Cefotaxim-mip 1 g

Leaflet attached to the packaging: information for the user

Cefotaxim-MIP 1 g, powder for solution for injection and infusion

Cefotaxim-MIP 2 g, powder for solution for injection and infusion

Cefotaxime

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Cefotaxim-MIP and what is it used for
• 2. Important information before using Cefotaxim-MIP
• 3. How to use Cefotaxim-MIP
• 4. Possible side effects
• 5. How to store Cefotaxim-MIP
• 6. Contents of the packaging and other information

1. What is Cefotaxim-MIP and what is it used for

Cefotaxime is a third-generation cephalosporin antibiotic for parenteral use.
The bactericidal mechanism of cefotaxime involves the inhibition of bacterial cell wall synthesis.
The range of antibacterial activity is very broad.

Indications

Cefotaxime is indicated for the treatment of the following infections, caused by susceptible microorganisms.

• -Lower respiratory tract infections.
• -Urinary tract infections.
• -Genital infections.
• -Septicaemia.
• -Skin and soft tissue infections.
• -Intra-abdominal infections, including peritonitis.
• -Bone and joint infections.
• -Meningitis.
• -Prevention of post-operative infections in cases where the patient is at increased risk of infection.

2. Important information before using Cefotaxim-MIP

When not to use Cefotaxim-MIP:

• if the patient is allergic to cefotaxime or other cephalosporins,
• if the patient is allergic to penicillins, as a cross-allergic reaction to cephalosporins may occur.
• if the patient has ever experienced a severe skin rash or exfoliation after taking cefotaxime or other cephalosporins.

See also section: "Warnings and precautions".
In the event of any of the above, Cefotaxim-MIP should not be taken and the doctor should be informed.

Warnings and precautions

Before starting treatment with Cefotaxim-MIP, the patient should discuss it with their doctor.

When to exercise special caution when using Cefotaxim-MIP

In connection with the use of cefotaxime, severe skin reactions have been reported, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). The use of cefotaxime should be discontinued and the doctor should be consulted immediately if any symptoms of these severe skin reactions occur, as described in section 4.
If the patient has a history of severe allergy or asthma, they should inform their doctor.
In patients with a tendency to allergies, an allergic reaction may occur after taking this medicine - in this case, its administration should be discontinued.
Patients allergic to cefotaxime may also be allergic to other beta-lactam antibiotics (e.g., other cephalosporins or penicillins).
Severe, including fatal, hypersensitivity reactions have been reported in patients receiving cefotaxime. If a hypersensitivity reaction occurs, treatment should be discontinued immediately.
The use of cefotaxime is contraindicated in patients with a history of immediate hypersensitivity to cephalosporins.
Cephalosporin therapy should be carried out with caution in patients allergic to penicillin, as cross-allergy between penicillins and cephalosporins may occur.
Special caution should be exercised in individuals who have previously experienced severe allergies or asthma.
If the patient experiences diarrhea during or after treatment, they should inform their doctor.
Severe and persistent diarrhea may indicate the occurrence of life-threatening pseudomembranous colitis. This is a rare complication that occurs during the use of broad-spectrum antibiotics. The doctor will decide whether to discontinue cefotaxime and, if necessary, initiate appropriate treatment (e.g., administration of specific antibiotics or chemotherapeutics). Antidiarrheal medications should not be taken.
If the patient has kidney problems, the doctor may adjust the dosage. Caution should be exercised if cefotaxime is administered with aminoglycosides or other nephrotoxic medications (see section "Cefotaxim-MIP and other medicines"). In these patients, as well as in the elderly and patients with pre-existing renal impairment, the doctor may recommend monitoring kidney function.
If the patient, especially with renal impairment, experiences symptoms such as changes in consciousness, abnormal movements, and seizures, this may indicate brain function disorders caused by the use of excessive doses of cefotaxime. Immediate contact with the doctor is necessary before continuing treatment.
In the event of long-term use of the medicine, the doctor may recommend monitoring liver and kidney function. If cefotaxime is used for more than 7-10 days, the doctor may recommend monitoring blood parameters, including white blood cell count.
If cefotaxime is administered too quickly through a central venous catheter (less than 1 minute), severe heart rhythm disturbances may occur.
The use of any antibiotic may cause the growth of microorganisms resistant to the given antibiotic. Attention should be paid to symptoms of new infections and, if they are observed, the doctor should be consulted, who will recommend appropriate treatment.
The use of cefotaxime may affect the results of diagnostic tests.
During treatment with cefotaxime, false-positive Coombs test results may occur in rare cases.
False-positive glucose test results may occur after reducing doses, unless a specific method with oxidase is used.
When determining glucose levels in urine and blood, depending on the method used, false-positive results may occur; this can be avoided by using enzymatic methods.

Children

Cefotaxime with lidocaine for intramuscular injection should not be used in children under one year of age.

Elderly patients

The age-related decline in renal function may lead to increased cefotaxime serum concentrations if the dose is not properly adjusted (see section 3).

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, suspects they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine.
The safety of cefotaxime in pregnant women has not been established. Cefotaxime crosses the placental barrier. Therefore, it should not be used during pregnancy, especially in the first three months, unless the expected benefits outweigh the risks. There are no adequate studies on the use of cefotaxime in pregnant women. Animal studies have not shown any harmful effects of cefotaxime on the fetus.
Cefotaxime is excreted in breast milk. When cefotaxime is used during breastfeeding, disturbances in the intestinal flora of newborns and diarrhea may occur, and fungi may multiply, and an allergic reaction may occur. In this regard, the doctor will consider whether to discontinue breastfeeding or discontinue treatment, taking into account the benefits of breastfeeding for the child and the benefits of treatment for the woman.

Driving and operating machinery

Cefotaxime administered in small or medium doses does not affect concentration and reaction speed.
High doses of cefotaxime, especially in patients with renal impairment, may cause brain function disorders (such as encephalopathy, characterized by changes in consciousness, abnormal movements, and seizures). Vehicles should not be driven, and machinery should not be operated if such symptoms occur.

Cefotaxim-MIP and other medicines

The patient should inform their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
Cefotaxime and other antibiotics
Due to the antagonistic effect of cefotaxime, it should not be used with other chemotherapeutics with bacteriostatic action (e.g., tetracyclines, erythromycin, chloramphenicol, sulfonamides).
Due to incompatibility with all aminoglycosides, cefotaxime should not be administered with aminoglycosides in the same injection or infusion solution. If the use of both antibiotics is necessary, they should be administered through separate devices and injected at different sites.
Cefotaxime and probenecid
Concomitant administration of probenecid leads to the inhibition of cefotaxime excretion by the kidneys, resulting in increased serum concentrations and prolonged action.
Cefotaxime and nephrotoxic or loop diuretic medications
If cefotaxime is used concomitantly with medications that may damage the kidneys (e.g., aminoglycoside antibiotics, polymyxin B, and colistin) and loop diuretics, the nephrotoxic effects of these medications may be enhanced. If concomitant treatment with cefotaxime and an aminoglycoside antibiotic is necessary, these medications should be administered separately, and kidney function should be monitored.

Cefotaxim-MIP contains sodium

The medicine contains 48 mg of sodium (the main component of common salt) per 1 g, which corresponds to 2.4% of the maximum recommended daily sodium intake in the diet for adults.

3. How to use Cefotaxim-MIP

This medicine should always be used in accordance with the doctor's recommendations. In case of doubts, the doctor or pharmacist should be consulted.
Dosage
The dosage and method of administration depend on the severity of the infection, the susceptibility of the microorganism, and the patient's condition.
Adults and children over 12 years old
Usually 1 to 2 g of cefotaxime per day, in two divided doses, administered every 12 hours. In severe cases, the daily dose can be increased to 12 g. Daily doses up to 6 g should be divided into at least two single doses, administered every 12 hours. Higher daily doses should be divided into at least 3 to 4 single doses, administered every 8 or 6 hours, respectively.
The following table may serve as a guideline for dosing:

Before starting treatment, tests to detect possible syphilis should be performed.
In the prevention of post-operative infections, a single dose of 1 g of cefotaxime should be administered 30 to 90 minutes before the planned surgery. Depending on the risk of infection, the administration of the medicine may be continued after the procedure.
Infants and children under 12 years old
Depending on the severity of the infection, 50 to 100 mg of cefotaxime per kilogram of body weight per day is used, divided into 2, 3, or 4 single doses of equal size, administered every 12, 8, or 6 hours, respectively. In individual cases - especially in life-threatening infections - it may be necessary to increase the daily dose to 200 mg of cefotaxime per kilogram of body weight.
Newborns, including premature infants
Due to immature renal function, the dose should not exceed 50 mg of cefotaxime per kilogram of body weight per day, in 2, 3, or 4 divided doses, administered every 12, 8, or 6 hours, respectively.
Dosage in patients with renal impairment
Due to the extrarenal elimination of cefotaxime, a dose reduction is only necessary in severe renal impairment (glomerular filtration rate below 5 mL/min, serum creatinine concentration of approximately 751 micromoles/L). After the initial loading dose of 1 g, the daily dose should be reduced by half without changing the frequency of administration, e.g., a dose of 1 g every 12 hours should be reduced to 500 mg every 12 hours, 1 g every 8 hours to 500 mg every 8 hours, 2 g every 8 hours to 1 g every 8 hours, etc. As with other patient groups, further dose adjustment may be necessary based on the course of the infection and the patient's overall condition.
In patients with significantly impaired renal function (glomerular filtration rate below 10 mL/min), special dosing rules apply (see dosing table).
Method of administration
Detailed instructions are provided at the end of the leaflet in the section "Information intended exclusively for healthcare professionals".
Duration of treatment
The duration of treatment depends on the type of infection, the clinical course of the disease, and the results of bacteriological tests.
The medicine should be administered regularly, at the same time every day.
The doctor will recommend how long to use the medicine. Treatment should not be discontinued prematurely, as this may render it ineffective.
In case of any further doubts regarding the use of this medicine, the doctor should be consulted.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Cefotaxime should be discontinued and the doctor informed immediately if the patient notices any of the following symptoms:

• red, flat, target-like, or circular patches on the torso, often with centrally located blisters, peeling skin, ulcers, and mouth, throat, nose, genital, and eye lesions. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome or toxic epidermal necrolysis).

A widespread rash, high body temperature, and swollen lymph nodes (DRESS or drug hypersensitivity syndrome).

• A red, scaly, widespread rash with thickening under the skin and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (acute generalized exanthematous pustulosis).
• Anaphylactic reactions, angioedema, bronchospasm, anaphylactic shock.

The following side effects and their frequencies are presented below.
Very common (may occur in more than 1 in 10 patients):

• pain at the injection site after intramuscular administration.

Common (may occur in up to 1 in 10 patients):

• allergic skin reactions (hives, rash), itching, drug fever, joint disorders (swelling),
• increased serum creatinine and urea levels.

Uncommon (may occur in up to 1 in 100 patients):

• decreased white blood cell count, increased eosinophil count (a type of white blood cell), decreased platelet count, Jarisch-Herxheimer reaction (symptoms occurring within a few weeks of starting treatment for borreliosis, such as skin rash, itching, fever, leukopenia, breathing difficulties, joint problems),
• seizures,
• diarrhea, loss of appetite,
• increased liver enzyme activity (ALT, AST, LDH, GGTP, alkaline phosphatase) and/or bilirubin levels,
• rash, itching, hives,
• worsening of kidney function and/or increased creatinine levels (especially when used with aminoglycosides),
• fever, inflammation at the injection site, including phlebitis or thrombophlebitis.

Rare (may occur in up to 1 in 10,000 patients):

• convulsions, central nervous system stimulation, myoclonus (sudden muscle contractions), especially after administration of high doses of cefotaxime in patients with renal impairment.

Frequency not known (cannot be estimated from available data):

• superinfections,
• decreased neutrophil count (a type of white blood cell), complete or almost complete absence of granulocytes in the blood and bone marrow smear (agranulocytosis), hemolytic anemia,
• headache, dizziness, encephalopathy (e.g., changes in consciousness, abnormal movements),
• arrhythmia caused by too rapid infusion of the medicine through a central venous catheter,
• nausea, vomiting, abdominal pain, pseudomembranous colitis,
• hepatitis (sometimes with jaundice),
• severe skin reactions (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis),
• interstitial nephritis,
• systemic reactions to lidocaine after intramuscular administration (if the solution contains lidocaine), nausea, and feeling of heat after rapid intravenous administration.

Reporting side effects

If any side effects occur, including any side effects not listed in the leaflet, the doctor, pharmacist, or nurse should be informed. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Cefotaxim-MIP

The medicine should be stored out of sight and reach of children.
This medicine should not be used after the expiry date stated on the packaging. The expiry date refers to the last day of the month stated.
Store at a temperature below 25°C. Protect from light.
The prepared solution should not be stored for more than 24 hours at a temperature between 2°C and 8°C.
It is best to administer the solution immediately after preparation.
A slightly yellowish color of the solution does not affect the efficacy and safety of the antibiotic.
Medicines should not be disposed of via wastewater or household waste. The pharmacist should be asked how to dispose of unused medicines. This will help protect the environment.

6. Contents of the packaging and other information

What Cefotaxim-MIP contains

• The active substance of the medicine is cefotaxime. Cefotaxim-MIP 1 g: 1 vial contains 1 g of cefotaxime in the form of cefotaxime sodium (1.048 g). Cefotaxim-MIP 2 g: 1 vial contains 2 g of cefotaxime in the form of cefotaxime sodium (2.096 g).
• The medicine does not contain any other ingredients.

What Cefotaxim-MIP looks like and what the packaging contains

Vials made of type II glass with a capacity of 15 mL, closed with a bromobutyl rubber stopper and an aluminum flip-off cap, in a cardboard box.
1 vial
5 vials
10 vials (2 x 5 vials)
25 vials (5 x 5 vials)
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder
MIP Pharma Polska Sp. z o.o.
ul. Orzechowa 5
80-175 Gdańsk
Phone: 58 303 93 62
Fax: 58 322 16 13
Email: info@mip-pharma.pl
Manufacturer
Chephasaar, Chemisch-pharmazeutische Fabrik GmbH
Mühlstrasse 50
D-66386 St. Ingbert
Germany

Date of last update of the leaflet:

Information intended exclusively for healthcare professionals

Cefotaxime is highly resistant to hydrolysis by beta-lactamases.
However, it may be hydrolyzed by beta-lactamases with an extended spectrum (e.g., Bacteroides fragilis, Proteus vulgaris).
The following is a summary of the in vitro activity of cefotaxime.

Gram-positive:

Staphylococcus spp. (penicillinase-producing and non-penicillinase-producing, coagulase-positive and coagulase-negative strains),
Streptococcus spp. beta-hemolytic and other streptococci, such as Streptococcus viridans(and other enterococcal strains, including relatively resistant Streptococcus faecalis),
Streptococcus(Diplococcus) pneumoniae,
Clostridium spp.

Gram-negative:

Escherichia coli
Haemophilus influenzae(including ampicillin-resistant strains)
Klebsiella spp.
Proteus spp.(including indole-positive and indole-negative strains)
Enterobacter spp.
Neisseria spp.(including N. gonorrhoeabeta-lactamase-producing strains)
Salmonella spp.(including Salmonella typhi)
Shigella spp.
Providencia spp.
Serratia spp.
Citrobacter spp.
Pseudomonas spp.and Bacteroides spp.- some Bacteroides fragilisstrains are resistant.

Instructions for intravenous and intramuscular administration

Intravenous injections
Before administering an intravenous injection of Cefotaxim-MIP 1 g, it should be dissolved in at least 4 mL, and Cefotaxim-MIP 2 g in at least 10 mL of water for injections, then administered directly into a vein or into the peripheral end of an infusion tube (after unlocking the infusion tube) within 3 to 5 minutes.
Intravenous infusions
Before administering a short-term infusion, 1 g or 2 g of cefotaxime should be dissolved in 40 to 50 mL of water for injections or another compatible infusion solution, and then administered intravenously over approximately 20 minutes.
Before administering a long-term infusion, 2 g of cefotaxime should be dissolved in 100 mL of isotonic sodium chloride solution or glucose, and then administered intravenously over approximately 50 to 60 minutes. Another compatible infusion solution may also be used as a solvent.
Intramuscular injections
Before administering an intramuscular injection, Cefotaxim-MIP 1 g should be dissolved in 4 mL of water for injections. Then, a deep injection into the gluteal muscle should be performed. To alleviate pain during intramuscular injection, Cefotaxim-MIP 1 g should be dissolved in 4 mL of 1% lidocaine solution. However, care should be taken not to administer the medicine into a blood vessel, as intravascular administration of lidocaine may cause restlessness, conduction disorders, vomiting, or seizures. Cefotaxim-MIP with lidocaine should not be administered to children under one year of age.
No more than 4 mL should be administered in a single injection. If the daily dose exceeds 2 g of cefotaxime or if cefotaxime is administered more frequently than twice a day, intravenous administration of the medicine is recommended.
Cefotaxime is incompatible with:

• sodium bicarbonate solutions,
• infusion solutions with a pH above 7,
• aminoglycosides.

Compatibility with intravenous infusion solutions
Cefotaxime can be mixed with the following fluids:

• water for injections,
• 0.9% sodium chloride solution,
• 5% glucose solution.