What is the dosage for Fixed-Dose Combination (FDC) in tuberculosis (TB) treatment?

From the Guidelines

The standard dosage for Fixed-Dose Combination (FDC) tablets in tuberculosis treatment is based on patient weight, with adults weighing 30-39 kg receiving 2 tablets, 40-54 kg patients receiving 3 tablets, and those 55 kg or more taking 4 tablets, as per the guidelines outlined in the executive summary by the American Thoracic Society 1.

The treatment regimen for tuberculosis typically involves a two-phase approach, with an intensive phase lasting 2 months and a continuation phase of 4 months. The intensive phase includes a combination of isoniazid, rifampicin, pyrazinamide, and ethambutol, while the continuation phase uses just isoniazid and rifampicin.

• The FDC tablets should be taken once daily, preferably on an empty stomach to maximize absorption.
• Patients should be monitored for side effects including hepatotoxicity, peripheral neuropathy, and visual disturbances.
• FDCs are preferred over individual drugs because they improve adherence, prevent selective drug taking, simplify prescribing, and reduce medication errors while ensuring all necessary medications are taken together.
• Each FDC tablet generally contains isoniazid (75 mg), rifampicin (150 mg), pyrazinamide (400 mg), and ethambutol (275 mg), as outlined in the guidelines 1.

The use of FDCs in tuberculosis treatment has been shown to be effective in improving treatment outcomes, as noted in the study published in the Clinical Infectious Diseases journal 1.

• The study provides guidelines for the treatment of drug-susceptible tuberculosis, including the use of FDCs.
• The guidelines emphasize the importance of directly observed therapy (DOT) in ensuring that patients complete their treatment regimen.
• The study also notes that FDCs can be administered 5 days per week, with the necessary number of doses adjusted accordingly, when DOT is used 1.

From the FDA Drug Label

For Treatment of Tuberculosis Isoniazid is used in conjunction with other effective anti-tuberculosis agents. Usual Oral Dosage (depending on the regimen used): Adults: 5 mg/kg up to 300 mg daily in a single dose; or 15 mg/kg up to 900 mg/day, two or three times/week Children: 10 - 15 mg/kg up to 300 mg daily in a single dose; or 20-40 mg/kg up to 900 mg/day, two or three times/week There are 3 regimen options for the initial treatment of tuberculosis in children and adults: Option 1: Daily isoniazid, rifampin, and pyrazinamide for 8 weeks followed by 16 weeks of isoniazid and rifampin daily or 2 to 3 times weekly. The addition of a fourth drug is optional if the relative prevalence of isoniazid-resistant Mycobacteriumtuberculosis isolates in the community is less than or equal to four percent Tuberculosis Adults: 10 mg/kg, in a single daily administration, not to exceed 600 mg/day, oral or IV Pediatric Patients: 10-20 mg/kg, not to exceed 600 mg/day, oral or IV

The dosage for FDC (First-Line Drugs) in TB treatment is as follows:

• Isoniazid:
  • Adults: 5 mg/kg up to 300 mg daily in a single dose; or 15 mg/kg up to 900 mg/day, two or three times/week
  • Children: 10 - 15 mg/kg up to 300 mg daily in a single dose; or 20-40 mg/kg up to 900 mg/day, two or three times/week
• Rifampin:
  • Adults: 10 mg/kg, in a single daily administration, not to exceed 600 mg/day, oral or IV
  • Pediatric Patients: 10-20 mg/kg, not to exceed 600 mg/day, oral or IV The treatment regimens include:
• Daily isoniazid, rifampin, and pyrazinamide for 8 weeks followed by 16 weeks of isoniazid and rifampin daily or 2 to 3 times weekly 2
• Daily isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol for 2 weeks followed by twice weekly administration of the same drugs for 6 weeks, subsequently twice weekly isoniazid and rifampin for 16 weeks 2
• Three times weekly with isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin for 6 months 2
• A three-drug regimen consisting of rifampin, isoniazid, and pyrazinamide is recommended in the initial phase of short-course therapy which is usually continued for 2 months 3

From the Research

FDC Dosage in TB Treatment

The dosage for Fixed-Dose Combination (FDC) in TB treatment varies based on factors such as patient weight, age, and formulation.

• According to a study published in 2022 4, the World Health Organization (WHO) revised dosing guidelines for treatment of childhood tuberculosis, and the current dispersible FDC tablet of rifampicin/isoniazid/pyrazinamide is 75/50/150 mg.
• The study suggests that administering 1,2,3, or 4 optimized FDC tablets (rifampicin/isoniazid/pyrazinamide 120/35/130 mg) to children < 6-13-20, and 20-25 kg, and 0.5 tablet in < 3-month-olds with immature metabolism, improved exposures to all 3 drugs.
• Another study published in 2019 5 compared the effectiveness of FDC formulation with separate-drug formulation (ethambutol, isoniazid, rifampicin, and pyrazinamide) for pulmonary tuberculosis patients, but does not specify the exact dosage used.

Determinants of FDC Pharmacokinetics

Several factors can affect the pharmacokinetics of FDC drugs, including:

• Patient factors such as human immunodeficiency virus infection, gender, age, and weight 6
• Formulation factors such as bioavailability 6
• Treatment factors such as dose per kilogram of body weight 6

Efficacy and Safety of FDC

The efficacy and safety of FDC formulations have been evaluated in several studies, including a systematic review and meta-analysis published in 2013 7 and a real-world clinical practice study published in 2019 5.

• The systematic review found no differences in acquired drug resistance, bacterial conversion after 2 months of treatment, or adverse drug reactions with FDC or separate drug formulations.
• The real-world clinical practice study found that FDC formulation had a better sputum conversion rate at 2 months compared to conventional separate-drug formulation, and a slight protective effect against all-cause death among TB patients.