallic taste and
sulphurous belching
Psychotic reactions e.g; hallucinations and depression
Hepatitis may occur in about 10% of cases, but rarely
serious
Precautions:
This drug should not be administered in pregnancy as it
has been shown to be teratogenic in animals. It should be
carefully monitored if given to patients with diabetes, liver
disease, alcoholism or mental instability
25. AE of Cycloserine
⦿ Dizziness, slurred speech, convulsions, headache,
tremor, insomnia, confusion, depression and altered
behavior.
⦿ The most dangerous risk is that of suicide so mood
should be carefully watched.
⦿ Rarely there may be generalized hypersensitivity
reaction or hepatitis.
Precautions
⦿ Avoided in patients with a history of epilepsy,
mental illness or alcoholism.
⦿ Use very carefully in patients with renal failure.
26. Adverse effects of anti-TB drugs
in HIV positives
⦿ Adverse drug reactions are more common.
⦿ Risk of drug reaction increases with increased immune-compromise.
⦿ Most reactions occur in the first 2 months of treatment.
Skin rash
⦿ This is the commonest reaction. Fever often precedes and
accompanies the rash. Mucous membrane involvement is common.
The usual drug responsible is thiacetazone. Streptomycin and
rifampicin are sometimes to blame. Severe skin reactions, which may
be fatal, include exfoliative dermatitis, Stevens-Johnson syndrome
and toxic epidermal necrolysis.
Other reactions
The commonest reactions necessitating change in treatment include
gastrointestinal disturbance and hepatitis. There may be an increased
risk of rifampicin-associated anaphylactic shock and
thrombocytopenia.
27. Conclusion
⦿ ADR are distressing to patient and physician
⦿ It is inevitable in modern day practice to avoid
these reactions because more effective and
potent drugs are being developed
⦿ It is incumbent on us as physicians to weigh
the benefits and risks of each and every
therapeutic decision carefully
⦿ We must be alert to potential adverse events
and to recognize them early for better
management
28. Conclusion…..
⦿ ADR are common reason for litigation
⦿ Not warning a patient about potential
adverse effects, prescribing a medicine to a
previously sensitized patient or prescribing a
related medication with cross-reactivity are
the most common medico-legal pitfalls;
therefore should not be ignored or taken
lightly
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43. “ADR is the inevitable price that we pay for
the modern drug” Nolan L et al
Thank you
