Pulmonary tuberculosis due to Mycobacterium tuberculosis

Active Ingredient: Pretomanid

Indication for Pretomanid

Population group: only adults (18 years old or older)
Therapeutic intent: Curative procedure

Pretomanid is indicated in combination with bedaquiline, linezolid and moxifloxacin for the treatment of

  • adults with pulmonary tuberculosis (TB) due to Mycobacterium tuberculosis resistant to rifampicin, with or without resistance to isoniazid. Pretomanid is indicated in combination with bedaquiline and linezolid for the treatment of
  • adults with pulmonary TB due to M. tuberculosis resistant to rifampicin and a fluoroquinolone, with or without resistance to isoniazid.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

For this indication, competent medicine agencies globally authorize below treatments:

200 mg once daily for 26 weeks

For:

Dosage regimens

Oral, 200 milligrams pretomanid, once daily, over the duration of 26 weeks.

Detailed description

Treatment with pretomanid should be initiated and monitored by a physician experienced in the management of TB due to drug-resistant M. tuberculosis.

Pretomanid should be administered by directly observed therapy (DOT) or in accordance with local practice.

Posology

The recommended dosage is 200 mg pretomanid once daily, for 26 weeks.

Pretomanid should be administered only in combination with bedaquiline (400 mg once daily for 2 weeks followed by 200 mg 3 times per week [with at least 48 hours between doses] orally for a total of 26 weeks) and linezolid (600 mg daily orally for up to 26 weeks), with or without moxifloxacin (400 mg once daily for 26 weeks). See also below, on treatment duration.

In case of confirmed pulmonary TB resistant to rifampicin and a fluoroquinolone, with or without resistance to isoniazid, pretomanid should be combined with bedaquiline and linezolid, and moxifloxacin should be omitted.

The product information for bedaquiline, linezolid and moxifloxacin should be consulted for additional information on the use of these medicinal products.

Discontinuation of the pretomanid-bedaquiline-linezolid +/- moxifloxacin treatment regimen

  • If either bedaquiline or pretomanid is discontinued for any reason, the entire combination regimen should be discontinued.
  • If linezolid is permanently discontinued during the initial four consecutive weeks of treatment, the entire combination regimen should be discontinued.
  • If linezolid is discontinued after the initial four weeks of consecutive treatment, the regimen may be continued with only bedaquiline, pretomanid and with or without moxifloxacin.

Missed doses

Any missed doses of pretomanid, bedaquiline and moxifloxacin should be made up at the end of treatment. Doses of linezolid that are missed due to linezolid adverse reactions should not be made up at the end of treatment.

Refer to the product information of bedaquiline, linezolid and moxifloxacin for additional information on these medicinal products.

Treatment duration

The total duration of treatment with pretomanid in combination with bedaquiline, linezolid and with or without moxifloxacin is 26 weeks. Pretomanid in combination with bedaquiline and linezolid can be extended to a total of 39 weeks. This extension is justified in cases of failure to convert culture between months 4 and 6 while on treatment and it can be based on the clinical judgement of the treating physician.

Elderly population (≥65 years of age)

There is limited clinical data on the use of pretomanid in elderly patients. Hence, the safety and efficacy of pretomanid in elderly patients have not been established.

Dosage considerations

Pretomanid should be taken with food.

Active ingredient

Pretomanid

The mechanism of action of pretomanid is thought to involve inhibition of the synthesis of cell wall lipids under aerobic conditions and generation of reactive nitrogen species under anaerobic conditions. Reductive activation of pretomanid by a mycobacterial deazaflavin (F420)-dependent nitro-reductase is required for activity under both aerobic and anaerobic conditions.

Read more about Pretomanid

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