Active ingredients: Linezolid
Zyvoxid 600 mg film-coated tablets for use in adults
Zyvoxid package inserts are available for pack sizes:- Zyvoxid 600 mg film-coated tablets for use in adults
- Zyvoxid 100 mg / 5 ml granules for oral suspension
- ZYVOXID 2mg / ml solution for infusion
Why is Zyvoxid used? What is it for?
Zyvoxid is an antibiotic of the oxazolidinone class, which works by stopping the growth of certain bacteria (germs) that cause infections. It is used to treat pneumonia and certain infections of the skin or under the skin. Your doctor will decide if Zyvoxid is suitable for treating your type of infection.
Contraindications When Zyvoxid should not be used
Do not take Zyvoxid
- if you are allergic to linezolid or any of the other ingredients of this medicine (listed in section 6);
- if you take or have taken within the last 2 weeks any of the medicines called monoamine oxidase inhibitors (MAOIs, e.g. phenelzine, isocarboxazid, selegiline, moclobemide). They are medicines generally used to treat depression or Parkinson's disease;
- if you are breastfeeding. Zyvoxid passes into breast milk and can affect the baby.
Precautions for use What you need to know before taking Zyvoxid
Talk to your doctor, pharmacist or nurse before taking Zyvoxid.
Zyvoxid may not be suitable for you if you answer yes to any of the following questions. In this case, tell your doctor, who will have to check your general health and blood pressure before and during treatment, or who may decide that alternative therapy is better for you.
Ask your doctor if you are unsure whether these categories apply to you.
- You have high blood pressure, whether you are taking medication for this condition or not
- You have been diagnosed with hyperthyroidism (overactive thyroid)
- Have a tumor of the adrenal glands (pheochromocytoma) or carcinoid syndrome (caused by tumors of the hormone system with symptoms of diarrhea, red skin, wheezing)
- Suffering from manic depression, schizoaffective disorder, mental confusion or any other mental disorder
- Take one of the following medicines
- decongestants, cold or flu preparations that contain pseudoephedrine or phenylpropanolamine
- medicines used in the treatment of asthma such as salbutamol, terbutaline, fenoterol
- antidepressants known as tricyclics or SSRIs (selective serotonin reuptake inhibitors), for example 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 and sudden allergic reactions such as adrenaline (epinephrine)
- medicines that raise blood pressure, such as noradrenaline (norepinephrine), dopamine and dobutamine
- medicines used to treat moderate to severe pain, such as pethidine
- medicines used to treat anxiety disorders, such as buspirone
- an antibiotic called rifampicin
Take special care with Zyvoxid Tell your doctor before taking this medicine if:
- is easily prone to bruising and bleeding episodes
- is anemic (has few red blood cells)
- is prone to getting infections
- have a history of seizures
- have liver or kidney problems, especially if you are on dialysis
- has diarrhea
Tell your doctor immediately if during treatment you suffer from:
- visual disturbances such as blurred vision, changes in color vision, difficulty seeing details, or if the field of vision becomes narrow.
- numbness in the arms or legs, or a tingling or prickling sensation in the arms or legs.
- you may develop diarrhea while taking antibiotics, or after you have finished taking antibiotics, including Zyvoxid. If your diarrhea becomes severe or persistent or if you notice that your stools contain blood or mucus, you must stop taking Zyvoxid immediately and consult your doctor. In these conditions, you should not take medicines that stop or slow down bowel movements.
- recurrent nausea or vomiting, abdominal pain, or rapid breathing.
Interactions Which drugs or foods may change the effect of Zyvoxid
There is a risk that Zyvoxid may sometimes interact with other medicines causing side effects such as changes in blood pressure, temperature or heart rate.
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.
Tell your doctor if you are taking or have taken within the last 2 weeks the following medicines, as Zyvoxid should not be taken if you are already taking these medicines or have recently taken them (see also section 2 above "Do not take Zyvoxid" ).
- monoamine oxidase inhibitors (MAOIs, e.g. phenelzine, isocarboxazid, selegiline, moclobemide). They are medicines generally used to treat depression or Parkinson's disease.
Also tell your doctor if you are taking the following medicines. Your doctor may decide to give you Zyvoxid anyway, but they will need to check your general health and blood pressure before and during treatment. In other cases, your doctor may decide that another treatment is better for you.
- Decongestants, cold or flu preparations that contain pseudoephedrine or phenylpropanolamine.
- Some medicines used in the treatment of asthma such as salbutamol, terbutaline, fenoterol.
- Some antidepressants such as tricyclics or SSRIs (selective serotonin reuptake inhibitors). There are many, including 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 and sudden allergic reactions such as adrenaline (epinephrine).
- Medicines that raise blood pressure, such as noradrenaline (norepinephrine), dopamine and dobutamine.
- Medicines used to treat moderate to severe pain, such as pethidine
- Medicines used to treat anxiety disorders, such as buspirone
- Medicines that block blood clotting, such as warfarin.
Tell your doctor, pharmacist or nurse if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Zyvoxid with food, drink and alcohol
- You can take Zyvoxid before, during or after meals.
- Avoid eating large quantities of aged cheeses, yeast or soybean derivatives, e.g. soy sauce, and drinking alcohol, especially draft beers and wine. The reason is that Zyvoxid can react to a substance called tyramine which is naturally present in some foods. This interaction can result in an increase in blood pressure.
- If you get a throbbing headache after eating or drinking, tell your doctor, pharmacist or nurse immediately.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
The effect of Zyvoxid on pregnant women is not known. Therefore, the medicine should not be taken during pregnancy unless specifically directed by your doctor. If you are pregnant, think you may be pregnant or are planning to become pregnant, or if you are pregnant. are breast-feeding ask your doctor or pharmacist for advice before taking this medicine.
You should not breast-feed while taking Zyvoxid, as the medicine passes into breast milk and may affect the baby.
Driving and using machines
Zyvoxid can make you feel slightly dizzy or cause vision problems. In this case, do not drive vehicles or use machines. Remember that if you feel unwell your ability to drive and operate machines may be impaired.
Dose, Method and Time of Administration How to use Zyvoxid: Posology
Adults
Always take this medicine exactly as described in this leaflet or as directed by your doctor, pharmacist or nurse.
If in doubt, consult your doctor, pharmacist or nurse.
The recommended dose is one film-coated tablet (linezolid 600 mg) twice daily (every 12 hours). Swallow the film-coated tablet whole with some water.
If you are on kidney dialysis, you should take Zyvoxid after dialysis.
A course of treatment generally lasts 10 to 14 days, but can last up to 28 days. The safety and efficacy of this medicine for periods longer than 28 days have not been established. Your doctor will decide how long the treatment should last.
While taking Zyvoxid, your doctor should regularly do blood tests to check the number of your blood cells.
If you take Zyvoxid for more than 28 days, your doctor should check your vision.
Use in children and adolescents
Zyvoxid is not normally used to treat children and adolescents (under 18 years of age).
If you forget to take Zyvoxid
Take the forgotten tablet as soon as you remember. Take the next film-coated tablet 12 hours later and continue taking the film-coated tablets every 12 hours. Do not take a double dose to make up for a forgotten film-coated tablet.
If you stop taking Zyvoxid
If your doctor does not specifically instruct you to stop treatment, it is important to continue taking Zyvoxid.
If you stop treatment and the original symptoms reappear, tell your doctor or pharmacist immediately.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
Overdose What to do if you have taken too much Zyvoxid
If you take more Zyvoxid than you should, tell your doctor or pharmacist immediately.
Side Effects What are the side effects of Zyvoxid
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor, nurse or pharmacist immediately if you notice any of these side effects during treatment with Zyvoxid:
- skin reactions such as red painful skin and peeling (dermatitis), rash, itching or swelling, especially on the face and neck. These may be signs of an allergic reaction and treatment with Zyvoxid may need to be stopped.
- visual disturbances such as blurred vision, changes in color vision, difficulty seeing details, or if the field of vision becomes narrow.
- severe diarrhea containing blood and / or mucus (antibiotic-associated colitis, including pseudomembranous colitis), which in rare cases can cause life-threatening complications.
- recurrent nausea or vomiting, abdominal pain, or rapid breathing.
- seizures or convulsions have been reported with Zyvoxid. If you experience agitation, confusion, delirium, stiffness, tremor, lack of coordination and convulsions while you are also taking antidepressant medicines called SSRIs (see section 2), you should tell your doctor.
Numbness, tingling sensation or blurred vision have been reported in patients receiving Zyvoxid for more than 28 days. If you have vision problems, consult your doctor as soon as possible.
Other side effects include:
Common (may affect up to 1 in 10 people):
- Fungal infections, especially vaginal or oral candidiasis
- Headache
- Metallic taste in the mouth
- Diarrhea, nausea or vomiting
- Changes in some blood test results, including readings to check kidney or liver function or blood sugar levels • Unexplained bleeding or bruising, possibly due to changes in the number of some blood cells that can affect clotting or lead to to anemia
- Difficulty falling asleep
- Increased blood pressure
- Anemia (few red blood cells)
- Changes in the number of some blood cells which can affect your ability to fight infections
- Rash
- Itching
- Dizziness
- Localized or general abdominal pain
- Constipation
- Indigestion
- Localized pain
- Fever
Uncommon (may affect up to 1 in 100 people):
- Inflammation of the vagina or genitals in women
- Sensations such as tingling or numbness
- Blurred vision
- Ringing in the ears (tinnitus)
- Inflammation of the veins (IV administration only)
- Dry or painful mouth, swelling, pain or discoloration of the tongue
- Need to urinate more frequently
- Chills
- Feeling tired or thirsty
- Inflammation of the pancreas
- Increased sweating
- Changes in blood proteins, salts or enzymes that measure kidney or liver function
- Convulsions
- Hyponatremia (low levels of sodium in the blood)
- Kidney failure
- Reduction of platelets
- Abdominal swelling
- Transient ischemic attacks (temporary disruption of blood supply to the brain causing short-term symptoms such as loss of vision, weakness in the arms and legs, difficulty with speech and loss of consciousness)
- Pain at the injection site
- Inflammation of the skin
- Increased creatinine
- Stomach ache
- Changes in heart rate (e.g. increased heart rate)
Rare (may affect up to 1 in 1,000 people)
- Narrowing of the visual field
- Superficial tooth discoloration, removable with professional dental cleaning (manual removal)
The following side effects have also been reported (frequency not known: frequency cannot be estimated from the available data):
- Serotonin syndrome (symptoms of which include rapid heart rate, confusion, excessive sweating, hallucinations, involuntary movements, chills and tremors)
- Lactic acidosis (symptoms of which include recurrent nausea and vomiting, abdominal pain, rapid breathing)
- Severe skin diseases
- Sideroblastic anemia (a type of anemia [few red blood cells])
- Alopecia (hair loss)
- Changes in color vision or difficulty in seeing details
- Reduction in the number of blood cells
- Weakness and / or sensory changes
Reporting of side effects
If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
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 carton or blister after "EXP". The expiry date refers to the last day of that month. This medicine does not require any special storage conditions.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other information
What Zyvoxid contains
- The active ingredient in this medicine is called linezolid. Each film-coated tablet contains 600 mg of linezolid
- The other ingredients are maize starch (maize derivative), microcrystalline cellulose (E 460), hydroxypropyl cellulose (E463), sodium starch carboxymethyl starch (type A), and magnesium stearate (E 572). The coating film contains opadry, white, YS-1-18202-A8 (e) consisting of: hypromellose (E464), titanium dioxide (E171), macrogol 400, and carnauba wax (E 903).
What Zyvoxid looks like and contents of the pack
Zyvoxid 600 mg film-coated tablets are ovoid, white tablets debossed with "ZYV" on one side and "600" on the other.
Zyvoxid film-coated tablets are available in blisters of 10 tablets packed in a carton. Each carton contains 10, 20, 30, 50, 60 or 100 film-coated tablets. It is also available in a white HDPE bottle with a polypropylene screw cap containing 10, 14, 20, 24, 30, 50, 60 or 100 (for hospital use only) film-coated tablets. Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ZYVOXID
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Solution for infusion: 1 ml contains 2 mg of linezolid. The 300 ml infusion bags contain 600 mg of linezolid.
Excipients with known effects: each 300 ml contains 13.7 g of glucose and 114 mg of sodium.
Film-coated tablets
Each tablet contains 600 mg of linezolid
Granules for oral suspension: after reconstitution with 123 ml of water, each 5 ml contains 100 mg of linezolid
Excipients with known effects: each 5 ml of suspension also contains 1052.9 mg of sucrose, 500 mg of mannitol (E421), 35.0 mg of aspartame (E951), 8.5 mg of sodium, 12 mg of fructose, 36 mg of sorbitol (E420).
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Solution for infusion
Clear, colorless to yellow isotonic solution.
Film-coated tablets
White, ovoid tablets debossed with "ZYV" on one side and "600" on the other.
Granules for oral suspension
White or slightly yellow granules, orange flavored.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Nosocomial pneumonia.
Community-acquired pneumonia.
Zyvoxid is indicated in adults for the treatment of community-acquired pneumonia and hospital-acquired pneumonia when it is suspected or certain that they are caused by susceptible Gram-positive bacteria. Results of microbiological tests or information on the prevalence of bacterial resistance of Gram positive bacteria should be considered to determine the appropriateness of treatment with Zyvoxid (see section 5.1 for appropriate organisms).
Linezolid is not active in infections caused by Gram-negative pathogens. In the event that the presence of Gram-negative pathogens is ascertained or suspected, a specific therapy for these microorganisms must be initiated at the same time.
Complicated skin and soft tissue infections (see section 4.4).
Zyvoxid is indicated in adults for the treatment of complicated skin and soft tissue infections only when the microbiological test has determined that the infection is caused by susceptible Gram positive bacteria.
Linezolid is not active in infections caused by Gram-negative pathogens.
Linezolid should be used in patients with complicated skin and soft tissue infections, when it is suspected or certain that they are caused by co-infections with Gram-negative pathogens, only when no other therapeutic alternatives are available (see section 4.4). Under these circumstances needs to be initiated at the same time as treatment against Gram-negative pathogens.
Linezolid treatment should only be initiated in a hospital setting and after consultation with a qualified specialist, such as a microbiologist or infectious disease specialist.
Official guidelines on the correct use of antibacterial agents should be considered.
04.2 Posology and method of administration
Dosage
Zyvoxid solution for infusion, film-coated tablets or oral suspension can be used as initial therapy. Patients starting treatment with the parenteral formulation may subsequently switch to oral formulations if clinically appropriate. In such circumstances no dose modification is required as the oral bioavailability of linezolid is approximately 100%.
Recommended dosage and duration of treatment in adults :
the duration of treatment depends on the pathogen, the site of the infection and its severity, as well as the patient's clinical response.
The following recommendations on duration of therapy reflect those adopted in clinical trials. Shorter treatment regimens may be suitable for some types of infections but have not been evaluated in clinical studies.
The maximum duration of treatment is 28 days. The safety and efficacy of linezolid administered for longer than 28 days have not been established (see section 4.4).
No dosage increase or duration of treatment is required for infections associated with concomitant bacteraemia.
The recommended dosage for the solution for infusion and for the tablets or granules for oral suspension is identical and is as follows:
Pediatric population :
There are insufficient data on the safety and efficacy of linezolid in children and adolescents (
Elderly patients :
No dose modification is required.
Patients with renal insufficiency :
No dose modification is required (see sections 4.4 and 5.2).
Patients with severe renal insufficiency (i.e. creatinine clearance :
no dose modification is required. Since the clinical significance of the higher (up to 10-fold) exposure to the two major metabolites of linezolid in patients with severe renal impairment is unknown, linezolid should be used with particular caution in these patients and only when the expected benefit is considered to be greater. the theoretical risk.
Since approximately 30% of a dose of linezolid is removed within 3 hours of hemodialysis, linezolid should be administered after dialysis in patients undergoing such treatment. The major metabolites of linezolid are eliminated to some extent by hemodialysis, but the concentrations of these metabolites still remain substantially higher after dialysis than those observed in patients with normal renal function or with mild or moderate renal impairment.
Linezolid should therefore be used with particular caution in patients with severe renal insufficiency undergoing dialysis, and only when the anticipated benefit outweighs the theoretical risk.
To date, there are no data on the administration of linezolid in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or alternative treatments for renal insufficiency (other than hemodialysis).
Patients with hepatic insufficiency :
No dose modification is required.
As clinical data are limited, it is recommended that linezolid be used in such patients only when the anticipated benefit is considered to outweigh the theoretical risk (see sections 4.4. And 5.2).
Method of administration:
The recommended dosage of linezolid should be administered intravenously or orally twice daily.
Solution for infusion
Route of administration: intravenous use.
The solution for infusion should be administered over a period of 30 to 120 minutes.
Tablets
Route of administration: oral use
The film-coated tablets can be taken with or without food.
Granules for oral suspension:
Route of administration: oral use
The oral suspension can be taken with or without food.
A dose of 600 mg corresponds to 30 ml of reconstituted suspension
(i.e. 6 full 5ml tablespoons)
04.3 Contraindications
Hypersensitivity to linezolid or to any of the excipients listed in section 6.1.
Linezolid should not be used in patients being treated with medicines that inhibit monoamine oxidase A or B (eg, phenelzine, isocarboxazid, selegiline, moclobemide) or within two weeks of taking such medicines.
Linezolid should not be given to patients who have the following clinical conditions or who are taking the following types of concomitant medicinal products if facilities for close patient observation and blood pressure monitoring are not available:
• Patients with uncontrolled hypertension, pheochromocytoma, carcinoid, thyrotoxicosis, bipolar depression, schizoaffective disorders, acute confusional states.
• Patients taking the following medicinal products: serotonin re-uptake inhibitors (see section 4.4), tricyclic antidepressants, serotonin 5HT1 receptor agonists (triptans), direct or indirect acting sympathomimetics (including adrenergic bronchodilators, pseudoephedramine and phenylpropanol ), vasopressor substances (e.g. adrenaline, noradrenaline), dopaminergic substances (e.g. dopamine, dobutamine), pethidine or buspirone.
Animal data suggest that linezolid and its metabolites can pass into milk, therefore breastfeeding should be discontinued before or during administration (see section 4.6).
04.4 Special warnings and appropriate precautions for use
Myelosuppression
Cases of myelosuppression (including anemia, leukopenia, pancytopenia and thrombocytopenia) have been reported in patients treated with linezolid. In cases with known outcome, altered haematological parameters were observed to rise back to pre-treatment values once linezolid was discontinued. The risk of these effects appears to be related to the duration of treatment. Elderly patients being treated with linezolid may be at a higher risk of developing blood dyscrasias than younger patients. Thrombocytopenia can occur more commonly in patients with severe renal insufficiency, whether on dialysis or not. Therefore, careful monitoring of blood count is recommended in patients with pre-existing anemia, granulocytopenia or thrombocytopenia; in patients receiving concomitant medications that may decrease hemoglobin levels, depress blood count or adversely affect platelet count or function; in patients with severe renal insufficiency; in patients on linezolid therapy for more than 10 - 14 days. In such patients, linezolid should only be given when accurate monitoring of hemoglobin levels is possible or blood and platelet counts can be performed.
If significant myelosuppression occurs during treatment with linezolid, administration should be discontinued, unless continuation of therapy is considered absolutely necessary; in such an event, intensive monitoring of blood count and appropriate treatment measures should be undertaken.
Comprehensive monitoring is also recommended, weekly, blood cell counts (including hemoglobin levels, platelets, and total and differentiated white blood cell counts) in patients receiving linezolid, regardless of baseline values.
In compassionate use studies, a higher incidence of severe anemia has been reported in patients treated with linezolid for longer than the maximum recommended duration of 28 days. In these patients the need for blood transfusion was more frequent. Cases of transfusional anemia have also been reported in post-marketing experience, with a higher incidence in patients receiving linezolid therapy for longer than 28 days.
Cases of sideroblastic anemia have been reported in post-marketing experience. In cases where time to onset was known, most patients had received linezolid treatment for more than 28 days. Most patients have shown full or partial recovery after discontinuation of linezolid therapy, with or without treatment for anemia.
Mortality imbalance in a clinical study of patients with catheter-related Gram positive blood infections
In an open-label clinical study in severe patients with intravascular catheter infections, a higher mortality rate was observed in patients treated with linezolid than with vancomycin, dicloxacillin or oxacillin [78/363 (21.5%) versus 58/363 (16.0%)]. The main factor influencing the mortality rate was the severity level of Gram-positive infection at baseline. Mortality was similar in patients with infections caused solely by Gram-positive bacteria (odds ratio 0.96; 95% confidence: 0.58-1.59), but was significantly higher (p = 0.0162) in the linezolid treatment group in patients with any other pathogen or no pathogen at baseline (odds ratio 2.48; range 95% confidence: 1.38-4.46). The greatest difference occurred during the course of treatment and within 7 days of stopping therapy. More patients in the linezolid treatment group developed Gram-negative pathogen infections during the study, and patients died from Gram-negative pathogen infections and polymicrobial infections. Therefore, in complicated skin and soft tissue infections, linezolid should be used in patients with known or suspected concomitant Gram-negative pathogen infections only when no other therapeutic alternatives are available (see section 4.1). In these circumstances, treatment against Gram-negative pathogens must be initiated at the same time.
Antibiotic associated diarrhea and colitis
The occurrence of pseudomembranous colitis has been reported with almost all antibacterial agents, including linezolid. It is therefore important to consider this diagnosis in patients who experience diarrhea after the administration of any antibacterial agent.
If antibiotic-associated colitis is known or suspected, it may be advisable to discontinue linezolid treatment. Therefore appropriate treatment will have to be instituted.
Antibiotic-associated diarrhea and antibiotic-associated colitis, including pseudomembranous colitis and diarrhea associated with antibiotics, have been reported with use of nearly all antibiotics, including linezolid. Clostridium difficile, the severity of which can range from mild diarrhea to fatal colitis. It is therefore important to consider this diagnosis in patients who develop severe diarrhea during or after treatment with linezolid. If antibiotic-associated diarrhea or antibiotic-associated colitis is suspected or confirmed, ongoing treatment with antibacterials, including linezolid, and immediately institute appropriate therapeutic measures In this situation, antiperistaltics are contraindicated.
Lactic acidosis
Cases of lactic acidosis have been reported with the use of linezolid. Patients who develop signs and symptoms of metabolic acidosis - including recurrent nausea or vomiting, abdominal pain, low bicarbonate or hyperventilation - during therapy with linezolid should receive immediate medical attention If lactic acidosis occurs, the advantages of continuing linezolid therapy should be weighed against the potential risks.
Mitochondrial dysfunction
Linezolid inhibits mitochondrial protein synthesis. As a consequence of this inhibition, adverse events such as lactic acidosis, anemia and neuropathy (optic and peripheral) may occur; these events are more common when the medicine is used for more than 28 days.
Serotonin syndrome
Spontaneous reports of serotonin syndrome associated with the concomitant administration of linezolid and serotonergic medicinal products, including antidepressants belonging to the selective serotonin reuptake inhibitor (SSRI) class, have been reported.Concomitant administration of linezolid and serotonergic medicinal products is therefore contraindicated (see section 4.3), except in cases where concomitant administration of linezolid and serotonergic medicinal products is essential. In such cases, patients should be carefully observed for any signs and symptoms of serotonin syndrome, such as impaired cognition, hyperpyrexia, hyperreflexia and lack of coordination. In the presence of these signs and symptoms, the physician should consider stopping one or both concomitant treatments; if the serotonergic medicine is stopped, withdrawal symptoms may occur.
Peripheral and optic neuropathy
Peripheral neuropathy, as well as optic neuropathy and optic neuritis, sometimes progressing to loss of vision, have been reported in patients receiving linezolid. These cases have mainly occurred in patients treated for periods longer than the maximum recommended duration of 28 days.
All patients should be advised to report symptoms of visual disturbances, such as changes in visual acuity, changes in color vision, blurred vision or visual field defects. In these cases, prompt examination and, if necessary, referral are recommended. Refer to an ophthalmologist In cases of taking linezolid for longer than the maximum recommended duration of 28 days, regular visual function checks should be performed in all patients.
In the event of an onset of peripheral or optic neuropathy, continuation of linezolid therapy in these patients should be evaluated considering the potential risks.
The risk of neuropathies may be increased when linezolid is used in patients who are taking concomitant or have recently taken antimycobacterial medicines to treat tuberculosis.
Convulsions
Cases of convulsions have been reported in patients receiving Zyvoxid. In most cases, a history of seizures or risk factors for seizures has been reported. In the presence of a history of seizures, patients should be advised to inform their treating physician.
Monoamine oxidase inhibitors
Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI); at the doses used for antibacterial therapy, however, it does not exert an antidepressant effect. Very limited data are available from both drug interaction studies and the safety of linezolid administered to patients with pre-existing medical conditions and / or undergoing concomitant drug therapies that may pose a risk to them due to MAO inhibition. The use of linezolid it is therefore not recommended in these circumstances unless close surveillance and monitoring of the patient is possible (see sections 4.3 and 4.5).
Use with tyramine rich foods
Patients should be advised not to consume large amounts of tyramine-rich foods (see section 4.5).
Superinfections
Clinical studies have not evaluated the effects of linezolid therapy on normal flora.
The use of antibiotics can sometimes cause an overgrowth of non-susceptible microorganisms. For example, approximately 3% of patients treated with the recommended dose of linezolid experienced drug-related candidiasis during clinical trials. superinfection during therapy appropriate measures should be taken.
Special populations
Linezolid should be used with particular caution in patients with severe renal impairment and only when the anticipated benefit outweighs the theoretical risks (see sections 4.2 and 5.2).
It is recommended that linezolid be administered to patients with severe hepatic impairment only when the anticipated benefit outweighs the theoretical risk (see sections 4.2 and 5.2).
Impaired fertility
Linezolid reversibly reduced fertility and induced morphological abnormalities in sperm from adult male rats at exposure levels equivalent to those expected in humans; possible effects of linezolid on the male reproductive system in humans are not known (see section 5.3).
Clinical studies
The safety and efficacy of linezolid administered for longer than 28 days have not been established.
The controlled studies did not include patients with diabetic foot injuries, pressure sores, or ischemic injuries, severe burns, or gangrene. Therefore, there is limited experience with the use of linezolid in the treatment of these lesions.
Solution for infusion - Excipients
Each ml of solution contains 45.7 mg (i.e. 13.7 g / 300 ml) of glucose. This should be taken into account in patients with diabetes mellitus or other conditions associated with glucose intolerance. Each ml of solution also contains 0.38 mg (114 mg / 300 ml) of sodium. The sodium content must be kept in mind. consideration in patients on a controlled sodium diet.
Granules for oral suspension - Excipients
The reconstituted oral suspension contains a source of phenylalanine (aspartame) equivalent to 20 mg / 5 ml. This formulation, therefore, can be risky for people with phenylketonuria. In patients with phenylketonuria, the use of Zyvoxid solution for infusion or tablets is recommended.
The suspension also contains sucrose, fructose, sorbitol, mannitol and sodium equivalent to 1.7 mg / ml. Therefore, it should not be used in patients with hereditary problems of fructose intolerance with glucose-galactose malabsorption or sucrase-isomaltase insufficiency.
Due to its mannitol and sorbitol content, the oral suspension may exert a mild laxative effect. The product contains 8.5 mg of sodium in each 5 ml dose. The sodium content should be considered in patients on a controlled sodium diet.
This medicine also contains a small amount of ethanol (alcohol): less than 100 mg for a 5 ml dose.
04.5 Interactions with other medicinal products and other forms of interaction
Monoamine oxidase inhibitors
Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI). Very limited data are available from both drug interaction studies and the safety of linezolid administered to patients on concomitant therapy with medicinal products that may carry a risk of MAO inhibition. The use of linezolid is therefore not recommended in these circumstances, unless that close surveillance and accurate monitoring of the recipient is possible (see sections 4.3 and 4.4).
Potential interactions that produce increases in blood pressure
In normotensive healthy volunteers, linezolid potentiated the increase in blood pressure induced by pseudoephedrine and phenylpropanolamine hydrochloride. Concomitant administration of linezolid with pseudoephedrine and phenylpropanolamine induced mean increases in systolic blood pressure of the order of 30-40 mmHg, compared to increases of 11-15 mmHg with linezolid alone, 14-18 mmHg with pseudoephedrine alone or phenylpropanolamine, and 8-11 mmHg with placebo. Similar studies have not been conducted in hypertensive subjects.
It is recommended that the dosage of vasopressor medicinal products, including dopaminergic substances, be carefully titrated in order to achieve the desired response when administered concomitantly with linezolid.
Potential serotonergic interactions
The potential drug-drug interaction with dextromethorphan was studied in healthy volunteers. Subjects were treated with dextromethorphan (two doses of 20 mg with an interval of 4 hours), with or without linezolid. No effect of serotonin syndrome (confusion, delirium, restlessness, tremors, erythema, diaphoresis, hyperpyrexia) was observed in normal subjects treated with linezolid and dextromethorphan.
Post-Marketing Experience: A patient report was reported who experienced effects similar to those of serotonin syndrome when taking concomitant linezolid and dextromethorphan, which resolved on discontinuation of both treatments.
Cases of serotonin syndrome have been reported in clinical experience with the concomitant use of linezolid and serotonergic medicinal products, including antidepressants belonging to the class of serotonin reuptake inhibitors (SSRIs). Concomitant administration is therefore contraindicated (see section 4.3), but the management of patients for whom treatment with linezolid and serotonergic medicinal products is essential is described in section 4.4.
Use with tyramine rich foods
Subjects treated with linezolid and less than 100 mg of tyramine showed no significant blood pressure response. This indicates that it is only necessary to avoid ingesting excessive amounts of foods and beverages with a high tyramine content (e.g., aged cheese, yeast extracts, non-distilled alcoholic beverages, and fermented soy products such as soy sauce).
Medicinal products metabolised by cytochrome P450
Linezolid is not metabolised to a detectable extent by the cytochrome P450 (CYP) enzyme system and does not inhibit any of the clinically significant isoforms of human CYP (1A2, 2C9, 2C19, 2D6, 2E1 and 3A4). Similarly, linezolid does not induce P450 isoenzymes in rats. Therefore, no CYP450-induced drug interactions are expected with linezolid.
Rifampicin
The effect of rifampicin on linezolid pharmacokinetics was studied in sixteen healthy adult male volunteers who were administered linezolid 600 mg twice daily for 2.5 days with and without rifampicin 600 mg once daily for 8 days. rifampicin lowered the Cmax and AUC of linezolid by 21% on average [90% CI, 15, 27] and 32% on average [90% CI, 27, 37], respectively. The mechanism of this interaction and its clinical significance are unknown.
Warfarin
When warfarin was combined with linezolid therapy, in steady-state conditions, a 10% reduction in mean maximum International Normalized Ratio (INR) was observed during concomitant administration, with a 5% reduction in AUC INR. It is not possible to define the clinical significance of these findings, if any, as there are insufficient data from patients treated with warfarin and linezolid.
04.6 Pregnancy and lactation
Pregnancy
There are no adequate data on the use of linezolid in pregnant women. Studies in animals have shown toxic effects on reproduction (see section 5.3). A potential risk exists for humans.
Linezolid should not be used during pregnancy unless strictly necessary, i.e. only when the anticipated benefits outweigh the theoretical risk.
Feeding time
Animal data indicate that linezolid and its metabolites can pass into breast milk and, consequently, breastfeeding should be discontinued before and during administration.
Fertility
In animal studies, linezolid caused decreased fertility (see section 5.3).
04.7 Effects on ability to drive and use machines
Patients should be advised of the potential for dizziness or visual impairment symptoms (as described in sections 4.4 and 4.8) during treatment with linezolid, and then they should be advised not to drive or operate machinery if any of these occur. any of these symptoms.
04.8 Undesirable effects
The table below lists adverse reactions with frequency based on all randomness data obtained from clinical trials enrolling over 2,000 adult patients who were treated for up to 28 days with the recommended doses of linezolid. reported were diarrhea (8.4%), headache (6.5%), nausea (6.3%) and vomiting (4.0%).
The most commonly reported drug-related adverse events leading to discontinuation of treatment were headache, diarrhea, nausea and vomiting. Approximately 3% of patients discontinued treatment following the onset of a drug-related adverse event.
Additional adverse reactions reported from post-marketing experience are included in the table under the "not known" category, as the actual frequency cannot be calculated from the available data.
The following undesirable effects have been observed and reported during treatment with linezolid at the following frequencies: Very common (≥1 / 10); common (≥1 / 100 e
* See section 4.4.
** See sections 4.3 and 4.5
† See information below
The following adverse reactions to linezolid have been considered serious in rare cases: localized abdominal pain, transient ischemic attacks and hypertension.
† In controlled clinical trials where linezolid was administered for up to 28 days of treatment, reported cases of anemia were 2.0% of patients. During a compassionate use program in patients with life-threatening infections and concomitant underlying medical conditions, the proportion of patients who developed anemia during treatment with linezolid for ≤ 28 days was 2.5% (33 / 1,326), compared with 12.3% (53/430) of cases in which therapy was> 28 days. The percentage of reported drug-related anemia requiring blood transfusion was 9% (3/33) in patients treated for ≤ 28 days and 15% (8/53) in those treated for> 28 days.
Pediatric population
Safety data from clinical studies in over 500 pediatric patients (from birth to 17 years) do not indicate that the safety profile of linezolid for pediatric patients differs from that of adults.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
A specific antidote is not known.
No cases of overdose have been reported. However, the following information may be useful:
Supportive treatment is recommended in conjunction with maintenance of glomerular filtration. Approximately 30% of a dose of linezolid is eliminated within 3 hours of hemodialysis, but no data is available on elimination of linezolid by peritoneal dialysis or hemoperfusion. Major metabolites of linezolid are eliminated to some extent by hemodialysis.
The signs of toxicity observed in rats after doses of 3000 mg / kg / day of linezolid were decreased activity and ataxia, while dogs treated with 2000 mg / kg / day experienced vomiting and tremors.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: other antibacterials, ATC code: J 01 X X 08.
General properties
Linezolid is a synthetic antibacterial agent belonging to a new class of antimicrobials, oxazolidinones. It manifests an in-vitro activity against Gram-positive aerobic bacteria and anaerobic microorganisms. Linezolid selectively inhibits bacterial protein synthesis through a peculiar mechanism of action. Specifically, it binds to a site of the bacterial ribosome (23S of the 50S subunit) and prevents the formation of a 70S functional initiation complex which is a fundamental component of the translation process.
The in-vitro post-antibiotic effect of linezolid for Staphylococcus aureus it was about 2 hours. The in vivo post-antibiotic effect, determined in animal models, was 3.6 hours and 3.9 hours per Staphylococcus aureus And Streptococcus pneumoniae, respectively. In animal studies, the key pharmacodynamic parameter for evaluating efficacy was the time during which the plasma level of linezolid exceeded the minimum inhibitory concentration (MIC) of the infecting organism.
Breakpoint
The sensitivity breakpoints established by"European Committee on Antimicrobial Susceptibility Testing (EUCAST) for staphylococci and enterococci correspond to MIC values ≤ 4mg / l, and resistance values correspond to MIC values> 4 mg / l. For streptococci (including S. pneumoniae) the sensitivity breakpoints correspond to MIC ≤ 2 mg / l and resistance breakpoints are> 4 mg / l.
The sensitivity breakpoints for other bacterial species correspond to MIC values ≤ 2 mg / l and resistance breakpoints correspond to MIC values> 4 mg / l; these breakpoints were determined mainly on the basis of pharmacokinetic and pharmacodynamic data and are independent of the MIC distribution for individual species. They are used only for organisms that have not been assigned a specific breakpoint, and not for species for which susceptibility testing is not recommended.
Sensitivity
The resistance of selected species, in terms of prevalence, can vary according to the geographical location and according to the time; local information on resistance is therefore desirable, especially when treating severe infections. If necessary, expert advice should be sought when the local prevalence of resistance is such as to question the actual usefulness of the drug, at least for some types of infections.
Category
Sensitive microorganisms
Gram-positive aerobes:
Enterococcus faecalis
Enterococcus faecium *
Staphylococcus aureus *
Coagulase-negative staphylococci
Streptococcus agalactiae *
Streptococcus pneumoniae*
Streptococcus piogenes *
Group C streptococci
Group G streptococci
Gram-positive anaerobes:
Clostridium perfringens
Peptostreptococcus anaerobius
Peptostreptococcus spp.
Resistant microorganisms
Haemophilus influenzae
Moraxella catarrhalis
Neisseria spp.
Enterobacteriaceae
Pseudomonas spp.
* Clinical efficacy has been demonstrated for sensitive isolates on approved clinical indications.
Although linezolid showed some activity in vitro against Legionella, Chlamydia pneumoniae And Mycoplasma pneumoniaeHowever, insufficient data are available to demonstrate its clinical efficacy.
Resistence
Cross resistance
The mechanism of action of linezolid differs from that of other classes of antibiotics. In-vitro studies on clinical isolates (including methicillin-resistant staphylococci, vancomycin-resistant enterococci, penicillin-resistant streptococci and erythromycin-resistant) indicate that linezolid is usually active against microorganisms that resist one or more other classes of antimicrobial agents.
Resistance to linezolid is associated with point mutations in the 23S rRNA.
As documented with other antibiotics used in patients with difficult-to-treat infections and / or for prolonged periods of therapy, decreases in sensitivity have also been observed with linezolid. Resistance to linezolid has been reported in enterococci, nel Staphylococcus aureus and in coagulase negative staphylococci. The phenomenon was generally related to prolonged periods of therapy and the presence of prosthetic materials or undrained abscesses. When antibiotic-resistant microorganisms are encountered in a hospital setting, the importance of clinical infection control practices should be borne in mind.
Results of clinical studies
Studies in the pediatric population:
In an open-label study, the efficacy of linezolid (10 mg / kg q8h) was compared with vancomycin (10-15 mg / kg q6-24h) in the treatment of infections caused by known or suspected resistant gram-positive pathogens (including which hospital-acquired pneumonia, complicated skin and adnexal infections, catheter-induced bacteremia, bacteremia of unknown origin and other infections), conducted on children aged between birth and 11 years. Clinical cure rates in the clinically evaluable population were 89.3% (134/150) and 84.5% (60/71) for linezolid and vancomycin, respectively (95% CI: -4.9, 14.6 ).
05.2 Pharmacokinetic properties
Zyvoxid mainly contains (s) -linezolid, which is biologically active and is metabolized to form inactive derivatives.
Absorption
Linezolid is rapidly and extensively absorbed following oral administration.
Maximum plasma concentrations are reached within 2 hours of administration.
The absolute oral bioavailability of linezolid (in a cross-over study with oral and intravenous administration) is complete (approximately 100%). Absorption is not significantly affected by food and the absorption of the oral suspension is similar to that obtained with the film-coated tablets.
Linezolid plasma Cmax and Cmin (mean and standard deviation [SD]) at steady state after intravenous administration of 600 mg twice daily were found to be 15.1 [2.5] mg / l and 3.68 [2.68 ] mg / l, respectively.
In another study with oral administration of 600 mg twice daily, Cmax and Cmin at steady state were found to be 21.2 [5.8] mg / l, and 6.15 [2.94] mg / l, respectively.
Steady state conditions are achieved by the second day of administration.
Distribution
The steady state volume of distribution averages 40-50 liters in healthy adults and approaches total body water. Plasma protein binding is approximately 31% and is independent of concentration.
Linezolid concentrations have been determined in various fluids, in a limited number of subjects, in some studies on volunteers after multiple dosing. The ratio of linezolid contained in saliva and sweat to plasma was 1.2: 1.0 and 0.55: 1.0, respectively.
The ratio for epithelial lining fluid and alveolar lung cells was 4.5: 1.0 and 0.15: 1.0, respectively, when measured at Cmax under steady state conditions. In a small study of subjects with ventricular-peritoneal shunts and essentially non-inflamed meninges, the ratio of CSF to plasma linezolid at Cmax was 0.7: 1.0 after multiple dosing.
Biotransformation
Linezolid is mainly metabolised by oxidation of the morpholine ring, with the formation of mainly two inactive derivatives of open-ring carboxylic acid: the aminoethoxyacetic acid metabolite (PNU-142300) and the hydroxyethyl glycine metabolite (PNU-142586). The predominant human metabolite hydroxyethyl glycine (PNU-142586) is thought to be formed by a non-enzymatic process. The aminoethoxyacetic acid metabolite (PNU-142300) is less abundant. Other minor inactive metabolites have also been characterized.
Elimination
Linezolid, under steady state conditions, is mainly excreted in the urine as PNU-142586 (40%), unchanged drug (30%) and PNU-142300 (10%) in patients with normal renal function or mild to moderate renal impairment. Virtually no unchanged drug is found in the faeces, while approximately 6% and 3% of each dose appear as PNU-142586 and PNU-142300, respectively. The elimination half-life of linezolid averages 5-7 hours.
Non-renal clearance accounts for approximately 65% of the total clearance of linezolid. A small degree of non-linearity in clearance is observed with increasing dose of linezolid. This appears to be due to lower renal and non-renal clearance at higher linezolid concentrations. However, the difference in clearance is small and is not reflected in the apparent elimination half-life.
Special populations
Patients with renal insufficiency:
After single doses of 600 mg, a 7-8-fold increase in exposure to the two primary metabolites of linezolid was observed in plasma of patients with severe renal impairment (i.e. creatinine clearance plasma levels of metabolites were substantially higher after dialysis than in those seen in patients with normal renal function or with mild or moderate renal insufficiency.
In 24 patients with severe renal insufficiency, 21 of whom regularly undergo hemodialysis, the maximum plasma concentrations of the two primary metabolites were approximately 10 times higher than those observed in patients with normal renal function after several days of dosing. Peak plasma levels of linezolid were not affected.
The clinical significance of these findings has not been determined as limited safety data are currently available (see sections 4.2 and 4.4).
Patients with hepatic insufficiency:
Limited data indicate that the pharmacokinetics of linezolid, PNU-142586 and PNU-142300 are not altered in patients with mild or moderate hepatic impairment (i.e. Child-Pugh class A or B). The pharmacokinetics of linezolid have not been evaluated in patients with severe hepatic impairment (i.e. Child-Pugh class C). However, as linezolid is metabolised by a non-enzymatic process, liver function impairment should not significantly affect its metabolism (see sections 4.2 and 4.4).
Pediatric population (below 18 years):
Data on the safety and efficacy of linezolid in children and adolescents (body weight) was greater in pediatric patients than in adults, but decreased with increasing age.
In children from 1 week to 12 years of age, administration of 10 mg / kg every 8 hours daily provides approximately "equivalent exposure" to that achieved in adults with the 600 mg twice daily dose.
In infants up to 1 week of age, the systemic clearance of linezolid (based on kilograms of body weight) increases rapidly in the first week of life. Infants receiving 10 mg / kg every 8 hours daily will therefore have the greatest systemic exposure on the first day after delivery. Excessive accumulation is not expected with this regimen during the first week of life, however, as clearance increases rapidly in this period.
In adolescents (12 to 17 years), the pharmacokinetics of linezolid were similar to that in adults following administration of a 600 mg dose. Therefore, daily dosing in adolescents of 600 mg every 12 hours will result in similar exposure to that seen in adults treated with the same dosage.
In pediatric patients with ventriculoperitoneal shunts administered linezolid 10 mg / kg every 12 hours or every 8 hours, variable concentrations of linezolid in CSF have been observed following both single and multiple doses of linezolid. Therapeutic concentrations were neither achieved nor maintained in the cerebrospinal fluid. Therefore, the use of linezolid for the empirical treatment of pediatric patients with central nervous system infections is not recommended.
Elderly patients: The pharmacokinetics of linezolid are not significantly altered in elderly patients 65 years of age or older.
Female patients: Females have a slightly lower volume of distribution than males and mean clearance is reduced by approximately 20% when corrected for body weight. Plasma concentrations are higher in females, and this can be partially attributed to a difference in body weight. However, since the mean half-life of linezolid is not significantly different between males and females, plasma concentrations in females should not substantially exceed those well tolerated and, therefore, no dose modification is required.
05.3 Preclinical safety data
Linezolid reduced the fertility and reproductive performance of male rats at exposure levels roughly equivalent to those expected in humans. These effects were reversible in sexually mature animals. These effects, however, were not reversible in animals Young people treated with linezolid for almost the entire period of sexual maturation.
In adult male rats, abnormal sperm morphology in the testes, and hypertrophy and hyperplasia of epithelial cells in the epididymis were observed.
Linezolid has been shown to influence rat sperm maturation.
Testosterone administration showed no effect on linezolid-mediated effects on fertility.
Dogs treated for one month did not show epididymal hypertrophy although weight changes in the prostate, testes and epididymis were evident.
Reproductive toxicity studies in mice and rats did not reveal any teratogenic effects, respectively at exposure levels 4 times higher or equivalent to those expected in humans.
The same concentrations of linezolid caused maternal toxicity in mice and were related to increased embryonic deaths - including total litter loss, decreased fetal body weight - and an exacerbation of the normal genetic predisposition to sternal variations in the mouse strain used.
Mild maternal toxicity was observed in rats at exposure levels below expected clinical exposures. Mild fetal toxicity was observed, manifested as decreased fetal body weight, reduced ossification of the sternebras, reduced birth survival and slight delay in maturation. These same offspring, once mated, showed a reversible, dose-related increase in pre-implantation losses together with a corresponding decrease in fertility.
In rabbits, the decrease in fetal body weight occurred only in the presence of maternal toxicity (clinical signs, decreased weight gain and dietary consumption), at exposure levels of 0.06 times the estimated human exposure based on AUC. The species is known to be sensitive to the effects of antibiotics.
Linezolid and its metabolites are excreted in the milk of lactating rats at concentrations higher than those found in maternal plasma.
Linezolid induced reversible myelosuppression in rats and dogs.
In rats given oral linezolid for 6 months, minimal to mild axonic degeneration of the sciatic nerve was observed at doses of 80 mg / kg / day; at this same dosage, a minimal degeneration of the sciatic nerve was also observed in a necropsy performed at 3 months in a male specimen. Sensitive morphological evaluation of perfusion-fixed tissues was conducted to look for evidence of optic nerve degeneration. Minimal to moderate optic nerve degeneration was evident in 2 of 3 male rats after 6 months of administration, but direct relationship to the drug was unclear due to the acute nature of the finding and its asymmetrical distribution. The observed optic nerve degeneration was microscopically comparable to the spontaneous unilateral optic nerve degeneration reported in elderly rats and may be an exacerbation of pre-existing general damage. -existing.
Preclinical data, based on conventional studies of repeated dose toxicity and genotoxicity, did not reveal any particular hazards to humans other than those set out in other sections of this Summary of Product Characteristics. Carcinogenicity / oncogenicity studies have not been conducted, given the short duration of administration and the absence of genotoxicity in the standard battery of studies performed.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Solution for infusion
Glucose monohydrate
Sodium citrate (E331)
Citric acid anhydrous (E330)
Hydrochloric acid (E507)
Sodium hydroxide (E524)
Water for injections
Tablets
Core of the tablets:
Microcrystalline cellulose (E 460)
Cornstarch
Sodium carboxymethyl starch (type A)
Hydroxypropylcellulose (E463)
Magnesium Stearate (E 572)
Coating film:
Hypromellose (E464)
Titanium dioxide (E 171)
Macrogol 400
Carnauba wax (E 903)
Granules for oral suspension
Sucrose
Mannitol (E421)
Microcrystalline cellulose (E460)
Carmellose sodium (E466)
Aspartame (E951)
Anhydrous colloidal silica (E 551)
Sodium citrate (E331)
Xanthan gum (E 415)
Sodium benzoate (E 211)
Citric acid anhydrous (E330)
Sodium chloride
Sweeteners (fructose, maltodextrin, monoammonium glycyrrhizinate, sorbitol).
Orange flavoring, orange cream, peppermint and vanilla (acetoin, alpha tocopherols, acetaldehyde, anisic aldehyde, betacaryophyllene, n-butyric acid, butyl butyryl lactate, delta decalactone, dimethyl benzyl carbacetate, ethyl alcohol, ethyl butyrate, ethyl maltol, ethyl vanillin, furaneol, grape terpenes, heliotropin, maltodextrin, modified food starch, monomethylsuccinate, orange aldehyde, orange oil FLA CP, orange oil Valenza 2X, orange oil Valenza 5X, essential oil d " orange, carbonyl orange juice, orange terpenes, peppermint essential oil, propylene glycol, tangerine oil, vanilla extract, vanillin, water).
06.2 Incompatibility
Solution for infusion
No additives should be added to this solution. If linezolid is to be administered in combination with another drug, each drug must be administered separately in accordance with the respective guidelines for use. Similarly, if the same intravenous line is to be used for the sequential infusion of different drugs, that line is to be used. should be irrigated with a compatible solution for infusion before and after administration of linezolid (see section 6.6).
Zyvoxid, solution for infusion, is physically incompatible with the following substances: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate, erythromycin lactobionate, phenytoin sodium and sulfamethoxazole / trimethoprim.
Furthermore, it is chemically incompatible with ceftriaxone sodium
Tablets
Not relevant
Granules for oral suspension
Not relevant
06.3 Period of validity
Solution for infusion
Before opening: 3 years
After opening: From a microbiological point of view, the product should be used immediately, except in cases where the method of opening precludes the risk of contamination.
If not used immediately, in-use storage times and conditions are the responsibility of the user.
Tablets
3 years
Granules for oral suspension
Before reconstitution: 2 years
After reconstitution: 3 weeks
06.4 Special precautions for storage
Solution for infusion
Store in the original package (jacket and box) until use to protect the medicine from light.
Tablets
No particular precautions
Granules for oral suspension
Before reconstitution: keep the bottle sealed
After reconstitution: keep the bottle inside the cardboard box.
06.5 Nature of the immediate packaging and contents of the package
Solution for infusion
Disposable infusion bags, ready to use, in latex-free film, polyolefin multilayer (Excel or Freeflex) sealed inside a laminate sheet.
The bags contain 300 ml of solution and are packed in a box. Each carton contains 1 *, 2 **, 5, 10, 20 or 25 infusion bags.
Note:
The aforementioned boxes can also be supplied in hospital packs of:
* 5, 10 or 20
** 3, 6 or 10
Not all pack sizes may be marketed.
Tablets
White high density polyethylene (HDPE) bottles, with polypropylene screw cap, containing 10 *, 14 *, 20 *, 24, 30, 50 or 60 tablets.
White high-density polyethylene (HDPE) bottles, with polypropylene screw cap, containing 100 tablets (for hospital use only).
Note: The bottles can also be supplied in "hospital packs" of * 5 or 10 bottles.
Polyvinyl chloride (PVC) / aluminum blisters each containing 10 tablets packed in a carton. Each carton contains 10 *, 20 *, 30, 50, 60 tablets.
Polyvinyl chloride (PVC) / aluminum blisters each containing 10 tablets packed in a carton. Each carton contains 100 tablets (for hospital use only).
Note: The cartons can also be supplied in "hospital packs" of * 5 or 10 cartons.
Not all pack sizes may be marketed.
Granules for oral suspension
Type III amber glass bottles with a nominal volume of 240 ml containing 66 g of granules for oral suspension. Each bottle has a hard-to-open polypropylene cap and is packaged in a box together with a 2.5ml / 5ml spoon-measuring cup.
Note: The bottles can also be supplied in "hospital packs" of 5 or 10 bottles.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Solution for infusion
For single use only.
Remove the wrapping package only at the time of use, then check for leaks by firmly squeezing the bag. If the bag is leaking, discard it, as sterility may be altered. The solution must be visually inspected before use and only the solution clear, without particles, must be used. Do not use these pockets in serial connections. Any unused solution should be discarded. No special requirements for disposal. Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations.
Do not reconnect partially used bags.
Zyvoxid solution for infusion is compatible with the following solutions: 5% glucose for intravenous infusion, 0.9% sodium chloride for intravenous infusion, Lactated Ringer's solution for injection (Hartmann's solution for injection).
Tablets
No special requirements for disposal.
Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations.
Granules for oral suspension
Dissolve the granules and reconstitute using 123 ml of water in two approximately equal parts to obtain 150 ml of oral suspension. Shake the suspension well after each addition of water.
Before use, gently invert the bottle a few times. DO NOT SHAKE.
No special requirements for disposal.
Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Limited, Ramsgate Road, Sandwich, Kent CT13 9NJ, United Kingdom.
Representative for Italy:
Pfizer Italia S.r.l. - Via Isonzo 71 04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
1 bag 300 ml for single use infusion of 2 mg / ml AIC 035410012
2 bags 300 ml for single use infusion of 2 mg / ml AIC 035410024
5 bags 300 ml for single use infusion of 2 mg / ml AIC 035410036
10 bags 300 ml for single use infusion of 2 mg / ml AIC 035410048
20 bags 300 ml for single use infusion of 2 mg / ml AIC 035410051
25 bags 300 ml for single use infusion of 2 mg / ml AIC 035410063
"2 mg / ml solution for infusion" 1 single use bag Freeflex AIC 035410366
"2 mg / ml solution for infusion" 2 disposable bags Freeflex AIC 035410378
"2 mg / ml solution for infusion" 3 disposable bags Freeflex AIC 035410380
"2 mg / ml solution for infusion" 5 disposable bags Freeflex AIC 035410392
"2 mg / ml solution for infusion" 6 disposable bags Freeflex AIC 035410404
"2 mg / ml solution for infusion" 10 disposable bags Freeflex AIC 035410416
"2 mg / ml solution for infusion" 20 disposable bags Freeflex AIC 035410428
"2 mg / ml solution for infusion" 25 disposable bags Freeflex AIC 035410430
1 bottle of granules for oral suspension of 100 mg / 5 ml AIC 035410075
1 blister of 10 film-coated tablets of 600 mg AIC 035410226
1 blister of 20 film-coated tablets of 600 mg AIC 035410238
1 blister of 30 film-coated tablets of 600 mg AIC 035410240
1 blister of 50 film-coated tablets of 600 mg AIC 035410253
1 blister of 60 film-coated tablets of 600 mg AIC 035410265
1 blister of 100 film-coated tablets of 600 mg AIC 035410277
1 bottle of 10 film-coated tablets of 600 mg AIC 035410289
1 bottle of 14 film-coated tablets of 600 mg AIC 035410291
1 bottle of 20 film-coated tablets of 600 mg AIC 035410303
1 bottle of 24 film-coated tablets of 600 mg AIC 035410315
1 bottle of 30 film-coated tablets of 600 mg AIC 035410327
1 bottle of 50 film-coated tablets of 600 mg AIC 035410339
1 bottle of 60 film-coated tablets of 600 mg AIC 035410341
1 bottle of 100 film-coated tablets of 600 mg AIC 035410354
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
15 May 2002/05 January 2011
10.0 DATE OF REVISION OF THE TEXT
June 28, 2016
