SIVEXTRO 200 mg POWDER FOR CONCENTRATE FOR INFUSION SOLUTION

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

Do not use Sivextro:

• if you are allergic to tedizolid phosphate or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Your doctor will decide if Sivextro is suitable for treating your infection.

Talk to your doctor or nurse before you are given Sivextro if any of the following apply to you:

• if you have had diarrhoea or have been treated with antibiotics in the past (or up to 2 months after taking them).
• if you are allergic to other medicines belonging to the group of "oxazolidinones" (e.g. linezolid, cycloserine).
• if you have a history of bleeding or bruising easily (which may be a sign of a low platelet count, the small cells involved in blood clotting).
• if you have kidney problems.
• if you are taking certain medicines for the treatment of depression, called tricyclics, SSRIs (selective serotonin reuptake inhibitors), opioids or MAOIs (monoamine oxidase inhibitors). The use of these medicines with tedizolid phosphate may lead to a serotonin syndrome, a potentially life-threatening condition (with symptoms such as feeling disoriented, difficulty concentrating, high temperature, increased reflexes, difficulty coordinating muscle movements). See Other medicines and Sivextro for examples.
• if you are taking certain medicines for the treatment of migraine called "triptans". See Other medicines and Sivextro for examples.

Talk to your doctor or pharmacist if you are not sure if you are taking any of these medicines.

Diarrhoea

Tell your doctor immediately if you get diarrhoea during or after your treatment. Do not take any medicine to treat diarrhoea without first talking to your doctor.

Resistance to antibiotics

Bacteria may become resistant to treatment with antibiotics over time. This is when antibiotics can no longer stop the growth of bacteria or treat your infection. Your doctor will decide if you should be given Sivextro to treat your infection.

Possible side effects

Some side effects have been seen with Sivextro or another member of the class of oxazolidinones when given for a longer period than recommended for Sivextro. Tell your doctor immediately if you experience any of the following while taking Sivextro:

• low white blood cell count
• anaemia (low red blood cell count)
• bleeding or bruising easily
• loss of sensation in hands or feet (e.g. numbness, tingling/pins and needles or stabbing pain)
• any vision problems, such as blurred vision, changes in colour perception, difficulty seeing details or if your field of vision is restricted.

Children

For adolescents and children weighing at least 35 kg, this medicine is available as 200 mg tablets.

Other medicines and Sivextro

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. It is especially important to tell your doctor if you are also taking:

• amitriptyline, citalopram, clomipramine, dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine, isocarboxazid, lofepramine, moclobemide, paroxetine, phenelzine, selegiline, sertraline, duloxetine and venlafaxine (used to treat depression). There is a risk that tedizolid phosphate may interact with certain medicines, including those listed, and cause side effects such as changes in blood pressure or temperature.
• sumatriptan, zolmitriptan (used to treat migraine)
• opioids (such as fentanyl)

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or nurse for advice before taking this medicine.

It is not known if Sivextro passes into breast milk. Ask your doctor before breast-feeding your baby.

Driving and using machines

Do not drive or use machines if you feel dizzy or tired after using this medicine.

Sivextro contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial; this is essentially "sodium-free".

3. How Sivextro will be given to you

Sivextro will be given to you by a doctor or nurse.

It will be given to you through a drip directly into a vein (by intravenous infusion) over about 1 hour.

Adults, adolescents and children weighing at least 35 kg

You will be given a 200 mg infusion of Sivextro once a day, for 6 days.

Adolescents and children weighing less than 35 kg

Sivextro will be given twice a day for 6 days. The dose will be given based on body weight.

Talk to your doctor if you do not get better, or if you get worse after 6 days.

If you are given more Sivextro than you should

Tell your doctor or nurse immediately if you think you may have been given too much Sivextro.

If you miss a dose of Sivextro

Tell your doctor or nurse immediately if you think you may have missed a dose.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

4. Possible side effects

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

Tell your doctor immediatelyif you get diarrhoea during or after your treatment.

Other side effects may include:

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

• Nausea
• Vomiting
• Headache
• Itching all over the body
• Tiredness
• Dizziness
• Pain or swelling at the infusion site.

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

• Fungal infections (thrush) of the skin, mouth and vagina (vaginal thrush/candidiasis)
• Itching (including itching caused by allergic reaction), hair loss, acne, rash with redness and/or itching or hives, excessive sweating
• Decreased or lost sensation in the skin, tingling/numbness sensation in the skin
• Hot flushes or redness/flushing of the face, neck or upper chest
• Abscess (swollen, infected area with pus)
• Vaginal infection, inflammation or itching
• Anxiety, irritability, restlessness or tremors
• Respiratory tract infection (sinusitis, throat and chest infection)
• Dry nose, chest congestion, cough
• Drowsiness, abnormal sleep pattern, difficulty sleeping, nightmares (unpleasant/disturbing dreams)
• Dry mouth, constipation, indigestion, stomach pain/discomfort (abdomen), retching, dry heaves, bright red blood in the stools
• Acid reflux disorder (heartburn, pain or difficulty swallowing), flatulence/gas
• Joint pain, muscle spasms, back pain, neck pain, pain/discomfort in the limbs, decreased hand grip strength
• Blurred vision, "floaters" (small floating shapes in the field of vision)
• Swollen or enlarged lymph nodes
• Allergic reaction
• Dehydration
• Poor control of diabetes
• Abnormal taste
• Slow heart rate
• Fever
• Swelling of ankles and/or feet
• Unusual urine odour, abnormal blood tests
• Infusion reactions (chills, shivering or chills with fever, muscle pain, facial swelling, weakness, fainting, shortness of breath, chest tightness and angina).

Frequency not known (cannot be estimated from the available data):

• Bleeding or bruising easily (due to a low platelet count, the small cells involved in blood clotting)

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 via 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 Sivextro

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 vial label after "EXP". The expiry date is the last day of the month shown.

This medicine does not require any special storage conditions.

Do not use this medicine if you notice the presence of particles or if the solution is cloudy.

Once opened, this medicine should be used immediately. Otherwise, the reconstituted and diluted solution should be stored at room temperature or in the refrigerator between 2°C and 8°C, and administered within 24 hours after reconstitution.

Disposal of the unused medicine and all materials that have come into contact with it, including materials used for reconstitution, dilution and administration, should be done in accordance with local regulations.

6. Container Contents and Additional Information

Sivextro Composition

• The active ingredient is tedizolid phosphate. Each vial of powder contains tedizolid phosphate disodium, equivalent to 200 mg of tedizolid phosphate.
• The other components are mannitol, sodium hydroxide (for pH adjustment), and hydrochloric acid (for pH adjustment).

Product Appearance and Container Contents

Sivextro is a white to off-white powder for concentrate for solution for infusion, packaged in a glass vial. The powder will be reconstituted in the vial with 4 ml of water for injectable preparations. The reconstituted solution will be withdrawn from the vial and added to a bag of 0.9% sodium chloride solution for hospital infusion.

Sivextro is available in packs of 1 or 6 vials.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

Netherlands

Manufacturer

Patheon Italia S.p.A.

2° Trav. SX Via Morolense, 5

03013 Ferentino

Italy

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Date of last revision of this prospectus: {MM/AAAA}.

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

--------------------------------------------------------------------------------------------------------------------

This information is intended for healthcare professionals only:

Important: Consult the summary of product characteristics before prescribing the medicinal product.

Patients who initiate treatment with the parenteral formulation may be switched to the oral formulation when clinically indicated.

Sivextro should be reconstituted with water for injectable preparations and subsequently diluted in 250 ml of 0.9% sodium chloride solution for infusion.

Only limited data are available on the compatibility of Sivextro with other substances for intravenous administration; consequently, no additives or other medicinal products should be added to the Sivextro single-dose vials, nor should they be co-infused simultaneously. If the same intravenous line is used for sequential infusion of different medicinal products, the line should be flushed before and after infusion with 0.9% sodium chloride solution. Do not use Ringer's lactate or Hartmann's solution.

Reconstitution

To prepare the infusion solution, aseptic technique should be followed. Reconstitute the vial contents with 4 ml of water for injectable preparations, and gently rotate until the powder is completely dissolved. Avoid shaking or rapid movements, as this may cause foam formation.

Dilution

For administration, the reconstituted solution should be diluted in 0.9% sodium chloride solution. Do not shake the bag. The resulting solution is a clear, colorless or pale yellow solution.

Infusion

Visually inspect the reconstituted solution for particles before administration. Reconstituted solutions containing visible particles should be discarded.

Sivextro is administered intravenously over approximately 1 hour.

The reconstituted solution should be administered exclusively as an intravenous infusion. It should not be administered as an intravenous bolus. Sivextro should not be mixed with other medicinal products.

Each vial is for single use only.

Dose preparation

For preparation of the 200 mg Sivextro dose for once-daily infusion (adults, adolescents, and children weighing ≥ 35 kg):

1. Withdraw 4 ml of the reconstituted solution from the vial using a syringe and add it to an infusion bag containing 250 ml of 0.9% sodium chloride solution for injectables.

1. Infuse the entire bag over 1 hour.

For preparation of weight-based doses for twice-daily infusion (for adolescents and children weighing < 35 kg):

1. Preparation of the mother solution (100 ml of 0.8 mg/ml tedizolid phosphate):

Withdraw 1.6 ml of the reconstituted solution from the vial using a syringe and add it to an infusion bag containing 98.4 ml of 0.9% sodium chloride solution for injectables.

1. Preparation of the required volume of the mother solution for infusion:

• Determine the appropriate amount of Sivextro in mg by consulting the following dosing table.

• Transfer the appropriate volume of the mother solution to an infusion bag or a syringe of suitable size. For smaller volumes, it may be necessary to adjust to the nearest graduation mark on a syringe of suitable size.

Table 1. Preparation of Sivextro for infusion from the 100 ml mother solution of 0.8 mg/ml tedizolid phosphate in pediatric patients weighing < 35 kg body weight

• Infuse over 1 hour via a pump or syringe driver.

• This process is repeated for the second dose of the day.

Note: Both doses should be used within the required validity period (see section 6.3 of the Summary of Product Characteristics).