Pretomanid

What is Pretomanid?

• Pretomanid Tablet is an antimycobacterial used as part of a combination regimen with bedaquiline and linezolid.

What are the uses of this medicine?

Pretomanid Tablets are a prescription medicine used as part of a combination regimen with bedaquiline and linezolid. The combination regimen of Pretomanid Tablets, bedaquiline, and linezolid includes three prescription antibiotics that are used together in adults to treat tuberculosis (TB) of the lungs that is extensively drug resistant (XDR) or who cannot tolerate or do not respond to treatment for multidrug-resistant (MDR) TB.

How does this medicine work?

• Pretomanid Tablet is a nitroimidazooxazine antimycobacterial drug.
• Pretomanid kills actively replicating M. tuberculosis by inhibiting mycolic acid biosynthesis, thereby blocking cell wall production.
• Under anaerobic conditions, against non-replicating bacteria, pretomanid acts as a respiratory poison following nitric oxide release.
• All of these activities require nitro-reduction of pretomanid within the mycobacterial cell by the deazaflavin-dependent nitroreductase, Ddn, which is dependent on the reduced form of the cofactor F420.
• Reduction of F420 is accomplished by the F420-dependent glucose-6-phosphate dehydrogenase, Fgd1.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• Drug-sensitive (DS) tuberculosis
• Latent infection due to Mycobacterium tuberculosis
• Extra-pulmonary infection due to Mycobacterium tuberculosis
• MDR-TB that is not treatment-intolerant or nonresponsive to standard therapy
• 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.

== What drug interactions can this medicine cause? ==

• Avoid co-administration of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid with rifampin, efavirenz, or other strong or moderate CYP3A4 inducers.
• If pretomanid is co-administered with OAT3 substrate drugs (e.g., methotrexate), monitor for OAT3 substrate drug-related adverse reactions and consider dosage reduction for OAT3 substrate drugs, if needed.

Is this medicine FDA approved?

• It was approved for use in the United States in 2019.

How should this medicine be used?

• Pretomanid Tablets must be used only in combination with bedaquiline and linezolid.

Recommended Dosage Administer Pretomanid Tablets in combination with bedaquiline and linezolid as follows:

• Pretomanid Tablet 200 mg orally 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 (1,200 mg daily orally for up to 26 weeks, with dose adjustments for known linezolid toxicities).

Administration

• Pretomanid Tablets must only be taken with bedaquiline and linezolid as part of the dosing regimen prescribed by your healthcare provider.
• Take the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid exactly as your healthcare provider tells you to take it.
• It is important that you complete the full course of treatment with the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid, and not miss any doses, even if you feel better before you have completed the full course of treatment. Missing doses may decrease the effectiveness of the treatment and increase the chance that your TB will not be treatable by the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid or other medicines.
• Take the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid for a total of 26 weeks.
• Your healthcare provider will tell you if you should take the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid for longer than 26 weeks.
• Your healthcare provider will tell you if you should stop taking linezolid before you have taken it for 26 weeks or if you should reduce your dose of linezolid due to side effects.
• Your healthcare provider or caregiver will watch you take your doses of Pretomanid Tablets, bedaquiline, and linezolid.
• Pretomanid Tablets, bedaquiline, and linezolid can be taken together.
• Swallow Pretomanid Tablets whole with water.
• Take Pretomanid Tablets, bedaquiline, and linezolid with food.

Week 1 and Week 2: Take 200 mg of Pretomanid Tablets (1 tablet), 400 mg of bedaquiline, and 1,200 mg of linezolid 1 time each day.

Week 3 to Week 26: Take 200 mg of Pretomanid Tablets (1 tablet) and 1,200 mg of linezolid 1 time each day. Take 200 mg of bedaquiline 3 times a week.

• Take your doses of bedaquiline at least 48 hours apart. For example, you may take bedaquiline on Monday, Wednesday, and Friday every week from Week 3 to Week 26.
• You may need to take the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid for longer than 26 weeks. Talk with your healthcare provider.
• Do not miss a dose of Pretomanid Tablets, bedaquiline, or linezolid unless instructed to do so by your healthcare provider. If you miss doses or do not complete the total 26 weeks of treatment, your treatment may not work as well, and your TB may be harder to treat.
• If your healthcare provider tells you to stop taking the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid for a period of time, follow the instructions given to you by your healthcare provider for taking the missed doses at the end of your treatment. You should not make up any missed doses of linezolid alone that your healthcare provider told you not to take due to side effects.
• If you miss a dose of Pretomanid Tablets, bedaquiline, or linezolid and you are not sure what to do, talk to your healthcare provider as soon as possible.
• If you take too much Pretomanid Tablets, go to the nearest hospital emergency room right away.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 200 mg

This medicine is available in fallowing brand namesː

• PRETOMANID TABLETS

What side effects can this medication cause?

The most common side effects of this medicine include:

• acne
• nausea
• vomiting
• muscle and bone pain
• headache
• abnormal blood tests that may be due to injury to your liver
• heartburn
• decreased appetite
• rash
• itching
• stomach area (abdominal) pain
• chest pain that worsens when you breathe or cough
• lower respiratory tract infection
• abnormal blood tests that may be due to injury to your pancreas
• coughing up blood
• cough
• low blood sugar
• unusual weight loss
• diarrhea

The combination regimen of Pretomanid Tablets, bedaquiline, and linezolid may cause serious side effects including:

• Liver problems
• Low blood cell counts
• Nerve problems in your arms, hands, legs, and feet (peripheral neuropathy)
• Vision problems
• Heart rhythm problem called QT prolongation
• Effects on male fertility
• Build-up of an acid in your blood (lactic acidosis)

What special precautions should I follow?

• You should not drink alcohol while taking the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid.
• 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.
• 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.
• 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.
• 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.
• Advise patients of reproductive toxicities seen in animal studies and that the potential effects on human male fertility have not been adequately evaluated.
• 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.

What to do in case of emergency/overdose?

There is no experience with the treatment of acute overdose with pretomanid.

Management for overdosage:

• Take general measures to support basic vital functions including monitoring of vital signs and ECG (QT interval) in case of deliberate or accidental overdose.

Can this medicine be used in pregnancy?

• There are no studies or available data on pretomanid use in pregnant women to inform any drug-associated risks.

Can this medicine be used in children?

• Safety and effectiveness of Pretomanid Tablets in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

• Active Ingredient: pretomanid
• Inactive Ingredients: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulfate, and sodium starch glycolate

Who manufactures and distributes this medicine?

• Manufactured by:

Mylan Laboratories Limited, Hyderabad, 500 096, India

• Manufactured for:

Mylan Specialty L.P., Morgantown, WV 26505 U.S.A.

What should I know about storage and disposal of this medication?

• Store Pretomanid Tablets, bedaquiline, and linezolid at room temperature below 86°F (30°C). Ask your pharmacist if you have questions about how to store bedaquiline and linezolid.
• Keep Pretomanid Tablets in the original container with the container tightly closed.
• Keep Pretomanid Tablets and all medicines out of the reach of children.

• Dailymed label info on Pretomanid
• FDA Pretomanid

Pretomanid Resources
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