8.2 Anti-TB drug formulations

8.2.1 Fixed-dose combinations (FDCs)

FDC formulations incorporate several (2, 3 or 4) individual drugs in the same tablet. FDCs are recommended as they have many advantages in improving adherence, removing the risk of patients taking only part of the prescribed medications, reducing the risk of failure and development of resistance. Quality assured FDC formations only exist for Group 1 drugs, and their composition is provided in Table 8.2

Table 8.2 - Quality-assured FDC formulations

FDC tablets

Formulations available for daily treatment*

Treatment in adults:

4 drug FDC

E275 mg/H75 mg/Z400 mg/R150 mg

3 drug FDC

E275 mg/H75 mg/R150 mg

3 drug FDC

H75 mg/Z400 mg/R150 mg

2 drug FDC

H75 mg/R150 mg

Treatment in children:

3 drug FDC

H50 mg/Z150 mg/R75 mg

3 drug FDC*

H30 mg/Z150 mg/R60 mg

2 drug FDC

H50 mg/R75 mg

2 drug FDC*

H30 mg/R60 mg

2 drug FDC*

H60 mg/R60 mg

* These formulations must be phased out if new paediatric FDCs are available that correspond to the WHO recommended doses for children2.

8.2.2 Single drug formulations

Quality assured FDCs do not exist for drugs in Groups 2 to 5. Therefore, the treatment of MDR-TB is provided by using a combination of individual drugs.

8.2.3 Paediatric formulations

Paediatric formulations are not available for all medicines, and the dosing thereof can be problematic. For some drugs, the only option is to manipulate the commercial formulations available for adults by doing the following:
– Splitting of tablets: if available use tablets with a score line. However not all tablets are meant to be split, as this can affect the bioavailability and the efficacy of the drug (e.g. ingredients protected from stomach acidity by an enteric coating).
– Crushing of tablets and opening of capsules: a fraction of the powder is estimated to deliver the required dose. The remaining powder should be discarded right after the administration. These powders can be mixed with food or liquid vehicles like juice, etc. Such manipulations should be done immediately before administrating the medicine. There is little information on the impact of mixing drugs with food or liquids. In some cases, interactions might occur that may change the bioavailability.
– An alternative to the manipulation of adult dosages are extemporaneous formulations. However, this can only be considered when qualified staffs are available to ensure the preparation of these formulations following good compounding procedures.