Cefepime

INSTRUCTIONS for medical use of the medicinal product CEFEPIME

Composition:

Active substance: cefepime;

1 vial contains cefepime hydrochloride equivalent to cefepime 500 mg or 1000 mg;

Excipient: L-arginine.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: powder from white to yellowish in color.

Pharmacotherapeutic group.

Antibacterial agents for systemic use. Fourth-generation cephalosporins.

ATC code J01D E01.

Pharmacological properties.

Pharmacodynamics.

Cefepime is a broad-spectrum β-lactam cephalosporin antibiotic of the fourth generation intended for parenteral administration. It exerts a bactericidal effect. It is active against Gram-positive and Gram-negative bacteria, including most strains resistant to aminoglycosides or third-generation cephalosporin antibiotics such as ceftazidime. Cefepime is highly resistant to hydrolysis by β-lactamases, has low affinity for β-lactamases encoded by chromosomal genes, and rapidly penetrates Gram-negative bacterial cells. The binding affinity of cefepime for penicillin-binding protein PBP 3 is significantly higher than that of other parenteral cephalosporins. Moderate affinity of cefepime for PBP 1a and 1b also contributes to its level of bactericidal activity. The ratio of MBC (minimum bactericidal concentration) to MIC (minimum inhibitory concentration) for cefepime is less than 2 for more than 80% of isolates of all susceptible Gram-positive and Gram-negative bacteria.

Cefepime acts by inhibiting bacterial cell wall synthesis enzymes.

Cefepime is active against the following microorganisms:

Gram-positive aerobes: Staphylococcus aureus (including β-lactamase-producing strains); Staphylococcus epidermidis (including β-lactamase-producing strains); other staphylococcal strains, including S. hominis, S. saprophyticus; Streptococcus pyogenes (Group A streptococci); Streptococcus agalactiae (Group B streptococci); Streptococcus pneumoniae (including strains with intermediate resistance to penicillin—MIC from 0.1 to 1 mcg/mL); other β-hemolytic streptococci (Groups C, G, F); S. bovis (Group D); Viridans group streptococci.

Most enterococcal strains, e.g., Enterococcus faecalis, and methicillin-resistant staphylococci are resistant to most cephalosporin antibiotics, including cefepime.

Gram-negative aerobes: Pseudomonas spp., including P. aeruginosa, P. putida, P. stutzeri; Escherichia coli; Klebsiella spp., including K. pneumoniae, K. oxytoca, K. ozaenae; Enterobacter spp., including E. cloacae, E. aerogenes, E. sakazakii; Proteus spp., including P. mirabilis, P. vulgaris; Acinetobacter calcoaceticus (including subspecies anitratus, Iwoffi); Aeromonas hydrophila; Capnocytophaga spp.; Citrobacter spp., including C. diversus, C. freundii; Campylobacter jejuni; Gardnerella vaginalis; Haemophilus ducreyi; Haemophilus influenzae (including β-lactamase-producing strains); Haemophilus parainfluenzae; Hafnia alvei; Legionella spp.; Morganella morganii; Moraxella catarrhalis (Branhamella catarrhalis) (including β-lactamase-producing strains); Neisseria gonorrhoeae (including β-lactamase-producing strains); Neisseria meningitidis; Providencia spp. (including P. rettgeri, P. stuartii); Salmonella spp.; Serratia (including S. marcescens, S. liquefaciens); Shigella spp.; Yersinia enterocolitica.

Cefepime is inactive against some strains of Xanthomonas maltophilia (Pseudomonas maltophilia).

Anaerobes: Bacteroides spp., including B. melaninogenicus and other oral cavity microorganisms belonging to Bacteroides; Clostridium perfringens; Fusobacterium spp.; Mobiluncus spp.; Peptostreptococcus spp.; Veillonella spp.

Cefepime is inactive against Bacteroides fragilis and Clostridium difficile.

Pharmacokinetics.

Cefepime is completely absorbed after intramuscular administration.

Mean plasma concentrations of cefepime in healthy adult males at various time points after single intravenous and intramuscular administration are shown in Table 1.

Plasma concentrations of cefepime (mcg/mL) following intravenous (i.v.) and intramuscular (i.m.) administration

Table 1

Cefepime dose	0.5 hour	1 hour	2 hours	4 hours	8 hours	12 hours
500 mg IV	38.2	21.6	11.6	5.0	1.4	0.2
1 g IV	78.7	44.5	24.3	10.5	2.4	0.6
2 g IV	163.1	85.8	44.8	19.2	3.9	1.1
500 mg IM	8.2	12.5	12	6.9	1.9	0.7
1 g IM	14.8	25.9	26.3	16.0	4.5	1.4
2 g IM	36.1	49.9	51.3	31.5	8.7	2.3

Therapeutic concentrations of cefepime are also achieved in urine, bile, peritoneal fluid, bronchial mucosal secretions, sputum, prostate, appendix, and gallbladder.

The average elimination half-life of cefepime is approximately 2 hours and is independent of dose within the range of 250 mg to 2 g. No accumulation of the drug was observed after intravenous administration of doses up to 2 g every 8 hours for 9 days.

Cefepime is metabolized to N-methylpyrrolidine, which is rapidly converted to N-methylpyrrolidine oxide. Cefepime is primarily eliminated via glomerular filtration (total cefepime clearance is approximately 120 mL/min, with mean hepatic clearance of 110 mL/min). Approximately 80–85% of the administered dose is excreted in urine as unchanged cefepime, 1% as N-methylpyrrolidine, approximately 6.8% as N-methylpyrrolidine oxide, and approximately 2.5% as the cefepime epimer. Protein binding of cefepime to plasma proteins is less than 19% and does not depend on drug concentration in serum.

Dose adjustment is not required for patients aged 65 years and older with normal renal function.

In patients with renal impairment, the elimination half-life of cefepime is prolonged, and a linear relationship is observed between total drug clearance and creatinine clearance. The half-life in patients with severe renal dysfunction requiring hemodialysis is 13 hours, and 19 hours in those undergoing continuous ambulatory peritoneal dialysis. Dosing should be individually adjusted for patients with abnormal renal function.

The pharmacokinetics of cefepime are not altered in patients with hepatic impairment or cystic fibrosis. Dose adjustment is not required for these patients.

Children. Pharmacokinetic studies of cefepime have been conducted in children aged 2 months to 11 years after single or multiple doses administered every 8 or every 12 hours. Following a single intravenous injection, the mean total clearance and steady-state volume of distribution were 3.3 (±1.0) mL/min/kg and 0.3 (±0.1) L/kg, respectively. Renal excretion of unchanged cefepime accounted for 60.4 (±30.4)% of the administered dose, and mean renal clearance was 2.0 (±1.1) mL/min/kg. Patient age and sex did not significantly affect total drug clearance or volume of distribution when corrected for body weight. When cefepime was administered at 50 mg/kg every 12 hours, no drug accumulation was observed, whereas with the regimen of 50 mg/kg every 8 hours, steady-state plasma maximum concentration, area under the curve, and elimination half-life increased by approximately 15%. Cefepime exposure in children after intravenous administration of 50 mg/kg was comparable to exposure in adults after intravenous administration of 2 g. After intramuscular administration, the mean steady-state maximum plasma concentration of cefepime was 68 µg/mL, reached within 0.75 hours. Eight hours after intramuscular injection, the mean plasma concentration of cefepime was 6 µg/mL. The absolute bioavailability of cefepime after intramuscular injection averaged 82%.

When identification of the causative pathogen and determination of its antibiotic susceptibility are not feasible or time is limited, cefepime may be used empirically due to its broad-spectrum antibacterial activity. In patients at risk for mixed aerobic-anaerobic infections, treatment with cefepime in combination with an anti-anaerobic agent may be initiated before pathogen identification.

Drug concentrations in cerebrospinal fluid (CSF) and plasma in children with bacterial meningitis

Time after administration (h)	Plasma concentration (μg/mL)*	CSF concentration (μg/mL)*	CSF/plasma concentration ratio*
0.5	67.7 ± 51.2	5.7 ± 0.14	0.12 ± 0.14
1	44.1 ± 7.8	4.3 ± 1.5	0.10 ± 0.04
2	23.9 ± 12.9	3.6 ± 2.0	0.17 ± 0.09
4	11.7 ± 15.7	4.2 ± 1.1	0.87 ± 0.56
8	4.9 ± 5.9	3.3 ± 2.8	1.02 ± 0.64

• Age from 3.1 months to 12 years with a standard deviation in age of ± 3 years.

Drug dosage of 50 mg/kg body weight administered intravenously over 5–20 minutes every 8 hours. Plasma concentration and MIC were determined at the end of infusion on day 2 or 3 of treatment with the drug.

Clinical characteristics.

Indications.

Adults.

Infections caused by microorganisms sensitive to the drug:

• respiratory tract infections, including pneumonia, bronchitis;
• skin and soft tissue infections;
• intra-abdominal infections, including peritonitis and biliary tract infections;
• urinary tract infections, including pyelonephritis;
• gynecological infections;
• sepsis;
• empirical therapy in patients with febrile neutropenia;
• prophylaxis of postoperative complications in intra-abdominal surgery.

Children.

• Pneumonia;
• urinary tract infections, including pyelonephritis;
• skin and soft tissue infections;
• sepsis;
• empirical therapy in patients with febrile neutropenia;
• bacterial meningitis.

Contraindications.

Hypersensitivity to cefepime or L-arginine, as well as to cephalosporin antibiotics, penicillins, and other β-lactam antibiotics.

Interaction with other medicinal products and other types of interactions.

When administering high doses of aminoglycosides concomitantly with cefepime, renal function should be closely monitored due to the potential nephrotoxicity and ototoxicity of aminoglycoside antibiotics. Increased nephrotoxicity has been observed after concomitant use of other cephalosporins with diuretics such as furosemide.

Cefepime at concentrations from 1 to 40 mg/mL is compatible with the following parenteral solutions: 0.9% sodium chloride injection; 5% or 10% dextrose injection; 6% sodium lactate injection; 5% dextrose and 0.9% sodium chloride injection; Ringer’s lactate with 5% dextrose injection.

To avoid potential drug interactions with other agents, solutions of cefepime (as with most other β-lactam antibiotics) should not be simultaneously administered with metronidazole, vancomycin, gentamicin, tobramycin sulfate, or netilmicin sulfate solutions. When co-administered with these agents, each antibiotic should be given separately.

Concomitant treatment with bacteriostatic antibiotics may affect the activity of beta-lactam antibiotics.

Effect on laboratory test results.

Cefepime administration may result in false-positive urine glucose tests when using Benedict’s reagent. Glucose tests based on enzymatic glucose oxidation reactions are recommended.

Special precautions.

Hypersensitivity

Before administering the drug, it is necessary to determine whether the patient has previously experienced immediate-type hypersensitivity reactions to cefepime, cephalosporins, penicillins, or other beta-lactam antibiotics.

Cefepime should be administered with caution to patients with asthma or allergic diathesis. The patient's condition should be closely monitored during the first administration. If an allergic reaction occurs, treatment should be discontinued immediately.

Antibiotics should be prescribed cautiously to all patients with any form of allergy, especially drug allergies. If an allergic reaction occurs, the drug should be discontinued. Severe immediate-type hypersensitivity reactions may require administration of epinephrine and other supportive therapies.

In patients at high risk of severe infections (e.g., patients with a history of bone marrow transplantation, reduced marrow activity due to malignant hemolytic disorders, and severe progressive neutropenia), monotherapy may be insufficient, and combination antimicrobial therapy is indicated.

Antibacterial activity of cefepime

It is unlikely that prescribing cefepime in the absence of proven or suspected bacterial infection, or its prophylactic use, will be beneficial. However, such use may increase the risk of developing bacteria resistant to this drug. Prolonged use of cefepime (as with other antibiotics) may lead to superinfection. The patient's condition should be reassessed regularly. If superinfection develops, appropriate therapeutic measures should be initiated.

Renal impairment

The dose of cefepime should be adjusted in patients with impaired renal function (creatinine clearance < 50 mL/min) to compensate for reduced renal elimination. Since high serum antibiotic concentrations may occur with standard doses in patients with renal impairment or other conditions that may worsen kidney function, the maintenance dose should be reduced when administering cefepime to such patients. The next dose should be determined based on the degree of renal impairment, severity of infection, and susceptibility of the causative microorganisms.

During post-marketing surveillance, the following serious, life-threatening or fatal adverse reactions have been reported: reversible encephalopathy (disturbances of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures (including epileptic status), and/or renal failure. Most cases occurred in patients with renal impairment who received cefepime doses exceeding the recommended ones.

Such reactions have occasionally occurred in patients receiving doses adjusted according to renal function. In most cases, symptoms of nephrotoxicity were reversible and resolved after discontinuation of cefepime and/or after hemodialysis.

Clostridium difficile-associated diarrhea

Antibiotic-associated diarrhea and antibiotic-associated colitis, including pseudomembranous colitis and diarrhea associated with Clostridium difficile, have been reported with nearly all antibiotics, including cefepime, and may range from mild diarrhea to fatal colitis. Therefore, this diagnosis should be considered in patients who develop severe diarrhea during or after cefepime therapy. If antibiotic-associated diarrhea or antibiotic-associated colitis is suspected or confirmed, antibacterial therapy, including cefepime, should be discontinued and appropriate therapeutic measures should be initiated immediately. Antiperistaltic agents are contraindicated in this situation.

Mild pseudomembranous colitis may resolve after discontinuation of the drug. In cases of moderate to severe pseudomembranous colitis, consideration should be given to the need for fluid and electrolyte replacement, protein supplementation, and administration of an antibacterial agent effective against Clostridium difficile.

Use with caution in patients with gastrointestinal disorders (particularly in medical history), especially colitis.

Elderly patients

Cefepime is substantially excreted by the kidneys, and the risk of toxic reactions to this drug may be greater in patients with renal impairment. Since elderly patients are more likely to have decreased renal function, dose selection should be cautious, and renal function should be monitored.

Serological testing

Cephalosporins tend to adsorb onto the surface of erythrocytes and react with antibodies directed against drugs, resulting in a positive Coombs' test. A positive Coombs' test has been reported in patients receiving cefepime twice daily, even in the absence of hemolysis.

When performing hematological or transfusion procedures involving blood grouping by the cross-matching method, or when performing the Coombs' test in newborns whose mothers received cephalosporin antibiotics before delivery, it should be considered that a positive Coombs' test may be due to prior drug administration.

False-positive results may occur in urine glucose testing. For this reason, urine glucose should be determined by glucose oxidase methods during treatment with this drug.

Many cephalosporins, including cefepime, have been associated with reduced prothrombin activity. Patients at risk include those with impaired liver or kidney function, malnourished patients, and those receiving prolonged courses of antimicrobial therapy. Prothrombin should be monitored in patients at risk, and vitamin K should be administered if necessary.

Prothrombin time should be monitored.

When lidocaine is used as a solvent in both pediatric and adult patients, safety information regarding lidocaine should be taken into account.

It has been demonstrated that L-arginine alters glucose metabolism and simultaneously increases serum calcium levels when administered at doses 33 times higher than the maximum recommended dose of cefepime. Effects at lower doses are currently unknown.

Use during pregnancy or breastfeeding.

The drug may be prescribed during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus.

Cefepime is excreted in breast milk in small amounts; therefore, breastfeeding should be discontinued during treatment with this drug.

Ability to affect reaction speed when driving or operating machinery.

The effect of cefepime on reaction speed during driving or operating machinery has not been studied; however, it should be considered that adverse reactions affecting the nervous system may occur during treatment.

Administration and Dosage.

The usual dosage for adults and children is 1 g administered intravenously or intramuscularly every 12 hours. The usual duration of treatment is 7–10 days. Severe infections may require prolonged treatment. However, dosage and route of administration vary depending on the sensitivity, location, and type of microorganisms, severity of the infection, as well as the patient's age and functional status. Dosage recommendations for cefepime in adults are provided in Table 2.

Table 2.

Infection	Dose	Frequency of administration
Urinary tract infections (mild to moderate severity)	500 mg – 1 g IV or IM	every 12 hours
Other infections (mild to moderate severity)	1 g IV or IM	every 12 hours
Severe infections	2 g IV	every 12 hours
Very severe and life-threatening infections	2 g IV	every 8 hours

Dose adjustment is not required for patients aged 65 years and older with normal renal function.

Prophylaxis of potential infection during surgical procedures. Administer 2 g of the drug intravenously by infusion over 30 minutes, 1 hour prior to the start of surgery. After completion of the infusion, additionally administer 500 mg of metronidazole intravenously. Metronidazole solution should not be administered simultaneously with cefepime. If both antibiotics are used concomitantly, each should be administered through separate infusion systems. If one infusion system is used for both drugs, it should be flushed before administering metronidazole.

During prolonged surgical procedures (exceeding 12 hours), repeat administration of the same dose of the drug is recommended 12 hours after the initial dose, followed by administration of metronidazole.

Infants aged 1 to 2 months. Should be used only for life-threatening indications. Administer at a dose of 30 mg/kg body weight every 12 or 8 hours, depending on the severity of infection. The condition of children with body weight below 40 kg receiving cefepime therapy must be continuously monitored.

Children aged 2 months and older. The maximum dose for children should not exceed the recommended adult dose. For children with body weight below 40 kg, the recommended dose for complicated or uncomplicated urinary tract infections (including pyelonephritis), uncomplicated skin infections, pneumonia, and empirical treatment of febrile neutropenia is 50 mg/kg every 12 hours (for patients with febrile neutropenia and bacterial meningitis—every 8 hours). The duration of therapy is 7–10 days; severe infections may require longer treatment. Children with body weight of 40 kg or more should receive the drug in the same manner as adults.

For children with impaired renal function, dose reduction or prolonged dosing intervals are recommended.

Renal impairment. Cefepime is eliminated by the kidneys via glomerular filtration; therefore, dosage regimens should be adjusted in patients with impaired renal function (creatinine clearance less than 30 mL/min). The initial dose of the drug should be the same as for patients with normal renal function. Recommended maintenance doses are shown in Table 3.

Table 3

Creatinine clearance (mL/min)	Recommended maintenance doses
	Urinary tract infections (mild to moderate severity)	Other infections (mild to moderate severity)	Severe infections	Very severe and life-threatening infections
> 50	500 mg every 12 hours	1 g every 12 hours	2 g every 12 hours	2 g every 8 hours
	Standard dosing appropriate to the severity of infection; dose adjustment not required
30–50	500 mg every 24 hours	1 g every 24 hours	2 g every 24 hours	2 g every 12 hours
11–29	500 mg every 24 hours	500 mg every 24 hours	1 g every 24 hours	2 g every 24 hours
≤ 10	250 mg every 24 hours	250 mg every 24 hours	500 mg every 24 hours	1 g every 24 hours
Hemodialysis*	500 mg every 24 hours	500 mg every 24 hours	500 mg every 24 hours	500 mg every 24 hours

*On the day of dialysis, the injection must be administered after the dialysis session.

If only serum creatinine concentration is known, creatinine clearance can be calculated using the formula below:

Men:

body weight (kg) × (140 – age)

creatinine clearance (mL/min) = ---------------------------------------------------

72 × serum creatinine (mg/dL)

Women:

creatinine clearance (mL/min) = value calculated by the above formula × 0.85

During hemodialysis, approximately 68% of the administered dose is eliminated from the body over 3 hours. After each hemodialysis session, a supplemental dose equal to the initial dose should be administered. For continuous ambulatory peritoneal dialysis (CAPD), the medicinal product can be used at the normal recommended doses of 500 mg, 1 g, or 2 g, depending on the severity of infection, with a 48-hour interval between single doses.

In children with impaired renal function, dose reduction or prolonged dosing intervals are recommended, as indicated in Table 3.

Calculation of creatinine clearance in children:

0.55 × height (cm)

creatinine clearance (mL/min/1.73 m²) = -----------------------------------------

serum creatinine (mg/dL)

or

0.52 × height (cm)

creatinine clearance (mL/min/1.73 m²) = ------------------------------------------ – 3.6

serum creatinine (mg/dL)

Administration of the drug. The drug can be administered intravenously or deeply intramuscularly into a large muscle mass (e.g., the upper outer quadrant of the gluteal muscle).

Intravenous administration. The intravenous route is preferred for patients with severe or life-threatening infections.

For intravenous administration, cefepime should be dissolved in 5 or 10 mL of sterile water for injection, 5% dextrose injection solution, or 0.9% sodium chloride injection solution, as specified in Table 4. Administer intravenously slowly over 3–5 minutes or via an intravenous infusion system.

Intramuscular administration. Dissolve the medicinal product in sterile water for injection, 0.9% sodium chloride injection solution, 5% dextrose injection solution, bacteriostatic water for injection with parabens or benzyl alcohol, or 0.5% or 1% lidocaine hydrochloride solution, at concentrations specified in Table 4.

Prepared solutions for intramuscular and intravenous administration may be stored for up to 24 hours at room temperature or for 7 days in a refrigerator (2–8°C).

Table 4

	Volume of diluent (ml)	Approximate volume of resulting solution (ml)	Approximate concentration of cefepime (mg/ml)
Intravenous administration
1 g/vial	10	11.4	90
Intramuscular administration
1 g/vial	3.0	4.4	230

As with other parenterally administered medicinal products, the prepared solutions of the drug must be inspected for the absence of particulate matter prior to administration.

Appropriate microbiological investigations should be carried out to identify the causative microorganism(s) and to determine susceptibility to cefepime. However, the drug may be used as monotherapy prior to identification of the causative microorganism due to its broad spectrum of antibacterial activity against Gram-positive and Gram-negative microorganisms. In patients at risk of mixed aerobic/anaerobic (including Bacteroides fragilis) infection, treatment may be initiated in combination with an agent active against anaerobes, pending identification of the causative organism.

Children.

The medicinal product may be administered to children aged 1 month and older.

Overdose.

Symptoms: In cases of significant overdose, particularly in patients with impaired renal function, adverse reactions may intensify. Symptoms of overdose include encephalopathy accompanied by hallucinations, disturbances of consciousness, stupor, coma, myoclonus, epileptiform seizures, and neuromuscular excitability.

Treatment: Administration of the drug should be discontinued and symptomatic therapy initiated. Hemodialysis accelerates the elimination of cefepime from the body; peritoneal dialysis is poorly effective. Severe immediate-type allergic reactions require prompt administration of epinephrine and other forms of intensive therapy.

Adverse Reactions

Adverse reactions are observed rarely.

Immune system disorders: hypersensitivity reactions, including anaphylaxis, anaphylactic shock, angioedema.

Skin and subcutaneous tissue disorders: skin rashes, pruritus, urticaria.

Gastrointestinal disorders: nausea, vomiting, oral candidiasis, diarrhea, colitis (including pseudomembranous colitis), constipation, abdominal pain, dyspepsia, altered taste sensation.

Hepatic and biliary disorders: hepatitis, cholestatic jaundice.

Nervous system disorders: dizziness, headache, restlessness, insomnia, paresthesia, confusion/loss of consciousness, seizures/epileptiform attacks, myoclonus, encephalopathy, hallucinations, stupor, coma.

General disorders and administration site conditions: increased body temperature, sweating, chest/back pain, asthenia, injection site reactions including inflammation, phlebitis, pain.

Infections: candidiasis, vaginitis, genital pruritus, pseudomembranous colitis, other superinfections.

Respiratory, thoracic and mediastinal disorders: breathing difficulties, cough, sore throat, dyspnea.

Cardiovascular disorders: tachycardia, vasodilation, chest pain.

Renal and urinary disorders: renal failure.

Blood and lymphatic system disorders: anemia, eosinophilia, transient leukopenia, neutropenia, agranulocytosis, thrombocytopenia.

Laboratory abnormalities: increased plasma levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin; prolonged prothrombin time or partial thromboplastin time (PTT); positive Coombs test without hemolysis; transient increases in blood urea nitrogen and/or serum creatinine; false-positive urine glucose test.

In addition to the above-mentioned adverse reactions, adverse effects typical for cephalosporin antibiotics may occur: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhages, liver function disorders, cholestasis, pancytopenia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report all suspected adverse reactions and lack of efficacy to the State Expert Center of the Ministry of Health of Ukraine via the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging, out of reach of children, at a temperature not exceeding 25 °C. Prepared solutions for intramuscular and intravenous administration may be stored for up to 24 hours at room temperature or for up to 7 days in a refrigerator (2–8 °C).

Incompatibilities.

Do not mix in the same container with other medicinal products (such as metronidazole, vancomycin, gentamicin, tobramycin or netilmicin solutions), except for the solvents specified in the section "Instructions for use and dosage".

Packaging.

1, 5 or 10 vials with powder for solution for injection in a cardboard box.

Prescription category.

Prescription only.

Manufacturer.

NSPC Hebei Huamin Pharmaceutical Company Limited.

Manufacturer's address and location of business activity.

No. 98 Huan Road, Economic and Technological Development Zone, Shijiazhuang, Hebei 052165, China.