Pretomanid
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omid Afkhami Ardakani
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Overview
Pretomanid is a Nitroimidazooxazine Antimycobacterial that is FDA approved for the treatment of Pulmonary extensively drug-resistant (XDR) tuberculosis (TB), Treatment-intolerant or nonresponsive multidrug-resistant (MDR) pulmonary TB. Common adverse reactions include Peripheral neuropathy, Acne, Anemia, Nausea, Vomiting, Headache, Increased transaminases, Dyspepsia, Rash, and Decreased appetite..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Pulmonary XDR-TB or Treatment-Intolerant/Nonresponsive MDR-TB: Pretomanid must be administered in combination with bedaquiline and linezolid. The recommended dosage is 200 mg (one tablet) taken orally once daily for 26 weeks. Bedaquiline and linezolid should be dosed according to their prescribing information.
Off-Label Use and Dosage (Adult)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Pretomanid FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Contraindications
Pretomanid is contraindicated in patients for whom bedaquiline and/or linezolid are contraindicated.
Warnings
Hepatotoxicity: Hepatic adverse reactions have been reported with the combination regimen of Pretomanid, bedaquiline, and linezolid. Monitor liver function tests prior to and during treatment. Avoid alcohol and hepatotoxic agents during therapy. Myelosuppression: Linezolid, a component of the combination regimen, has been associated with myelosuppression, including anemia and thrombocytopenia. Monitor complete blood counts weekly. Peripheral and Optic Neuropathy: Neuropathies have been reported with the combination regimen. Monitor for symptoms and consider discontinuation or dose adjustment of linezolid if necessary. QT Prolongation: QT prolongation has been observed with the combination regimen. Monitor ECGs and electrolytes periodically.
Adverse Reactions
Clinical Trials Experience
Peripheral neuropathy Acne Anemia Nausea Vomiting Headache Increased transaminases Dyspepsia Rash Decreased appetite
Postmarketing Experience
As of the latest update, specific postmarketing adverse reactions have not been detailed.
Drug Interactions
Bedaquiline and Linezolid: Pretomanid is indicated for use only in combination with bedaquiline and linezolid. Refer to the prescribing information for these drugs for detailed interaction profiles.
Other QT-Prolonging Agents: Caution is advised when co-administering with other QT-prolonging agents due to the risk of additive QT prolongation.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Pretomanid in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pretomanid in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Pretomanid during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Pretomanid in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Pretomanid in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Pretomanid in geriatric settings.
Gender
There is no FDA guidance on the use of Pretomanid with respect to specific gender populations.
Race
There is no FDA guidance on the use of Pretomanid with respect to specific racial populations.
Renal Impairment
Renal Impairment: The pharmacokinetics of Pretomanid in patients with severe renal impairment or those on hemodialysis have not been evaluated. Use caution when administering to such patients due to limited safety data. No dosage adjustment is required for mild to moderate renal impairment.
Hepatic Impairment
Hepatic Impairment: Pretomanid has not been specifically studied in patients with moderate to severe hepatic impairment. While no initial dosage adjustments are recommended for mild hepatic impairment, monitor closely for potential hepatic toxicity in all patients with liver conditions.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Pretomanid in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Pretomanid in patients who are immunocompromised.
Administration and Monitoring
Administration
Pretomanid is taken orally as part of a combination regimen with bedaquiline and linezolid. The recommended dose is 200 mg (one tablet) once daily for 26 weeks. Tablets should be swallowed whole with water, and they can be taken with or without food.
Monitoring
Liver function tests (ALT, AST, bilirubin) and complete blood counts should be performed prior to initiation. Monitor liver function tests and ECG periodically, particularly in patients at risk for hepatotoxicity or QT prolongation. Assess for peripheral neuropathy and myelosuppression, which may require dose adjustments or discontinuation of the combination regimen.
IV Compatibility
Not applicable, as Pretomanid is administered orally.
Overdosage
Symptoms of overdose may include exaggerated adverse reactions, such as peripheral neuropathy, liver enzyme elevations, and gastrointestinal discomfort. There is no specific antidote for Pretomanid. In case of overdose, provide supportive care and monitor for toxic effects.
Pharmacology
There is limited information regarding Pretomanid Pharmacology in the drug label.
Mechanism of Action
Pretomanid is a nitroimidazooxazine antimycobacterial that works by inhibiting mycolic acid biosynthesis, leading to disruption of the bacterial cell wall. Its mechanism also involves nitric oxide release, which contributes to bacterial killing in anaerobic conditions.
Structure
There is limited information regarding Pretomanid Structure in the drug label.
Pharmacodynamics
Pretomanid has bactericidal activity against Mycobacterium tuberculosis and exhibits synergistic effects when combined with bedaquiline and linezolid.
Pharmacokinetics
Absorption: Peak plasma concentrations occur 4 to 5 hours after oral administration. Metabolism: Pretomanid is primarily metabolized via non-CYP450 pathways. Elimination: Approximately 53% excreted in feces and 36% excreted in urine. Half-life: The terminal half-life is approximately 16 to 20 hours.
Nonclinical Toxicology
There is limited information regarding Pretomanid Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Pretomanid Clinical Studies in the drug label.
How Supplied
Pretomanid is supplied as 200 mg film-coated tablets. Tablets are white to off-white, round, and debossed with "M" on one side and "200" on the other.
Storage
Store Pretomanid at 20°C to 25°C (68°F to 77°F). Excursions are permitted to 15°C to 30°C (59°F to 86°F). Keep the medication in its original packaging to protect from light and moisture.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Patients should be informed to: Take Pretomanid as part of the prescribed combination regimen with bedaquiline and linezolid. Be vigilant for symptoms of liver toxicity (e.g., jaundice, dark urine, abdominal pain) and peripheral neuropathy (e.g., tingling, numbness). Avoid alcohol and other hepatotoxic substances during treatment. Use effective contraception during treatment and for at least 6 months after the last dose.
Precautions with Alcohol
Alcohol use during treatment is discouraged as it may increase the risk of hepatotoxicity. Patients should consult their healthcare provider regarding alcohol use.
Brand Names
Pretomanid is marketed under its generic name; there are no other brand names currently available.
Look-Alike Drug Names
There is limited information regarding Pretomanid Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.