DOVPRELA 200 mg Tablets

Зміст інструкції

1. Dovprela 200 mg tablets
   1. What is Dovprela and what is it used for
   2. What you need to know before taking Dovprela
   3. How to take Dovprela
   4. Possible side effects
   5. How to store Dovprela
   6. Package contents and other information

Dovprela 200 mg tablets

pretomanid

Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before you start taking this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

• 1. What Dovprela is and what it is used for
• 2. What you need to know before you take Dovprela
• 3. How to take Dovprela
• 4. Possible side effects
• 5. How to store Dovprela
• 6. Contents of the pack and other information

1. What is Dovprela and what is it used for

Dovprela contains the active ingredient pretomanid, a type of antibiotic. Antibiotics are medicines
used to kill bacteria that cause diseases.
Dovprela is used in adults (aged 18 years and over) in combination with two other
medicines, called linezolid and bedaquiline, to treat pulmonary tuberculosis:

• resistant to several other classes of antibiotics (isoniazid, rifampicin, any fluoroquinolone and any second-line injectable antimycobacterial drug) or
• resistant only to isoniazid and rifampicin, in case of failure or intolerance to standard treatment.

2. What you need to know before taking Dovprela

Do not take Dovprela

• if you are allergic to pretomanid, to nitroimidazole antibiotics or to any of the other ingredients of this medicine (listed in section 6).

Since pretomanid must be used in combination with other medicines against tuberculosis –
linezolid and bedaquilina – remember to also read the “Do not take” section of the package leaflets of
these medicines. If you have any doubts regarding information contained in the package leaflets, consult
your doctor or pharmacist.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Dovprela if:

• you suffer from reduced liver function
• you regularly drink alcoholic beverages
• you suffer from reduced kidney function
• you suffer from or have suffered from heart rhythm disorders or if someone in your family suffers from a heart rhythm problem
• you suffer from heart failure
• you suffer from or have suffered from underactive thyroid
• you suffer from low levels of calcium, magnesium or potassium in the blood

Liver damage
During treatment with Dovprela, linezolid and bedaquilina there is a risk of liver damage. Your
doctor will therefore monitor you to detect any signs of liver damage and will take
blood samples before the start of treatment and at regular intervals during treatment.
Tell your doctor if you experience symptoms such as:

• fatigue
• loss or lack of appetite
• nausea
• yellowing of the skin and eyes
• dark colored urine
• abdominal pain In case of liver problems, your doctor will modify the treatment.

Reduction in the number of blood cells
Treatment with Dovprela, linezolid and bedaquilina can severely reduce the number of blood cells,
such as platelets, red blood cells and white blood cells called neutrophils. Contact
your doctor immediately if you experience bruising, bleeding or infections.
Your doctor will check your complete blood count before the start of treatment and at regular
intervals during treatment. Your doctor will modify the treatment if the blood cell count is
low.

Nerve disorders in the hands, feet or eyes
Nerve disorders in the hands, feet or eyes may occur during treatment. Talk to your
doctor if you experience vision problems or numbness, tingling or
burning in your hands or feet during treatment. In this case, your doctor will modify the treatment. If you have problems with
your vision, see a doctor for a timely eye examination.

Increased levels of lactic acid in the blood
During treatment, an excessive acidification of the blood called lactic acidosis may occur.
Talk to your doctor if you repeatedly suffer from nausea or vomiting. In this case, your doctor may
modify the treatment.

Heart problems
An abnormality in the heartbeat known as prolongation of the QT interval may occur during treatment.
Your doctor will therefore perform an ECG before the start of treatment and at regular
intervals during treatment. If heartbeat abnormalities occur, the treatment will be modified.
In addition, potassium, calcium and magnesium levels will be checked and corrected if abnormal.
The safety and efficacy of Dovprela have not been studied in combination with medicines other
than linezolid and bedaquilina, and therefore the medicine should not be used as a component of other
combination therapies.

Children and adolescents
This medicine is not recommended for children and adolescents under 18 years of age. This is because it
has not been studied in this age group.

Other medicines and Dovprela
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines, including herbal remedies. Other therapies may alter the way
Dovprela works or increase the risk of side effects.

Avoid concomitant treatmentwith Dovprela and any of the following medicines. These
medicines may reduce the effect of Dovprela and therefore the treatment may be ineffective; therefore,
immediately inform your doctor about:

• rifampicin, rifamycin, rifapentine, rifabutin: other medicines for the treatment of tuberculosis or certain other infections
• efavirenz, etravirine: medicines for the treatment of HIV infection
• carbamazepine, phenytoin: medicines for the treatment of epilepsy and certain pain conditions
• St. John's wort: an herbal medicine for the treatment of depression and anxiety

You should also avoidthe use of medicines (other than bedaquilina and linezolid) that could have a
harmful effect on the liver. Consult your doctor, who will be able to tell you which medicines these are.
Tell your doctor if you are using:

• methotrexate: a medicine for the treatment of severe joint inflammation, malignant tumors and the skin disease psoriasis
• benzylpenicillin, ciprofloxacin: medicines for the treatment of bacterial infections
• indometacin: a medicine for the treatment of pain and inflammation
• ritonavir: a medicine for the treatment of HIV infection

Dovprela with alcohol
Avoid drinking alcoholic beverages during treatment with Dovprela, as this increases the
risk of serious liver damage.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant, are planning a pregnancy or are breastfeeding,
ask your doctor or pharmacist for advice before taking this medicine.

• PregnancyKnowledge about the use of Dovprela during pregnancy is very limited. Dovprela should therefore be used during pregnancy only if the benefit to the patient outweighs the potential risk to the fetus. The doctor will decide whether you should be treated with Dovprela.
• BreastfeedingIt is not known whether pretomanid passes into breast milk. Your doctor will have to decide whether to discontinue breastfeeding or avoid treatment with Dovprela.

Driving and operating machinery
After taking Dovprela, you may experience dizziness or vision problems. If this happens, do not drive
and do not operate machinery.

Dovprela contains lactose and sodium
If your doctor has told you that you have an intolerance to certain sugars, contact your doctor before taking
this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially
‘sodium-free’.

3. How to take Dovprela

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
Dovprela is used in combination with linezolid and bedaquilina. Also read the package leaflets of
these medicines. If you have any doubts, consult your doctor or pharmacist.

The recommended dose is

• Dovprela: 1 tablet once a day
• linezolid: 600 mg per day
• bedaquilina: 400 mg once a day for 2 weeks, followed by 200 mg 3 times a week (with an interval of at least 48 hours between doses). For example, you can take bedaquilina every week on Monday, Wednesday and Friday starting from week 3.

Method of administration
Take Dovprela at the same time as linezolid and bedaquilina. Swallow the tablets with a
glass of water during a meal.
The tablets should be taken under the direct supervision of a healthcare professional or according to local
practice.

Duration of administration
The duration of combination treatment with Dovprela, linezolid and bedaquilina is 26 weeks. The doctor
may decide to extend the treatment or to stop administration to ensure that the
treatment is safe and effective.

If you take more Dovprela than you should
Contact your doctor immediately and bring the medicine packaging with you.

If you forget to take Dovprela
Do not take a double dose to make up for a missed dose.
It is recommended to make up for any missed doses of pretomanid and bedaquilina at the end of
treatment. It is not recommended to make up for missed doses of linezolid due to adverse reactions to
linezolid. Contact your doctor or pharmacist if you have missed a dose and do not know what to do.

If you stop taking Dovprela
Do not stop treatment with Dovprela or with the medicines linezolid or bedaquilina, which must be
taken in combination, without your doctor's consent. If you skip doses or do not complete the entire cycle
of therapy, the treatment may be ineffective and tuberculosis may worsen. In addition, this
would increase the possibility that the bacteria become resistant to these medicines.
If you have any doubts about using this medicine, contact your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
The following side effects have been reported with the use of Dovprela together with linezolid and bedaquiline:

Seek medical attention immediatelyif you experience any of the following effects:

Very common(may affect more than 1 in 10 people)

• reduction in the number of red blood cells. Possible signs include feeling tired, weak, short of breath, loss of consciousness and increased thirst.
• increase in the levels in the blood of liver enzymes called transaminases such as ALT, AST. Inform your doctor if you experience symptoms such as fatigue, loss or decrease of appetite, nausea, yellowing of the skin and eyes, dark urine or abdominal pain.

Common(may affect up to 1 in 10 people)

• reduction in the number of white blood cells or platelets. Possible signs include bruising, bleeding or infections.
• increase in the levels in the blood of a liver enzyme called gamma GT (which indicates whether the liver is functioning correctly)
• increase in the level in the blood of lactic acid. Contact your doctor if you have recurrent nausea or vomiting.

Other side effects may occur with the following frequencies:

Very common(may affect more than 1 in 10 people)

• nausea, vomiting, digestive problems
• acne
• decreased appetite
• problems with the nerves in the hands or feet, such as pain, burning, abnormal sensation or numbness

Common(may affect up to 1 in 10 people)

• fungal infection (including Candida, yeasts, fungi) of the mouth or throat, which manifests with white spots
• difficulty sleeping
• fatigue
• taste disturbances
• dizziness
• headache
• muscle spasm, musculoskeletal pain, such as joint pain, back pain, muscle pain
• diarrhea, constipation
• inflammation of the stomach lining, inflammation of the pancreas
• reflux of gastric juice into the esophagus
• abdominal pain
• hair loss, dry skin, itching, rash
• eye irritation or pain, dry eyes, vision problems
• damage and/or inflammation of the optic nerve, with swelling and visual disturbances
• abnormalities in the electrical activity of the heart (prolongation of the QT interval on the electrocardiogram)
• increase in the levels in the blood of:
• amylase
• bilirubin, the yellow substance of blood pigment degradation
• lipase
• alkaline phosphatase
• creatinine
• creatine phosphokinase
• urea
• decreased blood sugar
• decreased level in the blood of magnesium

Uncommon(may affect up to 1 in 100 people)

• fungal infection
• excessive fluid loss, reduced fluid volume in the body
• anxiety, depression
• enlarged liver
• yellowish discoloration of the skin, internal organs and/or the whites of the eyes (jaundice)
• lens disorders of the eyes
• worsening of the ability to focus on nearby objects well
• eye itching, eye swelling
• swelling of the optic disc (resulting in vision loss)
• hearing loss
• feeling of increased heartbeat
• increased heart rate
• low blood pressure
• cough, nosebleeds
• feeling of fullness
• burning of the tongue, enlargement of the taste buds on the upper surface of the tongue
• eczema, excessive skin pigmentation
• inability to have or maintain an erection
• irregular uterine bleeding, especially between expected menstrual cycles
• feeling unwell
• abnormal presence of the albumin protein in the urine
• vomiting blood
• reduced elimination of creatinine, a product of muscle tissue degradation, through the kidneys
• deficiency of white blood cells, red blood cells and platelets in the blood
• decreased level in the blood of calcium
• increase in the levels in the blood of:
• isoenzyme of creatine phosphokinase (MB)
• uric acid

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. You can also report side effects directly through the national reporting system detailed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Dovprela

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the package, bottle or
blister after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any particular storage temperature.
Unused medicine and waste medicine must be disposed of in accordance
with local regulations.

6. Package contents and other information

What Dovprela contains

• The active ingredient is pretomanid. Each tablet contains 200 mg of pretomanid.
• The other ingredients are lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, colloidal silicon dioxide, sodium lauryl sulfate, povidone.

Description of the appearance of Dovprela and contents of the pack
Dovprela is an oval tablet of colour from white to off-white, with the inscription “M” embossed on one
side and “P200” on the other side. Tablet dimensions: 18 × 9 mm.
The tablets are supplied in:
Blister packs containing 14, 14 × 1, 182 or 182 × 1 tablets
Plastic bottles containing 26 tablets
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Mylan IRE Healthcare Limited
Unit 35/36 Grange Parade
Baldoyle Industrial Estate
Dublin 13
Ireland

Manufacturer
Mylan Hungary Kft.
H-2900, Komárom
Mylan utca 1
Hungary
Rottapharm Limited,
Damastown Industrial Park,
Mulhuddart,
Dublin 15,
D15 XD71
Ireland
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

Lietuva
Viatris UAB
Tel: +370 5 205 1288

България
Майлан ЕООД
Тел.: +359 2 44 55 400

België/Belgique/Belgien
Viatris
Tél/Tel: + 32 (0)2 658 61 00

Luxembourg/Luxemburg
Viatris
Tél/Tel: + 32 (0)2 658 61 00
(Belgique/Belgien)

Česká republika
Viatris CZ s.r.o.
Tel: + 420 222 004 400

Magyarország
Viatris Healthcare Kft.
Tel.: + 36 1 465 2100

Danmark
Viatris ApS
Tlf: +45 28 11 69 32

Malta
V.J. Salomone Pharma Ltd
Tel: + 356 21 22 01 74

Deutschland
Viatris Healthcare GmbH
Tel: +49 800 0700 800

Nederland
Mylan BV
Tel: +31 (0)20 426 3300

Eesti
Viatris OÜ
Tel: + 372 6363 052

Norge
Viatris AS
Tlf: + 47 66 75 33 00

Ελλάδα
Viatris Hellas Ltd
Τηλ: +30 2100 100 002

Österreich
Viatris Austria GmbH
Tel: +43 1 86390

España
Viatris Pharmaceuticals, S.L.
Tel: + 34 900 102 712

Polska
Viatris Healthcare Sp. z o.o.
Tel.: + 48 22 546 64 00

France
Viatris Santé
Tél: +33 1 40 80 15 55

Portugal
Viatris Healthcare, Lda
Tel: + 351 21 412 72 00

Hrvatska
Viatris Hrvatska d.o.o.
Tel: +385 1 23 50 599

România
BGP Products SRL
Tel: +40 372 579 000

Ireland
Viatris Limited
Tel: +353 1 8711600

Slovenija
Viatris d.o.o.
Tel: + 386 1 23 63 180

Ísland
Icepharma hf.
Sími: +354 540 8000

Slovenská republika
Viatris Slovakia s.r.o.
Tel: +421 2 32 199 100

Italia
Viatris Italia S.r.l.
Tel: + 39 (0)2 612 46921

Suomi/Finland
Viatris Oy
Puh/Tel: +358 20 720 9555

Κύπρος
GPA Pharmaceuticals Ltd
Τηλ: +357 22863100

Sverige
Viatris AB
Tel: + 46 (0) 8 630 19 00

Latvija
Viatris SIA
Tel: +371 676 055 80

United Kingdom (Northern Ireland)
Mylan IRE Healthcare Limited
Tel: +353 18711600

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency, http://www.ema.europa.eu