Linezolid - Instructions For Use, Price, Analogs, Tablets, Reviews

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

Linezolid

Linezolid: 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: Linezolid

ATX code: J01XX08

Active ingredient: linezolid (Linezolid)

Manufacturer: Novalek Pharmaceuticals Pvt. Ltd. (Novalek Pharmaceuticals Pvt. Ltd.) (India), Biochemist, OJSC (Russia), East-Pharm, CJSC (Russia), PharmConcept, LLC (Russia), Alium PFK, LLC (Russia)

Description and photo update: 2019-08-10

Prices in pharmacies: from 3979 rubles.

Buy

Linezolid is an antibacterial drug, oxazolidinone.

Release form and composition

Dosage forms of Linezolid:

• film-coated tablets: biconvex, from dark brown to light brown, round (dosage 200, 300 and 400 mg) or oval (dosage 600 mg); the color of the tablets in the cross section is white or white with a yellowish tinge (in a cardboard box 1, 2 or 3 cell contoured packages containing 10 tablets each);
• solution for infusion: from colorless to yellow with a brownish tint, transparent (in a cardboard box 1 glass bottle containing 100, 200 or 300 ml of solution).

Each pack also contains instructions for the use of Linezolid.

Composition of 1 tablet:

• active substance: linezolid - 200/300/400/600 mg;
• auxiliary components: magnesium stearate - 2.69 / 4.04 / 5.38 / 8.08 mg; sodium carboxymethyl starch - 13.44 / 20.17 / 26.89 / 40.34 mg; corn starch - 19.21 / 28.81 / 38.42 / 57.63 mg; microcrystalline cellulose - 37.65 / 56.47 / 75.3 / 112.95 mg;
• film shell: talc - 0.017 / 0.026 / 0.035 / 0.053 mg; titanium dioxide - 0.27 / 0.41 / 0.55 / 0.825 mg; polyethylene glycol 6000 (macrogol 6000) - 1.08 / 1.62 / 2.16 / 3.25 mg; hydroxypropyl methylcellulose (hypromellose) - 5.19 / 7.79 / 10.38 / 15.58 mg; iron dye yellow oxide - 0.302 / 0.453 / 0.604 / 0.906 mg; iron dye red oxide - 0.131 / 0.197 / 0.263 / 0.395 mg.

Composition of 1 ml solution:

• active substance: linezolid - 2 mg;
• auxiliary components: sodium citrate dihydrate - 1.9 mg; citric acid - 0.83 mg; dextrose monohydrate - 55.26 mg; water for injection - up to 1 ml; 1M hydrochloric acid solution or 1M sodium hydroxide solution - up to pH 4 to 5.

The theoretical osmolarity of the solution is 314.9 mOsm per liter.

Pharmacological properties

Pharmacodynamics

Linezolid is a synthetic antibiotic belonging to a new class of antimicrobial agents that are in vitro active against aerobic gram-positive bacteria, some anaerobic microorganisms and gram-negative bacteria.

The drug 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 during protein synthesis.

Linezolid is active against the following microorganisms:

• gram-positive aerobes (in vitro and in vivo): enterococcus fetium (including vancomycin-resistant strains), Staphylococcus aureus (including methicillin-resistant strains), group B streptococci, pneumococcus (including multi-resistant strains), pyogenic streptococcus;
• gram-positive aerobes (in vitro): fecal enterococcus (including vancomycin-resistant strains), fecium enterococcus (vancomycin-sensitive strains), epidermal staphylococcus (including methicillin-resistant strains), hemolytic staphylococcus virus, streptococcus virusidans;
• gram-negative aerobes (in vitro): pasteurella multicide.

Microorganisms resistant to linezolid include: Pseudomonas aeruginosa, Haemophilus influenzae, Enterobacteriaceae, Neisseria, Moraxella catarrhalis.

Since the mechanism of action of linezolid differs from that inherent in other classes of antimicrobial agents (for example, chloramphenicol, tetracyclines, streptogramins, rifamycins, quinolones, lincosamides, glycopeptides, folic acid antagonists, β-lactams, aminoglycosides), there is no overlap between these drugs. Linezolid is active against pathogenic microorganisms sensitive and resistant to these drugs.

In relation to linezolid, resistance develops slowly through a multistep mutation of 23 S ribosomal ribonucleic acid and occurs with a frequency of less than 1x10 ^-9 -1x10 ^-11.

Pharmacokinetics

• absorption: after oral administration, linezolid is absorbed rapidly and intensively from the gastrointestinal tract. Its maximum concentration in blood plasma (C _max) is 21.2 mg per 1 liter, and the average time period until the maximum concentration in blood (TC _max) is 2 hours. Absolute bioavailability is about 100%. Food intake has no effect on its absorption. On the second day of taking the drug, its equilibrium concentration in the blood is achieved. After intravenous administration of linezolid 2 times a day, 600 mg of its C _max and the average minimum concentration (C _min) in blood plasma in equilibrium are 15.1 and 3.68 mg per 1 liter, respectively. On the second day of drug administration, its equilibrium concentration in the blood is reached;
• distribution: when the equilibrium concentration is reached, the volume of distribution of linezolid in a healthy adult varies on average from 40 to 50 liters, which is approximately equal to the total water content in the body. Regardless of the plasma concentration of a substance, its binding to blood plasma proteins is 31%;
• metabolism: it has been established that cytochrome P ₄₅₀ isoenzymes do not participate in the metabolism of a drug in vitro. It does not potentiate or inhibit the activity of such clinically important cytochrome P ₄₅₀ isozymes as 3A4, 2E1, 1A2, 2D6, 2C9 and 2C19. In the process of metabolic oxidation, two inactive metabolites are formed - aminoethoxyacetic acid and hydroxyethylglycine. The first metabolite is formed in smaller quantities, and the second is the main metabolite in humans and is formed as a result of a non-enzymatic process. Other inactive metabolites are also described;
• elimination: almost 65% of the clearance of linezolid is renal clearance. With an increase in the dose of the drug, a slight degree of clearance nonlinearity is noted. This may be due to a decrease in renal and extrarenal clearance with a high dose of linezolid. At the same time, the differences in clearance are small and do not affect the apparent half-life. With normal renal function and mild / moderate renal failure, the drug is excreted by the kidneys: unchanged - 30–35%, in the form of aminoethoxyacetic acid - 10%, in the form of hydroxyethylglycine - 40%. Linezolid is excreted through the intestine: in the form of aminoethoxyacetic acid - 3%, in the form of hydroxyethylglycine - 6%, unchanged - practically not excreted. On average, its half-life varies within 5-7 hours.

In cases of a single dose of 600 mg of linezolid against the background of severe renal failure [creatinine clearance (CC) <30 ml per minute), the concentration of two metabolites of the substance increased by 7-8 times. The area under the concentration-time curve (AUC) of the parent drug did not increase.

During hemodialysis, the main metabolites were excreted in a certain amount, however, after taking 600 mg of the drug and the dialysis procedure, their concentration remained significantly higher compared to that against the background of normal renal function, mild / moderate renal failure.

There are limited data on the pharmacokinetics of linezolid and its two major metabolites in mild / moderate hepatic failure (Child-Pugh classes A and B). It is known that it does not change.

Pharmacokinetics in severe hepatic impairment (according to the Child-Pugh class C classification) has not been studied. Due to the fact that linezolid is metabolized in a non-enzymatic way, significant disturbances in its metabolism are not expected in this case.

The pharmacokinetics of linezolid at a dose of 600 mg in adolescents aged 12 to 17 years did not differ from the kinetics in adults. Based on this, when using the same dose in adolescents every 12 hours and in adults, the concentration of the drug will be the same.

Daily use of 10 mg of linezolid per 1 kg of body weight in children under the age of 12 every 8 hours can achieve the same concentration as in adults when 600 mg of the drug is used 2 times a day.

There are no significant changes in the pharmacokinetics of the drug in elderly patients aged 65 years and older.

The volume of distribution of the substance in women is slightly lower than in men. When calculated on body weight, they also have a reduced average ground clearance of 20%. Plasma concentrations of the drug are lower in men than in women, which may in part be due to differences in weight. Since the elimination half-life does not differ significantly depending on gender, there is no reason to expect an increase in the concentration of linezolid in the blood of women above the tolerated level, and, therefore, they do not need to adjust the dosage regimen.

Indications for use

Linezolid in the form of tablets and solution for infusion is prescribed for the treatment of infectious and inflammatory pathologies in cases where it is known or suspected that their pathogens (aerobic and anaerobic gram-positive microorganisms, including infections accompanied by bacteremia) are sensitive to linezolid, namely:

• community-acquired pneumonia caused by Staphylococcus aureus (methicillin-susceptible strains only) or pneumococcus (including multi-resistant strains), including cases accompanied by bacteremia;
• hospital pneumonia caused by pneumococcus, including multi-resistant strains, or Staphylococcus aureus, including methicillin-resistant and methicillin-susceptible strains;
• complicated infections of the skin and soft tissues, including those with diabetic foot syndrome, not accompanied by osteomyelitis, the causative agents of which are group B streptococci, pyogenic streptococcus or Staphylococcus aureus, including methicillin-resistant and methicillin-susceptible strains;
• infections caused by vancomycin-resistant enterococcus fetium, including cases accompanied by bacteremia.

Linezolid tablets are also used for uncomplicated skin and soft tissue infections caused by Streptococcus pyogenic or Staphylococcus aureus (only methicillin-susceptible strains).

Contraindications

Absolute:

• no careful monitoring of blood pressure and monitoring of patients with acute state of confusion, schizoaffective disorder, bipolar disorder, carcinoid syndrome, thyrotoxicosis, pheochromocytoma, uncontrolled hypertension, as well as in combination therapy, buspirone, meperidine, agonists of 5-HT ₁ receptors (triptans), tricyclic antidepressants, serotonin reuptake inhibitors, dopaminomimetics (for example, dopamine), adrenergic agonists (for example, dobutamine, norepinephrine, epinephrine, phenylpropanolamine, pseudoephedrine);
• combination therapy with drugs that inhibit monoamine oxidase A or B (for example, isocarboxazid, phenelzine) and within 14 days after their withdrawal;
• lactation period;
• children less than 3 years old (for tablets);
• individual intolerance to the components of the drug.

Relative (Linezolid is prescribed under medical supervision):

• liver failure;
• renal failure;
• life-threatening systemic infections (associated with venous catheters in intensive care units);
• pregnancy.

Linezolid, instructions for use: method and dosage

Film-coated tablets

Linezolid tablets are taken orally during or after meals. In cases where at the beginning of treatment the patient received the drug intravenously, in the future it can be transferred to any oral form of the drug. The selection of the dose is not carried out, since the bioavailability of linezolid when taken orally is almost 100%.

The duration of the course of therapy is determined by the doctor depending on the causative agent of the pathology, the severity and localization of the infection, as well as the clinical effect of Linezolid.

Recommended dosage regimen:

• community-acquired pneumonia caused by methicillin-susceptible strains of Staphylococcus aureus or pneumococcus (including multi-resistant strains), including cases accompanied by bacteremia: children aged 3 to 11 years - 10 mg per 1 kg of body weight every 8 hours; children over the age of 12 and adults - 600 mg every 12 hours. The duration of the course varies from 10 to 14 days;
• hospital pneumonia caused by pneumococcus, including multi-resistant strains, or Staphylococcus aureus, including methicillin-resistant and methicillin-susceptible strains: children aged 3 to 11 years - 10 mg per 1 kg of body weight every 8 hours; children over the age of 12 and adults - 600 mg every 12 hours. The duration of the course varies from 10 to 14 days;
• complicated infections of the skin and soft tissues, including those with diabetic foot syndrome, not accompanied by osteomyelitis, the causative agents of which are group B streptococci, pyogenic streptococcus or Staphylococcus aureus, including methicillin-resistant and methicillin-susceptible strains: children aged 3 to 11 years 10 mg per 1 kg of body weight every 8 hours; children over the age of 12 and adults - 600 mg every 12 hours. The duration of the course varies from 10 to 14 days;
• uncomplicated infections of the skin and soft tissues caused by streptococcus pyogenic or methicillin-susceptible strains of Staphylococcus aureus: children aged 3 to 5 years - 10 mg per 1 kg of body weight every 8 hours; children aged 5 to 11 years - 10 mg per 1 kg of body weight every 12 hours; children over the age of 12 and adults - 600 mg every 12 hours. The duration of therapy is 10-14 days;
• infections caused by vancomycin-resistant enterococcus fetium, including cases accompanied by bacteremia: children aged 3 to 11 years - 10 mg per 1 kg of body weight every 8 hours; children aged 12 years and adults - 600 mg every 12 hours. The duration of treatment varies from 14 to 28 days.

Correction of the dosage regimen for hepatic / renal failure and in elderly patients is not required.

Since 30% of linezolid is removed during hemodialysis within 3 hours, patients in need of the drug should take it after the procedure.

Solution for infusion

Linezolid solution is administered intravenously over a period of 30 to 120 minutes. Depending on the causative agent of the disease, the location and severity of the infection, the clinical efficacy of the drug, the doctor sets the dosage regimen and the duration of therapy.

Serial connection of infusion bags, as well as the addition of other drugs to the Linezolid solution, is prohibited. If it is necessary to use a solution for infusion with other drugs, they are prescribed separately in accordance with the recommended doses and routes of administration.

The drug is pharmaceutically incompatible with ceftriaxone, co-trimoxazole (trimethoprim + sulfamethoxazole), erythromycin lactobionate, phenytoin, diazepam, chlorpromazine and amphotericin B.

Solutions for infusion compatible with Linezolid include: 0.9% sodium chloride solution for injection, Ringer-Locke's solution for injection, 5% dextrose solution for injection.

Patients who received the drug intravenously at the beginning of treatment can be switched to any of its oral form. At the same time, no dose selection is required, since the bioavailability of linezolid when taken orally is almost 100%.

Recommended dosing regimen for Linezolid:

• community-acquired pneumonia caused by methicillin-susceptible strains of Staphylococcus aureus or pneumococcus (including multi-resistant strains), including cases accompanied by bacteremia: newborns and children under 12 years of age - 10 mg per 1 kg of body weight every 8 hours; children over the age of 12 and adults - 600 mg every 12 hours. The duration of treatment is from 10 to 14 days;
• hospital pneumonia caused by pneumococcus, including multi-resistant strains, or Staphylococcus aureus, including methicillin-resistant and methicillin-susceptible strains: newborns and children under the age of 12 years - 10 mg per 1 kg of body weight every 8 hours; children over the age of 12 and adults - 600 mg every 12 hours. The duration of treatment is from 10 to 14 days;
• complicated infections of the skin and soft tissues, including those with diabetic foot syndrome, not accompanied by osteomyelitis, the causative agents of which are group B streptococci, pyogenic streptococcus or Staphylococcus aureus, including methicillin-resistant and methicillin-susceptible strains: newborns and children aged 12 years 10 mg per 1 kg of body weight every 8 hours; children over the age of 12 and adults - 600 mg every 12 hours. The duration of treatment is from 10 to 14 days;
• infections caused by vancomycin-resistant enterococcus fetium, including cases accompanied by bacteremia: newborns and children under the age of 12 years - 10 mg per 1 kg of body weight every 8 hours; children over the age of 12 and adults - 600 mg every 12 hours. The duration of treatment is from 14 to 28 days.

The maximum daily dose for children and adults should not exceed 1200 mg.

Systemic clearance of linezolid in premature infants before 7 days of life (gestation duration <34 weeks) is lower and AUC values are higher than in most full-term infants and children. By the 7th day of life, the clearance of the drug and its AUC values in premature infants are close to those in full-term infants and children.

Correction of the dosage regimen for hepatic / renal failure and in elderly patients is not carried out.

Linezolid is administered to patients on hemodialysis after the end of the procedure.

Side effects

Usually, adverse events associated with taking Linezolid are mild to moderate. The most common symptoms are nausea, diarrhea, and headache.

Possible adverse reactions (> 10% - very common;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01%, including individual messages, - very rare; if it is impossible to determine the frequency of adverse reactions - the frequency is unknown):

• infectious and parasitic pathologies: often - fungal infections, candidiasis, including oral candidiasis and vaginal candidiasis; infrequently - vaginitis; rarely - colitis caused by the use of antibacterial agents, including pseudomembranous colitis;
• blood and lymphatic system: often - anemia; infrequently - eosinophilia, thrombocytopenia, neutropenia, leukopenia; rarely - pancytopenia; frequency unknown - sideroblastic anemia, myelosuppression;
• immune system: frequency unknown - anaphylaxis;
• metabolism and nutrition: infrequently - hyponatremia; frequency unknown - lactic acidosis;
• psyche: often - insomnia;
• nervous system: often - dizziness, taste perversion (metallic taste in the mouth), headache; infrequently - paresthesia, hypoesthesia, convulsions; frequency unknown - peripheral neuropathy, serotonin syndrome;
• organ of vision: infrequently - blurred vision; rarely - the appearance of visual field defects; frequency unknown - change in color vision / visual acuity, loss of vision, optic neuritis, optic neuropathy;
• organ of hearing and labyrinthine disorders: infrequently - ringing in the ears;
• heart: infrequently - transient ischemic attack, tachycardia (arrhythmia);
• vessels: often - increased blood pressure; infrequently - thrombophlebitis, phlebitis;
• gastrointestinal tract: often - dyspepsia, constipation, localized / diffuse pain in the abdomen, nausea, diarrhea, vomiting; infrequently - discoloration of the mucous membrane of the tongue and other disorders of the tongue, stomatitis, loose stools, glossitis, dry mouth, bloating, gastritis, pancreatitis; rarely - superficial discoloration of tooth enamel;
• liver and biliary tract: often - increased activity of liver enzymes, including alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase, changes in the results of liver function tests; infrequently - an increase in the concentration of total bilirubin;
• skin and subcutaneous tissues: often - rash, itching; infrequently - increased sweating, dermatitis, urticaria; frequency unknown - alopecia, angioedema, bullous skin lesions (toxic epidermal necrolysis, Stevens-Johnson syndrome);
• kidneys and urinary tract: often - an increase in the concentration of urea in the blood; infrequently - polyuria, an increase in the concentration of creatinine in the blood plasma, renal failure;
• genitals and mammary gland: infrequently - disorders of the vagina and vulva;
• general disorders and disorders at the injection site: often - localized pain, fever; infrequently - thirst, weakness, chills, pain at the injection site;
• laboratory and instrumental studies: often - an increase / decrease in potassium or bicarbonates, a decrease in calcium, albumin, sodium or total protein, an increase in glucose concentration not on an empty stomach, an increase in the activity of amylase, creatine kinase, lipase or lactate dehydrogenase, an increase / decrease in the number of leukocytes or platelets, a decrease in hematocrit, hemoglobin or erythrocyte count, increased eosinophil / neutrophil count; infrequently - a decrease in the number of neutrophils, an increase in the number of reticulocytes, an increase / decrease in blood chlorides, a decrease in glucose concentration not on an empty stomach, an increase in sodium or calcium in the blood plasma.

The side effects noted with the use of Linezolid in the form of arterial hypertension, transient ischemic attack and localized pain in the abdominal region were rarely considered serious.

In the course of controlled clinical studies of the use of the drug for a maximum of 28 days, anemia was found in only 2% of the subjects. In another study among patients with life-threatening infections, anemia developed in 2.5% of patients with the drug for less than 28 days (in 33 of 1326 subjects), and with linezolid for more than 28 days - in 12.3% (in 53 out of 430 participants).

The ratio of cases of anemia requiring blood transfusion was 9% in the group of volunteers who used the drug for a period not exceeding 28 days (in 3 of 33 patients), and 15% in patients who received linezolid for more than 28 days (in 8 out of 53 patients).

Overdose

Overdose cases of Linezolid have not been reported.

Symptomatic therapy is recommended, including maintaining the glomerular filtration rate. Almost 30% of the dose of the oral form of the drug is excreted within 3 hours during hemodialysis.

There are no data confirming the acceleration of drug excretion during hemoperfusion or peritoneal dialysis.

special instructions

An open study among critically ill patients with intravascular catheter-associated infections showed that with linezolid, deaths were more frequent (78 of 363 people, 21.5%) than with oxacillin / dicloxacillin / vancomycin (58 of 363 people, 16%) …

The main factor influencing the death was the gram-positive pathogen at the initial stage. The death rate was similar among patients with infections caused only by gram-positive organisms, but was significantly higher in patients receiving linezolid, when other organisms were detected, or if they could not be detected at the initial stage.

During the period of therapy and within 1 week after the end of the use of the antibacterial agent, the greatest imbalance was noted. In many cases, patients treated with linezolid were found to have gram-negative organisms during the study, and death was due to polymicrobial infections or an infection caused by gram-negative organisms. In this regard, with complicated infections of the skin and soft tissues, the appointment of Linezolid against the background of a suspected or known co-infection with gram-negative microorganisms is allowed only in the absence of alternative therapy options. In such patients, additional drugs should be used that affect the gram-negative microflora.

In some cases, the use of linezolid may serve the development of reversible myelosuppression (with pancytopenia, thrombocytopenia, anemia and leukopenia), depending on the duration of treatment. The likelihood of developing this condition is also increased in elderly patients. Thrombocytopenia was more common in renal failure, whether hemodialysis was used or not. In this regard, during the period of therapy, blood counts should be monitored in patients receiving the drug for more than 14 days, patients with severe renal failure, a history of myelosuppression or a high risk of bleeding, as well as when taking medications that lower hemoglobin / platelet count and / or their functional properties. In such cases, the appointment of Linezolid is allowed,only if close monitoring of hemoglobin, platelet / leukocyte count is possible.

If severe myelosuppression occurs during drug therapy, its use should be discontinued, unless continued treatment is considered absolutely necessary. In such patients, intensive monitoring of blood parameters and appropriate therapy should be carried out. It is also recommended to conduct a weekly blood test (including determining the level of hemoglobin, the number of platelets and leukocytes with the calculation of the leukocyte formula) in patients using the drug, regardless of the indicators of the initial blood test.

Most often, severe anemia was observed when the recommended course of treatment with linezolid was exceeded, the maximum duration of which is 28 days. Such patients more often had a need for blood transfusion.

In the post-registration period, cases of sideroblastic anemia were recorded. In most cases, the duration of treatment was more than 28 days. After discontinuation of linezolid, in most patients, the symptoms were completely or partially reversible with / without specific therapy for anemia.

The existing risk of developing pseudomembranous colitis of varying severity should be taken into account when using antibiotics, including linezolid. Clostridium difficile-associated diarrhea has been reported with almost all antibiotics, including linezolid. The severity of diarrhea can range from mild to severe. Antibacterial agents disrupt the normal microflora of the intestines, which leads to an overgrowth of these bacteria. These, in turn, produce toxins A and B, which cause Clostridium difficile-associated diarrhea. The excess amount of toxins produced by strains of these bacteria can increase mortality among patients, since such infections may be resistant to antimicrobial treatment, and colectomy may also be required. The use of drugs that inhibit intestinal peristalsis is not recommended. The likelihood of Clostridium difficile-associated diarrhea should be considered in all patients with diarrhea following antibiotic use. Patients who have experienced Clostridium difficile-associated diarrhea following antibiotic administration should be closely monitored for 2 months.

Deterioration of visual function, manifested in the form of visual field defects, blurred vision, changes in color perception or visual acuity, is the basis for an urgent appeal to an ophthalmologist for advice. In all patients receiving Linezolid for more than 28 days, and in all patients with newly emerging manifestations of visual impairment, regardless of the duration of treatment, visual function should be monitored.

When neuropathy of the optic nerve and peripheral neuropathy appear, an assessment is made of the ratio of the potential risk to the possible benefit of continuing treatment with the drug. The likelihood of neuropathy increases with the current or recent use of antimycobacterial agents for the treatment of tuberculosis.

There are reports of the development of lactic acidosis during the period of linezolid use. Careful medical supervision should be established for patients in whom the use of the drug causes unexplained acidosis, abdominal pain, repeated nausea or vomiting, as well as a decrease in the concentration of bicarbonate anions.

The drug inhibits mitochondrial protein synthesis. As a result of this inhibition, undesirable phenomena may occur in the form of neuropathy (optic nerve or peripheral), anemia and lactic acidosis. These effects are more common when linezolid is used for more than 28 days.

Seizures have been reported in patients receiving linezolid. In most cases, these patients had risk factors for the development of seizures or indications of them in the anamnesis. It is important to take a detailed history of previous seizure episodes.

In cases where linezolid must be used in combination with selective serotonin reuptake inhibitors, it is important to constantly monitor patients for signs and symptoms of serotonin syndrome in the form of impaired coordination of movements, hyperreflexia, hyperpyrexia, and impaired cognitive function. The appearance of these symptoms is an indication for the cancellation of one or both of the drugs taken. Discontinuation of serotonergic therapy may result in withdrawal symptoms.

Cases of reversible surface changes in the staining of tooth enamel have been reported during the period of linezolid use. These staining changes were removed by professional teeth cleaning.

There are reports of the development of symptomatic hypoglycemia against the background of diabetes mellitus in patients to whom the drug was prescribed in combination with hypoglycemic drugs or insulin. Despite the fact that a causal relationship has not been established between taking linezolid and the onset of hypoglycemia, it is important to warn patients with diabetes mellitus about the likelihood of pathology. If during the period of therapy manifestations of hypoglycemia are noted, the doses of hypoglycemic agents or insulin should be adjusted, or linezolid should be canceled.

Patients should be advised to avoid eating large amounts of food containing tyramine (for example, smoked meat, red wine, some alcoholic drinks, old cheese).

The study of the effect of the effect of linezolid on the normal microflora of the human body in the framework of clinical trials has not been carried out.

In some cases, the use of antibacterial agents leads to an increased growth of microorganisms that are resistant to them. Clinical studies have found that approximately 3% of patients receiving linezolid at the recommended doses developed antibiotic-associated candidiasis. If superinfection develops against the background of the use of the drug, appropriate medical measures should be taken.

The efficacy and safety of linezolid therapy for more than 28 days has not been established.

Among the participants in controlled clinical trials, there were no patients with gangrenous lesions, severe burns, ischemic disorders or pressure ulcers, or with diabetic foot syndrome. In this regard, experience with the use of the drug in the treatment of these conditions is limited.

Influence on the ability to drive vehicles and complex mechanisms

Patients during the period of linezolid therapy should refrain from driving vehicles and conducting potentially hazardous activities.

Application during pregnancy and lactation

The safety of using Linezolid during pregnancy has not been established, and therefore the drug can be used only in cases where the potential benefits of therapy to the mother are higher than the expected risks to the fetus.

Since the drug passes into breast milk, if it is necessary to use it during lactation, breastfeeding is stopped.

Pediatric use

Linezolid tablets are not prescribed for patients under 3 years of age.

With impaired renal function

Since the clinical significance of the two primary metabolites of linezolid in severe renal failure has not been studied, the drug in such cases can be used with caution and only if the potential benefit of treatment is higher than the possible risks.

For violations of liver function

In hepatic insufficiency, the drug is used with caution and only in cases where the expected benefit of therapy exceeds the expected risk.

Drug interactions

In vitro studies have established that cytochrome P ₄₅₀ isoenzymes do not participate in the metabolism of linezolid. The drug does not inhibit or induce the activity of such clinically important cytochrome P ₄₅₀ isozymes as 2D6, 3A4, 1A2, 2E1, 2C9 and 2C19. As a consequence, no CYP450-induced interaction is expected with linezolid.

The pharmacokinetic characteristics of warfarin with the combined use of linezolid and (S) -warfarin (largely metabolized by the CYP2C9 isoenzyme) do not change. Phenytoin and warfarin, which are substrates of the isoenzyme CYP2C9, can be combined with the drug without dose adjustment.

Since linezolid is a non-selective reversible inhibitor of monoamine oxidase, its use in some cases can lead to a moderate reversible increase in the pressor action of phenylpropanolamine and pseudoephedrine. Taking this into account, it is recommended to reduce the initial doses of dopaminomimetics (for example, dopamine) and adrenergic agonists (for example, dobutamine, norepinephrine, epinephrine, phenylpropanolamine, pseudoephedrine) and then titrate the dose selection.

Phase I, II and III studies did not reveal the occurrence of serotonin syndrome when linezolid was used together with serotonergic agents. However, there are several reports of the appearance of serotonin syndrome with the combined use of linezolid with antidepressants - selective serotonin reuptake inhibitors.

The pharmacokinetics of linezolid did not change with simultaneous treatment with gentamicin and aztreonam.

In patients receiving linezolid simultaneously with rifampicin showed a decrease its C _{m ax} and AUC an average of 21 and 32%, respectively.

Analogs

Linezolid analogs are: Rowlin-Routek, Linezolid-Krka, Infilinez, Amizolid, Selezolid, Bactolin, Linegen, Zivox, Linezolid-Teva, etc.

Terms and conditions of storage

Store in a place protected from light and moisture at temperatures up to 25 ° C. Keep out of the reach of children. The infusion solution must not be frozen.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Linezolid

There are few reviews about Linezolid, indicating the effectiveness of the drug.

Price for Linezolid in pharmacies

The approximate price for Linezolid (in a package of 10 film-coated tablets, 600 mg each) is from 12,200 to 12,700 rubles.

Linezolid: prices in online pharmacies

Drug name Price Pharmacy

Linezolid canon tablets p.p. 200mg 10pcs 3979 RUB Buy

Linezolid Canon 600 mg film-coated tablets 10 pcs. 12897 RUB Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, 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!