XENLETA 150 mg Concentrate And Solvent For Infusion Solution

Зміст інструкції

1. Xenleta 600 mg film-coated tablets
   1. What is Xenleta and what is it used for
   2. What you need to know before you take Xenleta
   3. How to take Xenleta
   4. Possible side effects
   5. How to store Xenleta
   6. Contents of the pack and other information
2. Xenleta 150 mg concentrate and solvent for infusion solution
   1. What is Xenleta and what is it used for
   2. What you need to know before you are given Xenleta
   3. How Xenleta will be administered to you
   4. Possible side effects
   5. How to store Xenleta
   6. Package contents and other information

Xenleta 600 mg film-coated tablets

lefamulina

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 they have the same symptoms as you, as it may 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 Xenleta is and what it is used for
• 2. What you need to know before you take Xenleta
• 3. How to take Xenleta
• 4. Possible side effects
• 5. How to store Xenleta
• 6. Contents of the pack and other information

1. What is Xenleta and what is it used for

Xenleta is an antibiotic medicine that contains the active ingredient lefamulin. It belongs to a group
of medicines called “pleuromutilins”.
Lefamulin works by killing certain bacteria that cause infections.
Xenleta is indicated for the treatment of adults with bacterial lung infections, also known as
pneumonia, when other treatments for pneumonia are not considered appropriate.

2. What you need to know before you take Xenleta

Do not take Xenleta

• if you are allergic to lefamulinor to any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to other medicinesof the pleuromutilin class;
• if you are taking certain medicinesthat could interact with Xenleta: certain medicines may cause Xenleta to lose its effect or cause unwanted effects if taken with Xenleta (see examples in the Other medicines and Xenletasection below);
• if you are taking medicinesthat can cause changes in the electrical activity of the heart as seen on an ECG (see the Other medicines and Xenletasection below) as lefamulin can cause a condition called prolongation of the QT interval, which is abnormal electrical activity that affects the heartbeat;
• if you have a salt imbalancein your blood (particularly low blood levels of potassium);
• if you have or have had an irregular heartbeat or an abnormal result on an ECG calledprolongation of the QT interval;
• if you have a very slow heartbeat(bradycardia);
• if your heart is not working well enough(heart failure).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Xenleta

• if you have kidney failureand are undergoing dialysis;
• if you have cirrhosis (severe liver disease). If any of these conditions apply to you, or if you are not sure, talk to your doctor before taking Xenleta. If you develop severe diarrhoeaduring or after taking Xenleta tablets, talk to your doctor as you may need to stop taking the medicine or take another medicine to treat the diarrhoea. Antibiotics can cause an overgrowth of some bacteria in the gut that can damage it and cause a severe form of diarrhoea. If you develop yellowing of the skin (jaundice) or the whites of your eyes become yellow(scleral icterus), talk to your doctor as you may need to stop taking Xenleta or other medicines. Other infections The risk of contracting a different infection caused by another bacterium during or after treatment with Xenleta is reduced. Your doctor will monitor you closely to detect any new infections and will prescribe another treatment if necessary. Children and adolescentsThe use of Xenleta is not recommendedin children and adolescents under 18 years of age. Other medicines and XenletaTell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, as some medicines may affect the effect of Xenleta or vice versa. The lists below contain only some examples of medicines that should be avoided while taking lefamulin or for which caution is needed. Your doctor will advise you if lefamulin is suitable for you. Do not take any of the following medicines with lefamulin:
• carbamazepine, phenytoin, primidone (for epilepsy);
• efavirenz, ritonavir (for HIV);
• St John's wort, a herbal remedy (for depression or low mood);
• bosentan diltiazem, amiodarone, sotalol, quinidine, procainamide (for angina, high blood pressure or heart rhythm problems);
• rifampicin, clarithromycin, erythromycin (for bacterial infections);
• fluconazole, itraconazole, posaconazole, voriconazole (for fungal infections);
• ketoconazole (for Cushing's disease);
• repaglinide (for diabetes);
• nefazodone, amitriptyline or pimozide (for depression or other mental illnesses). You may need to have your dose of some medicines adjusted while you are taking lefamulin. These medicines include:
• alprazolam, midazolam, triazolam or other drugs called benzodiazepines (for anxiety);
• alfentanil (an opioid, for pain);
• vardenafil (for erectile dysfunction);
• ibrutinib (for some types of cancer);
• lovastatin, rosuvastatin or simvastatin (to reduce cholesterol levels);
• metformin (for diabetes);
• zolpidem (for insomnia);
• ethinylestradiol (used in contraceptive pills);
• verapamil (for high blood pressure).

Xenleta with food and drink
Xenleta should be taken on an empty stomach at least 1 hour before or 2 hours after meals. This is because
food and some drinks can affect the way the medicine works.
During treatment with Xenleta, you should not eat grapefruit or drink grapefruit juice as
they may interact with Xenleta and increase its side effects.

Pregnancy and breastfeeding
Do not take Xenleta if you are pregnant or are breastfeeding. If you are pregnant, if
you suspect or are planning a pregnancy, or if you are breastfeeding, ask your doctor or
pharmacist for advice before taking this medicine.

Driving and using machines
Taking Xenleta does not affect your ability to drive or operate machines.

Xenleta contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, which is essentially
“sodium-free”.

3. How to take Xenleta

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
The recommended dose is one 600 mg Xenleta tablet, taken every 12 hours for 5 days. The
tablets must be swallowed whole with water.
Xenleta tablets can also be taken after the start of treatment with Xenleta for
intravenous infusion. In this case, the number of days for which you must take Xenleta tablets depends on the number of days for which you have been treated with intravenous infusion.
Your doctor will tell you how long to take Xenleta. It is important to complete the course of
treatment.

If you take more Xenleta than you should
In case of accidental intake of an excessive number of tablets, contact your doctor or
pharmacist.

If you forget to take Xenleta
Do not take a double dose to make up for a missed tablet. You should continue the
course with the next scheduled dose.

If you stop taking Xenleta
Take the complete course of tablets prescribed by your doctor, even if you begin to feel better
before you have finished it. If you stop taking the tablets too early, the infection
may return or your condition may worsen.
If you do not complete the course of treatment or if you do not take the tablets at the right time, bacteria
may remain and become resistant to antibiotics. This can cause the infection to recur or, in that case, the loss of effectiveness of the antibiotic.
If you experience an undesirable effect that worries you, consult your doctor immediately
before taking the next dose.
If you have any doubts about the use of this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Common: may affect up to 1 in 10 people

• low levels of potassium in the blood (hypokalaemia), which can cause muscle weakness, cramps or an irregular heartbeat
• difficulty sleeping (insomnia)
• headache
• alteration of the heart rhythm (observed by an ECG, which checks the electrical activity of the heart)
• diarrhoea
• feeling unwell (nausea) or being sick (vomiting)
• increase in a particular liver enzyme in the blood (transaminases). Uncommon: may affect up to 1 in 100 people
• inflammation of the bowel causing diarrhoea (colitis), due to an infection by a type of bacteria called Clostridioides difficile(previously called Clostridium difficile)
• fungal (yeast) infection of the throat and mouth (thrush or candidiasis)
• fungal (yeast) infection of the vagina and vulva (candidiasis or yeast infection)
• decrease in red blood cells (anaemia), which can make the skin pale and cause weakness or shortness of breath
• decrease in platelets (blood cells that help with blood clotting) leading to an increased risk of bleeding or bruising
• feeling anxious
• dizziness
• feeling tired or sleepy
• beating or irregular heartbeat or palpitations
• pain in the back of the nose and throat
• stomach pain, abdominal pain or around the stomach
• constipation
• indigestion, heartburn or inflammation of the stomach lining (gastritis)
• increase in a liver enzyme in the blood (gamma-glutamyl transferase and alkaline phosphatase)
• increase in a muscle enzyme contained in the blood (creatine phosphokinase)
• difficulty urinating or emptying the bladder completely (urinary retention). Reporting of side effectsIf you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Xenleta

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 and on the blister. The expiry
date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Xenleta contains

• The active ingredient is lefamulin. Each film-coated tablet contains lefamulin acetate equivalent to 600 mg of lefamulin.
• The other ingredients are silicon dioxide (E551), sodium croscarmellose (E468), magnesium stearate (E572), mannitol (E421), microcrystalline cellulose (E460), povidone K30, talc (E553b).
• Film coating: indigo carmine lacquer (E132), macrogol, polyvinyl alcohol (E1203), talc, titanium dioxide (E171).
• Printing ink: shellac (E904), black iron oxide (E172), propylene glycol. Description of the appearance of Xenleta and contents of the packXenleta 600 mg tablets are blue, oval-shaped, with the inscription “LEF 600” printed in black on one side. Xenleta film-coated tablets are supplied in blisters of 10 tablets.

Marketing Authorisation Holder and Manufacturer
Nabriva Therapeutics Ireland DAC
Alexandra House, Office 225/227
The Sweepstakes,
Ballsbridge
Dublin 4
D04 C7H2
Republic of Ireland
Further detailed information on this medicine is available on the European Medicines Agency website, http://www.ema.europa.eu .

Xenleta 150 mg concentrate and solvent for infusion solution

lefamulina

Read this leaflet carefully before you are given 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 or nurse.
• If any side effects occur, including those not listed in this leaflet, ask your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What is Xenleta and what is it used for

Xenleta is an antibiotic medicine that contains the active substance lefamulin. It belongs to a group
of medicines called “pleuromutilins”.
Lefamulin works by killing certain bacteria that cause infections.
Xenleta is indicated for the treatment of adults with bacterial lung infections, also known as
pneumonia, when other treatments for pneumonia are not considered appropriate.

2. What you need to know before you are given Xenleta

Do not be given Xenleta

• if you are allergic to lefamulinor to any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to other medicinesin the pleuromutilin class;
• if you are taking certain medicinesthat could interact with Xenleta: certain medicines may cause Xenleta to lose its effect or cause unwanted effects if given with Xenleta (see examples in the Other medicines and Xenletasection below);
• if you are taking medicinesthat can cause changes in the electrical activity of the heart as seen on an ECG (see the Other medicines and Xenletasection below) as lefamulin can cause a condition called prolongation of the QT interval, which is abnormal electrical activity that affects the heartbeat;
• if you have a salt imbalancein your blood (particularly low blood levels of potassium);
• if you have or have had an irregular heartbeat or an abnormal result on an ECG calledprolongation of the QT interval;
• if you have a very slow heartbeat(bradycardia);
• if your heart is not working well enough(heart failure).

Warnings and precautions
Talk to your doctor or nurse before you are given Xenleta

• if you have kidney failureand need dialysis;
• if you have cirrhosis (severe liver disease). If any of these conditions apply to you, or you are not sure, talk to your doctor before you are given Xenleta. If you develop severe diarrhoeaduring or after receiving Xenleta, contact your doctor immediately as you may need to stop treatment. Antibiotics can cause an overgrowth of some bacteria in the gut which can harm it and cause a severe form of diarrhoea. If you develop a yellowing of the skin (jaundice) or the whites of your eyes become yellow(scleral icterus), contact your doctor as you may need to stop taking Xenleta or other medicines. Other infections The chance of catching a different infection caused by another bacterium during or after treatment with Xenleta is reduced. Your doctor will monitor you closely to detect any new infections and will prescribe another treatment if necessary. Children and adolescentsThe use of Xenleta is not recommendedin children and adolescents under 18 years of age. Other medicines and XenletaTell your doctor if you are taking, have recently taken or might take any other medicines, as some medicines may affect the effect of Xenleta or vice versa. The lists below contain only some examples of medicines that should be avoided while taking lefamulin or for which caution is needed. Your doctor will advise you if lefamulin is suitable for you. Do not take any of the following medicines with lefamulin:
• carbamazepine, phenytoin, primidone (for epilepsy);
• efavirenz (for HIV);
• St John's wort, a herbal remedy (for depression or low mood);
• bosentan, diltiazem, amiodarone, sotalol, quinidine, procainamide (for angina, high blood pressure or heart rhythm problems);
• rifampicin, clarithromycin, erythromycin (for bacterial infections);
• fluconazole, itraconazole, posaconazole, voriconazole (for fungal infections);
• ketoconazole (for Cushing’s disease);
• repaglinide (for diabetes);
• nefazodone, amitriptyline or pimozide (for depression or other mental illnesses). Your doctor may need to adjust the dose of some medicines while you are taking lefamulin. These medicines include: * lovastatin, rosuvastatin or simvastatin (to reduce cholesterol levels); * metformin (for diabetes); * ethinylestradiol (used in contraceptive pills). Pregnancy and breastfeedingYou should not be given Xenleta if you are pregnant or if you are breastfeeding. If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor and nurse for advice before you are given this medicine. Driving and using machines

Taking Xenleta does not affect your ability to drive or operate machines.

Xenleta contains sodium
This medicine contains 1.055 mg of sodium (the main component of table salt) per each
administration unit, which is equivalent to 53% of the maximum recommended daily intake
of sodium for an adult.

3. How Xenleta will be administered to you

Xenleta will be administered to you by a doctor or a nurse.
The recommended dose for adults is 150 mg every 12 hours. Xenleta will be administered to you
through an infusion directly into a vein (intravenously) over 1 hour.
Usually a treatment cycle lasts 7 days or more if your doctor recommends it.
Your doctor may decide to complete the treatment cycle by switching from administering
Xenleta intravenously to oral administration for a total duration (infusion and tablets) of 7
days.

If you are given too much Xenleta
Xenleta will be administered to you in hospital by a doctor or a nurse, therefore it is unlikely
that you will be given an excessive amount. Tell your doctor or nurse if you are worried
that they may have given you too much Xenleta.

If you miss a dose of Xenleta
Xenleta will be administered to you in hospital by a doctor or a nurse, therefore it is unlikely
that you will miss a dose. Tell your doctor or nurse if you are worried that you have missed a dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Common: may affect up to 1 in 10 people

• low levels of potassium in the blood (hypokalaemia), which can cause muscle weakness, cramps or abnormal heartbeat
• difficulty sleeping (insomnia)
• headache
• diarrhoea
• feeling unwell (nausea) or being sick (vomiting)
• increase in a particular liver enzyme in the blood (transaminases)
• redness or swelling or pain at the injection site
• changes in heart rhythm (observed with an ECG, which checks the electrical activity of the heart) Uncommon: may affect up to 1 in 100 people
• inflammation of the bowel causing diarrhoea (colitis), due to an infection by a type of bacteria called Clostridioides difficile(previously called Clostridium difficile)
• fungal (yeast) infection of the throat and mouth (thrush or candidiasis)
• fungal (yeast) infection of the vagina and vulva (candidiasis or candidiasis)
• decrease in red blood cells (anaemia), which can make the skin pale and cause weakness or shortness of breath
• decrease in platelets (blood cells that help with blood clotting) leading to an increased risk of bleeding or bruising
• feeling anxious
• dizziness
• feeling tired or sleepy
• beating or irregular heartbeat or palpitations
• pain in the back of the nose and throat
• stomach pain, abdominal pain or around the stomach
• constipation
• indigestion, heartburn or inflammation of the stomach lining (gastritis)
• increase in a liver enzyme in the blood (gamma-glutamyl transferase and alkaline phosphatase)
• increase in a muscle enzyme contained in the blood (creatine phosphokinase)
• difficulty urinating or emptying the bladder completely (urinary retention) Reporting of side effectsIf you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Xenleta

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 label of the vial and on the
outer packaging indicated with EXP. The expiry date refers to the last day of that month.
Concentrate: store in a refrigerator (2°C – 8°C). Do not freeze.
Solvent: store at a temperature below 25 °C. Do not freeze.
After dilution:
the stability of the diluted solution has been demonstrated for 24 hours at room temperature and for 48 hours at
a temperature between 2 °C and 8 °C. Administer immediately after dilution. If not
used immediately, the storage times during use and the conditions before use
are the responsibility of the user and should normally not exceed 24 hours at a
temperature between 2 °C and 8 °C, unless the dilution takes place under controlled and validated aseptic
conditions.
The diluted solution must be clear and colourless and must not be used if it contains particles or if
the solution is cloudy.

6. Package contents and other information

What Xenleta contains

• The active ingredient is lefamulin. Each vial contains lefamulin acetate equivalent to 150 mg of lefamulin.
• The other components for the concentrate are: sodium chloride and water for injections.
• The other components for the solvent are: citric acid (E330), disodium citrate dihydrate (E331), sodium chloride and water for injections.

Description of Xenleta and package contents
Xenleta is a concentrate for infusion solution.
The concentrate is a clear and colourless solution in a glass vial, closed with a rubber stopper and sealed with a removable cap.
The solvent is a clear and colourless solution in a polypropylene infusion bag.
Xenleta is supplied in a package containing 2 vials each containing 15 ml of concentrate and
2 infusion bags each containing 250 ml of solvent.

Marketing authorisation holder and manufacturer
Nabriva Therapeutics Ireland DAC
Alexandra House, Office 225/227
The Sweepstakes,
Ballsbridge
Dublin 4
D04 C7H2
Republic of Ireland
More detailed information on this medicinal product is available on the European Medicines Agency website, http://www.ema.europa.eu .
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The following information is intended exclusively for healthcare professionals:
Instructions for dilution before administration
Parenteral (intravenous) medicines must be visually inspected before
administration to exclude the presence of particles or colour change. Only clear, colourless and particle-free solutions should be diluted.

How to prepare Xenleta for administration
General precautions
Each vial and infusion bag is for single use only.
Standard aseptic techniques must be adopted for the preparation and administration of the solution.
Instructions for dilution and infusion
Xenleta concentrate must be mixed within the solvent bag containing 250 mL
of saline solution buffered with 10 mM citrate and administered by infusion.

• 1. Aseptically withdraw 15 mL of Xenleta from the concentrate vial.
• 2. Transfer the concentrate into the solvent bag containing 250 mL of 0.9 % sodium chloride solution buffered with 10mM citrate.
• 3. Discard any unused portion of the concentrate vial. The concentrate vial and solvent bag are for single use only.
• 4. The diluted solution must be clear and colourless. Where the solution and container permit, parenteral medicines must be visually inspected before administration to exclude the presence of particulates and colour change.
• 5. Administer by intravenous infusion over a period of 60 minutes via direct infusion or a Y-site intravenous infusion set, previously positioned. Avoid rapid or bolus intravenous infusion.
• 6. Administer exclusively by intravenous infusion. Compatibility of reconstituted Xenleta with medicines, additives or substances administered intravenously other than 0.9 % sodium chloride intravenous infusion has not been established.

buffered with 10 mM citrate and 0.9 % sodium chloride intravenous infusion. If
a common intravenous catheter is used to administer other medicines other than Xenleta, it
is necessary to flush it before and after each Xenleta administration with an intravenous infusion of
0.9 % sodium chloride.
Disposal
Unused medicine or waste material from this medicine must be disposed of in accordance with
current local regulations.