Zivoxid

Leaflet attached to the packaging: patient information

Zyvoxid, 2 mg/ml, solution for infusion

Linezolid

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm them, even if their symptoms are the same as yours.
• If any of the side effects get worse or if you notice any side effects not listed in the leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Zyvoxid and what is it used for
• 2. Important information before taking Zyvoxid
• 3. How to take Zyvoxid
• 4. Possible side effects
• 5. How to store Zyvoxid
• 6. Contents of the pack and other information

1. What is Zyvoxid and what is it used for

Zyvoxid is an antibacterial medicine, belonging to the class of antibiotics - oxazolidinones.
Zyvoxid is used to treat pneumonia, complicated skin and soft tissue infections.
Your doctor will decide if Zyvoxid is suitable for treating a specific infection.

2. Important information before taking Zyvoxid

When not to take Zyvoxid

• If you are allergic (hypersensitive) to linezolid or any of the other ingredients of this medicine (listed in section 6).
• If you are currently taking or have taken in the last 2 weeks a medicine from a group called monoamine oxidase inhibitors (e.g. phenelzine, isocarboxazid, selegiline, moclobemide). These medicines are used to treat depression or Parkinson's disease.
• If you are breastfeeding. The medicine passes into human milk and may harm your baby.

Warnings and precautions

If any of the following cases occur, you should inform your doctor.
Your doctor may decide to use Zyvoxid or another treatment method. However, before starting treatment, you should have a general examination and blood pressure check, which will be repeated throughout the treatment period. If you have any doubts about the cases described below, ask your doctor.

• If you have high blood pressure.
• If you have hyperthyroidism.
• If you have a pheochromocytoma (a tumor of the adrenal gland) or a carcinoid (a tumor of the hormonal system with symptoms such as diarrhea, flushing, wheezing).
• If you have bipolar depression, schizoaffective disorders (disorders in which symptoms of schizophrenia and affective disorders, i.e. depression or mania, occur at the same time), disorientation or other mental disorders.
• If you have had hyponatremia (low sodium levels in the blood) or if you are taking medicines that lower sodium levels in the blood, such as certain diuretics (also called "water pills"), such as hydrochlorothiazide.
• If you are taking any opioid medicines.
• If you are taking any of the medicines listed in the "Zyvoxid and other medicines" section.

Taking Zyvoxid with other medicines may cause side effects, such as changes in blood pressure, temperature, or heart rate.

Inform your doctor if you are taking or have taken any of the following medicines in the last 2 weeks

the following medicines(see section 2):

• monoamine oxidase inhibitors (e.g. phenelzine, isocarboxazid, selegiline, moclobemide). These medicines are used to treat depression or Parkinson's disease.

You should also inform your doctor if you are taking any of the following medicines. In this case, your doctor will decide whether to use Zyvoxid. Before starting treatment with Zyvoxid, you should have a general examination and blood pressure check, which will be repeated throughout the treatment period. In other cases, your doctor will decide whether to use another treatment.

• Decongestant medicines used for colds or flu that contain pseudoephedrine or phenylpropanolamine.
• Medicines used to treat asthma, such as salbutamol, terbutaline, fenoterol.
• Tricyclic antidepressants or selective serotonin reuptake inhibitors, such as amitriptyline, citalopram, clomipramine, dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine, lofepramine, paroxetine, sertraline.
• Medicines used to treat migraines, such as sumatriptan and zolmitriptan.
• Medicines used to treat severe allergic reactions, such as adrenaline (epinephrine).
• Medicines that increase blood pressure, such as noradrenaline (norepinephrine), dopamine, dobutamine.
• Opioids, such as pethidine, used to treat moderate to severe pain.
• Anxiolytics, such as buspirone.
• Anticoagulants, such as warfarin.
• Antibiotics, such as rifampicin.

Tell your doctor about all the medicines you are taking or have recently taken, as well as any medicines you plan to take.

Zyvoxid with food and drink

• During treatment, you should limit your intake of foods such as mature cheeses, yeast extracts, soy products (e.g. soy sauce), and alcoholic beverages, especially beer and wine. These products contain tyramine, which can react with Zyvoxid, leading to increased blood pressure.
• If you experience a throbbing headache after eating or drinking, tell your doctor.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Zyvoxid should not be used in pregnant women unless your doctor considers that the potential benefit to the mother outweighs the risk to the fetus. If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, ask your doctor for advice before taking this medicine.
Zyvoxid should not be used during breastfeeding. You should stop breastfeeding before starting and during treatment with linezolid. The medicine passes into human milk and may harm your baby.

Driving and using machines

Zyvoxid may cause dizziness and vision disturbances. Do not drive or operate any machines in this case. Remember that feeling unwell can affect your ability to drive and use machines.

Zyvoxid contains glucose and sodium

Glucose

Each 1 ml of Zyvoxid solution for infusion contains 45.7 mg of glucose (i.e. 4.57 g in one infusion bag containing 100 ml of solution and 13.7 g of glucose in one infusion bag containing 300 ml of solution).
This should be taken into account in patients with diabetes or other conditions associated with glucose intolerance.

Sodium

Each 1 ml of Zyvoxid solution for infusion contains 0.38 mg of sodium (the main component of common salt) (i.e. 38 mg of sodium in one infusion bag containing 100 ml of solution and 114 mg of sodium in one infusion bag containing 300 ml of solution). This corresponds to 1.9% of the maximum recommended daily intake of sodium in the diet for adults in the case of a 100 ml infusion bag or 5.7% of the maximum recommended daily intake of sodium in the diet for adults in the case of a 300 ml infusion bag.
This should be taken into account in patients with reduced kidney function and in patients controlling their sodium intake.

3. How to take Zyvoxid

Zyvoxid is given by infusion into a vein by a doctor or qualified healthcare professional.
For detailed dosing and information on administration and incompatibilities, see "Information intended for healthcare professionals only" at the end of the leaflet.

Use in adults

The usual dose of Zyvoxid for adults (18 years and older) is 300 ml of solution (600 mg of linezolid) given twice a day by intravenous infusion over 30 to 120 minutes.
Dialysis patients are given Zyvoxid after dialysis.
Zyvoxid is usually given for 10 to 14 days, but no longer than 28 days. The safety and efficacy of using Zyvoxid for more than 28 days have not been established. Your doctor will decide on the duration of treatment.
During treatment with Zyvoxid, your doctor will recommend regular blood tests to monitor your blood cell count.
If Zyvoxid is given for more than 28 days, a vision test should be performed.

Use in children and adolescents

Zyvoxid should not be used in children and adolescents under 18 years of age.

Overdose of Zyvoxid

If you think you have been given too much medicine, contact your doctor or healthcare professional immediately.

Missed dose of Zyvoxid

Since the medicine will be given under close medical supervision, missing a dose is unlikely. However, if you suspect that a dose has been missed, you should always inform your doctor or nurse. Do not take a double dose to make up for a missed dose.
If you have any further questions about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Zyvoxid can cause side effects, although not everybody gets them.
If you experience any of the following side effects, tell your doctor, healthcare professional, or pharmacist immediately:

• severe skin reactions, such as redness, peeling of the skin (dermatitis), rash, itching, or swelling, especially on the face and neck (not very common), wheezing and (or) difficulty breathing (rare); these may be signs of an allergic reaction and in this case, it may be necessary to stop taking Zyvoxid; skin reactions, such as a purple rash caused by inflammation of blood vessels (rare);

Patients who took Zyvoxid for more than 28 days reported numbness, tingling, or changes in vision. If you experience any changes in vision, you should contact your doctor immediately.

Other side effects, listed by frequency

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

• fungal infections, especially oral thrush or vaginal thrush;
• headache;
• metallic taste in the mouth;
• diarrhea, nausea, or vomiting;
• changes in blood cell count or blood test results, including measurements of proteins, salts, or enzymes, used to evaluate kidney, liver, or blood sugar function;
• bleeding, bruising, or unexplained bleeding, which may be caused by changes in the blood cell count, affecting blood clotting and potentially leading to anemia;
• decrease in platelet count.

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

• vaginal or vulvar infection in women;
• sleep disorders (insomnia);
• dizziness, sensory disturbances, such as numbness, tingling, or loss of sensation;
• blurred vision;
• "ringing" in the ears (tinnitus);
• increased blood pressure, inflammation of veins with possible blood clots;
• indigestion, abdominal pain, constipation;
• dryness or pain in the mouth, swelling, irritation, or discoloration of the tongue;
• hives, skin inflammation, itching, rash;
• pain at the infusion site or in the area of the infusion site;
• inflammation of veins (including at the infusion site);
• polyuria;
• fever or chills, pain, or general discomfort;
• fatigue or thirst;
• pancreatitis;
• increased sweating;
• changes in blood cell count, which may affect the ability to fight infections;
• decrease in all types of blood cells;
• weakness or sensory changes.

Rare(may affect up to 1 in 1,000 people):

• changes in heart rate;
• transient ischemic attacks (temporary disturbances in blood flow to the brain, causing short-term symptoms such as loss of vision, weakness, slurred speech, loss of consciousness);
• kidney failure;
• anemia;
• allergic reactions (anaphylaxis);
• lactic acidosis (recurring nausea and vomiting, abdominal pain, increased respiratory rate).

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

• serotonin syndrome (increased heart rate, confusion, hallucinations, tremors, seizures, rapid breathing, and diarrhea, suggesting serotonin syndrome) when used with selective serotonin reuptake inhibitors or opioids (see section 2);
• seizures;
• hair loss;
• low sodium levels in the blood;
• color vision disturbances, difficulty seeing details, or narrowing of the visual field;
• bone marrow suppression.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder or its representative.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Zyvoxid

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after: EXP.
The expiry date refers to the last day of the month.
Store at a temperature not exceeding 25°C.
Do not use the medicine if the bag is leaking or the protective foil is damaged. Do not use the medicine if the solution is not clear or contains solid particles.
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. Contents of the pack and other information

What Zyvoxid contains

• The active substance is linezolid. 1 ml of solution contains 2 mg of linezolid.
• The other ingredients are: sodium citrate dihydrate; anhydrous citric acid; glucose; 10% sodium hydroxide solution to pH 4.8; 10% hydrochloric acid solution to pH 4.8; water for injections (see section 2 "Zyvoxid contains glucose and sodium").

What Zyvoxid looks like and contents of the pack

The solution is isotonic, clear, colorless to yellow.
Ready-to-use, single-dose infusion bags made of multi-layered polyolefin foil (Excel or Free flex), covered with a laminated foil. The bags contain 100 ml or 300 ml of solution and are packed in cardboard boxes, containing 1, 10, or 14 bags.

Marketing authorization holder

Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium

Manufacturer

HP Halden Pharma AS, Svinesundsveien 80, 1788 Halden, Norway
To obtain more detailed information on this medicine, contact the local representative of the marketing authorization holder:
Pfizer Polska Sp. z o.o., phone: 22 335 61 00

Date of last revision of the leaflet: 06/2024

Other sources of information

Detailed information on this medicine is available on the website of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products http://urpl.gov.pl

Information intended for healthcare professionals only:

Dosage and administration

Treatment can be started with Zyvoxid solution for infusion or tablets. In patients who started treatment with the intravenous formulation, the treatment can be switched to the oral formulation when clinically indicated.
There is no need to modify the dosage when switching from intravenous to oral administration, as the bioavailability of linezolid after oral administration is approximately 100%.
Recommended dosage and duration of treatment for adults
The duration of treatment depends on the type of pathogen, the location and severity of the infection, and the patient's clinical response to therapy.
The recommendations for the duration of treatment are based on those used in clinical trials. In some types of infections, a shorter treatment duration may be sufficient, but there are no clinical trial data to support this.
The maximum treatment duration is 28 days. The safety and efficacy of using linezolid for more than 28 days have not been established.
In infections with concomitant bacteremia, there is no need to increase the dose or extend the treatment duration.
The dosage recommendations for the solution for infusion and tablets are the same.
They are as follows:

Dosage in children
There are insufficient data on the safety and efficacy of linezolid in children and adolescents (under 18 years of age) to establish a recommended dosage. Therefore, until more data are available, linezolid should not be used in this age group.
Dosage in elderly patients
No dose adjustment is necessary.
Dosage in patients with renal impairment
No dose adjustment is necessary.
Patients with severe renal impairment (i.e. creatinine clearance <30 ml min)< em>
No dose adjustment is necessary. However, due to the unknown clinical significance of the increased exposure (up to 10-fold) to the two main metabolites of linezolid in patients with severe renal impairment, the product should be used with caution and only when the expected benefit outweighs the potential risk.
Since approximately 30% of the linezolid dose is removed from the body during 3 hours of hemodialysis, in dialysis patients, the product should be administered after dialysis. Hemodialysis also leads to the partial removal of linezolid's main metabolites from the body, but their concentrations remain significantly higher after dialysis than in patients with normal or mildly to moderately impaired renal function.
Therefore, in patients with severe renal impairment undergoing dialysis, the product should be used with caution and only when the expected benefit outweighs the potential risk.
So far, there are no data on the use of linezolid in patients undergoing continuous ambulatory peritoneal dialysis or other renal replacement therapy.
Dosage in patients with hepatic impairment
No dose adjustment is necessary. However, due to the limited number of clinical data, it is recommended that linezolid be used in these patients only when the expected benefit outweighs the potential risk.

Special warnings and precautions for use Myelosuppression

Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been observed in patients treated with linezolid. In cases where treatment outcomes are known, the changed blood test results returned to pre-treatment values after the end of treatment with linezolid. The occurrence of such symptoms appears to be related to the duration of therapy. Elderly patients treated with linezolid are at a higher risk of blood disorders than younger patients. Thrombocytopenia may occur more frequently in patients with severe renal impairment, regardless of dialysis, and in patients with moderate to severe liver function impairment. Therefore, the blood cell count should be closely monitored: in patients with pre-existing anemia, granulocytopenia, or thrombocytopenia, in patients taking concomitant medications that may decrease hemoglobin, blood cell count, or affect platelet function, in patients with severe renal impairment or moderate to severe liver function impairment, and in patients taking linezolid for more than 10 to 14 days. Linezolid can be administered to these patients only if close monitoring of hemoglobin, blood cell count, and platelet count is possible.
Administration
Recommended doses of linezolid are given twice daily by intravenous infusion.
Route of administration: intravenous.
The solution for infusion is administered over 30 to 120 minutes.

Pharmaceutical incompatibilities

Do not add any other substances to the solution. If linezolid is to be administered concurrently with other medications, each medication should be administered separately, according to its administration instructions. If the same intravenous line is used to administer linezolid and other medications alternately, the line should be flushed with a compatible solution for infusion before and after administering linezolid.
Zyvoxid solution for infusion is physically incompatible with the following medications: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate, erythromycin lactobionate, sodium phenytoin, and sulfamethoxazole with trimethoprim. Additionally, it is chemically incompatible with sodium ceftriaxone.

Special precautions for disposal and preparation of the medicinal product

The packaging is intended for single use only. Remove the outer foil immediately before administration, check for any minor leaks by firmly squeezing the bag. If the bag is leaking, do not use the product, as it may not be sterile. Before administration, inspect the solution. It can only be administered if it is clear and free of solid particles. Do not use bags in series. Unused portions of the solution should be discarded. Do not connect bags with partially used contents.
Zyvoxid solution for infusion is compatible with the following solutions: 5% glucose solution for infusion, 0.9% sodium chloride solution for infusion, Ringer's solution with lactate for injection (Hartmann's solution for injection).