Pretomanid Mylan 200 mg Tablets

PRETOMANID MYLAN contains the active substance pretomanid. PRETOMANID MYLAN is for use only as part of a combination antimycobacterial regimen that includes pretomanid, bedaquiline, and linezolid.

What is the combination regimen of Pretomanid Tablets, bedaquiline, and linezolid? PRETOMANID MYLAN is a prescription medicine used as part of a combination regimen with bedaquiline and linezolid. The combination regimen of PRETOMANID MYLAN, 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 MYLAN is 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 MYLAN is 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 MYLAN is safe and effective in children.

Do not take PRETOMANID MYLAN:

• if you are allergic (hypersensitive) to pretomanid, bedaquiline, linezolid or any other ingredients of PRETOMANID MYLAN (listed in section 6).
• if you are not allowed to take bedaquiline and/or linezolid. Please also refer to the individual patient information leaflets for these products.
• if you are using rifampicin (antibiotic used to treat several types of bacterial infections including tuberculosis) or efavirenz (antiretroviral drug used to treat human immunodeficiency disease).
• if you are pregnant or breastfeeding your baby (see section 4.6 pregnancy and breastfeeding and fertility).

Warnings and precautions

Take special care with PRETOMANID MYLAN:

• if you have liver problems.
• if you have kidney problems.
• if you have a decrease in bone marrow activity resulting in a reduction in red blood cell production (myelosuppression), or a decrease in the haemoglobin concentration within red blood cells (anaemia).
• if you have a reduced number of white blood cells (leukopenia).
• if you have a deficiency of platelets in the blood (thrombocytopenia).
• if you have weakness, numbness and pain in your arms, hands, legs and feet as a result of nerve damage (peripheral neuropathy).
• if you experience loss of vision or colours appearing subtly washed out due to damage to the optic nerve (optic neuropathy).
• if you have or have had an abnormal heart rhythm (ECG) or other heart problems, including heart failure.
• if you have a family history of a heart problem called "congenital long QT syndrome."
• if you have decreased thyroid gland function (hypothyroidism).
• if you have been told that you have low levels of calcium, magnesium or potassium in your blood.
• if you suffer from a condition where the body produces too much lactic acid (lactic acidosis).
• if you 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 MYLAN, bedaquiline, and linezolid while you are pregnant.
• if you 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 MYLAN, bedaquiline, and linezolid.
• if you have the rare hereditary conditions of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

Children and adolescents under 18 years of age

Safety and effectiveness of PRETOMANID MYLAN in paediatric patients have not been established.

Other medicines and PRETOMANID MYLAN

Always tell your healthcare provider if you are taking any other medicine (this includes complementary or traditional medicines). You should not take herbal products or medicines that can harm your liver during treatment with the combination regimen of PRETOMANID MYLAN, bedaquiline, and linezolid. The combination regimen of PRETOMANID MYLAN, bedaquiline, and linezolid regimen may affect how other medicines work, and other medicines may affect how the combination regimen of PRETOMANID MYLAN, bedaquiline, and linezolid works. Especially tell your healthcare provider if you take:

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

PRETOMANID MYLAN with food and drink and alcohol

PRETOMANID MYLAN should be taken with meals. You should not drink alcohol while taking the combination regimen PRETOMANID MYLAN, bedaquiline, and linezolid.

Do not share medicines prescribed for you with any other person. PRETOMANID MYLAN 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 MYLAN, 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 MYLAN, 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 MYLAN, bedaquiline, and linezolid or other medicines.

Take the combination regimen of PRETOMANID MYLAN, bedaquiline, and linezolid for a total of 26 weeks. Your healthcare provider will tell you if you should take the combination regimen of PRETOMANID MYLAN, 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 MYLAN, bedaquiline, and linezolid. PRETOMANID MYLAN, bedaquiline, and linezolid can be taken together. Swallow PRETOMANID MYLAN whole with water. Take PRETOMANID MYLAN, bedaquiline, and linezolid with food.

Week 1 and Week 2: Take 200 mg of PRETOMANID MYLAN (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 MYLAN (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 MYLAN, bedaquiline, and linezolid for longer than 26 weeks. Talk with your healthcare provider.

If you have the impression that the effect of PRETOMANID MYLAN is too strong or too weak, tell your doctor or pharmacist.

If you take more PRETOMANID MYLAN than you should In the event of overdosage, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison control centre.

If you forget to take or missed a dose of PRETOMANID MYLAN: If you miss a dose of PRETOMANID MYLAN, 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 MYLAN, 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.

Effect when treatment with PRETOMANID MYLAN is stopped: Do not stop taking PRETOMANID MYLAN, bedaquiline, or linezolid without first talking to your healthcare provider.

PRETOMANID MYLAN can have side effects. Not all side effects reported for PRETOMANID MYLAN are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking PRETOMANID MYLAN, please consult your doctor, pharmacist or other healthcare professional for advice.

If any of the following happens, stop taking PRETOMANID MYLAN and tell your doctor immediately or go to the casualty department at your nearest hospital:

• swelling of the hands, feet, ankles, face, lips, tongue and mouth or throat, which may cause difficulty in swallowing or breathing. These are all very serious side effects. If you have them, you may have had a serious reaction to PRETOMANID MYLAN. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

Liver problems:

Your healthcare provider should do blood tests to check your liver at least before you start taking the combination regimen of PRETOMANID MYLAN, 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 stomach-area (abdomen).

Low blood cell counts:

The combination regimen of PRETOMANID MYLAN, 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 MYLAN, 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 MYLAN, 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. 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.

Vision problems:

The combination regimen of PRETOMANID MYLAN, 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.

Heart rhythm problem called QT prolongation:

The combination regimen of PRETOMANID MYLAN, 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 MYLAN, 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) or 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 MYLAN, 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. These are all serious side effects. You may need urgent medical attention.

Tell your doctor if you notice any of the following:

Frequent side effects reported:

• acne,
• nausea,
• vomiting,
• muscle and bone pain,
• insomnia,
• distortion of the sense of taste (dysgeusia),
• dizziness
• visual impairment,
• eye irritation,
• eye pain,
• headache,
• abnormal blood tests that may be due to injury to your liver,
• heartburn,
• indigestion (dyspepsia),
• constipation,
• decreased appetite,
• rash,
• itching,
• dry skin,
• hair loss (alopecia),
• stomach 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,
• coughing,
• low blood sugar,
• unusual weight loss,
• fatigue,
• weakness,
• diarrhoea.

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects If you get side effects, talk to your doctor or pharmacist or nurse. You can also report side effects to SAHPRA via the “6.04 Adverse Drug Reactions & Quality Problem Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8. By reporting side effects, you can help provide more information on the safety of PRETOMANID MYLAN.

Store all medicines out of reach of children. Store at or below 30 ºC. Keep in original container and keep container tightly closed. Do not use after the expiry date stated on the packaging. Return all unused medicine to your pharmacist. Do not dispose of unused medicine in drains or sewerage systems (e.g. toilet).