The drugs used in the treatment of pediatric TB, including their doses and side effects, are summarized in Table 4. Only isoniazid (INH) is available as a commercial suspension. However, all others may be compounded into suspensions using published procedures (Table 4). Given the difficulties with taste (ethambutol is particularly unpalatable) and ability to swallow pills, administration of these medications to very young children may require multiple tries of different formulations (eg, crushed pills in different foods, suspensions, etc). More research is needed in this area for children, including the pharmacokinetics of newer TB drugs, the impact of mixing them with food and the stability of suspensions.60
In children under the age of 10 years, or weighing less than 30 kg, the recommended dose of INH is 10-15 mg/kg/day (maximum 300 mg).23 Administration is affected by food and INH is better absorbed on an empty stomach. Fat and sugars reduce its absorption.61 A sorbitol-based suspension avoids this problem but may cause diarrhea, especially in children weighing more than 5 kg.62 Crushed pills are ideally mixed with water but few children will accept this and administration with small amounts of food/liquid is often suggested.63 Doses of INH above 10 mg/kg/day are sometimes associated with pyridoxine deficiency. Pyridoxine supplementation should be given to children on meat and milk-deficient diets, breastfed infants, those with nutritional deficiencies, children with symptomatic HIV infection and adolescents who are pregnant or breastfeeding.23 Breastfed infants of mothers who are taking INH with supplementary pyridoxine but who themselves are not receiving INH do not need supplementary pyridoxine.
Pyrazinamide (PZA) is an essential component of a 6-month regimen; without it, treatment should be at least 9 months. It is available as crushed tablets or compounded by some pharmacies. It frequently causes hyperuricemia, which occasionally manifests as joint pain. Of the first line TB drugs, it is the most frequently associated with drug-induced hepatotoxicity. In children, it can cause (though rarely does) intense itching, with or without a rash. Doses of 30-40mg/kg/day are recommended.64
Rifampin (RMP) capsules may be opened and sprinkled into food or compounded into suspension by pharmacists. The usual dose of RMP is 10-20 mg/kg/day. The suspensions may lose up to 10% of effective drug after 28 days. Higher RMP doses in children and adults is an area of active review. Doses of 30 mg/kg/day have been advised by some experts for treatment of TB meningitis.23
Ethambutol (EMB) is routinely used as part of initial empiric therapy of TB disease in infants and children unless otherwise contraindicated.23 It should be discontinued once the strain is known to be fully drug-susceptible. It can cause a dose-dependent retrobulbar neuritis, which is very rare in children at usual doses but more likely to occur in patients with renal impairment. When possible, baseline ophthalmological assessment should be obtained and repeated if prolonged therapy is planned (as in drug-resistant TB cases). In accordance with World Health Organization (WHO) and American Academy of Pediatrics (AAP) guidance, 20 mg/kg/day should be used.23 If higher doses are used, baseline vision and renal function should be tested and serially monitored.
Information on second-line drugs for MDR-TB used in pediatrics are available in Chapter 8: Drug-resistant tuberculosis and in various recent reviews.67–70
Table 4. Drugs used for treatment of TB in children.
|Daily dose (range)||Thrice-weekly dose a (range)|
|By weight (mg/kg)||Max (mg)||By weight (mg/kg)||Max (mg)||Available dosage forms||Principal side effects|
|Isoniazid||10 (10-15) b||300||20-30||900||10 mg/mL suspension c
100 mg tablet
300 mg tablet
|Rifampin||Pulmonary: 15 (10-20)
Meningitis/ Disseminated: 20-30
|600, however if >60kg 10 mg/kg can be used up to 900 mg with close monitoring||10-20||600, however if >60kg 10 mg/kg can be used up to 900 mg with close monitoring||150 mg capsule
300 mg capsule
Non-commercial suspension 25 mg/mL d
|Pyrazinamide||35 (30-40)||2000||70 (60-80)||see footnotes e||500 mg scored tablet
Non-commercial suspension 100 mg/mL
|Ethambutol||20 (15-25)||see foonotes f||40 (30-50)||see foonotes g||100 mg tablet
400 mg tablet
Non-commercial suspension 50 mg/mL
|Pyridoxine(Used to prevent isoniazid neuropathy: has no anti-TB activity)||1 mg/kg||25||25 mg. tablet
50 mg tablet
Table adapted from Red Book.
Abbreviations: TB, tuberculosis; INH, isoniazid; ATS, American Thoracic Society.
a Intermittent doses should be prescribed only when directly observed therapy is available. In general, daily therapy is definitely preferred over intermittent regimens.
b Hepatotoxicity is greater when INH doses are more than 10-15mg/kg daily.
c Only isoniazid is available as a commercial suspension in Canada.
d Rifampin, pyrazinamide (PZA) and ethambutol (EMB) may be compounded into suspensions using these published references (English) 65 and (French). 66
e For PZA: 3000 mg according to ATS, 2000 mg according to Red Book.
f EMB: 1600 mg according to ATS, 2500 mg according to Red Book.
g For EMB: 2400 mg according to ATS, 2500 mg according to Red Book.
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