Cefotaxime dali pharma

Package leaflet: Information for the user

Cefotaxime Dali Pharma, 2 g, powder for solution for injection / infusion
Cefotaximum
Please read carefully the entire leaflet before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific person. Do not pass it on to others. The medicine may harm another person, even if their symptoms of illness are the same.
• If the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Table of contents of the leaflet

1. What Cefotaxime Dali Pharma is and what it is used for
2. Important information before using Cefotaxime Dali Pharma
3. How to use Cefotaxime Dali Pharma
4. Possible side effects
5. How to store Cefotaxime Dali Pharma
6. Contents of the pack and other information

1. What Cefotaxime Dali Pharma is and what it is used for

Cefotaxime Dali Pharma (an antibiotic belonging to the so-called cephalosporin group) is a medicine that fights bacteria.
It is used in the treatment of severe, acute and chronic bacterial infections, if they are
caused by pathogens sensitive to cefotaxime:

• respiratory tract infections,
• infections of the throat, nose and ears,
• kidney and urinary tract infections,
• skin and soft tissue infections,
• bone and joint infections,
• genital organ infections, including gonorrhoea,
• abdominal infections (including peritonitis),
• meningitis (inflammation of the meninges),
• blood poisoning (septicaemia),
• heart inflammation (endocarditis),
• Lyme disease (particularly stages II and III) (infection mainly transmitted by tick bites)

Cefotaxime Dali Pharma may also be used for the prevention of perioperative infections when the patient is at increased risk of infection.

2. Important information before using Cefotaxime Dali Pharma

When not to use Cefotaxime Dali Pharma

• if the patient is allergic to sodium cefotaxime.
• if the patient has a proven hypersensitivity to other cephalosporins.
• if the patient has a history of severe or serious hypersensitivity reaction to penicillins or other beta-lactam antibiotics. Cross-reactions may occur between penicillins and cephalosporins.
• if the patient has ever experienced severe skin rash, skin peeling, blisters, or oral mucosal ulcers after taking cefotaxime or other cephalosporins.

Cefotaxime Dali Pharma with lidocaine must never be used:

• intravenously
• in infants under 30 months of age
• in patients with previous hypersensitivity to this product
• in patients with uncorrected heart block (without pacemaker)
• in patients with severe heart failure. Refer to technical information regarding lidocaine-containing preparations.

Warnings and precautions
When to exercise special caution when using Cefotaxime Dali Pharma
Serious 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 with cefotaxime use.
Discontinue cefotaxime immediately and consult a doctor if any symptoms related to these serious skin reactions occur, as described in section 4.
Before starting or during treatment with Cefotaxime Dali Pharma, discuss the following with your doctor or pharmacist:

• if the patient has any known allergy to penicillins or other beta-lactam antibiotics (contraindications regarding known hypersensitivity reactions – see above under "When not to use Cefotaxime Dali Pharma").
• if the patient has an allergic condition (e.g. hay fever, bronchial asthma, urticaria) or a history of such reactions. In such cases, the risk of severe (and in rare cases, even fatal) hypersensitivity reactions is increased. Severe acute (including fatal) hypersensitivity reactions (e.g. angioedema, bronchospasm, anaphylaxis up to shock) may occur after cefotaxime administration. If the patient experiences chest tightness, dizziness, discomfort, or weakness, this may indicate such a hypersensitivity reaction (see section 2 "When not to use Cefotaxime Dali Pharma" and section 4 "Possible side effects"). If a hypersensitivity reaction occurs, treatment must be discontinued.
• if any skin or mucosal changes develop during treatment (see section 4, "Possible side effects"). Cefotaxime Dali Pharma may cause serious skin reactions requiring medical treatment. Inform your doctor immediately if such symptoms occur.
• if severe, persistent diarrhea develops during or within several weeks after treatment. Inform your doctor immediately, as diarrhea in its most severe form (known as pseudomembranous colitis) can be life-threatening and requires treatment. Do not take medications that inhibit intestinal motility.
• if the patient knows their kidney function is impaired. Inform your doctor so that this can be considered when determining dosage. Kidney function monitoring is also required.
• if the patient is being treated with aminoglycosides (a group of antibiotics), probenecid (a medication for gout), or other drugs that may be harmful to the kidneys, either concurrently or after cefotaxime administration. The doctor must monitor kidney function, as the nephrotoxic effects of these substances may be enhanced, requiring appropriate caution.
• if motor disturbances, seizures, confusion, or disturbances of consciousness occur. These may be symptoms of a condition called encephalopathy. The risk of this adverse effect is increased with high doses of cefotaxime, overdose, or impaired kidney function. Inform your doctor immediately if such reactions occur.
• if treatment lasts longer than 7 to 10 days. In such cases, blood tests should be performed, as blood changes may occur (see also section 4 "Possible side effects").
• if signs of a new infection occur (e.g. fungal infection of mucous membranes with redness and white deposits). Any antibiotic use may lead to overgrowth of pathogens resistant to the administered drug. Watch for signs of new infection and inform your doctor if necessary.
• If the patient is scheduled to undergo laboratory diagnostic tests: Coombs test or urine glucose test. Cefotaxime may cause a positive Coombs test result in some patients and may also affect cross-matching. Cefotaxime may cause false-positive results in urine glucose tests using non-specific reducing reagents, but not in tests based on glucose oxidase.

If Cefotaxime Dali Pharma is injected too rapidly (in less than 1 minute)
through a central venous catheter (CVC), severe cardiac arrhythmias may occur (see also
section 3).
Note:
Cefotaxime Dali Pharma 2 g must not be administered intramuscularly.
Cefotaxime Dali Pharma and other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Other antibiotics
Concurrent use of certain other antibiotics may reduce the effectiveness of Cefotaxime Dali Pharma. Inform your doctor if the patient is taking or has recently taken another antibiotic.
Diuretics and other potentially nephrotoxic drugs
When used concomitantly with other drugs that may harm the kidneys, such as antibiotics (e.g. aminoglycosides, polymyxin B, and colistin) or highly effective diuretics (e.g. furosemide), cefotaxime may enhance the nephrotoxic effects of these drugs.
Kidney function should be monitored when these drugs are used together with cefotaxime (see section 2, "Warnings and precautions").
Probenecid
Concomitant administration of probenecid leads to increased serum concentrations of cefotaxime and thus increased activity of Cefotaxime Dali Pharma, as probenecid inhibits its renal excretion. Inform your doctor about probenecid use, especially in patients with impaired kidney function, so that this can be considered when determining dosage.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.
Pregnancy
There are insufficient data on the use of Cefotaxime Dali Pharma in pregnant women. Animal studies have not shown harmful effects of cefotaxime.
However, during pregnancy, especially during the first trimester, Cefotaxime Dali Pharma should only be used after careful benefit-risk assessment by the treating physician.
Breastfeeding
Cefotaxime passes into human milk. If Cefotaxime Dali Pharma is administered during breastfeeding, it may affect the infant's intestinal flora, leading to diarrhea and yeast colonization, and may also cause sensitization. Taking into account both the benefits of breastfeeding for the infant and the benefits of treatment for the mother, the doctor will decide whether to discontinue breastfeeding or discontinue treatment with Cefotaxime Dali Pharma.
Driving and operating machinery
Based on previous experience, Cefotaxime Dali Pharma at low and medium doses does not affect concentration or reaction time.
If any adverse effects occur, such as dizziness, seizures, confusion, disturbances of consciousness or motor function, which may be related to encephalopathy, the patient should not drive or operate machinery.
Cefotaxime Dali Pharma contains sodium
This medicine contains approximately 4.2 mmol (96 mg) of sodium (main component of table salt) per vial.
This corresponds to 4.8% of the maximum recommended daily dietary sodium intake for adults. This should be taken into account in patients on a sodium-controlled (low sodium / low salt) diet.
3. How to use Cefotaxime Dali Pharma
This medicine should always be used exactly as prescribed by the doctor.
The dose, route of administration, intervals between injections, and duration of treatment depend on the pathogen's susceptibility, severity of infection, and the patient's condition. Unless otherwise directed by the doctor, the usual dose is:
Adults and adolescents over 12 years of age usually receive 1 to 2 g of cefotaxime every 12 hours. In severe cases, the daily dose may be increased up to 12 g of cefotaxime. Daily doses up to 6 g of cefotaxime may be divided into at least two single doses every 12 hours.
Higher daily doses should be divided into at least 3 to 4 single doses administered every 8 or 6 hours.
The following table may serve as a dosing guideline:

In the treatment of gonorrhoea, 0.5 g of cefotaxime should be administered intramuscularly as a single dose in adults.
An increase in dose may be necessary in case of less susceptible microorganisms. Before initiating treatment, syphilis should be excluded.

For perioperative infection prophylaxis, a dose of 1–2 g of cefotaxime is recommended to be administered 30–60 minutes before the start of surgery. Depending on the risk of infection, this same dose may be repeated multiple times.

In the case of Lyme disease (borreliosis), a daily dose of 6 g of cefotaxime (for 14 to 21 days) is used. The daily dose was usually divided into 3 divided doses (2 g of cefotaxime 3 times daily), but in individual cases, it was also administered in 2 divided doses (3 g of cefotaxime twice daily). These dosing recommendations are not based on controlled clinical trials, but on observations from individual cases.

Combination therapy
Combination therapy with Cefotaxime Dali Pharma and aminoglycosides is indicated in severe, life-threatening infections when susceptibility test results are not yet available. When using cefotaxime in combination with aminoglycosides, renal function should be closely monitored.
In infections caused by Pseudomonas aeruginosa, combination with other antibiotics effective against Pseudomonas may also be indicated.
Concomitant use of cefotaxime with other appropriate antibiotics may also be indicated for infection prophylaxis in immunocompromised patients.

Infants and children up to 12 years of age should receive 50 to 100 mg (up to 150 mg) of cefotaxime per kilogram of body weight per day, depending on the severity of infection. The daily dose should be divided into 2 or more equal doses administered at intervals of 12- (down to 6) hours.
In individual cases—particularly in life-threatening situations—the daily dose may need to be increased up to 200 mg of cefotaxime per kilogram of body weight.

In premature infants, due to the immature renal function, doses exceeding 50 mg of cefotaxime per kilogram of body weight per day should not be administered.

In patients with severe renal impairment (creatinine clearance less than 10 mL/min), after a normal initial dose (the first dose at the beginning of treatment), the maintenance dose must be reduced to half the normal dose, while maintaining the dosing interval.
Patients undergoing hemodialysis should receive 1 to 2 g of cefotaxime per day, depending on the severity of infection. On the day of hemodialysis, cefotaxime should be administered after completion of dialysis.
Patients undergoing peritoneal dialysis should receive 1 to 2 g of cefotaxime per day, depending on the severity of infection. Cefotaxime is not removed during peritoneal dialysis.

Cefotaxime Dali Pharma 2 g should be administered intravenously (into a vein) only.

Elderly patients
In elderly patients, renal function should be carefully monitored and the dose adjusted accordingly.

Method of administration

Intravenous injection
For intravenous injection, 2 g of cefotaxime should be dissolved in at least 10 mL of water for injections, then injected directly into a vein over 3 to 5 minutes.

Infusion
To prepare the infusion solution, the cefotaxime powder should first be dissolved in 10 mL of water for injections or one of the compatible solutions, then added to 40–50 mL or 100 mL of water for injections / compatible infusion solution and mixed.
For short-term infusion, 2 g of cefotaxime should be dissolved in 40–50 mL of water for injections or another compatible infusion solution and administered over approximately 20 minutes via intravenous infusion.
For continuous intravenous infusion, 2 g of cefotaxime should be dissolved in 100 mL of isotonic sodium chloride solution or glucose solution, then administered over 50–60 minutes via intravenous infusion. Another compatible infusion solution may also be used for the solution.

Intramuscular injection
Cefotaxime Dali Pharma 2 g must not be administered intramuscularly.

Compatibility
Unless chemical and physical compatibility with other infusion solutions has been demonstrated, cefotaxime solution should always be administered separately from other solutions.

Major incompatibilities
The following substances/solutions are incompatible with Cefotaxime Dali Pharma:

• sodium bicarbonate solution,
• infusion solutions with pH greater than 7,
• aminoglycosides.

Cefotaxime Dali Pharma must not be mixed with other antibiotics or medications in the same syringe. Cefotaxime Dali Pharma must not be mixed with aminoglycoside antibiotics in an infusion set or in a syringe.

Compatibility with infusion solutions
Cefotaxime Dali Pharma may also be dissolved in sodium chloride, glucose, or Ringer's solutions.

The duration of treatment depends on the course of the disease.

Administration of a higher than recommended dose of Cefotaxime Dali Pharma
Beta-lactam antibiotics, including cefotaxime, may lead to so-called encephalopathies, which may be accompanied by central nervous system excitation, myoclonus, seizures, confusion, disturbances of consciousness, and movement. The risk is higher with high doses, overdose, impaired renal function, epilepsy, or meningitis.
If Cefotaxime Dali Pharma is injected too rapidly (in less than 1 minute) through a central venous catheter (CVC), severe cardiac arrhythmias may occur (see also section 2).
If a patient believes they have received an excessive dose of Cefotaxime Dali Pharma, they should contact their doctor or nurse immediately.

Missed dose of Cefotaxime Dali Pharma
If a patient suspects that a dose of Cefotaxime Dali Pharma has been missed, they should inform their doctor or nurse immediately. A double dose must not be administered to make up for the missed dose.

For any further questions regarding the use of this medicine, please consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Treatment with cefotaxime must be stopped immediately and a doctor should be informed if the patient
notices any of the following symptoms:
Not common (may occur in up to 1 in 100 people)

• Convulsions.

Frequency unknown (cannot be estimated from available data)

• Severe acute allergic reactions, up to life-threatening anaphylactic shock, as well as swelling (angioedema) and narrowing of the airways (bronchospasm). If you feel chest tightness,
  dizziness, discomfort or weakness, this may be a sign of such an allergic reaction.

• Red, non-elevated, target-shaped or circular skin lesions on the trunk, often with centrally located blisters, skin peeling, and ulcers in 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 fever, and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

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

• Severe, persistent diarrhoea or blood in the stool due to potentially life-threatening colitis.

• Red blood cells break down (haemolytic anaemia), urine becomes brownish-red.

• Acute kidney failure.

Immediately inform a doctor or nurse if any of the following serious adverse effects occur – medical assistance will likely be required:
Frequency unknown (frequency cannot be estimated from available data)

• Jaundice as a sign of possible liver inflammation.
• Severe reduction in certain white blood cells (agranulocytosis), which may manifest as sudden onset of infection and inflammatory symptoms in the mouth, nose, throat, genital organs, and anus.
• Sudden drop in all blood cell counts and bone marrow failure. In this situation, symptoms such as acute infection and inflammation (see above), bleeding, bruising (reduced platelet count), fatigue, pallor, or shortness of breath (reduced red blood cells) may occur.

Tell your doctor, especially if any of the listed adverse effects are severe or persist for longer than a few days:
Very common (may occur in more than 1 in 10 people)

• Pain at the injection site, induration after intramuscular administration.

Common (may occur in up to 1 in 10 people)

• Joint problems (e.g. swelling).

Not common (may occur in up to 1 in 100 people)

• Increase in eosinophilic blood cells (eosinophilia);
• Decrease in platelet count (thrombocytopenia) and certain white blood cells (leukopenia, granulocytopenia);
• Jarisch-Herxheimer reaction (explanation below);
• Diarrhoea;
• Loss of appetite;
• Increased levels of bilirubin (bile pigment in blood) and (or) liver enzymes in serum (AlAT, AspAT, Gamma-GT, alkaline phosphatase, LDH);
• Allergic reactions such as rash, itching, urticaria;
• Kidney function disorders, e.g. increased serum creatinine and urea levels;
• Fever;
• Inflammatory reactions at the injection site, up to phlebitis (vein inflammation and (or) thrombophlebitis).

Frequency unknown (cannot be estimated from available data)

• Recurrent infections caused by bacteria or fungi (e.g. in the mouth or vagina);
• Decrease in certain white blood cells (neutropenia);
• Rapid heartbeat, irregular heartbeat (after rapid intravenous administration via central venous access);
• Central nervous system stimulation, disturbances of consciousness, confusion, motor disturbances, muscle tremors (encephalopathy symptoms; particularly with high doses, overdose, and impaired kidney function);
• Headache;
• Dizziness;
• Nausea, vomiting, abdominal pain;
• Kidney inflammation (interstitial nephritis);
• Intolerance reactions such as sensation of warmth or nausea after rapid intravenous administration.

Jarisch-Herxheimer reaction: This may develop at the beginning of treatment for spirochetal infections (e.g. Lyme disease) and may be accompanied by fever, chills, headache, and joint problems. During several weeks of Lyme disease treatment, one or more of the following symptoms have been reported: rash, itching, fever, decreased white blood cell count, increased liver enzyme activity, breathing difficulties, joint problems. These symptoms partly correspond to the manifestations of the underlying disease in treated patients.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at the 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 effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Cefotaxime Dali Pharma
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "EXP".
The expiry date refers to the last day of the stated month.

Storage conditions
Before reconstitution: No special temperature requirements for storage.
Store vials in the outer packaging to protect from light.

Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 4 hours at 25°C. From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the user is responsible for storage conditions and duration prior to use, and such duration shall not exceed the times indicated above for chemical and physical stability during use.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Cefotaxime Dali Pharma contains

• The active substance is cefotaxime sodium. 1 vial of Cefotaxime Dali Pharma 2 g contains 2.096 g of cefotaxime sodium (equivalent to 2 g of cefotaxime).
• Other components: None.

What Cefotaxime Dali Pharma looks like and contents of the pack
White to slightly yellowish powder.
Cefotaxime Dali Pharma 2 g powder for solution for injection/infusion is packed in a colourless and transparent type III glass vial with a capacity of 15 mL, closed with a chlorobutyl rubber stopper (partially coated with FEP) and secured with a green flip-off aluminium cap.
Pack sizes: 10 tightly closed vials.
Marketing Authorisation Holder
Dali Pharma GmbH
Brehmstraße 56
40239 Düsseldorf
Germany
e-mail: [email protected]
Importer
SciencePharma Sp. z o.o.
Chełmska 30/34
00-725 Warsaw
Poland
This medicinal product is authorised for marketing in the Member States of the European Economic Area under the following names:
Germany Cefotaxim Dali Pharma 2 g, Pulver zur Herstellung einer Injektions-/Infusionslösung
Poland Cefotaxime Dali Pharma

Information intended exclusively for healthcare professionals:

PREPARATION OF MEDICINAL PRODUCT AND METHOD OF ADMINISTRATION
The solution should be used only if it is clear and free from particles.
Intravenous injection
Dissolve Cefotaxime Dali Pharma 2 g in 10 mL of water for injections. Shake the vial until the contents are completely dissolved. Inject the solution directly into the vein over 3 to 5 minutes.

During rapid intravenous injection via central venous catheter, potentially life-threatening cardiac arrhythmias have been observed.

Infusion
For short-term infusion, dissolve Cefotaxime Dali Pharma 2 g in 40 to 50 mL of water for injections or compatible infusion solution (listed below), and then administer intravenously over approximately 20 minutes.

In the case of continuous intravenous infusion, dissolve Cefotaxime Dali Pharma 2 g in 100 mL of isotonic sodium chloride solution or glucose solution, and then administer the resulting solution over 50–60 minutes as an intravenous infusion. Other compatible infusion solutions may also be used for the solution (listed below).

To prepare an infusion solution, the cefotaxime powder should first be dissolved in 10 mL of water for injections or one of the compatible solutions, then water for injections or a compatible infusion solution should be added to a final volume of 40–50 mL or 100 mL, and mixed thoroughly.
After administration, it is recommended to flush the intravenous line with 9 mg/mL (0.9%) sodium chloride solution for injection to ensure complete delivery of the dose.
Cefotaxime is compatible with several commonly used intravenous infusion solutions, e.g. sodium chloride solution, glucose solutions, and Ringer's solutions.

Pharmaceutical incompatibilities
Cefotaxime Dali Pharma must not be mixed with: sodium bicarbonate solutions, infusion solutions with pH higher than 7, or aminoglycosides.
Cefotaxime and aminoglycosides must not be mixed in the same syringe or infusion fluid.
If simultaneous administration is necessary, these drugs should be administered at different injection sites.
Cefotaxime Dali Pharma 2 g must not be administered intramuscularly.

SHELF LIFE AND SPECIAL PRECAUTIONS FOR STORAGE
Before opening: 2 years. This medicinal product does not require special storage temperature conditions. Store vials in the outer packaging to protect from light.

Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 4 hours at 25°C.
From a microbiological standpoint, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately after opening. If not used immediately, the responsibility for the storage duration and conditions prior to use lies with the user and should normally not exceed the times indicated above for chemical and physical stability during use.