Pretomanid is an oral nitroimidazooxazine antimycobacterial agent. As part of a combination therapeutic regimen with bedaquiline and linezolid, it is specifically indicated for the treatment of specific types of drug-resistant pulmonary tuberculosis in adult patients. Its eligible population is strictly restricted, and close attention to safety and necessary monitoring are required during the course of administration.
What are the Precautions for Pretomanid Administration?
Strict Restrictions on Eligible Population
(1) Pretomanid shall only be used as part of a combination therapeutic regimen, administered concomitantly with bedaquiline and linezolid.
(2) It is indicated for pulmonary tuberculosis resistant to isoniazid, rifamycins, a fluoroquinolone agent, and a second-line injectable antibacterial agent.
(3) It is indicated for pulmonary tuberculosis resistant to isoniazid and rifampicin in patients who are intolerant to or have failed standard therapy.
(4) This medicinal product is not indicated for drug-susceptible pulmonary tuberculosis, latent tuberculosis infection, extrapulmonary tuberculosis infection, patients with drug-resistant tuberculosis who are susceptible to and tolerant of standard therapy, or patients with known resistance to any component of this combination regimen.
Combination Medication and Administration Method
(1) Mandatory combination use: Pretomanid must be administered only in combination with bedaquiline and linezolid, and shall not be used as monotherapy or in combination with other medicinal products.
(2) Directly Observed Therapy (DOT): Administration of this combination regimen is recommended to be conducted via DOT to ensure patient compliance.
(3) Administration with food: All three medicinal products should be taken with food to improve absorption efficiency.
(4) Management of dysphagia: For patients with dysphagia, pretomanid tablets may be crushed and suspended in room-temperature water for administration, or soaked prior to crushing. The prepared suspension shall be taken immediately and shall not be stored for later use.
Drug Interactions
(1) Strong or moderate CYP3A4 inducers (e.g., rifampicin, efavirenz): Concomitant use should be avoided, as such agents can significantly reduce the plasma concentration of pretomanid.
(2) OAT3 substrate drugs (e.g., methotrexate, indomethacin, ciprofloxacin): Close monitoring for relevant adverse reactions is required during concomitant use; dosage reduction of these medicinal products should be considered when necessary.
Monitoring Requirements for Pretomanid Administration
Hepatic Function Monitoring
(1) The combination regimen may cause hepatic injury.
(2) Clinical symptoms associated with hepatic dysfunction (e.g., fatigue, anorexia, nausea, jaundice, darkening of urine color, tenderness in the hepatic region) and laboratory parameters (ALT, AST, alkaline phosphatase, bilirubin) should be monitored prior to treatment, at Week 2 of treatment, and monthly thereafter.
(3) Temporary interruption of the entire therapeutic regimen should be considered in case of marked elevation of transaminases accompanied by hyperbilirubinemia, or persistent abnormal transaminase levels.
Hematological System Monitoring
(1) Linezolid is known to cause myelosuppression (e.g., anemia, leukopenia, thrombocytopenia).
(2) Complete blood count should be monitored prior to treatment, at Week 2 of treatment, and monthly thereafter.
(3) Dosage reduction or temporary interruption of linezolid should be considered in case of significant myelosuppression or progressive deterioration of hematological parameters.
Neurological System Monitoring
(1) Prolonged use of linezolid may result in peripheral neuropathy and optic neuropathy.
(2) Visual function should be monitored in all patients.
(3) If patients develop symptoms such as decreased visual acuity, numbness, tingling, or balance disturbances, immediate ophthalmologic evaluation should be performed, and dosage reduction or interruption of linezolid should be implemented as appropriate.
