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TB Adverse Drug Reactions Flashcards

1
Q

Name common side effects of TB drugs

A

Anorexia, nausea, abdominal pain
Joint pain
Orange urine
Pruritis/rash
Peripheral neuropathy

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2
Q

Which TB drugs are responsible for anorexia, nausea and abdominal pain side effects?

A

All TB drugs

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3
Q

How do you manage anorexia, nausea and abdominal pain side effects secondary to TB drugs?

A
  1. Continue TB drugs
  2. Give TB drugs at night
  3. Give anti-emetics
  4. Exclude liver toxicity
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4
Q

Which TB drug is responsible for joint paint side effects?

A

Pyrazinamide

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5
Q

How do you manage joint point secondary to pyrazinamide?

A

Continue TB drugs
NSAIDs if normal eGFR

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6
Q

Which TB drug is responsible for peripheral neuropathy?

A

INH

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7
Q

How do you manage peripheral neuropathy secondary to INH?

A
  1. Continue TB drugs
  2. Increase pyridoxine to 100mg daily
  3. Give amitryptiline 25mg note OR gabapentin 300mg tds
  4. Exclude other causes (DM, renal, B12 deficiency)
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8
Q

Which TB drug is responsible for orange urine?

A

Rifampicin

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9
Q

How do you manage orange urine secondary to rifampicin?

A

Reassurance

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10
Q

Which TB drug is responsible for pruritis/rash

A

All TB drugs
Most common E->P->R->I
Consider ART
Cotrimoxazole

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11
Q

How do you manage pruritis/rash secondary to TB drugs?

A

Mild - continue therapy, symptomatic treatment
Moderate - rechallenge 1 drug at a time I->R->P->E every 3-5 days
Severe - stop all drugs

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12
Q

What are severe side effects of TB drugs?

A

Hepatotoxicity
Visual impairment
Thrombocytopenia
Haemolytic anemia
Psychiatric
Seizures

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13
Q

Which TB drugs are responsible for hepatotoxicity?

A

RIP

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14
Q

What is the management of hepatotoxicity secondary to TB drugs?

A
  1. Stop treatment
  2. LFTs
  3. Refer
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15
Q

Which TB drugs are responsible for visual impairment?

A

Ethambutol
Rifabutin

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16
Q

What is the management of visual impairment secondary to TB drugs?

A

Stop ethambutol
Refer to ophthalmologist
Consider differential (CMV, CCM, toxoplasmosis)

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17
Q

Which TB drugs are responsible for thrombocytopenia or haemolytic anaemia?

A

Rifampicin

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18
Q

What is the management of thrombocytopenia/hemolytic anaemia secondary to TB drugs?

A
  1. Consider differential
  2. Start rifampicin-sparing regimen
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19
Q

Which TB drugs cause psychiatric side effects?

A

INH
Terizidone
Ethionamide

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20
Q

Which TB drugs cause seizures?

A

INH

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21
Q

What is the management of seizures secondary to TB drugs?

A

Diagnosis of exclusion -> differential diagnosis
Exclude CNS lesion

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22
Q

What is the pattern of injury in pyrazinamide DILI?

A

Hepatocellular

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23
Q

What is the mechanism of injury in pyrazinamide DILI?

A

Extensive metabolism by the liver
Dose-related injury suggesting direct toxic effect of drugs/metabolites

24
Q

What is the pattern of injury in INH DILI?

A

Hepatocellular

25
What is the mechanism of injury in INH DILI?
Accumulation of toxic metabolites Immune mediated component (less common)
26
What increases risk of INH DILI?
Increasing age
27
What is the pattern of injury in rifampicin DILI?
Hepatocellular Cholestatic Mixed
28
What is the mechanism of injury in rifampicin DILI?
Extensive metabolism by the liver Direct toxic effect of metabolites Immune mediated component
29
What is the pattern of injury in moxifloxacin DILI?
Hepatocellular Cholestatic Mixed
30
What is the mechanism of injury in moxifloxacin DILI?
Immune mediated component
31
Which drugs may cause asymptomatic transient elevation in transaminases during hepatic adaptation?
RIP Moxifloxacin
32
What are the most important risk factors for hepatotoxicity in individuals on TB treatment?
Alcohol use Chronic hepatitis infection HIV coinfection Extensive TB disease Malnutrition Age ? Female
33
How is drug induced hepatitis defined?
ALT > 120 and symptomatic OR ALT > 200 regardless of symptoms Total serum bilirubin >40 ALT 2x baseline if pre-existing liver disease/ALT>120 pretreatment
34
What is the management of TB DILI?
1. Confirm TB diagnosis 2. Check phase of treatment 3. Stop all drugs immediately 4. Conduct LFTs, hepatitis serology and INR 5. Admit to hospital
35
What is the differential diagnosis for TB DILI?
Alcohol Pre-existing liver disease Viral hepatitis Other drugs TB of the liver IRIS Bacterial sepsis
36
How do we classify DILI?
Mild (no symptoms, INR<1.5) Moderate (symptoms, INR<1.5) Severe (INR>1.5)
37
What is the management of mild/moderate DILI?
1. Hospitalize 2. Differential diagnosis 3. Pregnancy test 4. Abdominal U/S if cholestatic pattern 5. ART If ART<6 months, stop If ART > 6 months, switch to dolutegravir 6. Discontinue other hepatotoxic drugs 7. Treatment phase If in intensive phase of treatment, switch to 'liver friendly' regimen If in continuation phase, stop anti-TB treatment until LFTs recover
38
What is the 'liver friendly' TB regimen?
Levofloxacin Ethambutol Linezolid
39
If Hb <8g/dL, what can you consider instead of linezolid for the 'liver friendly' TB regimen?
Clofazimine Terizidone
40
How do you reintroduced TB drugs in mild/moderate TB DILI?
Monitor ALT and bilirubin 2-3 times weekly Once ALT <100 with bilirubin on downward trend, reintroduce TB drugs Day 1. Start INH 300mg daily and stop linezolid Day 3. Check ALT/bilirubin Day 4. Add rifampicin 600mg daily Day 7. Check ALT/bilirubin Day 8. Stop LFX and ethambutol Check ALY weekly for 4 weeks and closely monitor for symptoms
41
At what point can you rule out TB DILI?
If ALT does not improve after 10 days post treatment stopped
42
Do we rechallenge with pyrazinamide?
No! Assoc with DILI recurrence Only recommended for TBM or INH/RIF not tolerated
43
What is the final regimen for patients who don't tolerate pyrazinamide and developed DILI during intensive phase?
RIE (2 months) RI (7 months)
44
What is the final regimen for patients who don't tolerate pyrazinamide and developed DILI during continuation phase?
RI for 4 months or remainder of continuation phase
45
What is the final regimen for patients who don't tolerate INH and developed DILI during intensive phase?
RPE + LFX (6 months)
46
What is the final regimen for patients who don't tolerate INH and developed DILI during continuation phase?
Rif + LFX for 4 months or remainder of continuation phase
47
What is the final regimen for patients who don't tolerate rifampicin and developed DILI during intensive phase?
BPaL (6 months)
48
What is the final regimen for patients who don't tolerate rifampicin and developed DILI during continuation phase?
BPaL for 4 months or remainder of continuation phase
49
What is the final regimen for patients with TBM who did not tolerate pyrazinamide?
RIE + LFX for 12 months
50
What is the final regimen for patients with TBM who did not tolerate INH?
RPE + LFX for 12 months
51
Which drugs does rifampicin reduce the concentration of?
1. ART (lopinavir/ritonavir/DTG) 2. Azoles 3. Corticosteroids 4. OCPs 5. Warfarin 6. Anticonvulsants 7. Cyclosporin 8. Cardiovascular 9. Theophylline 10. Sulfonylurea 11. Methadone
52
Why does rifampicin interact with many drugs?
Induces CYP450 -> increased metabolism -> less drug
53
Why does INH interact with many drugs?
Inhibits CYP450 -> decreased metabolism -> more drug
54
Which drugs does INH increase the concentration of?
Antiepileptics Warfarin Corticosteroids Theophyllin Disulfiram EFV in some patients
55

DTMH (5 decks)

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