Puruini Putomamitini Tablets

1. Indications and Usage
Treatment-Resistant Tuberculosis:
Pretomanid is indicated as part of a three-drug regimen (BPaL: Bedaquiline, Pretomanid, and Linezolid) for the treatment of adult patients with extensively drug-resistant (XDR-TB), treatment-intolerant, or nonresponsive multidrug-resistant (MDR-TB) pulmonary tuberculosis.
Note: It is not indicated as a single agent or for latent tuberculosis infection.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage:
Dose: 200 mg once daily.
Duration: The recommended treatment duration is 6 months (26 weeks).
Administration: Administer with food to enhance absorption.
Monitoring:
Baseline and periodic monitoring of liver function, complete blood count (due to Linezolid), and ECG (due to Bedaquiline) is required during the combination regimen.
3. Mechanism of Action
Nitroimidazole Antibiotic:
Pretomanid is a first-in-class nitroimidazole antimicrobial.
Bacterial Cell Death:
Upon entering the mycobacterial cell, it is reduced by the dehydrogenase enzyme (F420) to toxic metabolites. These metabolites inhibit the synthesis of mycolic acids (essential components of the bacterial cell wall) and generate reactive oxygen species, leading to bacterial death.
4. Safety and Warnings
Hepatotoxicity:
Pretomanid can cause severe liver injury (hepatitis). Baseline and monthly monitoring of liver enzymes (ALT, AST) and bilirubin is mandatory.
Serotonin Syndrome:
There is a risk of serotonin syndrome when Pretomanid is used in combination with Linezolid (which has monoamine oxidase inhibitory activity). Patients should be monitored for symptoms like agitation, hallucinations, or rapid heart rate.
Pregnancy:
Pretomanid can cause fetal harm. It is contraindicated in pregnant women.
5. Adverse Reactions
Most Common:
Hepatic: Hepatitis, elevated liver enzymes.
Gastrointestinal: Nausea, vomiting, diarrhea.
Hematologic: Anemia (often due to Linezolid in the regimen).
Neurologic: Peripheral neuropathy, headache, insomnia.
6. Drug Interactions
Metabolic Pathway:
Pretomanid is metabolized primarily by the liver (CYP450 enzymes).
Strong CYP Inducers/Inhibitors:
Co-administration with strong inducers (e.g., Rifampin, Carbamazepine) may decrease Pretomanid exposure. Strong inhibitors (e.g., Ketoconazole) may increase exposure.
Serotonergic Drugs:
Caution is advised when combining with other serotonergic agents due to Linezolid in the BPaL regimen.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Pretomanid.
Appearance: White to off-white, film-coated tablets.
Storage: Store at controlled room temperature (15°C–30°C).