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DTMH > TB Adverse Drug Reactions > Flashcards

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
Q

What is the mechanism of injury in INH DILI?

A

Accumulation of toxic metabolites
Immune mediated component (less common)

26
Q

What increases risk of INH DILI?

A

Increasing age

27
Q

What is the pattern of injury in rifampicin DILI?

A

Hepatocellular
Cholestatic
Mixed

28
Q

What is the mechanism of injury in rifampicin DILI?

A

Extensive metabolism by the liver
Direct toxic effect of metabolites
Immune mediated component

29
Q

What is the pattern of injury in moxifloxacin DILI?

A

Hepatocellular
Cholestatic
Mixed

30
Q

What is the mechanism of injury in moxifloxacin DILI?

A

Immune mediated component

31
Q

Which drugs may cause asymptomatic transient elevation in transaminases during hepatic adaptation?

A

RIP
Moxifloxacin

32
Q

What are the most important risk factors for hepatotoxicity in individuals on TB treatment?

A

Alcohol use
Chronic hepatitis infection
HIV coinfection
Extensive TB disease
Malnutrition
Age
? Female

33
Q

How is drug induced hepatitis defined?

A

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
Q

What is the management of TB DILI?

A
  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
Q

What is the differential diagnosis for TB DILI?

A

Alcohol
Pre-existing liver disease
Viral hepatitis
Other drugs
TB of the liver
IRIS
Bacterial sepsis

36
Q

How do we classify DILI?

A

Mild (no symptoms, INR<1.5)
Moderate (symptoms, INR<1.5)
Severe (INR>1.5)

37
Q

What is the management of mild/moderate DILI?

A
  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
Q

What is the ‘liver friendly’ TB regimen?

A

Levofloxacin
Ethambutol
Linezolid

39
Q

If Hb <8g/dL, what can you consider instead of linezolid for the ‘liver friendly’ TB regimen?

A

Clofazimine
Terizidone

40
Q

How do you reintroduced TB drugs in mild/moderate TB DILI?

A

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
Q

At what point can you rule out TB DILI?

A

If ALT does not improve after 10 days post treatment stopped

42
Q

Do we rechallenge with pyrazinamide?

A

No! Assoc with DILI recurrence
Only recommended for TBM or INH/RIF not tolerated

43
Q

What is the final regimen for patients who don’t tolerate pyrazinamide and developed DILI during intensive phase?

A

RIE (2 months)
RI (7 months)

44
Q

What is the final regimen for patients who don’t tolerate pyrazinamide and developed DILI during continuation phase?

A

RI for 4 months or remainder of continuation phase

45
Q

What is the final regimen for patients who don’t tolerate INH and developed DILI during intensive phase?

A

RPE + LFX (6 months)

46
Q

What is the final regimen for patients who don’t tolerate INH and developed DILI during continuation phase?

A

Rif + LFX for 4 months or remainder of continuation phase

47
Q

What is the final regimen for patients who don’t tolerate rifampicin and developed DILI during intensive phase?

A

BPaL (6 months)

48
Q

What is the final regimen for patients who don’t tolerate rifampicin and developed DILI during continuation phase?

A

BPaL for 4 months or remainder of continuation phase

49
Q

What is the final regimen for patients with TBM who did not tolerate pyrazinamide?

A

RIE + LFX for 12 months

50
Q

What is the final regimen for patients with TBM who did not tolerate INH?

A

RPE + LFX for 12 months

51
Q

Which drugs does rifampicin reduce the concentration of?

A
  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
Q

Why does rifampicin interact with many drugs?

A

Induces CYP450 -> increased metabolism -> less drug

53
Q

Why does INH interact with many drugs?

A

Inhibits CYP450 -> decreased metabolism -> more drug

54
Q

Which drugs does INH increase the concentration of?

A

Antiepileptics
Warfarin
Corticosteroids
Theophyllin
Disulfiram
EFV in some patients

DTMH (5 decks)

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