Tuberculosis: Anti-TB Regimens & Doses in Adults and Children, LTBI, Renal

The drugs of the CPG Management of Tuberculosis (Fourth Edition, 2021) in one place: the standard regimen, how many FDC tablets by weight, the dose of each first-line drug in adults and children, extrapulmonary TB, renal impairment and latent TB. Recommendations, tables and doses are copied word for word from the CPG (© MaHTAS, Ministry of Health Malaysia). The same doses are on Drugs.

Pulmonary TB in adults

Recommendation 3

• Standard anti-tuberculosis regimen of 2EHRZ/4HR* should be used in the treatment of pulmonary tuberculosis.
  • Pyridoxine 10 mg/day should be given to patients on isoniazid. Those with high risk of neuropathy** should be given pyridoxine 30 mg/day.

*Two months of ethambutol, isoniazid, rifampicin and pyrazinamide followed by four months of isoniazid and rifampicin. **Those at high risk of isoniazid induced neuropathy including pregnant women, PLHIV, elderly patients, patients with diabetes, alcoholism, malnutrition or chronic renal failure.

On pyridoxine the CPG says: "Pyridoxine 25 - 50 mg/day is recommended by ATS for individuals receiving INH who are at high risk of neuropathy. In Malaysia, pyridoxine has been given at 10 mg/day for all adult patients. The CPG DG now recommends a higher pyridoxine dose of 30 mg/day for individuals at high risk of neuropathy."

Recommendation 4

• Fixed-dose combination is preferred over separate drug formulation in the treatment of pulmonary tuberculosis.

Recommendation 5

• Only daily anti-tuberculosis regimen should be used throughout the treatment of pulmonary tuberculosis.

FDC tablets by body weight

Table 2 of the CPG:

*FDC refers to either 2-, 3- or 4-anti-TB drug combinations.

A 4-drug FDC tablet contains isoniazid 75 mg, rifampicin 150 mg, ethambutol 275 mg and pyrazinamide 400 mg.

A 3-drug FDC tablet contains isoniazid 75 mg, rifampicin 150 mg and pyrazinamide 400 mg.

A 2-drug FDC tablet contains isoniazid 75 mg and rifampicin 150 mg.

Separate first-line drugs

For patients who can't take FDC tablets, Table 3 of the CPG:

*High dose rifampicin for the treatment of TB is being evaluated.

**The maximum dose of anti-TB drugs may be adjusted according to the individual's pharmacokinetic/pharmacodynamic data.

Extrapulmonary TB

Recommendation 10

• The following regimens should be used for extrapulmonary tuberculosis (EPTB):
  • 2EHRZ/4-7HR* for tuberculosis of the bone or joint
  • 2EHRZ/10HR** for tuberculous meningitis
  • 2EHRZ/4HR*** for other forms of EPTB

*two months of ethambutol, isoniazid, rifampicin and pyrazinamide, followed by four to seven months of isoniazid and rifampicin **two months of ethambutol, isoniazid, rifampicin and pyrazinamide, followed by 10 months of isoniazid and rifampicin ***two months of ethambutol, isoniazid, rifampicin and pyrazinamide, followed by four months of isoniazid and rifampicin

Recommendation 11

• Corticosteroids should be used in tuberculous meningitis and pericarditis.
• Patients who develop complications of EPTB (e.g. hydrocephalus or constrictive pericarditis) need to be referred to specialists.

TB meningitis: dexamethasone

Table 6 of the CPG:

*According to the modified British Medical Research Council criteria for disease severity:

Stage 1: GCS of 15 without focal neurological deficits; alert and oriented

Stage 2: GCS of 14 - 11 or 15 with focal neurological deficits

Stage 3: GCS of 10 or less, with or without focal neurological deficits

Source: National Institute of Health and Care Excellence. Tuberculosis (NG 33). London: NICE; 2019.

Pregnancy and renal impairment

Recommendation 13

• Standard anti-tuberculosis (TB) regimens should be used in pregnant and breastfeeding women with TB.
  • Pyridoxine 30 mg/day should be given to those taking isoniazid.
• Women on rifampicin-based anti-TB treatment should use alternative contraception methods other than oral contraceptive pills.

Recommendation 14

• Standard anti-tuberculosis (TB) regimens should be used in patients with TB and renal failure.
  • Pyrazinamide and ethambutol should be given three times per week in patients with a creatinine clearance <30 ml/min or those receiving haemodialysis.

Renal dosing in adults and children

The renal columns of Appendix 6 (its dose ranges are the same as Tables 3 and 9):

CrCl=creatinine clearance, HD=haemodialysis, CAPD=continuous ambulatory peritoneal dialysis, HDF=haemodiafiltration, High Flux=high-flux haemodialysis, CAV/VVHD= CAVHD(continuous arteriovenous haemodialysis)/CVVHD(continuous veno-venous haemodialysis)

*For paediatric patients, anti-TB dose should be calculated based on measured body weight except in obese patients where ideal body weight should be used.

TB in children

The regimens are the same as in adults; the doses are per kg and higher. Table 9 of the CPG:

ᵃThe higher end of the range for INH dose applies to younger children. As the children grow older the lower end of the dosing range becomes more appropriate.

Source: World Health Organization. Guidance for National Tuberculosis Programmes on The Management of Tuberculosis in Children (2nd Edition). Geneva: WHO;2014

Pyridoxine 5 - 10 mg daily needs to be added if INH is prescribed.

Recommendation 19

• Child-friendly fixed-dose combinations* should be used to treat tuberculosis in children.

*The WHO recommended child-friendly FDC is not yet available in Malaysia.

Latent TB in adults

Recommendation 22

• In the treatment of all adults with latent tuberculosis infection (LTBI):
  • 3HR or 3HP* regimens should be the first-line regimen unless contraindicated
  • 4R may be used for patients who cannot tolerate or who are contraindicated for INH-based regimens
  • 6H or 9H may be used for patients who cannot tolerate or who are contraindicated for rifamycin-based regimens
  • 1HP* may be considered for HIV-positive adults
• The use of 3HR/3HP/4R:
  • is contraindicated in patients receiving protease inhibitor-based antiretroviral therapy
  • requires dose adjustment of dolutegravir and raltegravir

3HR=three months daily isoniazid and rifampicin, 3HP=three months weekly isoniazid and rifapentine, 4R=four months daily rifampicin, 6H=six months daily isoniazid, 9H=nine months daily isoniazid, 1HP=one month daily isoniazid and rifapentine *rifapentine is not yet available in Malaysia

Table 12 of the CPG:

Adapted: World Health Organization. WHO Consolidated Guidelines on Tuberculosis: Tuberculosis Preventive Treatment: Module 1: Prevention. Geneva: World Health Organization; 2020

Note: Pyridoxine 10 mg/day should be given for all adult patients on INH and a higher dose of 30 mg/day for individuals at high risk of neuropathy.

Latent TB in children

Recommendation 24

• In the treatment of children with latent tuberculosis infection (LTBI), the preferred regimens are:
  • 4R for all children >28 days of age or 3HP* for children aged >2 years.
  • 6H for all newborns aged 28 days and below.
• Alternative regimens of LTBI in children are 3HR, 6H or 9H.
• In HIV-infected children with LTBI, 6H is the preferred regimen for:
  • children <2 years of age.
  • children ≥2 years of age# on antiretroviral treatment with rifamycin drug interaction.

*Rifapentine is not yet available in Malaysia. #for HIV-infected children ≥2 years old on ART without rifamycin drug interaction, follow the recommendation for HIV-negative children ≥2 years old.

Table 14 of the CPG:

*Given in total of 12 doses

Pyridoxine 5 - 10 mg/day should be given to patients on Isoniazid.

Source: World Health Organization. WHO Consolidated Guidelines on Tuberculosis: Tuberculosis Preventive Treatment: Module 1: Prevention. Geneva: World Health Organization; 2020

*Rifapentine is not yet available in Malaysia.

Sources

• Malaysian Health Technology Assessment Section (MaHTAS), Ministry of Health Malaysia. Clinical Practice Guidelines: Management of Tuberculosis, Fourth Edition. 2021. Recommendations 3-5, 10, 11, 13, 14, 19, 22, 24; Tables 2, 3, 6, 9, 12, 14; Appendix 6. MaHTAS