Cefotaxime dali pharma

Package leaflet: Information for the user

Cefotaxime Dali Pharma, 1 g, powder for solution for injection or infusion
Cefotaximum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

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

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, provided 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 membranes surrounding the brain and spinal cord),
• blood poisoning (sepsis),
• 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 experienced a severe or serious allergic reaction to penicillins or other beta-lactam antibiotics. Cross-reactions may occur between penicillins and cephalosporins.
• if the patient has ever developed severe skin rash, skin peeling, blisters, or oral mucosal ulcers after receiving cefotaxime or other cephalosporins.

Cefotaxime Dali Pharma with lidocaine must never be used:

• intravenously
• in infants under 30 months of age
• in patients who have previously shown hypersensitivity to this product
• in patients with uncorrected heart block (without a 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
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 with cefotaxime use.
Discontinue cefotaxime and seek immediate medical advice if any symptoms associated with these severe skin reactions, described in section 4, occur.
Before starting or during treatment with Cefotaxime Dali Pharma, discuss with your doctor or pharmacist:

• if the patient has any 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 serious (and in rare instances, 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 treatment. Inform the doctor immediately if such symptoms occur.
• if severe, persistent diarrhea develops during or within several weeks after treatment. Inform the doctor immediately, as diarrhea in its most severe form (called pseudomembranous colitis) can be life-threatening and requires treatment. Do not take drugs that inhibit intestinal motility.
• if the patient knows their kidney function is impaired. Inform the doctor so that this can be considered when determining dosage. Kidney function monitoring is also necessary.
• 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. If such reactions occur, inform the doctor immediately.
• 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 appear (e.g. oral candidiasis with redness and white deposits). Any antibiotic use may lead to overgrowth of pathogens resistant to the drug used. Watch for signs of new infection and inform the doctor if necessary.
• If the patient is scheduled for laboratory diagnostic tests: the Coombs test or urine glucose testing. 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 agents, 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 rhythm disturbances may occur (see also section 3).

Cefotaxime Dali Pharma and other medicines
Inform your doctor or pharmacist about all medicines currently or 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 the 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 (diuretics such as 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
Concurrent 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 the doctor about probenecid use, especially in patients with impaired kidney function, so that dosage adjustments can be considered.

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 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 in the first trimester, Cefotaxime Dali Pharma should only be used after careful assessment of benefit versus risk by the treating physician.

Breastfeeding
Cefotaxime passes into human milk. If Cefotaxime Dali Pharma is used during breastfeeding, it may affect the infant's intestinal flora, causing diarrhea and fungal 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.
However, if any adverse effects such as dizziness, seizures, confusion, disturbances of consciousness or motor function, which may be related to encephalopathy, occur, the patient should not drive or operate machinery.

Cefotaxime Dali Pharma contains sodium
This medicine contains approximately 2.1 mmol (48 mg) of sodium (the main component of table salt) per vial.
This corresponds to 2.4% of the maximum recommended daily sodium intake in the diet of 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 given every 8 or 6 hours.

The following table may serve as a dosing guideline:

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

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

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

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.
Combination with other antibiotics effective against Pseudomonas aeruginosa may also be indicated in infections caused by Pseudomonas aeruginosa.
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 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 is divided into 2 or more equal doses administered at intervals of 12 to (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, considering the immature renal function, doses should not exceed 50 mg of cefotaxime per kilogram of body weight per day.

In patients with severe renal impairment (creatinine clearance less than 10 mL/min), after a normal initial dose (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 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 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 1 g is administered intravenously (into a vein), but may also be given intramuscularly.

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

Method of administration

Intravenous injection
For intravenous injection, 1 g of cefotaxime is dissolved in at least 4 mL of water for injections and then injected directly into the vein over 3 to 5 minutes.

Infusion
To prepare the infusion solution, the cefotaxime powder should first be dissolved in 5 mL of water for injections or one of the compatible solutions, then added to a volume of 40–50 mL of water for injections or compatible infusion solution and mixed.
For short-term infusion, 1 g of cefotaxime is dissolved in 40–50 mL of water for injections or another compatible infusion solution and administered over approximately 20 minutes by intravenous infusion.

Intramuscular injection
For intramuscular injection, 1 g of cefotaxime is dissolved in 4 mL of water for injections. The injection should then be administered deeply into the gluteal muscle. Pain associated with intramuscular injection can be avoided by dissolving 1 g of cefotaxime in 4 mL of 1% lidocaine solution. Intra-arterial injection (injection into a blood vessel) should be avoided, as lidocaine may cause restlessness, tachycardia, cardiac conduction disturbances, as well as vomiting and seizures. Cefotaxime Dali Pharma with lidocaine should not be administered to children under 30 months of age. The instructions for use of lidocaine-containing preparations should be taken into account.

It is recommended not to inject more than 4 mL of cefotaxime solution into one gluteal muscle at a time. If the daily dose exceeds 2 g of cefotaxime or if Cefotaxime Dali Pharma is administered more than twice daily, intravenous injection is recommended.

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 should not be mixed with other antibiotics or medicines 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 can also be dissolved in lidocaine, sodium lactate, glucose, or Ringer's solution.

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 encephalopathy, which may be accompanied by central nervous system excitation, myoclonus, seizures, confusion, disturbances of consciousness, and movement. The risk is higher with large doses, overdose, renal impairment, 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 too much Cefotaxime Dali Pharma, they should contact their doctor or nurse immediately.

Missed dose of Cefotaxime Dali Pharma
If a patient believes 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 reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Cefotaxime should be discontinued immediately and the doctor informed if the patient
notices any of the following symptoms:
Uncommon (may affect up to 1 in 100 people)

• Convulsions.

Frequency unknown (cannot be estimated from the available data)

• Severe acute hypersensitivity 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 a hypersensitivity reaction.
• Red, non-elevated, target-shaped or round spots 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 occur at the beginning of treatment (acute generalized exanthematous pustulosis).
• Severe, persistent diarrhoea or blood in the stool due to potentially life-threatening intestinal inflammation.
• Breakdown of red blood cells (hemolytic anaemia), resulting in brown-red urine.
• Acute kidney failure.

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

• Jaundice as a sign of possible liver inflammation.
• Serious reduction in certain white blood cells (agranulocytosis), which may present as sudden onset of severe 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 severe infections and inflammation (see above), bleeding, bruising (due to reduced platelet count), fatigue, pallor or shortness of breath (due to reduced red blood cells) may occur.

Tell your doctor, especially if any of the adverse reactions listed below
are severe or last longer than a few days:
Very common (may affect more than 1 in 10 people)

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

Common (may affect up to 1 in 10 people)

• Joint problems (e.g. swelling).

Uncommon (may affect 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;
• Impaired kidney function, e.g. increased serum creatinine and urea levels;
• Fever;
• Inflammatory reactions at the injection site up to phlebitis (inflammation of veins and (or) thrombophlebitis).

Frequency unknown (frequency cannot be estimated from the 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 (symptoms of encephalopathy; particularly with high doses, overdose, and impaired kidney function);
• Headache;
• Dizziness;
• Nausea, vomiting, abdominal pain;
• Kidney inflammation (interstitial nephritis);
• Intolerance reactions manifesting 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 symptoms of the underlying disease in treated patients.

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 of 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 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 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 of the medicine.
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 responsibility for storage conditions and duration prior to use lies with the user and should not exceed the times indicated above for chemical and physical stability during use.

Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. These 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. One vial of Cefotaxime Dali Pharma 1 g contains 1.048 g of cefotaxime sodium (equivalent to 1 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 1 g powder for solution for injection/infusion is packed in a colourless and transparent vial made of type III glass with a capacity of 15 mL, closed with a chlorobutyl rubber stopper of type I (locally coated with FEP) and sealed with a blue aluminium flip-off cap.
Pack size: 10 tightly sealed 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 Warszawa
Poland
This medicinal product is authorised for sale in the European Economic Area countries under the following names:
Germany Cefotaxim Dali Pharma 1 g, Pulver zur Herstellung einer Injektions-/Infusionslösung
Poland Cefotaxime Dali Pharma

Information intended exclusively for medical professionals:

PREPARATION OF THE 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 1 g in 4 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.

Potentially life-threatening cardiac arrhythmias have been observed during rapid injection through a central venous catheter.
Infusion
For short-term infusion, dissolve Cefotaxime Dali Pharma 1 g in 40 to 50 mL of water for injections or a compatible infusion solution (listed below), and then administer intravenously over approximately 20 minutes.

To prepare an infusion solution, the cefotaxime powder should first be dissolved in 5 mL of water for injections or one of the compatible solutions, and then water for injections or a compatible infusion solution should be added to a final volume of 40–50 mL and mixed thoroughly.
After administration, it is recommended to flush the intravenous line with 9 mg/mL (0.9%) sodium chloride solution for injections to ensure complete delivery of the dose.
Cefotaxime is compatible with several commonly used intravenous infusion solutions, e.g. lidocaine, sodium chloride solution, glucose, Ringer's solution.

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

Intramuscular injection
Dissolve Cefotaxime Dali Pharma 1 g in 4 mL of water for injections. Shake the vial until the contents are completely dissolved. Administer by deep intramuscular injection into the gluteal muscle.

Pain during intramuscular injection can be avoided by dissolving 1 g of cefotaxime in 4 mL of 1% lidocaine solution. Intravascular injection must be avoided, as lidocaine may cause restlessness, tachycardia, cardiac conduction disturbances, as well as vomiting and seizures following intravenous administration. Cefotaxime Dali Pharma with lidocaine should not be administered to children under 30 months of age. The instructions for use of the lidocaine-containing preparation should be taken into account.
Do not inject more than 4 mL on one side. If the daily dose exceeds 2 g of cefotaxime or if Cefotaxime Dali Pharma is administered more than twice daily, intravenous injection is recommended.
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 user is responsible for the storage duration and conditions prior to use, and these should generally not exceed the times indicated above for chemical and physical stability during use.