XERAVA 100 mg POWDER FOR CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Xerava 100 mg powder for concentrate for solution for infusion

eravacycline

Read all of this leaflet carefully before you start receiving this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

1. What is Xerava and what is it used for
2. What you need to know before you receive Xerava
3. How Xerava will be administered
4. Possible side effects
5. Storage of Xerava
6. Contents of the pack and other information

1. What is Xerava and what is it used for

What is Xerava

Xerava is an antibiotic that contains the active substance eravacycline. It belongs to a group of antibiotics called "tetracyclines" that work by stopping the growth of certain infectious bacteria.

What Xerava is used for

Xerava is used to treat adults who have a complicated infection in the abdomen.

2. What you need to know before you receive Xerava

You must not receive Xerava

• if you are allergic to eravacycline or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to any antibiotic of the tetracycline group (e.g. minocycline and doxycycline), as you may also be allergic to eravacycline.

Warnings and precautions

Talk to your doctor or nurse before you start receiving Xerava if you are concerned about any of the following:

Anaphylactic reactions

Anaphylactic reactions (allergic reactions) have been reported with other antibiotics of the tetracycline group. These reactions can occur suddenly and can be life-threatening. Seek urgent medical attentionif you suspect you are having an anaphylactic reaction during treatment with Xerava. The symptoms to watch out for are skin rash, swelling of the face, feeling dizzy or faint, chest tightness, difficulty breathing, rapid heartbeat, or loss of consciousness (see also section 4).

Diarrhea

Talk to your doctor or nurse if you have diarrhea before receiving Xerava. If you get diarrhea during or after treatment, tell your doctor immediately. Do not take any medicine to treat diarrhea without talking to your doctor first (see also section 4).

Infusion site reactions

Xerava is given by infusion (drip) directly into a vein. Tell your doctor or nurseif you notice any of the following effects at the infusion site during or after treatment: skin redness, skin rash, inflammation, and pain or tenderness.

New infection

Although Xerava fights certain bacteria, other bacteria and fungi can still grow. This is called "overgrowth" or "superinfection". Your doctor will monitor you closely for any new infection or will stop treatment with Xerava and give you another treatment if necessary.

Pancreatitis

Severe abdominal and back pain with fever may be a sign of pancreas inflammation. Tell your doctor or nurse if you notice any of these side effects during treatment with Xerava.

Liver problems

Tell your doctor if you have liver problems or are overweight, especially if you are also taking itraconazole (a medicine used to treat fungal infections), ritonavir (a medicine used to treat viral infections), or clarithromycin (an antibiotic), as your doctor will monitor you for possible side effects.

Children and adolescents

This medicine must not be used in children and adolescents under 18 years of age, as it has not been studied sufficiently in these populations. Xerava must not be used in children under 8 years of age, as it may affect teeth permanently with a change in color.

Other medicines and Xerava

Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines, such as rifampicin and clarithromycin (antibiotics), phenobarbital, carbamazepine, and phenytoin (used to treat epilepsy), St. John's Wort (a herbal medicine used to treat depression and anxiety), itraconazole (a medicine used to treat fungal infections), ritonavir, atazanavir, lopinavir, and saquinavir (medicines used to treat viral infections), and cyclosporin (a medicine used to suppress the immune system).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before receiving this medicine. Xerava is not recommended during pregnancy, as it may:

• permanently stain the fetus's teeth;
• delay the natural formation of the fetus's bones.

It is not known if Xerava passes into breast milk. Long-term use of other similar antibiotics by breastfeeding mothers may permanently stain the child's teeth. Ask your doctor for advice before breastfeeding your child.

Driving and using machines

Xerava may affect your ability to drive or use machines. Do not drive or use machines if you feel dizzy, drowsy, or unsteady after receiving this medicine.

3. How Xerava will be administered

Your doctor or nurse will administer Xerava to you.

The recommended dose for adults depends on body weight and is 1 mg/kg every 12 hours. Your doctor may increase the dose (1.5 mg/kg every 12 hours) if you are taking other medicines such as rifampicin, phenobarbital, carbamazepine, phenytoin, or St. John's Wort.

It will be administered by infusion directly into a vein (intravenously) over approximately 1 hour.

A treatment cycle usually lasts from 4 to 14 days. Your doctor will decide how long you should receive treatment.

If you receive more Xerava than you should

A doctor or nurse will administer Xerava to you in a hospital. Therefore, it is unlikely that you will receive too much. Tell your doctor or nurse immediately if you are concerned that you may have received too much Xerava.

If you miss a dose of Xerava

A doctor or nurse will administer Xerava to you in a hospital. Therefore, it is unlikely that you will miss a dose. Tell your doctor or nurse immediately if you are concerned that you may have missed a dose.

4. Possible side effects

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

Seek urgent medical attentionif you suspect you are having an anaphylactic reaction or experience any of the following symptoms during treatment with Xerava:

• skin rash
• swelling of the face
• feeling dizzy or faint
• chest tightness
• difficulty breathing
• rapid heartbeat
• loss of consciousness

Tell your doctor or nurse immediatelyif you experience diarrhea during or after treatment. Do not take any medicine to treat diarrhea without talking to your doctor first.

Other side effects may be:

Common(may affect up to 1 in 10 people):

• nausea
• vomiting
• inflammation and pain caused by blood clots at the injection site (thrombophlebitis)
• inflammation of a vein that causes pain and swelling (phlebitis)
• redness or swelling at the injection site
• low levels of fibrinogen in the blood (a protein involved in blood clotting)
• blood test results that indicate a decrease in blood clotting ability

Uncommon(may affect up to 1 in 100 people):

• diarrhea
• allergic reaction
• inflammation of the pancreas, which causes severe abdominal or back pain (pancreatitis)
• skin rash
• dizziness
• headache
• increased sweating
• abnormal liver test results in blood tests

Tell your doctor or nurse if you experience any of these side effects.

Other tetracycline antibiotics

Other side effects have been reported with other tetracyclines, such as minocycline and doxycycline. These include sensitivity to light, headache, vision problems, or abnormal blood test results. Tell your doctor or nurse if you notice any of these side effects during treatment with Xerava.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Xerava

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 after "EXP" and on the carton after "CAD". The expiry date is the last day of the month shown.

Store in a refrigerator (2°C - 8°C). Keep the vial in the outer carton to protect it from light.

Once the powder has been reconstituted and diluted and is ready for use, it must be administered immediately. Otherwise, it can be stored at room temperature and used within 12 hours.

Xerava reconstituted must be a clear solution with a color between light yellow and orange. The solution must not be used if it appears to contain solid particles or is cloudy.

6. Container Content and Additional Information

Xerava Composition

The active ingredient is eravacycline. Each vial contains 100 mg of eravacycline.

The other components are mannitol (E421), hydrochloric acid (for pH adjustment), and sodium hydroxide (for pH adjustment).

Product Appearance and Container Content

Xerava is a compacted powder with a color ranging from light yellow to dark yellow in a 10 ml glass vial. The powder for concentrate for solution for infusion (powder for concentrate) will be reconstituted in the vial with 5 ml of water or with 5 ml of a 9 mg/ml (0.9%) sodium chloride solution for injectable preparations. The reconstituted solution will be extracted from the vial and added to an infusion bag of injectable solution of 9 mg/ml (0.9%) sodium chloride in the hospital.

Xerava is available in containers that contain 1 vial, 10 vials, or in multiple containers that contain 12 boxes, each with 1 vial.

Only some package sizes may be marketed.

Marketing Authorization Holder

PAION Pharma GmbH

Heussstraße 25

52078 Aachen

Germany

Manufacturer

PAION Pharma GmbH

Heussstraße 25

52078 Aachen

Germany

PAION Deutschland GmbH

Heussstraße 25

52078 Aachen

Germany

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Prospectus:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

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This information is intended only for healthcare professionals:

Important: Before prescribing this medicinal product, consult the Summary of Product Characteristics or Package Leaflet.

Xerava must be reconstituted with water for injectable preparations or with a 9 mg/ml (0.9%) sodium chloride solution for injectable preparations and then diluted with a 9 mg/ml (0.9%) sodium chloride injectable solution.

Xerava must not be mixed with other medicinal products. If the same intravenous line is used for the sequential infusion of different medicinal products, the line must be flushed before and after infusion with a 9 mg/ml (0.9%) sodium chloride injectable solution.

The dose must be calculated based on the patient's weight: 1 mg/kg body weight.

Reconstitution Instructions

Aseptic technique must be used to prepare the infusion solution. Each vial must be reconstituted with 5 ml of water for injectable preparations or with 5 ml of a 9 mg/ml (0.9%) sodium chloride solution for injectable preparations and gently rotated until the powder is completely dissolved. Avoid agitation or rapid movement, as this may cause foam formation.

Reconstituted Xerava must be a clear solution with a color ranging from light yellow to orange. The solution must not be used if it contains solid particles or is turbid.

Preparation of the Infusion Solution

For administration, the reconstituted solution must be further diluted with a 9 mg/ml (0.9%) sodium chloride injectable solution. The calculated volume of the reconstituted solution must be added to the infusion bag to achieve a target concentration of 0.3 mg/ml, within a range of 0.2 to 0.6 mg/ml. Table 1 provides examples of calculations.

Gently invert the bag to mix the solution.

Table 1: Examples of Calculations for Weights between 40 kg and 200 kg1

1 The exact dose must be calculated based on the patient's specific weight.

For patients who weigh between ≥ 40 kg and 49 kg:

Calculate the required volume of reconstituted solution based on the patient's weight and inject it into a 100 ml infusion bag.

For patients who weigh between 50 kg and 100 kg:

Calculate the required volume of reconstituted solution based on the patient's weight and inject it into a 250 ml infusion bag.

For patients who weigh > 100 kg:

Calculate the required volume of reconstituted solution based on the patient's weight and inject it into a 500 ml infusion bag.

Infusion

The infusion solution must be visually inspected for the presence of solid particles before administration.

Reconstituted and diluted solutions that contain visible solid particles or appear turbid must be discarded.

After dilution, Xerava is administered intravenously over approximately 1 hour. The recommended dosage regimen for Xerava is 1 mg/kg every 12 hours for 4 to 14 days.

The reconstituted and diluted solution must be administered only by intravenous infusion. It must not be administered as an intravenous bolus.

For single use; unused solution must be discarded.