Pretomanid is an oral nitroimidazooxazine antimycobacterial agent indicated for the treatment of pulmonary tuberculosis (TB) in adults with extensively drug-resistant (XDR) or multidrug-resistant (MDR) tuberculosis who are intolerant to or have failed standard therapy. This medicinal product must be administered in combination with bedaquiline and linezolid as a three-drug regimen.

Adverse Reactions of Pretomanid

Common Adverse Reactions

(1) Peripheral neuropathy: Manifested as numbness, tingling, burning sensation or paresthesia in the hands and feet.

(2) Anemia: Symptoms including fatigue, asthenia and pallor may occur.

(3) Nausea and vomiting: Gastrointestinal reactions are relatively common.

(4) Acne: Papules or acneiform rash may appear on the skin.(5) Hepatic dysfunction: Elevated transaminases, which may be accompanied by fatigue and anorexia.

Serious Adverse Reactions of Pretomanid

Hepatotoxicity

(1) Manifestations: Fatigue, anorexia, nausea, jaundice, darkening of urine color and tenderness in the hepatic region.

(2) Monitoring and management: Liver function should be monitored prior to treatment, at Week 2 of treatment and monthly thereafter. Treatment should be immediately interrupted in case of markedly elevated transaminases (>8 times the upper limit of normal) or elevated transaminases accompanied by hyperbilirubinemia.

Myelosuppression

(1) Manifestations: Anemia, leukopenia and thrombocytopenia, which may be life-threatening in severe cases.

(2) Monitoring and management: Routine blood tests should be performed regularly. In case of significant myelosuppression, the dosage of linezolid should be reduced or the medication should be temporarily discontinued.

Peripheral Neuropathy and Optic Neuropathy

(1) Manifestations: Numbness and tingling of extremities, blurred vision and impaired visual acuity.

(2) Monitoring and management: Neurological function and visual acuity should be regularly assessed during treatment. Upon the onset of symptoms, the dosage of linezolid should be immediately adjusted or treatment should be interrupted, and an ophthalmologic examination should be performed promptly.

QT Prolongation

(1) Manifestations: Prolonged QTc interval detected on electrocardiogram (ECG), which may induce cardiac arrhythmia.

(2) Monitoring and management: ECG monitoring should be conducted prior to treatment and at Week 2, Week 12 and Week 24 of treatment. Treatment should be discontinued if the QTc interval is greater than 500 ms or ventricular arrhythmia occurs.

Precautions for Pretomanid

Restrictions on Medication Use

(1) It is indicated only for adult patients with pulmonary XDR-TB or MDR-TB who are intolerant to or have failed standard anti-tuberculosis therapy.

(2) It is not indicated for drug-susceptible tuberculosis, latent tuberculosis infection, extrapulmonary tuberculosis, or patients with known resistance to any of the components in the regimen.

Requirements for Combination Therapy

(1) Pretomanid must be used in combination with bedaquiline and linezolid, and shall not be administered as a monotherapy.

(2) Directly Observed Therapy (DOT) is recommended to ensure treatment adherence.

Drug Interactions

(1) Concomitant use with strong or moderate CYP3A4 inducers (e.g., rifampicin, efavirenz) should be avoided.

(2) Close monitoring for adverse reactions is required when co-administered with OAT3 substrate drugs (e.g., methotrexate, indomethacin).