Zivox, 600 mg 10 pcs

Pharmacotherapeutic group: Oxazolidinone antibiotic.

ATX code: J01XX08

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics

Linezolid, a synthetic antibacterial drug, belongs to a new class of antimicrobial agents, oxazolidinones, active in vitro against aerobic Gram-positive bacteria, some Gram-negative bacteria and anaerobic microorganisms. Linezolid selectively inhibits protein synthesis in bacteria. Through binding to bacterial ribosomes, it prevents the formation of the functional initiating complex 70S, which is an important component of the translation process during protein synthesis.

Indications

Treatment of infectious and inflammatory diseases if it is known or suspected that they are caused by aerobic and anaerobic gram-positive microorganisms sensitive to linezolid (including infections accompanied by bacteremia):

– community-acquired pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant strains), including cases accompanied by bacteremia, or Staphylococcus aureus (only methicillin-sensitive strains);

– hospital-acquired pneumonia caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains) or Streptococcus pneumoniae (including multidrug-resistant strains);

– complicated infections of the skin and soft tissues, including infections in diabetic foot syndrome, not accompanied by osteomyelitis, caused by Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains), Streptococcus pyogenes or Streptococcus agalactiae;

– uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (only methicillin-sensitive strains) or Streptococcus pyogenes;

– infections resistant to vancomycin caused by Enterococcus faecium, including those accompanied by bacteremia.

Pharmacological effect

Pharmacotherapeutic group: antibiotic-oxazolidinone.

ATX code: J01XX08

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics

Linezolid, a synthetic antibacterial drug, belongs to a new class of antimicrobial agents, the oxazolidinones, that are active in vitro against aerobic gram-positive bacteria, some gram-negative bacteria, and anaerobic microorganisms. Linezolid selectively inhibits protein synthesis in bacteria. By binding to bacterial ribosomes, it prevents the formation of a functional 70S initiation complex, which is an important component of the translation process in protein synthesis.

Special instructions

In case of established infection (or suspected infection) caused by concomitant gram-negative microorganisms, additional use of agents acting on gram-negative flora is indicated.

Some patients receiving linezolid may develop reversible myelosuppression (with anemia, thrombocytopenia, leukopenia and pancytopenia), depending on the duration of therapy. In this regard, during treatment it is necessary to monitor blood counts in patients with an increased risk of bleeding, a history of myelosuppression, as well as with simultaneous use of drugs that reduce hemoglobin content or platelet count and/or their functional properties, as well as in patients receiving linezolid for more than 2 weeks.

In patients taking antibacterial drugs, including linezolid, the risk of developing pseudomembranous colitis of varying severity should be considered.
Cases of Clostridium difficile-associated diarrhea have been reported in association with the use of virtually all antibacterial drugs, including linezolid. The severity of diarrhea can vary from mild to severe.

Treatment with antibacterial drugs disrupts the normal intestinal microflora, which leads to excessive growth of Clostridium difficile. Clostridium difficile produces toxins A and B, which lead to Clostridium difficile-associated diarrhea. Excessive amounts of toxins produced by Clostridium difficile strains may cause increased mortality in patients, as such infections may be resistant to antimicrobial therapy and may require colonectomy.

The possibility of developing Clostridium difficile-associated diarrhea should be considered in all patients with diarrhea following antibiotic use. Close medical observation for 2 months is necessary for patients who experience diarrhea associated with Clostridium difficile after administration of antibacterial drugs.

If symptoms of deterioration in visual function appear, such as changes in visual acuity, changes in color perception, blurred vision, visual field defects, it is recommended to immediately consult an ophthalmologist for consultation. Visual function should be monitored in all patients taking linezolid long-term (more than 3 months) and in all patients with new-onset symptoms of visual impairment, regardless of the duration of therapy. In the event of development of peripheral neuropathy and optic neuropathy, the risk/benefit ratio of continuing linezolid therapy in these patients should be assessed.

Lactic acidosis has been reported in association with linezolid use. Patients who experience repeated nausea or vomiting, unexplained acidosis, or a decrease in bicarbonate anion concentrations while taking linezolid require careful monitoring by a physician.

Convulsions have been reported in patients taking linezolid, with most cases having a history of convulsions or risk factors for their development. If it is necessary to use the drug ZIVOX® in combination with selective serotonin reuptake inhibitors, patients should be constantly monitored in order to identify signs and symptoms of serotonin syndrome, such as impaired cognitive function, hyperpyrexia, hyperreflexia and impaired motor coordination. If these symptoms appear, one or both medications should be discontinued.

When you stop taking a serotonergic drug, withdrawal symptoms may occur.

Cases of reversible superficial discoloration of tooth enamel have been reported with the use of linezolid. These discolorations were removed by professional teeth cleaning.

Impact on the ability to drive vehicles. Wed and fur.:

During treatment with linezolid, driving vehicles, special equipment or engaging in activities associated with increased risk is not recommended.

Active ingredient

Linezolid

Composition

1 film-coated tablet contains:

Active ingredient: linezolid – 600 mg;

Excipients: corn starch 60 mg, microcrystalline cellulose 117.6 mg, hyprolose 12 mg, sodium carboxymethyl starch 42 mg, magnesium stearate 8.4 mg;

Film coating: carnauba wax 0.0336 mg, Opadry white YS-1-18202-A (titanium dioxide 31%, hypromellose 63%, macrogol 6%) 21 mg.

Pharmaceutical ink (shellac 39.663%, butanol 7%, macrogol 3.5%, red iron oxide dye 22.5%, concentrated ammonia solution 2.479%, purified water 24.858%).

Pregnancy

There have been no studies of the safety of linezolid during pregnancy, therefore the use of ZIVOX® during pregnancy is possible only if the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

It is unknown whether linezolid is excreted in the breast milk of lactating women, so breastfeeding should be discontinued when prescribing the drug to a mother during lactation.

Contraindications

Hypersensitivity to linezolid and/or other components of the drug.

Concomitant use of linezolid with drugs that inhibit monoamine oxidases A or B (for example, phenelzine, isocarboxazid), as well as for two weeks after stopping these drugs.

In the absence of blood pressure monitoring, linezolid should not be prescribed to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, and/or patients receiving the following types of drugs: adrenergic agonists (eg, pseudoephedrine, phenylpropanolamine, epinephrine, norepinephrine, dobutamine), dopaminomimetics (eg, dopamine).

Unless closely monitored in patients who may develop serotonin syndrome, linezolid should not be prescribed to persons with carcinoid syndrome and/or to patients receiving the following medications: serotonin reuptake inhibitors, tricyclic antidepressants, 5-HT1 receptor agonists (triptans), meperidine, or buspirone.

The use of linezolid in tablet form in children under 12 years of age is contraindicated due to the impossibility of adequate dose selection.

WITH CAUTION

Patients with renal failure

Due to the unknown clinical significance of linezolid’s two primary metabolites in patients with severe renal impairment, linezolid should be used with caution in such patients and only if the expected benefit outweighs the potential risk.

Patients with liver failure

There is limited clinical data to recommend that linezolid be used in these patients only if the expected benefit outweighs the potential risk.
Linezolid should be used with caution in patients with systemic infections that pose a risk to life, such as infections associated with venous catheters in intensive care units.

Side Effects

The frequency of adverse reactions is presented according to the following classification:

Very common: ≥10%

Frequent: ≥1% and <10%

Uncommon: ≥0.1% and <1%

Rare: ≥0.01% and <0.1%

Very rare: <0.01%

Adverse events associated with linezolid are usually mild or moderate in severity. The most common symptoms are diarrhea, headache and nausea.

Adult patients

From the digestive system:

Frequent: diarrhea, nausea, vomiting, constipation, abdominal pain (including cramping), flatulence, candidiasis of the oral mucosa

Uncommon: Discoloration of the tongue

Laboratory indicators:

Common: thrombocytopenia

Uncommon: increased concentration of triglycerides in the blood, increased activity of liver enzymes (including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), lipase, amylase, total bilirubin and creatinine concentrations), increased prolactin concentration

From the nervous system:

Common: headache, dizziness, convulsions

Uncommon: taste disturbance

From the central nervous system:

Common: insomnia

From the genitourinary system:

Common: vaginal candidiasis

From the skin:

Common: rash

Others:

Common: fever

Uncommon: opportunistic fungal infection

Also noted: increased blood pressure, dyspepsia, itching

Teenagers (12 to 17 years old)

From the digestive system:

Frequent: diarrhea, nausea, vomiting, abdominal pain (local and generalized), loose stools

Laboratory indicators:

Uncommon: eosinophilia, increased blood triglyceride concentrations, increased alanine aminotransferase (ALT), lipase, creatinine concentrations

From the nervous system:

Common: headache, vertigo

From the skin:

Common: rash

Uncommon: itching

From the respiratory system:

Common: upper respiratory tract infections, pharyngitis, cough

Others:

Common: fever, pain of unspecified localization

Spontaneous (post-marketing) data

Laboratory findings: reversible myelosuppression (thrombocytopenia, anemia, leukopenia, pancytopenia)

From the senses: cases of optic neuropathy, sometimes leading to loss of vision (see “Special Instructions”).

Allergic reactions: anaphylaxis

From the skin: rash, angioedema; bullous skin lesions similar to Stevens-Johnson syndrome

Metabolism: lactic acidosis

From the nervous system: peripheral neuropathy, seizures (see “Special instructions”)

From the digestive system: discoloration of tooth enamel (see “Special Instructions”)

Other: chills, fatigue, serotonin syndrome (see sections “Interaction with other drugs” and “Special instructions”)

Interaction

It has been established that cytochrome P450 isoenzymes are not involved in the metabolism of linezolid in vitro. Linezolid does not inhibit or potentiate the activity of clinically important cytochrome P450 isoenzymes (1A2, 2C9, 2C19, 2D6, 2E1, 3A4).

Monoamine oxidase inhibitors

Linezolid is a non-selective, reversible monoamine oxidase inhibitor, and some patients receiving linezolid may experience a mild, reversible increase in the pressor effects of pseudoephedrine and phenylropanolamine. In this regard, it is recommended to reduce the initial doses of the following groups of drugs: adrenergic agonists (for example, pseudoephedrine, phenylpropanolamine, epinephrine, norepinephrine, dobutamine), dopaminomimetics (for example, dopamine) and then titrate the dose.

In phase I, II and III studies, the development of serotonin syndrome was not observed in patients receiving linezolid in combination with serotonergic drugs. However, there have been several reports of the development of serotonin syndrome during the use of linezolid and antidepressants – selective serotonin reuptake inhibitors. When used concomitantly with aztreonam and gentamicin, no changes in the pharmacokinetics of linezolid were observed.

Rifampicin caused a decrease in Cmax and AUC of linezolid by an average of 21% and 32%, respectively.

Overdose

No cases of linezolid overdose have been reported. Symptomatic treatment is recommended (including the need to maintain glomerular filtration rate). There are no data regarding acceleration of linezolid elimination by peritoneal dialysis or hemoperfusion.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Manufacturer

Polisan NTFF LLC, Russia