TENKASI 400 MG POWDER FOR CONCENTRATE FOR PERFUSION SOLUTION

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

You must not be givenTenkasi:

• if you are allergic to oritavancin or any of the other ingredients of this medicine (listed in section 6).
• if you are expected to need a medicine that makes your blood less thick (unfractionated heparin) in the next 5 days (120 hours) after the dose of Tenkasi.

Warnings and precautions

Tell your doctor or nurse before you receive Tenkasi if:

• you have ever had an allergic reaction to another glycopeptide antibiotic (such as vancomycin and telavancin)
• you have had severe diarrhea during or after antibiotic treatment in the past.
• you have or are suspected to have a bone infection caused by bacteria (osteomyelitis). Your doctor will treat you accordingly
• You have or are suspected to have a painful accumulation of pus in the skin (abscess). Your doctor will treat you accordingly.

Intravenous infusions of Tenkasi may cause redness of the upper body, hives, itching, and/or rash. Infusion-related reactions such as chest pain, chest discomfort, chills, shivers, back pain, neck pain, shortness of breath, abdominal pain, fever, and headache, fatigue, drowsiness that could be symptoms of hypoxia have also been observed. If you experience reactions of this type, your doctor may decide to stop or slow down the infusion.

Tenkasi may interfere with laboratory tests that measure blood clotting and may produce a false reading.

Although antibiotics, including Tenkasi, fight certain bacteria, they may not be active against other bacteria or fungi, which may continue to grow. This is called overgrowth. Your doctor will monitor you for this and treat you if necessary.

After you are given Tenkasi, you may develop a new infection in another area of the skin. Your doctor should monitor you for this and treat you accordingly.

Children and adolescents

Tenkasi must not be used in children under 3 months of age. The use of Tenkasi has not been studied in this age group.

Use of Tenkasi with other medicines

Tell your doctor if you are using, have recently used, or might use any other medicines.

If you are going to be given a medicine to make your blood less thick called unfractionated heparin, tell your doctor if you have received Tenkasi in the last 5 days (120 hours).

It is especially important that you tell your doctor if you are using medicines that prevent blood clotting (oral anticoagulants, e.g. coumarin anticoagulants). Tenkasi may interfere with laboratory tests or self-tests that measure blood clotting (INR), and may produce a false reading up to 12 hours after infusion.

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 using this medicine.

You should not receive this medicine during pregnancy unless your doctor considers that the benefit is greater than the risk to the baby.

Driving and using machines

Tenkasi can make you feel dizzy, so it may affect your ability to drive or use machines.

3. How you will be given Tenkasi

Your doctor or nurse will give you Tenkasi by infusion (drip) into a vein.

In adults, the recommended dose of Tenkasi is a single infusion of 1,200 mg administered into a vein over 3 hours.

For pediatric patients from 3 months of age, the recommended dose of Tenkasi will be calculated based on weight and age: a single infusion of 15 mg per kilogram of body weight administered into a vein over 3 hours (maximum 1,200 mg). See section 6 for further details.

If you use more Tenkasi than you should

Your doctor will decide how to treat you, as well as when to stop treatment and monitor signs of side effects.

4. Possible side effects

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

Tell your doctor or nurse immediately if you experience an infusion reaction, including any of the following symptoms:

• redness of the face and upper body, hives, itching, and/or rash;
• wheezing (high-pitched sound when breathing);
• shortness of breath;
• swelling around the throat or under the skin that appears in a short space of time;
• chills or shivers;
• fast or weak pulse;
• chest pain or tightness;
• Decrease in blood pressure (may make you feel weak or dizzy).

Such reactions can be life-threatening.

Other side effects occur with the following frequencies:

Common side effects (may affect up to 1 in 10 patients):

• fewer red blood cells or less hemoglobin than normal;
• dizziness;
• headache;
• feeling sick (nausea) or vomiting;
• diarrhea;
• constipation;
• pain or irritation at the injection site;
• itching, skin rash;
• muscle pain;
• higher levels of liver enzymes (as shown by blood tests);
• fast heart rate;
• worsening of an infection or new infection in another area of the skin;
• swollen and red area of the skin or under the skin with a feeling of heat and pain when touched;
• accumulation of pus under the skin.

Uncommon side effects (may affect up to 1 in 100 patients):

• higher than normal levels of eosinophils, a type of white blood cell (eosinophilia);
• low blood sugar levels;
• high levels of uric acid in the blood;
• increased levels of bilirubin in the blood;
• severe skin rash;
• hot flashes;
• inflammation around a tendon (known as tenosynovitis);
• bone infection caused by bacteria (known as osteomyelitis);
• decrease in platelet count in the blood below the lower limit of normal (known as thrombocytopenia);
• Abdominal pain
• Chest pain
• Fever
• Shortness of breath

Rare side effects (may affect up to 1 in 1,000 patients):

• Headache, fatigue, drowsiness that may be symptoms of hypoxia;
• Back pain
• Neck pain
• Chills
• Shivers

Additional side effects in children and adolescents

The side effects in pediatric patients are similar to those observed in adults. The side effects observed only in pediatric patients are: irritability, changes in the ECG tracing (transient, asymptomatic, and not associated with other changes in the ECG tracing), intestinal infection (Clostridioides difficile colitis).

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 Tenkasi

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. The expiry date is the last day of the month stated.

Do not store above 25°C.

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

6. Container Contents and Additional Information

Composition ofTenkasi

• The active ingredient is oritavancin. Each vial contains oritavancin diphosphate equivalent to 400 mg of oritavancin.
• The other ingredients are mannitol and phosphoric acid.

Appearance and Container Contents of the Product

• Tenkasi is a powder for concentrate for solution for infusion
• Tenkasi is a white to off-white powder, supplied in a 50 ml glass vial.
• Tenkasi is marketed in boxes of 3 vials.

Marketing Authorization Holder

Menarini International Operations Luxembourg S.A.

1, Avenue de la Gare

L-1611, Luxembourg

Luxembourg

Manufacturer

Biologici Italia Laboratories S.r.l

Via Filippo Serpero 2

20060 Masate (MI)

Italy

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:07/2021

Other Sources of Information

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 for healthcare professionals only:

Tenkasi is intended for intravenous (IV) administration only after reconstitution and dilution.

Tenkasi should be prepared using aseptic techniques in a pharmacy.

The powder should be reconstituted with water for injections and the resulting concentrate should be diluted in an intravenous infusion bag with 5% glucose before use. Both the reconstituted solution and the diluted infusion solution should be clear and colorless or pale yellow. Parenteral drugs should be inspected visually for particulate matter after reconstitution. Aseptic techniques should be used for the preparation of Tenkasi.

Adults

It is necessary to reconstitute and dilute three vials of Tenkasi 400 mg to prepare a single IV dose of 1200 mg for single use.

Reconstitution: an aseptic technique should be used to reconstitute three vials of 400 mg of Tenkasi.

• 40 ml of water for injections should be added using a sterile syringe to reconstitute each vial to provide a 10 mg/ml solution per vial.
• In order to avoid excessive foam formation, it is recommended to add the water for injections carefully along the walls of the vials.
• Each vial should be gently swirled to avoid foam formation and to ensure that all the Tenkasi powder is completely reconstituted in the solution.

The reconstituted solution should be further diluted in an intravenous infusion bag with 5% glucose immediately.

Dilution: three reconstituted vials are required for dilution for the administration of a single IV infusion of 1200 mg. Only a 5% glucose intravenous bag (D5W) should be used for dilution.

For dilution:

• 120 ml should be withdrawn and discarded from a 1000 ml intravenous bag of 5% glucose.
• 40 ml should be withdrawn from each of the three reconstituted vials and added to a 5% glucose intravenous bag to bring the bag volume to 1000 ml. This provides an oritavancin concentration of 1.2 mg/ml. PP (polypropylene) or PVC (polyvinyl chloride) bags should be used for preparation for administration.

Use in the pediatric population (from 3 months to <18 years of age)< p>

Calculate the required dose of oritavancin based on the patient's weight (a single infusion of 15 mg/kg administered intravenously over 3 hours).

Determine the number of oritavancin vials required for the patient (each vial contains 400 mg).

Reconstitution:

• 40 ml of water for injections should be added using a sterile syringe to reconstitute each vial to obtain a 10 mg/ml solution per vial.
• • In order to avoid excessive foam formation, it is recommended to add the water for injections carefully along the walls of the vials.

• Each vial should be gently swirled to avoid foam formation and to ensure that all the powder is completely reconstituted in the solution.

Dilution: only a 5% glucose intravenous bag (D5W) should be used for dilution. Sodium chloride solution should not be used for dilution (see section 6.2).

Dilution:

Withdraw the required volume of oritavancin with a sterile syringe and add it to the intravenous bag containing sterile D5W (see the corresponding example in Table 1). The size of the intravenous bag will depend on the total administered volume. For small volumes, a syringe pump can be used.

Table 1: 15 mg/kg of Oritavancin: 3-hour Infusion (Concentration of 1.2 mg/ml)

Calculations

1. Use the patient's actual weight - ROUND ONLY TO THE NEAREST WHOLE NUMBER
2. Dose: Weight (kg) x 15 mg/kg = ______ mg (Maximum dose 1200 mg)
3. Total infusion volume: Dose (mg) ÷ 1.2 mg/ml = _______ ml
4. Volume of Reconstituted Oritavancin: Dose (mg) ÷ 10 =______ ml
5. Volume of D5W to add to IV bag: Total infusion volume (C) - Volume of Reconstituted Oritavancin (D) = _______ ml

The diluted solution should be used immediately.

From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally should not exceed 12 hours at a temperature of 25 °C and 24 hours at a temperature between 2 °C and 8 °C for Tenkasi diluted in an intravenous infusion bag with 5% glucose, unless the reconstitution and dilution have taken place in controlled and validated aseptic conditions.