Zyvox - Instructions For The Use Of An Antibiotic, Price, Reviews, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Zyvox

Zyvox: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Drug interactions
14. 14. Analogs
15. 15. Terms and conditions of storage
16. 16. Terms of dispensing from pharmacies
17. 17. Reviews
18. 18. Price in pharmacies

Latin name: Zivox

ATX code: J01XX08

Active ingredient: linezolid (Linezolid)

Manufacturer: Fresenius Kabi Norge (Norway); Pfizer Pharmaceuticals LLC (Puerto Rico); Pharmacia & Upjohn Company (USA), etc.

Description and photo updated: 2019-27-08

Prices in pharmacies: from 6725 rubles.

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Zyvox is an antimicrobial drug of the oxazolidinone class that is active against anaerobic microorganisms, a wide range of aerobic gram-positive bacteria, and some gram-negative bacteria.

Release form and composition

Zyvox is available in the following dosage forms:

• Solution for infusion: clear, colorless or slightly yellowish liquid (100, 200 or 300 ml in disposable infusion bags made of Excel film, sealed in laminated foil, 1, 2, 5, 10 or 25 bags in a cardboard box);
• Film-coated tablets: oval, white or almost white, on one of the sides the inscription "ZYVOX 600 mg" is made in red paint (10 pcs. In blisters or blisters, 1 blister or packaging in a cardboard box);
• Granules for oral suspension: white or light yellow; a suspension prepared from granules is homogeneous, from white to light yellow (66 g each in 150 ml dark glass bottles, complete with a measuring spoon, 1 bottle in a cardboard box).

Each carton also contains instructions for using Zivox.

The composition of 1 ml of infusion solution includes:

• Active ingredient: linezolid - 2 mg;
• Auxiliary components: anhydrous citric acid, sodium citrate dihydrate, glucose monohydrate, water for injection.

The composition of 1 tablet includes:

• Active ingredient: linezolid - 600 mg;
• Auxiliary components: corn starch, hydroxypropyl cellulose, microcrystalline cellulose (MCC), magnesium stearate, sodium starch glycolate, Opadry white dye, red pharmaceutical ink, carnauba wax.

The composition of 1 dose of a suspension prepared from granules (5 ml) includes:

• Active ingredient: linezolid - 100 mg;
• Auxiliary components: citric acid, sucrose, sodium citrate, xanthan gum, sodium salt of carboxymethyl cellulose and MCC, aspartame, sodium benzoate, mannitol, colloidal silicon dioxide, flavors (orange, mint, vanilla, orange cream), sodium chloride, sweeteners.

Pharmacological properties

Pharmacodynamics

The active substance of Zivox, linezolid, is a synthetic antibiotic. Refers to oxazolidinones, a new class of antimicrobial agents. Shows activity against aerobic gram-positive bacteria, some gram-negative bacteria and anaerobic microorganisms.

The substance selectively inhibits protein synthesis in bacteria. Prevents the formation of a functional 70S initiation complex (due to binding to bacterial ribosomes), which is an important component of the translation process during protein synthesis.

Linezolid is active:

• Aerobic gram-positive bacteria: Staphylococcus aureus (strains with intermediate sensitivity to glycopeptides), Staphylococcus lugdunensis, Streptococcus Staphylococcus haemolyticus, pneumoniae (including strains with intermediate sensitivity to penicillin-s) and penicillin-resistant penicillin (streptococci of groups C and G), Streptococcus intermedius, Streptococcus viridans, Streptococcus pyogenes, Corynebacterium jeikeium, Enterococcus faecalis (including glycopeptide-resistant strains), Enterococcus gallinarum, Enterococcus gallinarum, Enterococcus gallinarum, Enterococcus-casselcium-casselcium-casselcium resistant strains), Staphylococcus aureus (including methicillin-resistant strains), Staphylococcus epidermidis (including methicillin-resistant strains), Listeria monocytogenes;
• Aerobic gram-negative bacteria: Pasteurella multocida, Pasteurella canis;
• Anaerobic gram-positive bacteria: Peptostreptococcus spp. (including Peptostreptococcus anaerobius), Clostridium perfringens;
• Anaerobic gram-negative bacteria: Prevotella spp., Bacteroides fragilis, Chlamydia pneumoniae.

Moderate sensitivity is shown to Zyvox: Mycoplasma spp., Moraxella catarrhalis, Legionella spp.

Resistant to linezolid: Pseudomonas spp., Neisseria spp., Haemophilus influenzae, Enterobacteriaceae.

Cross-resistance between linezolid and chloramphenicol, tetracyclines, streptogramins, folic acid antagonists, aminoglycosides, rifampicins, β-lactam antibiotics, glycopeptides, lincosamides, quinolones is not observed. This is due to the fact that these drugs have different mechanisms of action.

Linezolid resistance develops gradually by a multistep mutation of 23S ribosomal RNA (ribonucleic acid) and is observed with a frequency of less than 1 × 10 ^-9 –1 × 10 ^-11.

The estimated post-antibiotic effect of linezolid is approximately 2 hours for Staphylococcus aureus, in experimental studies on animals it was found that for Staphylococcus aureus and Staphylococcus pneumoniae the indicator is 3.6 and 3.9 hours, respectively.

Pharmacokinetics

Linezolid after oral administration is intensively and rapidly absorbed from the gastrointestinal tract. C _max (maximum concentration) in plasma is 21.2 mg / l, the average TC _max (time of maximum concentration) in a blood - 2 hour absolute bioavailability - about 100%. Food intake has no effect on the absorption of linezolid.

After intravenous administration, 2 times a day, 600 mg, the average C _max and C _min (minimum concentration) in blood plasma in the equilibrium state is 15.1 and 3.68 mg / l, respectively.

The equilibrium concentration of the substance in the blood is reached on the second day of administration.

In healthy adult patients, V _d (volume of distribution) of a substance upon reaching the equilibrium concentration is on average 40–50 l, which is approximately equal to the total water content in the body. Plasma protein binding is 31%, this indicator does not depend on the concentration of linezolid in the blood.

It is known that cytochrome P450 isoenzymes are not involved in the metabolism of linezolid. The substance does not inhibit or potentiate the activity of clinically important cytochrome P450 isoenzymes (1A2, 2C9, 2C19, 2D6, 2E1, 3A4).

Due to metabolic oxidation, two inactive metabolites are formed: hydroxyethylglycine (the main metabolite, formed as a result of a non-enzymatic process) and aminoethoxyacetic acid (formed in a smaller amount). There is also evidence of other inactive metabolites.

Extrarenal clearance is approximately 65% of the clearance of linezolid. With an increase in the dose of the substance, a small degree of clearance nonlinearity is noted. This can be explained by a decrease in renal / extrarenal clearance in the presence of a high dose of linezolid. However, the differences in clearance are small and do not affect the apparent T _1/2 (half-life).

In the absence of impaired renal function and against a background of mild and moderate renal failure, linezolid is excreted by the kidneys as hydroxyethylglycine, aminoethoxyacetic acid and unchanged substance (40, 10 and 30–35%, respectively). It is excreted by the intestines as hydroxyethylglycine and aminoethoxyacetic acid (6 and 3%, respectively). Linezolid is practically not excreted unchanged by the intestine.

T _{1/2 of the} substance is in the range from 5 to 7 hours.

In patients with severe renal impairment (with creatinine clearance <30 ml / min), after a single dose of 600 mg of linezolid, the concentration of the two main metabolites increases by 7-8 times. At the same time, no increase in the AUC value (area under the concentration-time curve) of the starting substance is observed. During hemodialysis, a certain amount of the main metabolites is excreted, despite this, their plasma concentration in the blood after taking 600 mg of linezolid and carrying out the dialysis procedure in patients with severe renal failure significantly exceeds the concentration in the blood in patients with no impaired renal function or with mild or moderate renal failure …

The pharmacokinetic parameters of linezolid in severe hepatic insufficiency (according to the Child-Pugh classification, class C) have not been studied. Significant disturbances in the metabolism of linezolid in liver failure are not expected, since it occurs in a non-enzymatic way.

Indications for use

The antibiotic Zyvox is used to treat infectious and inflammatory diseases when it is suspected or known for certain that they are caused by aerobic and anaerobic gram-positive microorganisms sensitive to linezolid (including infections accompanied by bacteremia):

• Community-acquired pneumonia: causative agent - Streptococcus pneumoniae (including its multidrug-resistant strains, including those accompanied by bacteremia); pathogen - Staphylococcus aureus (only strains sensitive to methicillin);
• Nosocomial (hospital) pneumonia: causative agent - Staphylococcus aureus (including methicillin-resistant and methicillin-susceptible strains); pathogen - Streptococcus pneumoniae (including multi-resistant strains);
• Complicated infections of soft tissues and skin, including infections with diabetic foot syndrome (DFS), without signs of osteomyelitis: pathogens - Staphylococcus aureus (including methicillin-resistant and methicillin-susceptible strains), Streptococcus agalactiae and Streptococcus pyogenes;
• Uncomplicated infections of soft tissues and skin: pathogens - Staphylococcus aureus (exclusively strains sensitive to methicillin) or Streptococcus pyogenes;
• Vancomycin-resistant infections: the causative agent is Enterococcus faecium, including infections accompanied by bacteremia.

Contraindications

All forms of release of Zivox are contraindicated in case of hypersensitivity to the components of the drug.

Absolute contraindications for oral administration of Zivox (tablets, granules):

• Simultaneous intake of monoamine oxidase inhibitors A or B (isocarboxazid, phenelzine), as well as a two-week period after stopping their use;
• Inability to control blood pressure during therapy of patients with pheochromocytoma, uncontrolled arterial hypertension, thyrotoxicosis, as well as patients receiving adrenergic agonists (phenylpropanolamine, pseudoephedrine, epinephrine, dobutamine) and / or dopaminomimetics (levodopa, amantadine, dopamine);
• Inability to monitor patients at risk of serotonin syndrome;
• Carcinoid syndrome and / or taking serotonin reuptake inhibitors, tricyclic antidepressants, 5-HT ₁ receptor agonists (triptans), meperidine or buspirone;
• Children under 12 years of age (for tablets, due to the impossibility of adequate dose selection).

Relative contraindications (increased risk of side effects):

• Severe renal impairment;
• Liver failure;
• Systemic infections that pose a risk to life (with the use of venous catheters in intensive care units);
• Pregnancy;
• Lactation period.

Zyvox, instructions for use: method and dosage

Depending on the causative agent of the infection, the localization and severity of the course of the disease, as well as on the clinical efficacy, the duration of the course of therapy and the dosage regimen are determined.

Solution for infusion

Zyvox solution should be administered intravenously, the duration of administration is from 30 to 120 minutes, it is recommended to divide the daily dose by 2 times.

The following dosage regimen of Zivox is recommended for adults and children over 12 years of age:

• Community-acquired pneumonia, pneumonia, hospital, soft tissue infections, and skin (including accompanied by bacteremia..) - 600 mg every 12 hours for 1 ¹ / ₂ -2 weeks;
• Enterococcal infections (including those accompanied by bacteremia) - 600 mg every 12 hours for 2-4 weeks.

The following dosage regimen for Zivox is recommended for children under 12 years of age:

• Community-acquired pneumonia, pneumonia, hospital, soft tissue infections, and skin (including accompanied by bacteremia..) - 10 mg / kg every 8 h for 1 ¹ / ₂ -2 weeks;
• Enterococcal infections (including those accompanied by bacteremia) - 10 mg / kg every 8 hours for 2-4 weeks.

Immediately before using the solution, remove the protective foil, then squeeze the infusion bag for about a minute to make sure there are no leaks. The leakage of the package indicates a violation of its tightness, therefore, the solution is not sterile and is not suitable for use.

Do not connect infusion bags in series and use packages that are partially filled.

At the end of the procedure, the remains of the unused solution must be discarded.

Patients who have started therapy with the parenteral form of Zyvox can be switched to the oral dosage form according to clinical indications. In this case, dose selection is not required, since the bioavailability of linezolid when taken orally is almost 100%.

Granules for preparation of oral suspension, coated tablets

Suspension made from granules and Zyvox tablets are taken orally, regardless of food intake.

The recommended dosage regimen for the treatment of infections (including those accompanied by bacteremia):

• Community-acquired pneumonia, hospital pneumonia - 600 mg every 12 hours for 1 ¹ / ₂ -2 weeks;
• Soft tissue infections and skin - from 400 to 600 mg (depending on the severity of the disease) every 12 hours for 1 ¹ / ₂ -2 weeks;
• Enterococcal infections - 600 mg every 12 hours for 2-4 weeks.

For children from 5 years old and older (from 12 years old - for tablets) Zyvox is recommended at a dose of 10 mg / kg of body weight per day, divided into 2 doses.

For children and adults, the maximum dose should not exceed 600 mg 2 times a day.

Preparation of a suspension for oral administration from granules:

1. Tap the bottle lightly so that the caked powder crumbles;
2. Measure exactly 123 ml of water with a graduated cylinder;
3. Add the first portion of water (about half of 123 ml) to the bottle, then shake the bottle vigorously to evenly moisten its contents;
4. Add the remaining water and shake the bottle again until a homogeneous 150 ml suspension is obtained.

Before use, the suspension must be resuspended by inverting the bottle 3-5 times. Do not shake.

Side effects

Usually, there are undesirable effects associated with the intake of oral forms of Zyvox, mild to moderate. Headache, nausea, and diarrhea were most commonly reported.

Classification of the frequency of adverse reactions: very rare (<0.01%), rarely (≥0.01% - <0.1%), infrequently (≥0.1% - <1%), often (≥1% - < 10%), very often (≥10%).

In adult patients:

• Digestive system: infrequently - discoloration of the tongue; often - nausea, vomiting, diarrhea, abdominal pain (including spastic ones), constipation, flatulence, candidiasis of the oral mucosa;
• Central and peripheral nervous system: infrequently - perversion of gustatory perception; often - insomnia, convulsions, dizziness, headache;
• Genitourinary system: often - vaginal candidiasis;
• Skin: often - rash;
• Laboratory indicators: infrequently - an increase in the concentration of triglycerides in the blood, an increase in the activity of liver enzymes (including ALT (alanine aminotransferase), AST (aspartate aminotransferase), ALP (alkaline phosphatase), LDH (lactate dehydrogenase), amylase, lipase, and total creatinine concentration bilirubin), increasing the concentration of prolactin; often - thrombocytopenia;
• Others: infrequently - opportunistic fungal infection; often fever.

In addition, were noted: itching, dyspepsia, increased blood pressure (blood pressure).

In adolescents aged 12 to 17:

• Digestive system: often - nausea, vomiting, diarrhea, abdominal pain (generalized and local), loose stools;
• Nervous system: often - vertigo, headache;
• Skin: infrequently - itching; often a rash;
• From the respiratory system: often - upper respiratory tract infections, cough, pharyngitis;
• Laboratory indicators: infrequently - an increase in the concentration of triglycerides in the blood, eosinophilia, an increase in the activity of ALT, the concentration of creatinine, lipase;
• Others: often - pain of unspecified localization, fever.

Post-marketing research data (spontaneous):

• Nervous system: seizures, peripheral neuropathy;
• Digestive system: discoloration of tooth enamel;
• Senses: episodes of optic neuropathy, possibly leading to loss of vision;
• Metabolism: lactic acidosis;
• Allergic responses: anaphylaxis;
• Skin: angioedema, rash, bullous skin lesions (like Stevens-Johnson syndrome);
• Laboratory indicators: reversible myelosuppression (anemia, leukopenia, thrombocytopenia, pancytopenia);
• Others: fatigue, chills, serotonin syndrome.

Adverse reactions when using Zivox in the form of a solution for infusion:

• Digestive system: often - nausea, vomiting, taste perversion, diarrhea, flatulence, epigastric pain (including spastic), changes in indicators: total bilirubin, AST, ALT, ALP;
• Hematopoietic system: often - reversible anemia, leukopenia, thrombocytopenia, pancytopenia;
• Others: rarely - cases of peripheral neuropathy and neuropathy of the optic nerve when used for more than 28 days *; often - headache, candidiasis.

Note

* the relationship between the use of the Zyvox infusion solution and the development of neuropathy has not been proven, since in most of the observed cases, patients either received drugs that could cause neuropathy (paroxetine, amitriptyline, isoniazid), and / or had diseases that could lead to the development of neuropathy (arterial hypertension, diabetes mellitus, chronic renal failure, brain abscess, osteosarcoma).

Adverse reactions during parenteral administration do not depend on the dose of Zivox and, as a rule, do not require discontinuation of treatment.

Overdose

There is no information about Zivox overdose.

If necessary, symptomatic treatment is prescribed (including measures to maintain the level of glomerular filtration). About 30% of the dose is excreted during hemodialysis for 3 hours.

special instructions

In the case of an established infection or suspicion of infections caused by concomitant gram-negative microorganisms, it is recommended to additionally use agents acting on gram-negative flora.

In some cases, patients receiving linezolid, depending on the duration of treatment, may develop reversible myelosuppression (with thrombocytopenia, leukopenia, anemia, and pancytopenia). Therefore, during therapy, blood counts should be monitored in patients with a history of myelosuppression, with an increased risk of bleeding, while the use of linezolid with drugs that reduce the number of platelets, hemoglobin content and / or their functional properties, as well as with a duration of therapy for more than 2 weeks …

When taking antibacterial drugs, incl. linezolid, the risk of developing pseudomembranous colitis of varying severity should be considered, especially if diarrhea is present.

As a result of the use of almost all antibacterial drugs, including Zyvox, cases of Clostridium difficile-associated diarrhea (from mild to severe) have been reported. Antibiotic therapy disrupts the natural intestinal microflora, activating the growth of the microorganism Clostridium difficile, which produces toxins A and B, which causes diarrhea. The excess amount of toxins may increase the likelihood of death among patients, since these infections may be resistant to antimicrobial therapy, in some cases colectomy may be necessary. Careful monitoring of the condition of patients after antibiotic therapy who have had diarrhea associated with Clostridium difficile is necessary for 2 months.

If symptoms of visual impairment appear (change in acuity, change in color perception, visual field defects, blurred vision), you should immediately seek advice from an ophthalmologist. Monitoring of visual function is necessary for all patients using Zyvox for a long period of time (3 months or more), as well as for patients with new symptoms of visual impairment, regardless of the duration of therapy. With the development of neuropathy of the optic nerve and peripheral neuropathy, it is recommended to assess the risk / benefit ratio to decide whether to continue therapy with linezolid.

Cases of lactic acidosis have been reported in connection with the use of linezolid, therefore, close medical supervision is required for the condition of patients who, against the background of antibiotic therapy, experience repeated vomiting or nausea, unexplained acidosis, or a decrease in the mass concentration of bicarbonate anions.

The occurrence of seizures in patients taking linezolid was observed in most cases with a history of data on previous seizures or the risk of their development.

If Zyvox is to be used in combination with selective serotonin reuptake inhibitors, then constant monitoring of patients is needed in order to identify symptoms and signs of serotonin syndrome (hyperpyrexia, impaired cognitive function, hyperreflexia, impaired coordination of movements). When they appear, immediate withdrawal of one or both of the drugs taken is required. Stopping the serotonergic drug may cause withdrawal.

In the case of a reverse superficial change in the staining of tooth enamel, it is recommended to carry out a professional cleaning of the teeth at the dentist.

Influence on the ability to drive vehicles and complex mechanisms

Parenteral administration of the drug has no effect on the rate of psychomotor reactions.

During therapy with oral forms of Zivox, it is not recommended to drive special equipment and vehicles, to engage in activities associated with an increased risk.

Application during pregnancy and lactation

The safety profile of Zivox in pregnant and lactating women has not been studied.

During pregnancy, therapy can be prescribed only in cases where the expected benefit outweighs the possible risk. If Zivox is used during lactation, breastfeeding should be discontinued.

Pediatric use

For children under 12 years of age, Zyvox tablets are contraindicated.

With impaired renal function

In severe renal failure, therapy should be carried out with caution.

For violations of liver function

In case of liver failure, the antibiotic Zyvox is used under medical supervision.

Drug interactions

Cytochrome isozymes, according to in vitro studies, do not take part in the metabolism of linezolid, which, in turn, does not potentiate or inhibit the activity of clinically significant cytochrome isoenzymes.

Linezolid is a reversible non-selective inhibitor of monoamine oxidase, therefore, in some patients receiving it, there may be a moderate reversible increase in the pressor action of phenylpropanolamine and pseudoephedrine, and therefore it is recommended to reduce the initial doses of such groups of drugs as dopaminomimetics (levodopa, amantadine, dopamine), adrenomimetics (phenylpropanolamine, pseudoephedrine, epinephrine, dobutamine, norepinephrine), and further dose selection by titration.

There was no development of serotonin syndrome (in the results of studies of phases I, II and III) when linezolid was used in conjunction with serotonergic drugs, but several reports contained data on the development of serotonin syndrome against the background of the simultaneous use of Zyvox and antidepressants - selective serotonin reuptake inhibitors.

As a result of the simultaneous use with gentamicin and aztreonam, there was no change in the pharmacokinetics of linezolid.

Rifampicin caused a decrease in Cmax (maximum concentration of a substance in the blood) and AUC (Area Under Curve) of linezolid by an average of 21% and 32%, respectively.

Zyvox in the form of a solution for infusion is compatible with 0.9% sodium chloride solution, 5% glucose (dextrose) solution, Ringer's solution for injection with lactose.

Pharmaceutical solution for infusion is incompatible with chlorpromazine, diazepam, amphotericin B, pentamidine isethionate, erythromycin, phenytoin, co-trimoxazole.

Chemically, the solution for infusion is incompatible with ceftriaxone sodium.

It is contraindicated to introduce additional components into the solution for infusion, therefore, when Zivox is prescribed simultaneously with other drugs, each of them should be administered separately.

Analogs

Analogs of Zivox are: Sanguirithrin, Dioxidin, 5-NOK, Hexamethylenetetramine, Ristomycin sulfate, Rowlin-Routek, Galenofillipt, Dixin, Kirin, Nitroxolin, Cubicin, Monural, Urofosfabol, Fosfomycin, Amizolideva, Linezolide, Zeniksolide

Terms and conditions of storage

Store in a dry, dark place out of reach of children. Storage temperature of tablets and granules - no higher than 30 ° C, solution - no higher than 25 ° C.

Shelf life of tablets and solution for infusion is 3 years, granules for suspension preparation is 2 years.

A bottle with a suspension made from granules is recommended to be stored in a cardboard box at room temperature up to 25 ° C, no more than 3 weeks. A bottle with granules for preparation of a suspension for oral administration must be tightly closed.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Zivoks

Reviews about Zivoks are mostly positive. There are reports of the development of side effects, mainly in the form of nausea and headache. In some cases, they go away on their own after a few days, but in case of severe disorders, the drug is canceled. The cost of the funds is assessed as high.

Price for Zyvox in pharmacies

The approximate price for Zyvox is: tablets (10 pcs.) - 12,000-20,552 rubles, infusion solution (10 sachets of 300 ml each) - 9461-16,791 rubles, granules for suspension preparation (1 bottle of 66 g each) - RUB 10,487

Zyvox: prices in online pharmacies

Drug name Price Pharmacy

Zyvox 2 mg / ml solution for infusion 100 ml 10 pcs. RUB 6725 Buy

Zivoks solution for inf. 2mg / ml 100ml n10 RUB 7614 Buy

Zyvox 600 mg film-coated tablets 10 pcs. RUB 9499 Buy

Zyvox 100 mg / 5 ml granules for preparation of suspension for oral administration 66 g 5 pcs. RUB 9729 Buy

Zyvox 100 mg / 5 ml granules for preparation of suspension for oral administration 66 g 1 pc. RUB 10,021 Buy

Zyvox 2 mg / ml solution for infusion 300 ml 10 pcs. 14350 RUB Buy

Zivox tablets p.p. 600mg 10pcs RUB 17663 Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!