The Invitation to Manufacturers of Antituberculosis Medicines to submit an Expression of Interest for Product Evaluation to the WHO Prequalification Unit was recently updated following a request by the WHO Global Tuberculosis Programme.
In particular, two fixed-dose combinations (FDCs) of isoniazid, rifapentine, moxifloxacin, with and without pyrazinamide were added that can be used in the WHO-recommended 4-month regimen for drug-susceptible TB for people aged 12 years and above (2HPMZ/2HPM). The development of these FDCs will tackle one of the barriers reported for uptake of this regimen:
- Isoniazid 75 mg / Rifapentine 300 mg/ Moxifloxacin 100 mg / Pyrazinamide 375 mg tablet
- Isoniazid 75 mg / Rifapentine 300 mg / Moxifloxacin 100 mg tablet
A child-friendly formulation of delamanid (25 mg dispersible tablet), was also added to the EOI. This will improve treatment options for children with multidrug-/rifampicin-resistant TB (MDR/RR-TB). Since 2022, delamanid is recommended by WHO for people with MDR/RR-TB of all ages.
- Delamanid 25 mg dispersible tablet
Following on from the second Paediatric Drug Optimization meeting for TB (PADO-TB) convened by WHO in October 2023, a co-pack of rifapentine 150 mg dispersible tablets (scored) and isoniazid 100 mg dispersible tablets (scored) has also been included in the EOI. This co-packaging consists of separate blisters of the two medicines included in the same box. PADO-TB – clinicians, researchers, technical partners (including funders), and other stakeholders – discussed the importance of making isoniazid 100 mg dispersible tablets available alongside the child-friendly formulation of rifapentine, to deliver both components of the 3-month regimen of weekly isoniazid and rifapentine (3HP) as TB preventive treatment to children. A co-packaging option was proposed to facilitate supply and logistics at the country level, as well as dispensing at the point of care.
- Co-pack of Rifapentine dispersible tablets 150 mg (scored) + Isoniazid dispersible tablets 100 mg (scored) (Separate blisters in the same box)
Full alignment between the PQ EOIs for TB and for HIV products is promoted, and thus, a new formulation was added to the TB EOI:
- Sulfamethoxazole/Trimethoprim/Isoniazid/Pyridoxine (400 mg / 80 mg / 150 mg / 12.5 mg scored tablet).
A new formulation of pyridoxine (vitamin B6), used to prevent or treat adverse drug reactions to isoniazid, was added as it can reduce the pill burden in most adults and older children:
- Pyridoxine 100 mg scored tablet
Several medicines and formulations were removed from the EOI, including some that are no longer recommended by WHO (gatifloxacin) or are only used for salvage therapy (amikacin, imipenem/cilastatin, meropenem, streptomycin) and for which the current availability is deemed sufficient to cover country demand. Linezolid oral powder for suspension was removed to promote the development of an age-appropriate formulation of this medicine for use in children with TB, ie 150 mg dispersible tablets. Terizidone tablet/capsules 500 mg were removed considering limited use given that 250 mg tablet/capsules allow for a higher dose flexibility across weight bands. Further, “Para-aminosalicylic Acid (PAS), 4 g, granules, sachet” was replaced with its sodium salt “Para-aminosalicylate sodium: 5.52 g in sachet (equivalent to 4 g p-aminosalicylic acid)”.