Pretomanid Mylan

What is Pretomanid?

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.

Pretomanid Tablets are not for use in people who have:

• TB that is not resistant to antibiotics.
• an inactive (latent) TB infection.
• a type of TB other than TB of the lungs.
• MDR TB who can tolerate or who respond to medicines usually used to treat MDR TB.

It is not known if Pretomanid Tablets are safe and effective for use except in combination with bedaquiline and linezolid as part of the recommended dosing regimen.

It is not known if Pretomanid Tablets are safe and effective in children.

Pretomanid Tablets were approved by FDA using the Limited Population pathway. This means FDA has approved this drug for a limited and specific patient population, and studies on the drug may have only answered focused questions about its safety and effectiveness.

What is the most important information I should know about Pretomanid?

Pretomanid Tablets are for use only as part of a combination antibiotic regimen that includes Pretomanid Tablets, bedaquiline, and linezolid.

Treatment with the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid can cause serious side effects. See “What are the possible side effects of Pretomanid?”

Read the Medication Guide that comes with bedaquiline. Ask your healthcare provider for information about linezolid. The serious side effects that can happen when taking bedaquiline and linezolid can also happen when taken in the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid.

Who should not take Pretomanid?

Do not take the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid if:

• you have been told by your healthcare provider not to take bedaquiline or linezolid.

What should I tell my healthcare provider before taking Pretomanid?

Before you take the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid, tell your healthcare provider about all of your medical conditions, including if you:

• have liver problems. See “What are the possible side effects of Pretomanid?”
• have kidney problems.
• have or have had an abnormal heart rhythm (ECG) or other heart problems, including heart failure.
• have a family history of a heart problem called “congenital long QT syndrome.”
• have decreased thyroid gland function (hypothyroidism).
• have HIV infection.
• have been told that you have low levels of calcium, magnesium or potassium in your blood.
• have ever had a seizure.
• are pregnant or plan to become pregnant. It is not known if pretomanid will harm your unborn baby. Talk to your healthcare provider about the possible risks to your baby if you take the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid while you are pregnant.
• are breastfeeding or plan to breastfeed. It is not known if pretomanid passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. You should not take herbal products or medicines that can harm your liver during treatment with the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid.

The combination regimen of Pretomanid Tablets, bedaquiline, and linezolid regimen may affect how other medicines work, and other medicines may affect how the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid works.

Especially tell your healthcare provider if you take:

• a type of medicine called a CYP3A4 inducer, such as efavirenz or rifampin. Ask your healthcare provider if you are not sure.

How should I take Pretomanid?

• 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.

Do not stop taking Pretomanid Tablets, bedaquiline, or linezolid without first talking to your healthcare provider.

What should I avoid while taking Pretomanid?

• You should not drink alcohol while taking the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid.

What are the possible side effects of Pretomanid?

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

• See “What is the most important information I should know about Pretomanid?”
• Liver problems. Your healthcare provider should do blood tests to check your liver at least before you start taking the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid, 2 weeks after starting treatment, and then monthly during treatment. Tell your healthcare provider right away if you have symptoms of liver problems, such as:
  • unusual tiredness
  • loss of appetite
  • nausea
  • yellowing of your skin or the whites of your eyes
  • dark (tea-colored) urine
  • tenderness in the upper right side of your stomach-area (abdomen)
    See “What should I avoid when taking Pretomanid?”
• Low blood cell counts. The combination regimen of Pretomanid Tablets, bedaquiline, and linezolid can cause low red blood cell counts (anemia), low white blood cell counts (leukopenia), low blood platelet counts (thrombocytopenia) or a combination of low red and white blood cell counts and low blood platelet counts (pancytopenia). Low blood cell counts are a side effect of linezolid. Anemia is a common side effect of linezolid, but can be serious and life-threatening. Low blood cell counts were reversible when linezolid treatment was reduced, stopped for a period of time, or stopped permanently. Your healthcare provider should check your blood cell counts at least before you start taking the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid, 2 weeks after starting treatment, and then monthly during treatment.
• Nerve problems in your arms, hands, legs, and feet (peripheral neuropathy). The combination regimen of Pretomanid Tablets, bedaquiline, and linezolid can cause nerve problems in your arms, hands, legs, and feet. Tell your healthcare provider if you have symptoms of nerve problems in your arms, hands, legs, or feet, including:
  • numbness
  • burning
  • a feeling of “pins and needles”
  • tremors
  • problems with balance
  • weakness
• Vision problems. The combination regimen of Pretomanid Tablets, bedaquiline, and linezolid can cause nerve problems in your eyes (optic neuropathy). Nerve problems in your eyes can cause problems with your vision. Tell your healthcare provider right away if you have symptoms of nerve problems in your eyes, such as changes in vision.
• Nerve problems in your arms, hands, legs, feet, and eyes are common side effects of long-term use of linezolid, but can be serious. Nerve problems caused by linezolid were generally reversible or improved when symptoms of nerve problems were monitored by the healthcare provider and linezolid treatment was reduced, stopped for a period of time, or stopped permanently.
• Heart rhythm problem called QT prolongation. The combination regimen of Pretomanid Tablets, bedaquiline, and linezolid can cause a heart rhythm problem. Heart rhythm problem is a side effect of bedaquiline. Your healthcare provider should do a test called an electrocardiogram (ECG) to check your heart before you start taking the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid and at least 2, 12, and 24 weeks after starting treatment. Tell your healthcare provider right away if you:
  • have a change in heartbeat (a fast or irregular heartbeat)
  • feel dizzy or faint.
• Effects on male fertility. It is not known if pretomanid can cause fertility problems in males. This could affect your ability to father a child. Talk to your healthcare provider if this is a concern for you.
• Build-up of an acid in your blood (lactic acidosis). The combination regimen of Pretomanid Tablets, bedaquiline, and linezolid can cause a build-up of acid in your blood. A build-up of acid in your blood is a side effect of linezolid. Call your healthcare provider right away if you have nausea and vomiting that keep coming back.

The most common side effects of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid 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

These are not all the possible side effects of the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Pretomanid

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Pretomanid Tablets, bedaquiline, or linezolid for a condition for which it was not prescribed. Do not give Pretomanid Tablets, bedaquiline, or linezolid to other people, even if they have the same symptoms that you have. This may harm them. You can ask your pharmacist or healthcare provider for information about Pretomanid Tablets, bedaquiline, and linezolid that is written for health professionals.

How should I store Pretomanid?

• 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.

What are the ingredients in Pretomanid?

Pretomanid Tablets active ingredient: pretomanid

Pretomanid Tablets inactive ingredients: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulfate, and sodium starch glycolate

The ingredients for bedaquiline can be found in the Medication Guide for bedaquiline. The ingredients for linezolid can be found in the information about linezolid that is written for health professionals.

SRC: NLM .