Xerava 100 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Xerava 100 mg powder for concentrate for solution for infusion

eravacycline

Read the entire leaflet carefully before you start receiving this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

1. What Xerava is and what it is used for
2. What you need to know before receiving Xerava
3. How Xerava is administered
4. Possible adverse effects
5. How to store Xerava
6. Contents of the pack and other information

1. What Xerava is and what it is used for

What Xerava is

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

What Xerava is used for

Xerava is used to treat adolescents from the age of 12 who weigh at least 50 kg and adults who have a complicated infection in the abdomen.

2. What you need to know before you start receiving Xerava

Do not receive Xerava

• if you are allergic to eravacycline or to 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 starting Xerava if you are concerned about any of the following:

Anaphylactic reactions

Anaphylactic (allergic) reactions have been reported with other antibiotics in the tetracycline group. These reactions may occur suddenly and can be potentially life-threatening. Seek urgent medical attention if you suspect you are experiencing an anaphylactic reaction during treatment with Xerava. Symptoms to watch for include rash, facial swelling, dizziness or fainting, 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 develop diarrhea during or after treatment, inform your doctor immediately. Do not take any medication for diarrhea without first consulting your doctor (see also section 4).

Infusion site reactions

Xerava is administered by intravenous infusion (drip) directly into a vein. Inform your doctor or nurse if you notice any of the following at the infusion site during or after treatment: redness of the skin, rash, swelling and pain, or tenderness.

New infection

Although Xerava fights certain bacteria, other bacteria and fungi may continue to grow. This is known as "overgrowth" or "superinfection." Your doctor will closely monitor you for any new infection or may stop treatment with Xerava and provide alternative treatment if necessary.

Pancreatitis

Severe pain in the abdomen and back accompanied by fever may be a sign of inflammation of the pancreas. Inform your doctor or nurse if you experience any of these adverse effects during treatment with Xerava.

Liver problems

Inform 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 adverse effects.

Children and adolescents

This medicine must not be used in children under 12 years of age or in adolescents weighing less than 50 kg. Xerava must not be used in children under 8 years of age, as it may permanently affect teeth, causing discoloration.

Other medicines and Xerava

Inform your doctor or nurse if you are taking, have recently taken, or might need to 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 cyclosporine (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 become pregnant, consult your doctor before receiving this medicine. Xerava is not recommended during pregnancy, as it may:

• permanently stain the unborn baby’s teeth;
• delay the natural formation of the unborn baby’s bones.

It is not known whether Xerava passes into breast milk. Long-term use of other similar antibiotics in breastfeeding mothers may permanently stain the child’s teeth. Consult your doctor before breastfeeding your baby.

Driving and using machines

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

3. How Xerava will be administered to you

Your doctor or nurse will administer Xerava to you.

The recommended dose 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 given by intravenous infusion (directly into a vein) over approximately 1 hour.

A course of treatment usually lasts from 4 to 14 days. Your doctor will decide how long your treatment should continue.

If you receive more Xerava than you should

Xerava will be administered to you by a doctor or nurse in a hospital. Therefore, it is unlikely that you will receive an excessive amount. Immediately inform your doctor or nurse if you are concerned that you may have received too much Xerava.

If you miss a dose of Xerava

Xerava will be administered to you by a doctor or nurse in a hospital. Therefore, it is unlikely that you will miss a dose. Immediately inform your doctor or nurse if you are concerned that a dose may have been missed.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Seek immediate medical attention if you suspect you are having an anaphylactic reaction or develop any of the following symptoms during treatment with Xerava:

• rash
• swelling of the face
• dizziness or fainting
• chest tightness
• difficulty breathing
• rapid heartbeat
• loss of consciousness

Tell your doctor or nurse immediately if you develop diarrhoea during or after treatment. Do not take any medicine for diarrhoea without first consulting your doctor.

Other possible adverse effects include:

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

• nausea

• vomiting

• swelling and pain due to blood clots at the injection site (thrombophlebitis)

• inflammation of a vein causing 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 indicating reduced blood clotting ability

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

• diarrhoea
• allergic reaction
• inflammation of the pancreas causing severe abdominal or back pain (pancreatitis)
• rash
• dizziness
• headache
• increased sweating
• abnormal liver function test results in blood tests

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

Other antibiotics in the tetracycline group

Other adverse effects have been reported with other tetracyclines such as minocycline and doxycycline. These include sensitivity to light, headache, vision problems, or abnormalities in blood tests. Inform your doctor or nurse if you notice any of these adverse effects during treatment with Xerava.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or nurse, even if it is an adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse 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 refers to the last day of the month indicated.

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

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

Reconstituted Xerava should be a clear solution ranging in colour from pale yellow to orange. Do not use the solution if it appears to contain solid particles or is cloudy.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Xerava

The active substance 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).

Appearance of the product and contents of the container

Xerava is a compacted powder ranging in color 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 9 mg/ml (0.9%) sodium chloride solution for injectable preparations. The reconstituted solution will be withdrawn from the vial and added to an intravenous infusion bag containing 9 mg/ml (0.9%) sodium chloride injectable solution in the hospital.

Xerava is available in pack sizes containing 1 vial, 10 vials, or multiple packs containing 12 boxes, each with 1 vial.

Only certain pack 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

For further information regarding this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this package leaflet:

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

This information is intended for healthcare professionals only:

Important: Before prescribing this medicine, consult the Summary of Product Characteristics.

Xerava must be reconstituted with Water for Injections or with 9 mg/ml (0.9%) Sodium Chloride Solution for Injections and subsequently diluted with 9 mg/ml (0.9%) Sodium Chloride Solution for Infusion.

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 administration with 9 mg/ml (0.9%) Sodium Chloride Solution for Infusion.

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

Reconstitution instructions

Aseptic technique must be used when preparing the infusion solution. Each vial must be reconstituted with 5 ml of Water for Injections or with 5 ml of 9 mg/ml (0.9%) Sodium Chloride Solution for Injections and gently swirled until the powder is completely dissolved. Shaking or rapid movements should be avoided, as they may cause foaming.

Reconstituted Xerava must be a clear solution ranging in colour from pale yellow to orange. The solution must not be used if it contains solid particles or appears cloudy.

Preparation of the infusion solution

For administration, the reconstituted solution must be further diluted with 9 mg/ml (0.9%) Sodium Chloride Solution for Infusion. The calculated volume of reconstituted solution should 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. Examples of dosage calculations are provided in Table 1 (adults) and Table 2 (adolescents aged 12 to 17 years weighing at least 50 kg).

Gently invert the infusion bag to mix the solution.

Table 1: Examples of dosage calculations for adult patients weighing between 40 kg and 200 kg¹

1 The exact dose must be calculated according to the patient's body weight.

For adult patients weighing between ≥ 40 kg and < 50 kg:

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

For adult patients weighing 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 adult patients weighing > 100 kg:

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

Table 2 Examples of calculations for adolescent patients (12–17 years) weighing between 50 and 90 kg¹

1 The exact dose should be calculated according to the weight of each individual patient.

For adolescent patients weighing between 50 kg and 90 kg:

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

Infusion

The infusion solution should be visually inspected for the presence of solid particles prior to administration.

Reconstituted and diluted solutions containing visible solid particles or appearing cloudy should be discarded.

After dilution, Xerava must be administered intravenously over approximately 1 hour. The recommended dosing regimen for Xerava is 1 mg/kg every 12 hours for a duration of 4 to 14 days.

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

For single use only; any unused solution must be discarded.