Indications for Pretomanid:
As part of a combination regimen with bedaquiline and linezolid for the treatment of pulmonary extensively drug resistant (XDR), treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB).
Limitations of Use:
Not for treating drug-sensitive TB, latent infection, or extra-pulmonary infection due to Mycobacterium tuberculosis, or MDR-TB that is not treatment-intolerant or nonresponsive to standard therapy. The safety and efficacy for use in combination with drugs other than bedaquiline and linezolid have not been established.
See full labeling. Swallow whole with water. Take with food. Pretomanid 200mg once daily for 26wks (in combination with bedaquiline 400mg once daily for 2wks, then 200mg 3 times weekly [with ≥48hrs between doses] for 24wks; linezolid 1200mg once daily for 26wks [with adjustments to 600mg daily, and further reduction to 300mg daily or interrupt as necessary if linezolid adverse reactions develop]). Combination regimen can be extended beyond 26wks, if needed.
Monitor for hepatotoxicity; if new or worsening liver dysfunction occurs, test for viral hepatitides and discontinue other hepatotoxic medications. Interrupt if aminotransferase elevations are >8×ULN, or >5×ULN and persist over 2wks, or if accompanied by total bilirubin elevation >2×ULN. Myelosuppression. Monitor LFTs, CBCs at baseline, at 2wks, then monthly during treatment and as needed. Decrease or interrupt linezolid dosing if significant myelosuppression develops or worsens. History of Torsade de Pointes. Congenital long QT syndrome. Ongoing hypothyroidism or bradyarrhythmia. Uncompensated heart failure. Obtain ECG prior to initiation, and at least 2,12, and 24 weeks after starting treatment. Obtain serum potassium, calcium, and magnesium at baseline; correct if abnormal. Monitor electrolytes if QT prolongation is detected. Discontinue combination regimen if significant ventricular arrhythmia develops or a QTcF interval >500ms. Monitor visual function; if impairment occurs, interrupt linezolid dosing and perform ophthalmic evaluation. Pregnancy. Nursing mothers.
Avoid concomitant strong or moderate CYP3A4 inducers (eg, rifampin, efavirenz), alcohol, hepatotoxic agents (including herbal supplements). Concomitant organic anion transporter-3 substrates (eg, methotrexate); monitor and consider dose reduction of substrates.
Peripheral neuropathy, acne, anemia, nausea, vomiting, headache, increased transaminases, dyspepsia, decreased appetite, rash, pruritus, abdominal pain, pleuritic pain, increased gamma-glutamyltransferase, lower respiratory tract infection, hyperamylasemia, hemoptysis, back pain, cough, visual impairment, hypoglycemia, abnormal loss of weight, diarrhea; optic neuropathy, QT prolongation, lactic acidosis, male infertility and testicular atrophy.