Active Disease in Children - Standard TB Medications

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Regimens should include 4 different first-line anti-tuberculosis medications for the initial treatment of tuberculosis (TB) in children and adolescents. All patients should be started on INH, RIF, PZA, EMB unless there are contraindications, or if there is evidence of resistance to any of the drugs in the patient or source case.

Administration and Monitoring — Directly Observed Therapy (DOT) is the international standard of care for all patients with TB disease particularly with intermittent regimens. All anti-TB medications should be given concurrently, as a single dose, in order to prevent development of resistant organisms, enhance adherence, and achieve optimum serum blood levels. Adjust weightbased dosages as weight changes. Liver function tests are only recommended for children with severe TB disease or history of liver disease. Monthly medical examination is standard for all cases to assess disease process and medication toxicities. 

Drug

Isoniazid (INH) 

 

 

 

Dosage Forms
Scored tablets 100 mg, 300 mg
Syrup 10 mg/mL

Daily mg/kg [Max Dose]
10-15 [300 mg]

Twice Weekly mg/kg [Max Dose]
20-30 [900 mg]
All intermittent regimens must be directly observed

Adverse Reactions
Mild hepatic enzyme elevation, hepatitis, peripheral neuropathy, hypersensitivity; gastrointestinal disturbance with use of syrup

Comments
When treated with INH, breastfed infants, pregnant adolescents, and symptomatic HIV-infected or malnourished patients and patients on milk and/or meat-deficient diets, should receive pyridoxine (B6) supplementation.

Fixed-dose combinations of INH+RIF+PZA (Rifater) and INH+RIF (Rifamate) are preferred when DOT is not used. Dosing, however, needs to be weight based. 

Rifampin (RIF)

 

 

 

Dosage Forms
Capsules
150 mg, 300 mg
Syrup formulated capsules

Daily mg/kg [Max Dose]
10-20 [600 mg]

Twice Weekly mg/kg [Max Dose]
10-20 [600 mg]
All intermittent regimens must be directly observed

Adverse Reactions
Hepatitis, influenza-like symptoms, orange discoloration of bodily fluids

Comments
RIF decreases serum levels of many drugs. Significant interactions can occur when patients are treated with certain HIV medications. For adolescents,oral contraceptives may also be ineffective.c Rifabutin is an alternative for use with HIV medications; use in children, however, has been limited. Educate patients about normal discoloration of bodily fluids.
See MMWR 2003; 52(RR-11), p. 47.

Fixed-dose combinations of INH+RIF+PZA (Rifater) and INH+RIF (Rifamate) are preferred when DOT is not used. Dosing, however, needs to be weight based.  

Pyrazinamide (PZA) 

 

 

 

Dosage Forms
Scored tablets
500 mg

Daily mg/kg [Max Dose]
20-40 [2 g]

Twice Weekly mg/kg [Max Dose]
50 [2 g]
All intermittent regimens must be directly observed

Adverse Reactions
Hepatitis, hyperuricemia

Comments
Little known information about safety of PZA use during pregnancy. In pregnancy, use INH+RIF+EMB for 9 months.

Fixed-dose combinations of INH+RIF+PZA (Rifater) and INH+RIF (Rifamate) are preferred when DOT is not used. Dosing, however, needs to be weight based.  

Ethambutol (EMB)

 

 

 

Dosage Forms
Tablets
100 mg, 400 mg

Daily mg/kg [Max Dose]
15-25 [2.5 g]

Twice Weekly mg/kg [Max Dose]
50 [2.5 g]
All intermittent regimens must be directly observed

Adverse Reactions
Optic neuritis, decreased red-green color discrimination, gastrointestinal disturbance, hypersensitivity

Comments
If drug resistance is a concern, EMB may be added to the initial regimen. Conduct baseline and monthly monitoring for visual acuity and red-green color discrimination tests; however, in young children, monitoring for visual acuity may not be possible. In such cases, weigh risk vs. benefit.