Cefotaxim-mip 1 g

Package leaflet: 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
Cefotaximum
Please read all of this leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else even if their symptoms are the same.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Cefotaxim-MIP is and what it is 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 pack and other information

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

Cefotaxime is an antibiotic belonging to the third-generation cephalosporins, administered by parenteral route.
The bactericidal mechanism of action of cefotaxime involves inhibition of bacterial cell wall synthesis. It has a broad spectrum of antibacterial activity.
Indications
Cefotaxime is indicated for the treatment of the following infections caused by susceptible microorganisms:

• Lower respiratory tract infections.
• Urinary tract infections.
• Genital tract infections.
• Septicaemia.
• Skin and soft tissue infections.
• Intra-abdominal infections, including peritonitis.
• Bone and joint infections.
• Meningitis.
• Prophylaxis of perioperative infections in patients 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 an allergic reaction to cephalosporins may occur (cross-sensitivity).
• if after taking cefotaxime or other cephalosporins the patient has ever experienced severe skin rash, skin peeling, blisters, or oral mucosal ulcers.

See also section: "Warnings and precautions".
If any of the above conditions occur, Cefotaxim-MIP should not be used, and the patient should inform the doctor.
Warnings and precautions
Before starting treatment with Cefotaxim-MIP, discuss it with your doctor.
When to exercise special caution when using Cefotaxim-MIP
Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP), have been reported during cefotaxime therapy. Treatment with cefotaxime must be discontinued and immediate medical advice sought if any symptoms associated with these severe skin reactions occur, as described in section 4.
If the patient has previously had severe allergy or asthma, this must be reported to the doctor.
Allergic reactions may occur in patients predisposed to allergies after administration of this medicine – treatment should be discontinued in such cases.
Patients hypersensitive to cefotaxime may also show allergic reactions 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 must be immediately discontinued.
Cefotaxime is absolutely contraindicated in patients with a history of immediate-type hypersensitivity to cephalosporins.
Cephalosporin therapy should be initiated with special caution in patients hypersensitive to penicillin, due to cross-allergenicity between penicillins and cephalosporins.
Special caution is required in patients who have previously experienced severe allergy or asthma.
If the patient develops diarrhoea during or after completion of treatment, this must be reported to the doctor.
Severe and persistent diarrhoea may indicate life-threatening pseudomembranous colitis. This is a complication that may occur in isolated cases during treatment with broad-spectrum antibiotics. The doctor will decide whether to discontinue cefotaxime and, if necessary, immediately initiate appropriate treatment (e.g. administration of specific antibiotics or chemotherapeutic agents). Medications inhibiting intestinal peristalsis should not be used.
If the patient has impaired renal function, the doctor may adjust the dosage. Caution is required when cefotaxime is administered concomitantly with aminoglycosides or other nephrotoxic drugs (see section "Cefotaxim-MIP and other medicines"). In these patients, elderly patients, and patients with pre-existing renal impairment, the doctor may recommend monitoring of renal function.
If symptoms such as altered consciousness, abnormal movements, or seizures occur in a patient, particularly with renal impairment, this may indicate brain dysfunction caused by excessive doses of cefotaxime. Immediate contact with the doctor is required before continuing treatment.
If the drug is used for a prolonged period, the doctor may recommend monitoring of liver and kidney function. If cefotaxime is used for longer than 7–10 days, the doctor may recommend monitoring blood parameters, including white blood cell count.
If cefotaxime is administered too rapidly by intravenous injection via a central venous catheter (in less than 1 minute), severe cardiac arrhythmias may occur.
Any antibiotic use may lead to overgrowth of microorganisms resistant to that antibiotic. Be alert for signs of new infection and consult the doctor if they appear; appropriate treatment will be recommended.
Cefotaxime may affect the results of diagnostic tests.
During cefotaxime treatment, Coombs test results may rarely be falsely positive.
Falsely positive glucose test results may occur after dose reduction, unless a specific oxidase method is used.
Depending on the method used, false-positive results may occur when measuring glucose levels in urine and blood; this can be avoided by using enzymatic methods.
Children
Cefotaxime with lidocaine should not be used for intramuscular injection in children during the first year of life.
Elderly patients
Age-related natural decline in renal function may lead to increased cefotaxime plasma concentrations if the dose is not appropriately adjusted (see section 3).
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine.
The safety of cefotaxime use in pregnant women has not been established. Cefotaxime crosses the placental barrier. Therefore, it should not be used during pregnancy, especially during the first trimester, unless the expected benefits outweigh the risks. Adequate studies on cefotaxime use in pregnant women are currently lacking. Animal studies have not shown harmful effects of cefotaxime on the fetus.
Cefotaxime passes into breast milk. When cefotaxime is used during breastfeeding, newborns may develop disturbances in intestinal bacterial flora and diarrhoea, fungal overgrowth, or allergic reactions. Therefore, 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 mother.
Driving and operating machinery
Cefotaxime administered in low or medium doses does not affect concentration or reaction speed.
High doses of cefotaxime, especially in patients with renal impairment, may cause brain dysfunction (so-called encephalopathy), manifesting as altered consciousness, abnormal movements, or seizures. Driving or operating machinery should be avoided if such symptoms occur.
Cefotaxim-MIP and other medicines
Inform the doctor about all medicines currently or recently taken, as well as any medicines the patient plans to take.
Cefotaxime and other antibiotics
Due to antagonistic effects, cefotaxime should not be used concomitantly with other bacteriostatic chemotherapeutic agents (e.g. tetracyclines, erythromycin, chloramphenicol, sulfonamides).
Because of incompatibility with all aminoglycosides, cefotaxime should not be administered in the same injection or infusion solution with aminoglycosides. If both antibiotics are required, they should be administered separately using different equipment and injected at different sites.
Cefotaxime and probenecid
Concomitant administration of probenecid inhibits renal excretion of cefotaxime, resulting in increased serum concentration and prolonged duration of action.
Cefotaxime and nephrotoxic drugs or diuretics acting on the loop of Henle
Concomitant use of drugs that may damage the kidneys (e.g. aminoglycoside antibiotics, polymyxin B, colistin) or diuretics acting on the loop of Henle with cefotaxime may enhance the nephrotoxic effects of these drugs. If concomitant treatment with cefotaxime and an aminoglycoside antibiotic is necessary, the drugs should be administered separately and renal function should be monitored.
Cefotaxim-MIP contains sodium
The medicine contains 48 mg of sodium (the main component of table salt) in 1 g. This corresponds to 2.4% of the maximum recommended daily sodium intake in the adult diet.

3. How to use Cefotaxim-MIP

This medicine should always be used as directed by the physician. In case of doubt, consult a doctor or pharmacist.
Dosage
The dosage and route of administration depend on the severity of infection, microbial susceptibility, and the patient's condition.
Adults and children over 12 years of age
Typically 1 to 2 g of cefotaxime per day, divided into two doses administered every 12 hours. In severe cases, the daily dose may be increased up to 12 g. Daily doses up to 6 g should be divided into at least two single doses given 12 hours apart. 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:

In the treatment of gonorrhea in adult women, a single dose of 500 mg of cefotaxime should be administered. In men and in the treatment of infections caused by less sensitive microorganisms, it may be necessary to increase the dose to 1 g. Before starting treatment, tests to detect possible syphilis infection should be performed.

For perioperative prophylaxis of 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, administration of the drug may be continued after the procedure.

Infants and children up to 12 years of age
Depending on the severity of infection, the recommended dose is 50 to 100 mg of cefotaxime per kilogram of body weight per day, divided into 2, 3, or 4 equal single doses administered every 12, 8, or 6 hours, respectively. In individual cases—especially in life-threatening infections—the daily dose may need to be increased up 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, divided into 2, 3, or 4 doses administered every 12, 8, or 6 hours, respectively.

Dosing in patients with renal impairment
Due to extrarenal elimination of cefotaxime, dose reduction is necessary only in severe renal failure (glomerular filtration rate below 5 mL/min, serum creatinine concentration approximately 751 micromoles/L). After an initial loading dose of 1 g, the daily dose should be halved without changing the frequency of administration; for example, a dose of 1 g every 12 hours should be reduced to 500 mg every 12 hours, 1 g every 8 hours should be reduced to 500 mg every 8 hours, 2 g every 8 hours should be reduced to 1 g every 8 hours, etc. As with other patient groups, further dose adjustments may be necessary depending on the course of infection and the patient's general condition.

For patients with severely impaired renal function (glomerular filtration rate below 10 mL/min), separate dosing guidelines apply (see dosing table).

Method of administration
Detailed instructions are provided at the end of this leaflet under the section "Information intended exclusively for healthcare professionals."

Duration of treatment
The duration of treatment depends on the type of infection, clinical course of the disease, and bacteriological test results.

The medicine should be administered regularly, each time at the same time.

Your doctor will advise how long the medicine should be taken. Do not discontinue treatment prematurely, as this may render the treatment ineffective.

If you have any further doubts regarding the use of this medicine, consult your doctor.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Treatment with cefotaxime should be stopped immediately and a doctor should be informed if the patient notices
any of the following symptoms:

• Red, non-elevated, target-shaped or circular skin lesions on the trunk, often with central blisters, skin peeling, and ulceration of the mouth, throat,
  nose, genital organs and eyes. These severe skin rashes may be preceded by fever and
  flu-like symptoms (Stevens-Johnson syndrome or toxic epidermal necrolysis).

• Widespread rash, high body temperature and enlarged lymph nodes (DRESS syndrome or drug-induced hypersensitivity syndrome).

• Red, scaly, widespread rash with subcutaneous nodules and blisters, accompanied by fever. Symptoms usually occur at the beginning of treatment (acute generalized exanthematous pustulosis).

• Anaphylactic reactions, angioedema, bronchospasm, anaphylactic shock.

The following is a list of adverse reactions and their frequency of occurrence.
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 (urticaria, 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, Herxheimer reaction (symptoms appearing within a few weeks of starting Lyme disease treatment such as skin rash, itching, fever, leukopenia, breathing difficulties, joint complaints),
• Seizures,
• Diarrhea, loss of appetite,
• Increased liver enzyme activity (AlAT, AspAT, LDH, GGTP, alkaline phosphatase) and/or increased bilirubin levels,
• Rash, skin itching, urticaria,
• Worsening kidney function and/or increased creatinine levels (especially when used concomitantly with aminoglycosides),
• Fever, injection site inflammatory reactions including phlebitis or thrombophlebitis.

Very rare (may occur in less than 1 in 10,000 patients):

• Muscle spasms, central nervous system excitation, myoclonus (sudden muscle jerks), particularly after 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 near-complete absence of granulocytes in blood and bone marrow smear (agranulocytosis), hemolytic anemia,
• Headache and dizziness, encephalopathy (e.g. altered consciousness, abnormal movements),
• Arrhythmia caused by too rapid infusion of the drug via 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 hot flushes after rapid intravenous administration.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions
can be reported directly to the
Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Cefotaxim-MIP

Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Store below 25°C. Protect from light.
The prepared solution should be stored for no longer than 24 hours at a temperature between 2°C and 8°C.
It is best to administer immediately after preparation.
A slightly yellowish colour of the solution does not affect the efficacy or safety of the antibiotic.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What Cefotaxim-MIP contains

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

What Cefotaxim-MIP looks like and contents of the pack
Vials made of type II glass with a capacity of 15 mL, closed with a bromobutyl rubber stopper and an aluminium "flip-off" cap, packed in a cardboard box.
1 vial
5 vials
10 vials (2×5 vials)
25 vials (5×5 vials)
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
MIP Pharma Polska Sp. z o.o.
Orzechowa 5 Street
80-175 Gdańsk
Poland
Tel.: 58 303 93 62
Fax: 58 322 16 13
E-mail: [email protected]

Manufacturer
Chephasaar, Chemisch-pharmazeutische Fabrik GmbH
Mühlstrasse 50
D-66386 St. Ingbert
Germany

Information intended exclusively for medical professionals

Cefotaxime is highly resistant to hydrolysis by beta-lactamases.
However, it may be hydrolyzed by beta-lactamases with extended spectrum (e.g. Bacteroides fragilis, Proteus vulgaris).
The following presents the in vitro spectrum of activity of cefotaxime.
Gram-positive:
Staphylococcus spp. (both penicillinase-producing and non-producing strains, coagulase-positive and coagulase-negative strains),
Streptococcus spp. beta-haemolytic and other streptococci such as Streptococcus viridans (and other enterococcal strains, including the 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 beta-lactamase-producing N. gonorrhoeae strains)
Salmonella spp. (including Salmonella typhi)
Shigella spp.
Providencia spp.
Serratia spp.
Citrobacter spp.
Pseudomonas spp. and Bacteroides spp. – some strains of Bacteroides fragilis are resistant.

Instructions for intravenous and intramuscular administration
Intravenous injections
Before performing an intravenous injection, Cefotaxim-MIP 1 g should be dissolved in at least 4 mL, and Cefotaxim-MIP 2 g in at least 10 mL of water for injections. The solution should then be injected directly into a vein or into the peripheral end of an infusion line (after unclamping the infusion line) over 3 to 5 minutes.

Intravenous infusions
For 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, followed by an intravenous infusion lasting approximately 20 minutes.
For prolonged infusion, 2 g of cefotaxime should be dissolved in 100 mL of isotonic sodium chloride solution or glucose solution, followed by an intravenous infusion lasting approximately 50 to 60 minutes. Alternatively, other compatible infusion solutions may be used as solvent.

Intramuscular injections
Before performing an intramuscular injection, Cefotaxim-MIP 1 g should be dissolved in 4 mL of water for injections. A deep intramuscular injection should then be administered into the gluteal muscle. To reduce pain during intramuscular injection, Cefotaxim-MIP 1 g may be dissolved in 4 mL of 1% lidocaine solution. Care must be taken to avoid intravascular administration, as inadvertent intravenous injection of lidocaine may cause restlessness, conduction disturbances, vomiting, or seizures. Cefotaxim-MIP with added lidocaine must 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 daily, intravenous administration is recommended.

Cefotaxime is incompatible with:

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

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

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