PRETOMANID Tablet Ref.[10178] Active ingredients: Pretomanid

2.1 Important Administration Instructions

• Pretomanid Tablets must be used only in combination with bedaquiline and linezolid as part of the recommended dosing regimen [see Dosage and Administration (2.2)].
• Emphasize the need for compliance with the full course of therapy to patients [see Patient Counseling Information (17)].
• Administer the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid by directly observed therapy (DOT).

2.2 Recommended Dosage

Pretomanid Tablets must be administered in combination with bedaquiline and linezolid. The recommended dosage and duration for bedaquiline and linezolid when used in the combination regimen with Pretomanid Tablet are as follows:

• Pretomanid Tablet 200 mg orally (1 tablet of 200 mg), once daily, for 26 weeks. Swallow Pretomanid Tablets whole with water.
• Bedaquiline 400 mg orally once daily for 2 weeks followed by 200 mg 3 times per week, with at least 48 hours between doses, for 24 weeks for a total of 26 weeks
• Linezolid starting at 1,200 mg orally per day for 26 weeks, with dose adjustments to 600 mg daily and further reduction to 300 mg daily or interruption of dosing as necessary for known linezolid adverse reactions of myelosuppression, peripheral neuropathy, and optic neuropathy [see Dosage and Administration (2.4) and Warnings and Precautions (5.3, 5.4)].
• Take the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid with food [see Clinical Pharmacology (12.3)].
• If the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid is interrupted by a healthcare provider for safety reasons, missed doses can be made up at the end of the treatment; doses of linezolid alone missed due to linezolid adverse reactions should not be made up.
• Dosing of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid can be extended beyond 26 weeks, if necessary [see Clinical Studies (14)].

2.3 Assessments Prior to Initiating the Combination Regimen of Pretomanid Tablets, Bedaquiline, and Linezolid

• Assess for symptoms and signs of liver disease (such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, and hepatomegaly). Obtain laboratory tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, and bilirubin) [see Warnings and Precautions (5.2)].
• Obtain complete blood count [see Warnings and Precautions (5.3)]. Obtain serum potassium, calcium, and magnesium and correct if abnormal [see Warnings and Precautions (5.5)]. Obtain an ECG before initiation of treatment [see Warnings and Precautions (5.5)].

2.4 Discontinuation of Dosing

If either bedaquiline or Pretomanid Tablets are discontinued, the entire combination regimen should also be discontinued.

If linezolid is permanently discontinued during the initial four consecutive weeks of treatment, bedaquiline and Pretomanid Tablets should also be discontinued. If linezolid is discontinued after the initial four weeks of consecutive treatment, continue administering bedaquiline and Pretomanid Tablets [see Dosage and Administration (2.2)].

There is no experience with the treatment of acute overdose with pretomanid. Take general measures to support basic vital functions including monitoring of vital signs and ECG (QT interval) in case of deliberate or accidental overdose.

Store below 30°C (86°F).

Dispense only in original container and keep container tightly closed.