management of adverse effects of antitubercular drugs

2. MANAGEMENT OF
ADVERSE EFFECTS OF
ATT & ATT IN SPECIAL
SITUATIONS
Dr G.VENKATA RAMANA
MBBS DNB FAMILY MEDICINE

3. FIRST LINE ANTI-TB DRUGS
Isoniazid H
Rifampicin R
Pyrazinamide Z
Ethambutol E

4. GROUPS OF SECOND LINE ANTI-TB DRUGS
GROUP NAME OF DRUG
GROUP A Levofloxacin or
Moxifloxacin
Bedaquiline
Linezolid
Lfx
Mfx
Bdq
Lzd
GROUP B Clofazimine
Cycloserine or
Terizidone
Cfz
Cs
Trd
GROUP C Ethambutol
Delamanid
Pyrazinamide
Imipenem-cilastatin or
Meropenem
Amikacin
(or) Streptomycin
Ethionamide or
Prothionamide
p-aminosalicylic acid
E
Dlm
Z
Ipm-Cln
Mpm
Am
S
Eto
Pto
PAS

5. Adverse drug effects of first-line anti-TB drugs
Drug Main Effects Rare Effects
Isoniazid Peripheral neuropathy
Skin rash
Hepatitis
Sleepiness and lethargy
Convulsion
Psychosis
Arthralgia
Anaemia
Rifampicin Gastro-intestinal: Abdominal pain
nausea, vomiting
Hepatitis
General cutaneous reactions
Thrombocytopenic purpura
Osteomalacia
Pseudomembranous colitis
Pseudo-duodenal crisis
Acute renal failure
Haemolytic anaemia
Pyrazinamide Arthralgia
Hepatitis
Gastrointestinal problems
Cutaneous reactions
Sideroblastic anaemia
Ethambutol Retrobulbar neuritis Generalized cutaneous
reactions
Arthralgia
Peripheral neuropathy
Hepatitis (very rare)

6. Name of drug Main side effect
Levofloxacin (Lfx) Seizures, headache
Moxifloxacin (Mfx) Q-Tc prolongation with moxifloxacin, especially high
dose
Bedaquiline (Bdq) Gastritis, hepatotoxicity, Q-Tc prolongation,
dyselectrolytemia, myopathy
Linezolid (Lzd) Peripheral neuropathy, optic neuritis, bone marrow
depression
Clofazimine (Cfz) Reddish discoloration of skin, Q-Tc prolongation,
phototoxicity
Cycloserine (Cs) Psychosis, depression, insomnia
Terizidone (Trz) Headache, tremors, insomnia, depression,
convulsions,
altered behaviour and suicidal tendencies

7. Name of drug Main side effect
Delamanid (Dlm) Q-Tc prolongation
Imipenem + Cilastatin
(Ipm-Cln)
Diarrhoea, nausea, vomiting
Meropenem (Mpm) Fever, chills, light-headedness,
dizziness, sweating,
rapid shallow breathing, skin rash
Amikacin (Am) Nephrotoxicity, ototoxicity
Streptomycin (S) Nephrotoxicity, ototoxicity
Ethionamide (Eto) Gastritis, hypothyroidism
Prothionamide (Pto) Gastritis, hypothyroidism
P-aminosalicylic Acid (PAS) Gastritis, hypothyroidism

8. CASE SCENARIO 1
• 40 year old female came with c/o fever,abominal
distension,abdominal pain and weight loss for 2 weeks.
• on evaluation USG showed ascites with omental
thickening.Diagnostic ascitic tap was suggestive of tubercular
etiology.
• Diagnosis:ABDOMINAL TUBERCULOSIS
• She was started on ATT after pretreatment evaluation
• After starting ATT patient developed vomiting,epigastric discomfort
• What is your diagnosis and how will u manage this patient?

9. • Do LFT,RFT
• If LFT normal,Probable diagnosis-ATT induced gastritis
• Reassure patient.
• Give drugs with less water and over a longer period of time(e.g. 20
minutes)
• Donot give drugs on an empty stomach
• Maintain hydration
• Consider treatment with anti-emetics (e.g.domperidone) and
proton pump inhibitors (e.g.Omeprazole)

10. CASE SCENARIO 2
• 25 year old female came with c/o fever,cough for 2 weeks,weight
loss,hemoptysis.chest xray suggestive of PTB.sputum positive for
AFB and there is no drug resistance.
• Diagnosis-pulmonary TB
• Patient was started on ATT (HRZE) after pretreatment evaluation.
• After few days patient developed jaundice,anorexia, vomiting.lab
investigations showed deranged LFT with elevated bilirubin (>2ULN)
and liver enzymes (AST/ALT>3ULN).
• What is your diagnosis? How will you manage this patient?

11. ATTASSOCAITED
HEPATOTOXICITY
• Stop all hepatotoxic drugs
• Need urgent ATT: Change to non-hepatotoxic drugs (Fluroquinolones,
ethambutol & aminoglycosides)
• No need for urgent ATT:
• Repeat LFT after a week & reintroduce only if ALT and AST < 2 ULN &
normal bilirubin
• Start one drug at time: helps identify the culprit
• Rifampicin may be introduced at 10 mg/kg dose
• After one week add Isoniazid 5 mg/kg if LFT normal
• After one week add pyrazinamide 25 mg/kg if LFT is normal
• Duration of ATT: count only when full ATT is started

12. ATTASSOCAITED HEPATOTOXICITY
• IF R and H tolerated
• Donot restart Z
• Prolong treatment with R,H and E for 9 months
• If R is implicated in hepatitis
• Give SHE for 2 months f/b HE for 10 months
• If H is implicated in hepatitis
• Give REZ for 9months

13. CASE SCENARIO 3
• 23 year old male came with c/o fever,cough, shortness of
breath.His Xray showed right sided pleural
effusion,diagnostic pleural tap was suggestive of tubercular
effusion
• started on ATT after pretreatment evaluation.
• A few days later patient came with c/o decreased vision and
not able to identify red,green colors.
• How will you evaluate and manage this patient?

14. • Probable diagnosis:Ethambutol induced optic neuritis
• Stop Ethambutol
• Refer to Opthalmologist to rule out other cause
• Impaired vision may, within a few weeks, or may not
return to normal after stopping Ethambutol.
• Don’t restart ethambutol.

15. CASE SCENARIO 4
• 40 year old female came with c/o fever,cough for 2 weeks
and weight loss.on evaluation CXR suggestive of
PTB.Sputum for microscopy AFB negative.CBNAAT-
negative.
• Diagnosed as Clinically diagnosed PTB
• Patient was started on ATT after pretreatment
evaluation.
• After few days patient came with complaints of joint
pains.
• How will u evaluate and manage this patient?

16. • Probable diagnosis-Arthralgia secondary to
pyrazinamide>>ethambutol>isoniazid
• Encourage patients to increase intake of liquids
• Give NSAIDs like paracetamol,Aspirin or ibuprofen and in
severe cases Indomethacin for a week to 10 days
• In severe cases estimate serum uric acid levels If uric acid
levels are significantly raised treat with NSAIDs and colchicine.
• Allopurinol is not effective
• In severe cases with normal or slightly elevated uric acid
consider reduction of the dose of Pyrazinamide

17. CASE SCENARIO 5
• 30 year old male with no comorbidities came with c/o
fever,swelling in the neck for 2 weeks,weight loss.
• FNAC was done suggestive of tubercular lymphadenitis.
• Patient was started on ATT after pretreatment evaluation.
• After few days patient developed Tingling in the hands and
feet.
• what is ur diagnosis and how will u manage this patient?

18. • Probable diagnosis:Isoniazid induced peripheral
neuropathy
• Give pyridoxine100-200mg/day until symptoms subside.
• Patients not responding to pyridoxine will require
treatment with amitryptiline

19. CASE SCENARIO 6
• 25 year old male came with c/o fever cough,shortness of
breath,chest pain.chest xray showed globular heart.2Decho
showed massive pericardial effusion.
• Diagnostic pericardiocentesis suggestive of tubercular
etiology.
• Diagnosis –TB pericarditis
• Patient was started on ATT after pretreatment evaluation
• After few days patient developed skin rashes,itching
• How will u manage this patient ?

20. • Itching without rash or a mild rash
• Continue treatment and give antihistamines
• Itching with moderate to severe rash Stop all drugs till symptoms subside
• Treat with antihistamines
• Patients with mucosal involvement, fever and hypotension will require treatment
with corticosteroids
• When the reaction subsides reintroduce drugs one by one in this order
INH,Rifampicin,Pyrazinamide and Ethambutol
• Re-introduce each drug in a small dose and gradually increase over 3 days before
introducing the next drug.

21. CASE SCENARIO 7
• 30 year old male diagnosed to have pulmonary TB with
chronic liver disease was sarted on no hepatotoxic drug
regimen SLE.
• After 1 month patient developed ringing in the ear, loss of
hearing,dizziness and loss of balance
• How will u evaluate this patient?

22. • STOP Streptomycin
• Refer to ENT specialist for opinion
• As hearing loss is usually not reversible do not restart
Streptomycin