retomanid Tablet 200 mg is packaged in either white, round, high-density polyethylene bottles with polypropylene child-resistant closure or child-resistant blister packages comprised of a polyvinylchloride film with foil and paper backing. These highlights do not include all the information needed to use PRETOMANID TABLETS safely and effectively. See full prescribing information for PRETOMANID TABLETS.
PRETOMANID tablets, for oral use
Initial U.S. Approval: 2019
LIMITED POPULATION
INDICATIONS AND USAGE
Limited Population: Pretomanid Tablet is an antimycobacterial indicated, as part of a combination regimen with bedaquiline and linezolid for the treatment of adults with pulmonary extensively drug resistant (XDR), treatment-intolerant or nonresponsive multidrug?resistant (MDR) tuberculosis (TB). Approval of this indication is based on limited clinical safety and efficacy data. This drug is indicated for use in a limited and specific population of patients. (1)
Limitations of Use (1):
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Pretomanid Tablets are not indicated for patients with:
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Drug-sensitive (DS) tuberculosis
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Latent infection due to Mycobacterium tuberculosis
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Extra-pulmonary infection due to Mycobacterium tuberculosis
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MDR-TB that is not treatment-intolerant or nonresponsive to standard therapy
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Safety and effectiveness of Pretomanid Tablets have not been established for its use in combination with drugs other than bedaquiline and linezolid as part of the recommended dosing regimen.
DOSAGE AND ADMINISTRATION
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Pretomanid Tablets must be administered only as part of a regimen in combination with bedaquiline and linezolid.
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Administer Pretomanid Tablets in combination with bedaquiline and linezolid as follows: (2.2)
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Pretomanid Tablet 200 mg orally once daily for 26 weeks. Swallow Pretomanid Tablets whole with water.
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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
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Linezolid (1,200 mg daily orally for up to 26 weeks, with dose adjustments for known linezolid toxicities).
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Take the combination regimen with food.
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Doses of the regimen missed for safety reasons can be made up at
the end of treatment; doses of linezolid alone missed due to
linezolid adverse reactions should not be made up. (2.2)
DOSAGE FORMS AND STRENGTHS
Tablets: 200 mg (3)
CONTRAINDICATIONS
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Pretomanid Tablets used in combination with bedaquiline and linezolid are contraindicated in patients for whom bedaquiline and/or linezolid is contraindicated. (4)
WARNINGS AND PRECAUTIONS
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Hepatic adverse reactions were reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Monitor symptoms and signs and liver?related laboratory tests. Interrupt treatment with the entire regimen if evidence of liver injury occurs. (5.2)
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Myelosuppression was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Monitor complete blood counts. Decrease or interrupt linezolid dosing if significant myelosuppression develops or worsens. (5.3)
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Peripheral and optic neuropathy were reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Monitor visual function. Obtain an ophthalmologic evaluation if there are symptoms of visual impairment. Decrease or interrupt linezolid dosing if neuropathy develops or worsens. (5.4)
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QT prolongation was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Use with drugs that prolong the QT interval may cause additive QT prolongation. Monitor ECGs. Discontinue the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid if significant ventricular arrhythmia or if QTcF interval prolongation of greater than 500 ms develops. (5.5)
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Reproductive effects: Pretomanid caused testicular atrophy and impaired fertility in male rats. Advise patients of reproductive toxicities seen in animal studies and that the potential effects on human male fertility have not been adequately evaluated. (5.7, 13.1)
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Lactic acidosis was reported with the use of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. Consider interrupting linezolid or the entire combination regimen of Pretomanid Tablets, bedaquiline, and linezolid dosing if significant lactic acidosis develops. (5.8)
ADVERSE REACTIONS
Most common adverse reactions (?10%) are 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, and diarrhea. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
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Strong or moderate CYP3A4 inducers such as rifampin or efavirenz: Avoid co-administration. (5.6, 7.1)
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Organic anion transporter-3 (OAT3) substrates: Monitor for OAT3 substrate drug-related adverse reactions and consider dosage reduction for OAT3 substrate drugs, if needed. (7.2)
USE IN SPECIFIC POPULATIONS
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Lactation: Breastfeeding is not recommended. (8.2)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 9/2019
Pretomanid Tablet 200 mg is a white to off-white, oval-shaped tablet debossed with M on one side and P200 on the other side.
NDC Number
Size
49502-476-26
Bottle of 26
49502-476-14
Unit dose blister pack of 14 (1 strip of 14 tablets)
Store below 30 �C (86 �F).
Dispense only in original container and keep container tightly closed.
