Puruini Pretomanid Tablets

1. Indications and Usage
Pretomanid Linezolid Bedaquiline (BPaL) Regimen: Indicated in combination with bedaquiline and linezolid for the treatment of adult patients with pulmonary extensively drug-resistant tuberculosis (XDR-TB) or multidrug-resistant tuberculosis (MDR-TB) for whom an effective treatment regimen cannot be devised.
Use Limitations: Pretomanid must be used as part of the BPaL regimen. It is not indicated for use as a monotherapy or in combination with any other medication.
2. Dosage and Administration
Route of Administration: Oral administration.
Recommended Dosage: 200 mg once daily for 26 weeks.
Administration Details:
Tablets should be swallowed whole with water.
Must be taken with food to increase absorption and tolerability.
If tablets cannot be swallowed whole, they may be crushed and suspended in water immediately before administration.
3. Mechanism of Action
Cell Wall Synthesis Inhibition: Pretomanid is a prodrug that undergoes intracellular reduction by bacterial enzymes.
Target: The reduced active metabolites inhibit the synthesis of mycolic acids, which are essential components of the cell wall in mycobacteria, ultimately leading to bacterial death.
4. Safety and Warnings
Hepatotoxicity: Monitor liver function tests (LFTs) at baseline, at 2 weeks, and monthly thereafter. Interrupt treatment if ALT >8×ULN, or >5×ULN with elevated bilirubin.
QT Prolongation: The BPaL regimen is associated with QT prolongation. Obtain ECGs at baseline and weeks 2, 12, and 24. Avoid use in patients with a history of ventricular arrhythmias.
Bone Marrow Suppression: Monitor complete blood counts (CBC) regularly, as the regimen (particularly due to linezolid) can cause anemia, neutropenia, and thrombocytopenia.
Peripheral and Optic Neuropathy: Monitor for visual impairment and peripheral neuropathy; interrupt linezolid if severe symptoms occur.
Lactic Acidosis: Monitor for signs of lactic acidosis (e.g., persistent nausea and vomiting) and manage promptly.
5. Adverse Reactions
Most Common Adverse Reactions: Peripheral neuropathy, acne, anemia, nausea, vomiting, headache, elevated transaminases, dyspepsia, musculoskeletal pain, rash, pruritus, abdominal pain, pleuritic pain, and elevated gamma-glutamyltransferase.
Serious Adverse Reactions: Hepatotoxicity, bone marrow suppression, QT prolongation, lactic acidosis, and male testicular toxicity (based on animal studies).
6. Drug Interactions
CYP3A4 Inducers: Avoid concomitant use with strong or moderate CYP3A4 inducers (e.g., rifampin, efavirenz) as they may decrease pretomanid plasma concentrations.
Organic Anion Transporter-3 (OAT3) Substrates: Pretomanid may inhibit OAT3; caution is advised if co-administered with substrates such as methotrexate or ciprofloxacin.
Other Hepatotoxic Agents: Avoid concomitant use with other hepatotoxic drugs, including alcohol and herbal supplements, due to increased risk of liver injury.
7. Pharmaceutical Information
Chemical Composition: Active ingredient: Pretomanid.
Appearance: Film-coated tablets.
Packaging: Available in 200 mg strength.
Storage: Store at 20°C to 25°C (68°F to 77°F); protect from moisture.