What is the standard 6-month Tx regimen for TB?
- 2 month intensive phase of daily Rifampicin, Isoniazid, Pyrazinamide, Ethambutol (RIPE); followed by
- 4 month continuation phase of daily or 3x/ week Rifampicin, Isoniazid (RI) (if pt’s MTC isolate has no resistance to these drugs)
When do we give a 9-month regimen for TB?
For pts unlikely to tolerate Pyrazinamide (e.g. elderly, liver disease pts)
Close monitoring of drug-induced liver injury
What is the 9-month Tx regimen for special populations of TB?
- 2 month intensive phase of daily Rifampicin, Isoniazid, Ethambutol (RIE)
- 7 month continuation phase of daily or 3x/ week Rifampicin, Isoniazid (RI) (if pt’s MTC isolate has no resistance to these drugs)
What are the ADEs of all first-line anti-TB drugs? And management?
- Cutaneous: pruritus with/ without rash
- Mgmt: Self-limiting, give antihistamines & moisturisers, and continue anti-TB drugs
Be alert for rare occurrence of SJS, DRESS, TEN - GI [Rifampicin, Isoniazid, Pyrazinamide (RIP)]: anorexia, nausea, abdominal discomfort
- Mgmt: Take after light meals/ before bedtime
What to assess at the follow-up for each monthly clinical visit?
- SSx of hepatitis: unexplained fatigue, poor appetite, abdominal pain, jaundice, tea-coloured urine) → if have SSx, measure LFTs
- Weight
- If on ethambutol: visual acuity and colour vision
- Major rare ADEs like SCAR, respiratory distress, shock, haematological events
- Other minor SEs
What conditions/ LFT results warrant us to stop Tx?
Hepatitis SSx + ALT > 3x ULN, or ALT 5x ULN in the absence of SSx
Dosing of Rifampicin + available preparations?
10 mg/kg (max 600 mg daily or 3x/week)
Available preparations: 150 mg, 300 mg
ADEs of Rifampicin
- Cutaneous: flushing and/ or pruritus with/ without rash, red and watery eyes
- Flu-like SSx: fever, chills, malaise, headache, bone pains
- Respiratory: SOB, shock (rare)
- Hepatitis
- Orange discoloration of bodily fluids
- Rare: thrombocytopenic purpura, hemolytic anemia, acute renal failure
DDIs of rifampicin?
Induction of hepatic enzymes: ↓ serum conc. of oral contraceptives, warfarin, corticosteroids, methadone, protease inhibitors, cyclosporine
Dosing for Isoniazid + available preparations?
- 5 mg/kg (max 300 mg/day); or
- 15 mg/kg (max 900 mg 3x/week)
Available preparations: 100 mg, 300 mg
What is the supplement we need to give with Isoniazid and why?
Supplement Pyridoxine (B6) 10–25 mg OD or 3x/weekly to reduce risk of peripheral neuropathy
ADEs of Isoniazid?
- Peripheral neuropathy: paraesthesia, pricking pain, burning sensation in hands and feet
- Hepatitis: risk factors include age, alcohol, use of other hepatotoxic agents
- Rare: toxic psychosis, hematological reactions, convulsions, lupus-like syndrome, hypersensitivity reactions
DDIs of Isoniazid? Drug-food interactions?
- ↑ serum conc. of PHT, CBZ, oral anticoagulants
Drug-food interactions:
- Avoid with tyramine and histamine-rich foods (cheese, fish, red wine) → SEs of flushing, headache
- Space apart antacids by 2h
Which are the 2 drugs which do not need renal dose adjustments?
Rifampicin/ Isoniazid
Dosing of Pyrazinamide + available preparations?
25 mg/kg (max 2g/day)
Available preparation: 500 mg
ADEs of Pyrazinamide + management?
- Hepatitis: risk ↑ greatly when given tgt with Rifampicin and Isoniazid.
Should be withheld/ used cautiously in elderly, alcohol users, or liver disease pts - Arthralgia (joint stiffness); rare (gout)
- Mgmt: Analgesics and colchicine (for gout) - Hyperuricemia
- Mgmt: No need withdraw Tx if asymptomatic hyperuricemia - Hypersensitivity
Dose adjustment for Pyrazinamide when CrCl < 30ml/min?
25 mg/kg TIW
What must you check before initiating a patient on Ethambutol?
Check visual acuity and colour vision at baseline
Dosing for Ethambutol + available preparations?
15–20 mg/kg daily for first 2 months; then
15 mg/kg daily
Max 1600 mg/day
Available preparations: 100 mg, 400 mg
ADEs of Ethambutol?
- Optic neuritis: ↓ in visual acuity, red-green colour blindness, blurring, central scotoma
Mgmt: dose-dependent toxicity, can recover if withdraw drug early
DDI of Ethambutol
Space apart antacids by 2h
Dose adjustment for Ethambutol when CrCl ≤ 30ml/min?
15–25 mg/kg TIW
When is Streptomycin used?
In place of Ethambutol (if strain is resistant to ethambutol/ pt cannot tolerate ethambutol due to optic neuritis or other SEs)
Dosing of Streptomycin + available preparations?
- 15 mg/kg daily (max 1 g/day in persons ≤59 y/o); or
- 10 mg/kg daily (max 0.75 g/day in persons >59 y/o)
Available preparations: 1 g vial
