Cefotaxime

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CEFOTAXIME (CEFOTAXIME)

Composition:

Active substance: cefotaxime;

1 vial contains 1 g of sterile sodium cefotaxime, calculated as cefotaxime.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: white or slightly yellowish powder. Hygroscopic.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Other β-lactam antibiotics. Third-generation cephalosporins. ATC code J01DD01.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Cefotaxime is a broad-spectrum antibiotic of the third-generation cephalosporin class for parenteral administration. Cefotaxime inhibits enzymes responsible for bacterial cell wall synthesis. This leads to lysis of the bacterial cell.

Resistance mechanisms

Bacterial resistance to cefotaxime may result from one or more of the following mechanisms:

• Hydrolysis by beta-lactamase. Cefotaxime can be hydrolyzed by many so-called broad-spectrum beta-lactamases. It is also hydrolyzed by chromosomally encoded (Amp-C type) beta-lactamases.
• Resistance due to impermeability.
• Mechanism of efflux pump expression.

Several of these mechanisms may coexist simultaneously in a single bacterium.

Bacteria resistant to cefotaxime may exhibit varying degrees of cross-resistance to other beta-lactam antibiotics. Gram-negative bacteria resistant to cefotaxime show cross-resistance to other broad-spectrum third-generation cephalosporins (ceftazidime, ceftriaxone).

Breakpoints

The minimum inhibitory concentration (MIC) breakpoints for cefotaxime, as recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), which differentiate susceptible microorganisms from resistant ones, are provided in the table below.

Clinical breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for cefotaxime:

Pathogenic microorganism	Susceptible	Resistant
Enterobacteriaceae	≤ 1 mg/l	> 2 mg/l
S. pneumoniae	≤ 0.5 mg/l	> 2 mg/l
Other Streptococci	≤ 0.5 mg/l	> 0.5 mg/l
H. influenzae	≤ 0.12 mg/l	> 0.12 mg/l
M. catarrhalis	≤ 1 mg/l	> 2 mg/l
N. gonorrhoeae	≤ 0.12 mg/l	> 0.12 mg/l
N. meningitidis	≤ 0.12 mg/l	> 0.12 mg/l
Intermediate values not species-related	≤ 1 mg/l	> 2 mg/l
Susceptibility of staphylococci (Staphylococcus) to cephalosporins follows from their susceptibility to methicillin. Susceptibility of streptococci (Streptococcus) groups A, B, C, G follows from their susceptibility to benzylpenicillin.

Antibacterial spectrum

The prevalence of resistance among individual species may vary depending on the region and time. When treating serious infections, it is advisable to consider local information on resistance. If necessary, consultation with specialists should be sought when local resistance prevalence has reached a level at which the benefit of use is questionable.

Usually susceptible microorganisms

Aerobic gram-positive bacteria Methicillin-susceptible Staphylococcus aureus Methicillin-susceptible coagulase-negative staphylococci Methicillin-susceptible Staphylococcus epidermidis Methicillin-susceptible Staphylococcus haemolyticus Group A streptococci (including Streptococcus pyogenes) Group B streptococci Streptococcus pneumoniae Streptococcus viridans group Aerobic gram-negative bacteria Citrobacter spp. (excluding Citrobacter freundii) Escherichia coli Haemophilus influenzae Moraxella catarrhalis Neisseria gonorrhoeae Neisseria meningitidis Klebsiella spp. Proteus mirabilis Serratia spp. Yersinia enterocolitica Other microorganisms Borrelia spp.

Microorganisms that may develop resistance

Bacteroides fragilis Enterobacter spp. Aerobic gram-positive bacteria Methicillin-resistant Staphylococcus aureus Methicillin-resistant coagulase-negative staphylococci Aerobic gram-negative bacteria Acinetobacter spp. Citrobacter freundii Morganella morganii Providencia spp. Pseudomonas aeruginosa Stenotrophomonas maltophilia

Inherently resistant microorganisms

Aerobic gram-positive bacteria Enterococcus spp. Other microorganisms Chlamydia spp. Legionella pneumophila Listeria spp. Mycoplasma spp. Treponema pallidum

Pharmacokinetics.

Cefotaxime is administered parenterally. After a single intravenous dose of 1 g, serum concentrations of cefotaxime were approximately 81–102 mg/L at 5 minutes and 46 mg/L at 15 minutes. After a single intravenous dose of 2 g, serum concentrations ranged from 167–214 mg/L at 8 minutes.

Following intramuscular administration, maximum serum concentration of cefotaxime (approximately 20 mg/L after a 1-g dose) is achieved within 30 minutes.

Distribution

Cefotaxime rapidly penetrates tissues, crosses the placental barrier, and reaches high concentrations in fetal tissues (up to 6 mg/kg). It appears in breast milk only in low amounts (concentration in breast milk 0.4 mg/L after a 2-g dose).

In cases of inflammation of the meninges, cefotaxime and its metabolite desacetylcefotaxime penetrate into the cerebrospinal fluid (CSF) and achieve therapeutically effective concentrations (e.g., in infections caused by gram-negative bacteria and pneumococci).

The apparent volume of distribution is 21–37 L. Plasma protein binding is approximately 25–40%.

Metabolism

Cefotaxime is extensively metabolized in the human body. About 15–25% of an intravenously administered dose is excreted as desacetylcefotaxime, an active metabolite with antibacterial activity.

In addition to desacetylcefotaxime, two other inactive metabolites (lactones) are formed. The lactone is formed from desacetylcefotaxime as a short-lived intermediate product, which is rapidly no longer detectable in urine or plasma, as it quickly converts into stereoisomers of the lactone with an open ring (β-lactam ring). These isomers are also excreted in urine.

Excretion

Excretion of cefotaxime and desacetylcefotaxime occurs primarily via the renal route. A small percentage (about 2%) is excreted in bile. Within 6 hours, 40–60% of the dose is recovered unchanged in urine and approximately 20% as desacetylcefotaxime. After intravenous administration of radiolabeled cefotaxime, more than 80% is excreted in urine, of which 50–60% is unchanged and the remainder as three metabolites.

Total clearance of cefotaxime is 240–390 mL/min, and renal clearance is 130–150 mL/min.

The elimination half-life of cefotaxime and its active metabolite in serum is 50–80 minutes and 125 minutes, respectively. In elderly patients (>80 years of age), the elimination half-life of cefotaxime and the active metabolite is prolonged to 120–150 minutes and 5 hours, respectively.

In cases of severe renal impairment (creatinine clearance 3–10 mL/min), the elimination half-life of cefotaxime may be prolonged to 2.5–10 hours.

Under these conditions, cefotaxime accumulates only to a minor extent, in contrast to active and inactive metabolites.

Both cefotaxime and desacetylcefotaxime are significantly removed from the blood by hemodialysis.

Clinical characteristics.

Indications.

To be used for the treatment of the following serious infections caused by, or highly likely to be caused by, microorganisms sensitive to cefotaxime (see section "Pharmacodynamics"):

• Bacterial pneumonia (cefotaxime does not act against bacteria causing atypical pneumonia or against various other bacterial strains that may cause atypical pneumonia, including P. aeruginosa — see section "Pharmacodynamics").
• Complicated infections of the kidneys and upper urinary tract.
• Serious skin and soft tissue infections.
• Genital tract infections caused by gonococci, particularly when penicillin therapy has proven ineffective or is unsuitable.
• Intra-abdominal infections (including peritonitis): when treating intra-abdominal infections, cefotaxime should be used in combination with an antibiotic active against anaerobic microorganisms.
• Acute bacterial meningitis (particularly caused by H. influenzae, N. meningitidis, S. pneumoniae, E. coli, Klebsiella spp.).
• Lyme disease, or tick-borne borreliosis (particularly stages II and III).
• Bacteraemias associated with, or likely associated with, any of the listed infections (if the infection is caused by Gram-negative bacteria, it should be combined with another appropriate antibiotic).
• Endocarditis (if the infection is caused by Gram-negative bacteria, it must be combined with another appropriate antibiotic).

For perioperative prophylaxis of infectious complications (before/after surgical procedures, particularly on the colon and rectum (colorectal surgery), gastrointestinal tract, prostate gland, genitourinary system, and obstetric-gynecological surgeries in patients with a significant risk of postoperative infections).

Official guidelines on the appropriate use of antibacterial agents should be taken into account.

Contraindications.

Hypersensitivity to cephalosporin antibiotics and to other β-lactam antibiotics.

Contraindications for solutions containing lidocaine:

• Hypersensitivity to lidocaine or other amide-type local anesthetics;
• Atrioventricular block without an implanted pacemaker;
• Severe heart failure;
• Intravenous administration;
• Age under 1 year (for intramuscular administration).

Interaction with other medicinal products and other forms of interaction.

Uricosuric agents

Probenecid blocks tubular secretion of cefotaxime.

This increases cefotaxime exposure by approximately two-fold and reduces renal clearance by about 50% at therapeutic doses. Due to the wide therapeutic range of cefotaxime, dosage adjustment is not required in patients with normal renal function. However, dosage adjustment may be necessary in patients with impaired renal function.

Aminoglycoside antibiotics and diuretics

Like other cephalosporins, cefotaxime may enhance the nephrotoxic effect of nephrotoxic drugs such as aminoglycosides and potent diuretics (e.g., furosemide). Renal function should be monitored in these patients.

Cefotaxime should not be combined with bacteriostatic antibiotics (e.g., tetracycline, erythromycin, and chloramphenicol) due to the possibility of an antagonistic effect.

The following solutions may be used for infusions: water for injection, 0.9% sodium chloride solution, 5% dextrose solution, Ringer's solution.

Special precautions for use.

As with other antibiotics, the use of cefotaxime, especially prolonged use, may lead to overgrowth of non-susceptible microorganisms. It is important to monitor the patient's condition regularly. If superinfection occurs during treatment, appropriate measures should be taken.

With prolonged use, liver and kidney function should be monitored.

Anaphylactic reactions

Serious, including fatal, hypersensitivity reactions have been reported in patients receiving cefotaxime. If an allergic reaction occurs, treatment should be discontinued.

Cefotaxime is strictly contraindicated in patients with a history of immediate-type hypersensitivity reactions to cephalosporins.

Since cross-allergenicity between penicillins and cephalosporins occurs in 5–10% of cases, cephalosporins should be used with particular caution in individuals with hypersensitivity to penicillin.

The drug should be prescribed cautiously to patients with allergic diathesis or asthma.

Severe cutaneous adverse reactions (SCARs)

During the post-marketing period, cases of severe cutaneous adverse reactions associated with cefotaxime therapy have been reported, including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), which may be life-threatening or result in death.

Patients should be informed about the signs and symptoms of skin reactions when prescribing the drug.

If signs or symptoms indicating these reactions occur, cefotaxime should be discontinued immediately. If a patient develops AGEP, SJS, TEN, or DRESS during cefotaxime therapy, re-administration of cefotaxime is contraindicated and treatment must be permanently discontinued.

In children, the appearance of a rash may be mistakenly interpreted as the primary infection or an alternative infectious process; therefore, physicians should consider the possibility of a reaction to cefotaxime in children who develop rash and fever during therapy.

Clostridium difficile-associated diseases (e.g., pseudomembranous colitis)

The onset of diarrhea, particularly if severe and/or persistent, during or within several weeks after treatment may be symptomatic of Clostridium difficile-associated disease. Clostridium difficile-associated diseases may vary in severity from mild to life-threatening, with pseudomembranous colitis being the most severe form. Diagnosis of this rare but potentially fatal condition can be confirmed by detection of toxins via endoscopy and/or histological examination. This diagnosis should be considered in patients who develop diarrhea during or after cefotaxime therapy. If pseudomembranous colitis is suspected, cefotaxime therapy should be discontinued immediately and appropriate specific antibiotic treatment should be initiated promptly.

Fecal stasis may promote the development of Clostridium difficile-associated diseases. Medicinal products that inhibit intestinal peristalsis should be avoided.

Hematological reactions

Leukopenia, neutropenia, and, less frequently, bone marrow suppression, pancytopenia, and agranulocytosis may occur during cefotaxime therapy, especially with prolonged treatment. If treatment lasts longer than 7–10 days, blood composition should be monitored. If blood test results (hemogram) deviate from normal, treatment should be discontinued.

Several cases of eosinophilia and thrombocytopenia, which resolved rapidly after discontinuation of treatment, have been reported. Cases of hemolytic anemia have also been reported.

Patients with renal impairment

Dosage should be adjusted based on calculated creatinine clearance. Caution should be exercised when cefotaxime is used concomitantly with aminoglycosides, furosemide, probenecid, or other nephrotoxic medicinal products. In these patients, elderly patients, and patients with pre-existing renal impairment, renal function should be monitored regularly.

Neurotoxicity (encephalopathy)

Administration of high doses of beta-lactam antibiotics, including cefotaxime, particularly in patients with renal impairment, may lead to encephalopathy (altered/loss of consciousness, abnormal movements, confusion, and seizures).

Patients should be advised to seek immediate medical attention if such reactions occur.

During post-marketing surveillance, potentially life-threatening arrhythmias have been reported in a very small number of patients receiving cefotaxime via rapid intravenous administration through a central venous catheter. Therefore, the recommended infusion time must be strictly followed.

Effect on laboratory test results

As with other cephalosporins, a positive Coombs test has been observed in some patients receiving cefotaxime. This phenomenon may interfere with cross-matching blood.

False-positive results may occur in urine glucose testing using non-specific reducing agents. To avoid this, a glucose oxidase test should be used.

Sodium content

This medicinal product contains 48.18 mg of sodium per 1 g of sodium cefotaxime. Caution should be exercised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Cefotaxime crosses the placental barrier. Animal studies have not shown teratogenic effects of the drug. However, the safety of cefotaxime use during human pregnancy has not been established; therefore, the drug should not be used during pregnancy.

Use in women of childbearing potential requires careful assessment of expected benefits versus potential risks.

Cefotaxime is excreted in breast milk.

An effect on the physiological intestinal flora of the infant cannot be excluded, which may lead to diarrhea, colonization with yeast-like fungi, or sensitization of the infant.

Therefore, a decision must be made whether to temporarily discontinue breastfeeding or to discontinue therapy, weighing the benefits of breastfeeding for the infant against the benefits of treatment for the mother.

Ability to affect reaction speed when driving or operating machinery.

If adverse effects such as dizziness or encephalopathy (e.g., altered/loss of consciousness, abnormal movements, confusion, and seizures) occur, patients should refrain from driving vehicles or operating machinery.

Administration and Dosage

The medicinal product is administered intravenously (as a slow injection or infusion) or intramuscularly.

Treatment may be initiated before the results of antimicrobial susceptibility testing are available. Cefotaxime exerts a synergistic effect when used in combination with aminoglycosides.

Dosage

The dosage and route of administration depend on the severity of infection, microbial susceptibility, and the patient's condition.

Duration of Treatment

The duration of treatment with Cefotaxime depends on the patient's clinical condition and may vary according to the course of the disease.

Treatment should last at least 10 days if the infection is caused by Streptococcus pyogenes (parenteral therapy may be switched to oral therapy before completion of the 10-day period).

Adults and adolescents (aged 12 to 16–18 years)

The usual dose is 1 g of cefotaxime every 12 hours. In severe infections, the daily dose may be increased up to 12 g. Daily doses up to 6 g may be divided into at least two separate administrations given at 12-hour intervals. Higher daily doses should be divided into at least 3 or 4 separate administrations given at 8- or 6-hour intervals, respectively.

The table below may serve as a guideline for dosage.

Type of infection	Single dose of cefotaxime	Interval between administrations	Daily dose of cefotaxime
Typical infections where microbial sensitivity has been demonstrated or is expected	1 g	12 hours	2 g
Infections where high or moderate sensitivity of various microorganisms has been demonstrated or is expected	2 g	12 hours	4 g
Bacterial diseases of unknown etiology that cannot be localized and the patient's condition is critical	2–3 g	8 hours 6 hours	6–9 g 8–12 g

Infants and children (from 28 days to 11 years of age)

Usually 50–100 mg/kg body weight per day, depending on the severity of the infection (up to 9150 mg), divided into 2–4 equal doses (every 12–6 hours).

The table below may serve as a guide for dosing.

Type of infection	Interval between administrations of the drug	Daily dose of cefotaxime
Typical infections in which microbial sensitivity has been demonstrated or is expected	6–12 hours	50 mg/kg
Infections in which high or moderate sensitivity of various microorganisms has been demonstrated or is expected	6–12 hours	100 mg/kg
Bacterial diseases of unknown etiology that cannot be localized and the patient's condition is critical	6–8 hours	150 mg/kg*

In exceptional cases, especially if there is a life-threatening situation, it may be necessary to increase the daily dose up to 200 mg/kg body weight per day. However, the maximum daily dose of 12 grams should not be exceeded.

Preterm and full-term neonates (aged 0–27 days)

Usually 50 mg/kg body weight per day, divided into 2–4 equal doses (every 12–6 hours). In life-threatening situations, an increase in the daily dose may be required. For severe infections, a dose of 150 mg/kg body weight per day is administered.

The table below may serve as a guide for dosing.

Type of infection	Age	Interval between doses	Daily dose of cefotaxime
Typical infections caused by susceptible microorganisms, or cases where high or moderate sensitivity has been demonstrated or is expected	0–7 days 8 days — 1 month	6–12 hours	50 mg/kg
Bacterial diseases of unknown etiology that cannot be localized and the patient's condition is critical	0–7 days 8 days — 1 month	6–12 hours	100 mg/kg* 150 mg/kg*

*In exceptional cases, especially if there is a life-threatening condition, it may be necessary to increase the daily dose up to 200 mg/kg body weight per day. This dose should not be exceeded due to insufficient renal excretory function (parameter: endogenous creatinine clearance).

Elderly patients

Dose adjustment is not required in elderly patients with normal renal and hepatic function.

Dosing in patients with renal impairment

For patients with creatinine clearance less than 10 mL/min, after the initial standard dose, maintenance doses should be reduced to half the standard dose, without changing the interval between administrations.

For patients undergoing hemodialysis: 1 to 2 g per day, depending on the severity of infection. On the day of hemodialysis, cefotaxime should be administered after completion of the dialysis session.

For patients undergoing peritoneal dialysis: 1 to 2 g per day, depending on the severity of infection. Cefotaxime is not removed by peritoneal dialysis.

Other recommendations

Gonorrhea

Single dose (intramuscularly or intravenously) of 0.5 g to 1 g of cefotaxime. In case of complicated infections, official guidelines should be followed. Syphilis should be ruled out before starting treatment.

Urinary tract infections

For uncomplicated urinary tract infections: 1 g every 12 hours.

Bacterial meningitis

Adults: recommended daily doses of 6 to 12 g per day, divided into equal doses every 6–8 hours.
Children: recommended daily doses of 150 to 200 mg/kg body weight per day, divided into equal doses every 6–8 hours.
Newborns from day 1 to day 7 of life: 50 mg/kg body weight of cefotaxime every 12 hours.
Newborns from day 7 to day 28 of life: 50 mg/kg body weight every 8 hours.

Intra-abdominal infections

Intra-abdominal infections should be treated with cefotaxime in combination with other appropriate antibiotics.

Perioperative prophylaxis

For perioperative prophylaxis of infectious complications, a single dose of 1 to 2 g of cefotaxime is recommended 30–60 minutes before the start of surgery. An additional antibiotic is required to provide protection against anaerobic microorganisms. If surgery lasts longer than 90 minutes, an additional dose is needed.

Lyme disease (tick-borne borreliosis)

The daily dose of cefotaxime is 6 g (for 14–21 days). The daily dose is usually divided into three doses (2 g of cefotaxime three times daily).

Administration method

Cefotaxime and aminoglycosides should not be mixed in the same syringe or infusion solution.

Preparation of solutions must be carried out under aseptic (sterile) conditions. Use immediately after preparation.

Intravenous administration

For intravenous (IV) infusion, 1 g or 2 g of the drug should be dissolved in 40–100 mL of sterile water for injection or infusion solution. The infusion duration should be 50–60 minutes.

For intravenous bolus injection, 1 g of powder should be dissolved in 8 mL of sterile water for injection. The solution should be injected slowly over 3–5 minutes, as life-threatening arrhythmias may occur when cefotaxime is administered via a central venous catheter.

Intramuscular administration

For intramuscular (IM) injection, cefotaxime should be reconstituted with 4 mL of sterile water for injection per 1 g. The contents of the vial may be dissolved in water for injection or in 1% lidocaine solution. The solution should then be injected deeply into the gluteal muscle. If lidocaine is used, intravenous administration is strictly contraindicated.

Children.

Intramuscular administration of the drug is contraindicated in children under 1 year of age (see section "Contraindications").

Overdose

Symptoms of overdose largely correspond to the profile of adverse reactions.

Particularly in patients with renal impairment and when high doses of beta-lactam antibiotics, including cefotaxime, are used, there is a risk of developing encephalopathy.

In case of overdose, cefotaxime treatment should be discontinued. Supportive therapy should be initiated, including measures to accelerate drug elimination from the body, and symptomatic treatment of adverse reactions (e.g., seizures).

There is no specific antidote. Hemodialysis may reduce cefotaxime serum concentration. Peritoneal dialysis is ineffective.

Adverse reactions.

The frequency of adverse reactions is defined as follows: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1,000, < 1/100), rare (> 1/10,000, < 1/1,000), very rare (< 1/10,000), and frequency not known (cannot be estimated from the available data).

System Organ Class	Very common	Common	Uncommon	Rare	Very rare	Frequency unknown*
Infections and parasitic disorders						Superinfection
Blood and lymphatic system disorders			Leukopenia Eosinophilia Thrombocytopenia			Bone marrow depression Pancytopenia Neutropenia Agranulocytosis Hemolytic anemia
Immune system disorders			Jarisch–Herxheimer reaction (exacerbation)			Anaphylactic reactions Angioneurotic edema Bronchospasm Malaise Anaphylactic shock
Nervous system disorders			Seizures			Headache Dizziness Encephalopathy
Cardiac disorders						Arrhythmia after rapid bolus infusion via central venous catheter
Gastrointestinal disorders			Diarrhea			Nausea Vomiting Abdominal pain Pseudomembranous colitis
Hepatobiliary disorders (hepato-biliary disorders)			Elevated liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (γ-GT) and/or alkaline phosphatase) and/or bilirubin			Hepatitis* (sometimes with jaundice)
Skin and subcutaneous tissue disorders			Rash Pruritus Urticaria			Multiform erythema Stevens–Johnson syndrome Toxic epidermal necrolysis Acute generalized exanthematous pustulosis Drug reaction with eosinophilia and systemic symptoms (DRESS) (see section "Special precautions")
Renal and urinary disorders			Decreased renal function/increased creatinine concentration (especially when administered concomitantly with aminoglycosides)			Acute renal failure Interstitial nephritis
General disorders and administration site conditions	Pain at injection site (with intramuscular administration)		Fever Inflammatory reactions at injection site, such as phlebitis/thrombophlebitis

* Post-marketing surveillance.

Jarisch-Herxheimer reaction

During treatment of borreliosis, a Jarisch-Herxheimer reaction may occur within the first days of treatment. Cases of the following symptoms have been reported after several weeks of treatment for borreliosis: skin rashes, pruritus, fever, leukopenia, increased levels of liver enzymes, dyspnea, joint pain.

Encephalopathy

Administration of high doses of beta-lactam antibiotics, including cefotaxime, particularly in patients with renal impairment, may lead to encephalopathy (with symptoms such as impaired/loss of consciousness, abnormal movements, confusion, and seizures).

Hepatobiliary disorders

Elevated levels of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], gamma-glutamyl transferase [γ-GT], and/or alkaline phosphatase) and/or bilirubin have been observed. In some cases, these parameters may exceed the upper limit of normal values by up to two times, indicating hepatic involvement, usually cholestatic in nature and generally asymptomatic.

Reporting suspected adverse reactions

Reporting of adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of this medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

*** Shelf life ***

3 years.

** Storage conditions **

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

*** Incompatibility ***

The drug solution is incompatible with aminoglycoside solutions in the same syringe or infusion. Use only the diluents specified in the sections "Directions for use and dosage" and "Interaction with other medicinal products and other forms of interaction".

** Packaging ** 1 g in vials, 10 vials per pack.

** Prescription category ** Prescription only.

** Manufacturer ** JSC "Kyivmedpreparat".

** Manufacturer's address and location of business activity **

139 Saksaganskogo Street, Kyiv, 01032, Ukraine.