Cefotaxime - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Unwanted Effects Shelf Life and Storage Other Information

Active ingredients: Cefotaxime

Cefotaxime Hospira “500 mg / 2 ml powder and solvent for solution for injection
Cefotaxime Hospira “1000 mg / 4 ml powder and solvent for solution for injection
Cefotaxime Hospira “1000 mg / 4 ml powder and solvent for solution for injection for intramuscular use
Cefotaxime Hospira “2000 mg / 10 ml powder and solvent for solution for injection for intravenous use

Why is Cefotaxime used? What is it for?

Cefotaxime Hospira contains the active substance cefotaxime sodium which belongs to a group of medicines called antibiotics (beta-lactam antibiotics or 3rd generation cephalosporins) which are used to treat infections caused by bacteria.

Cefotaxime Hospira is indicated for the treatment of serious bacterial infections caused by certain bacteria (difficult Gram-negative germs) or by a set of different types of bacteria (mixed flora) in the presence of gram-negative bacteria resistant to the most common antibiotics. In these cases it is indicated, in particular, for debilitated people or people with reduced immune defenses (immunosuppressed). This medicine is also indicated for the prevention of infections caused by surgery.

Contraindications When Cefotaxime should not be used

Do not use Cefotaxime Hospira

  • if you are allergic to cefotaxime sodium, other similar antibiotics (cephalosporins) or any of the other ingredients of this medicine (listed in section 6);
  • if you are taking antibiotics belonging to the same group as Cefotaxime Hospira called penicillins, because allergic cross-reactions may occur (see section "Warnings and Precautions").

Cefotaxime Hospira "1000 mg / 4 ml powder and solvent for solution for injection for intramuscular use" contains a local anesthetic called lidocaine, therefore it should not be given in case of:

  • allergy to lidocaine or other similar anesthetics;
  • severe heart problems (heart block without a pacemaker and severe heart failure);
  • administration given into a vein (intravenous administration);
  • infants under the age of 30 months.

Contraindicated in pregnancy and lactation (see section "Pregnancy and lactation).

Precautions for use What you need to know before taking Cefotaxime

Talk to your doctor or nurse before you are given Cefotaxime Hospira.

As with other similar medicines (antibiotics), the use of this medicine, especially if prolonged, may favor the appearance of other infections caused by bacteria against which Cefotaxime Hospira is not effective (superinfections). to the doctor who will indicate a suitable therapy.

During the use of Cefotaxime Hospira the following may occur:

  • allergic reactions. Before starting therapy with this medicine, your doctor will carry out specific tests to make sure that you are not allergic to cefotaxime, cephalosporins, penicillins or other medicines. Use this medicine with caution and tell your doctor if you have had any allergies in the past, especially to penicillins (beta-lactam antibiotics). If you notice an allergic reaction, stop taking this medicine and tell your doctor immediately, or go to the nearest hospital: a doctor, depending on your condition, will decide on the appropriate therapy;
  • appearance of blisters on the skin (severe bullous eruptions such as Stevens-Johnson syndrome or toxic epidermal necrolysis). If you notice skin or mucosal reactions, blistering or blistering, stop the treatment and contact your doctor immediately;
  • bowel problems caused by a bacterium called Clostridium difficile. You may experience mild or severe diarrhea in the case of inflammation of the bowel (pseudomembranous colitis). If you experience severe or long-lasting diarrhea while being treated with Cefotaxime Hospira, your doctor may carry out specific tests (endoscopy or histological examination) to confirm whether it is a disease caused by this bacterium. If you experience mild colitis, stop the treatment to make the symptoms go away. If you experience moderate or severe colitis, contact your doctor who will advise you on the appropriate therapy. If you are taking medicines that act on the intestine (peristalsis inhibitors), you should not be given Cefotaxime Hospira as they can favor the onset of diseases associated with Clostridium difficile; if you have suffered, even in the past, from bowel diseases, colitis in particular, tell your doctor;
  • irritation at the injection site following administration into a vein. It can be avoided by giving the medicine very slowly (3-5) minutes;
  • blood disorders (leukopenia, neutropenia, eosinophilia, bone marrow failure, pancytopenia, agranulocytosis, thrombocytopenia, haemolytic anemia), especially if you use the medicine for prolonged periods. Therefore, if you have been prescribed treatment for 7-10 days or more, you should have a blood test. Stop treatment with Cefotaxime Hospira if you experience changes in your blood as some problems go away after stopping treatment;
  • damage to the nervous system (neurotoxicity) especially if you have been prescribed high doses of this medicine, other antibiotics of the same class or if you have kidney problems (kidney failure). Symptoms can be: loss of consciousness, abnormal movements and convulsions (encephalopathies). If you notice any of these symptoms, stop the treatment and contact your doctor immediately.

This medicine, when given quickly into a vein through a small tube (central venous catheter), can cause changes in the heart rhythm (arrhythmias), which can be life-threatening (See section "How to use Cefotaxime Hospira").

Use this medicine with caution and tell your doctor if you have severe kidney problems (severe kidney failure). In this case, your doctor may decide to halve the maintenance dose according to your condition. Get your kidney checked if you are taking medicines to treat severe infections (aminoglycoside antibiotics), probenecid (medicine to lower the level of uric acid in the blood), medicines that are harmful to the kidneys (medicines nephrotoxic), if you are elderly or if you have kidney problems.

Cefotaxime Hospira may not be effective (antibiotic resistance), especially against some families of bacteria (Enterobacteriaceae and Pseudomonas), in people with immune defenses (immunosuppressed) or following the simultaneous use of similar medicines (antibiotics).

Interactions What medications or foods may change the effect of Cefotaxime

Tell your doctor or nurse if you are using, have recently used or might use any other medicines.

Cefotaxime Hospira must not be mixed in the same syringe with other medicines and in particular with medicines to treat infections caused by bacteria (antibiotics).

This medicine should be given to you with caution if you are using any of the following medicines:

  • aminoglycoside antibiotics, medicines to treat infections caused by bacteria or diuretics, medicines to facilitate the elimination of fluids such as furosemide. Talk to your doctor because in this case you will need to check the function of the kidneys.
  • probenecid, a medicine used to reduce uric acid levels in the blood, as it can slow down the elimination of Cefotaxime Hospira in the urine.

Warnings It is important to know that:

Cefotaxime Hospira and laboratory tests

Tell your doctor that you are using this medicine before undergoing certain tests because Cefotaxime Hospira can interfere with some laboratory tests, such as: Coombs test, blood compatibility test, urine sugar tests (Benedict, Fehling methods , "Clinitest").

Pregnancy and breastfeeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor, pharmacist or nurse for advice before using this medicine.

If you are pregnant, use Cefotaxime Hospira only when absolutely necessary and under the direct supervision of your doctor.

If you are breast-feeding, talk to your doctor, who will evaluate the need to stop breastfeeding or treatment with this medicine. Babies who are breast-fed by mothers taking Cefotaxime Hospira may have diarrhea.

Driving and using machines

This medicine can cause dizziness, impaired ability to concentrate and react properly and if given in high doses to people with kidney problems it can cause unconsciousness, abnormal movements and convulsions. This can affect the ability to drive and use machines. If these effects occur, avoid driving and using machines.

Cefotaxime Hospira contains sodium

A 1000 mg dose of CEFOTAXIME HOSPIRA may contain up to 48.2 mg (2.1 mmol) of sodium. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet.

Dosage and method of use How to use Cefotaxime: Dosage

This medicine will be given to you by medical personnel always following exactly the instructions of your doctor or nurse. If you are unsure, consult your doctor or nurse.

Your doctor will determine the dose needed, the method of administration (intramuscular or intravenous) and the duration of treatment depending on the type of infection, your condition and your body weight. The duration of therapy varies according to the therapeutic response. It is however recommended to continue the treatment for at least 3 days after the fever has passed.

If Cefotaxime Hospira is being administered directly into a vein (intermittent intravenous administration), the solution should be injected over 3-5 minutes.

It is recommended to always use freshly prepared solutions, even if the medicine once dissolved in water can be stored in the refrigerator for up to 24 hours, and not to mix Cefotaxime Hospira with sodium bicarbonate solutions or medicines to treat infections caused by bacteria (aminoglycoside antibiotics).

The recommended dose for adults, for injections into muscle or into a vein, is 2 grams per day divided into two 1 gram doses every 12 hours. This dose can be increased to 3-4 grams and in very severe cases up to 12 grams by administration into a vein, reducing the interval between administrations to 8-6 hours.

Use in children under 12 years of age

The recommended dose is 50-100 mg / kg of body weight per day, divided into 2-4 injections.

If the child is in danger of life or in very severe cases, a dose of 200 mg / kg of body weight per day has been administered. Cefotaxime Hospira "1000 mg / 4 ml powder and solvent for solution for injection for intramuscular use" should not be given to children under 12 years of age as it contains lidocaine.

Use in premature babies

The recommended dose should not exceed 50 mg / kg body weight per day as kidney function is not yet fully developed.

Use in people with severe kidney problems

In case of severe renal insufficiency, lower dosages are indicated

If you forget to use Cefotaxime Hospira

This medicine will be given to you by a doctor or nurse, so it is unlikely that you will miss a dose. Do not use a double dose to make up for a forgotten dose. If you have any further questions on the use of this medicine, ask your doctor or nurse.

Overdose What to do if you have taken too much Cefotaxime

If you use more CEFOTAXIME HOSPIRA than you should

This medicine will be given to you by a doctor or nurse, so an overdose is unlikely to occur. Symptoms of an overdose may correspond to side effects (see section 4) and brain damage (encephalopathies) may occur. In this case, the administration of this medicinal product must be discontinued and your doctor will advise you of appropriate therapy. If you think you have been given too much of this medicine tell your doctor immediately or go to the nearest hospital.

Side Effects What are the side effects of Cefotaxime

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Very common (may affect more than 1 in 10 people)

  • pain at the site of injection for administration into muscle (intramuscular administration).

Uncommon (may affect up to 1 in 100 people)

  • decreased number of white blood cells (leukopenia), increased number of eosinophils (eosinophilia), decreased number of platelets (thrombocytopenia);
  • redness of the skin (rash), itching, hives, increased liver blood test values ​​(ALAT, ASAT, LDH, gamma-GT, alkaline phosphatase, bilirubin), Jarisch-Herxheimer reaction (manifesting as fever, chills, headache, muscle pain and joint discomfort, skin irritation, decrease in white blood cells, abnormal liver blood tests, trouble breathing);
  • convulsions (see section "Warnings and Precautions");
  • diarrhea (see Section "Warnings and Precautions";
  • decreased kidney function and increased creatinine, a substance that indicates kidney function, especially when this medicine has been prescribed to you together with other medicines to treat infections caused by bacteria (aminoglycoside antibiotics);
  • fever and inflammatory reactions at the injection site, including inflammation of a vein with or without blood clots (thrombophlebitis / phlebitis).

Not known (the frequency of which cannot be estimated from the available data)

  • infections caused by bacteria or fungi (superinfections, see section "Warnings and Precautions");
  • reduction in the number of certain types of white blood cells (bone marrow failure, pancytopenia, neutropenia, agranulocytosis, granulocytopenia) (see section "Warnings and Precautions"), decrease in red blood cells (haemolytic anemia);
  • allergic reactions, including severe ones (anaphylactic reactions, anaphylactic shock), swelling due to fluid accumulation around the mouth and eyes (angioedema), constriction of the bronchi with difficulty in breathing (bronchospasm);
  • headache (headache), dizziness;
  • loss of consciousness and abnormal movements (encephalopathy) due to brain damage (neurotoxicity) especially if you have been prescribed high doses of this medicine, other antibiotics of the same class or if you have kidney problems (kidney failure). See Section "Warnings and Precautions");
  • alterations in the heartbeat (arrhythmias) following a rapid bolus infusion through a tube inserted directly into the vein (central venous catheter);
  • nausea, vomiting, abdominal pain (abdominal pain), severe inflammation of the bowel (pseudomembranous colitis) (see section "Warnings and Precautions");
  • skin lesions, including severe skin lesions such as: erythema multiforme (diffuse redness), Stevens Johnson syndrome and toxic epidermal necrolysis (blisters, blisters and bleeding in the lips, eyes, mouth, nose and genitals), acute generalized exanthematous pustulosis (PEAG) (See Section "Warnings and Precautions");
  • liver problems (hepatitis) sometimes with yellowing of the skin and eyes (jaundice);
  • acute kidney failure, inflammation of the kidneys (interstitial nephritis), increased nitrogen levels in the blood (azotemia), severe kidney failure (acute kidney failure);
  • reactions affecting several organs (systemic reactions) to lidocaine (a local anesthetic) present in the solvent for administration only into muscle;
  • chest pain (chest tightness), pain in the joints (arthralgia);
  • loss of appetite (anorexia), inflammation of the tongue (glossitis), heartburn (heartburn);
  • inflammation of the vagina caused by a fungus (Candida vaginitis), agitation, confusion, decreased muscle strength (asthenia), night sweats.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.

Expiry and Retention

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the package. The expiry date refers to the last day of that month.

Keep away from light. The product does not contain preservatives. After use it should be thrown away even if used only partially.

Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

Deadline "> Other information

What Cefotaxime Hospira "500 mg / 2 ml powder and solvent for solution for injection" contains

  • The active substance is cefotaxime sodium: one bottle of powder contains 524 mg of cefotaxime sodium corresponding to 500 mg of cefotaxime.
  • The other component of the solvent vial is water for injections.

What Cefotaxime Hospira "1000 mg / 4 ml powder and solvent for solution for injection" contains

  • The active substance is cefotaxime sodium: one bottle of powder contains 1.048 g of cefotaxime sodium corresponding to 1 g of cefotaxime.
  • The other component of the solvent vial is water for injections.

What Cefotaxime Hospira "1000 mg / 4 ml powder and solvent for solution for injection for intramuscular use" contains

  • The active substance is cefotaxime sodium: one bottle of powder contains 1.048 g of cefotaxime sodium corresponding to 1 g of cefotaxime.
  • The other ingredients of the solvent ampoule are: water for injections and 40 mg of lidocaine hydrochloride (1% solution).

What Cefotaxime Hospira "2000 mg / 10 ml powder and solvent for solution for injection for intravenous use" contains

  • The active substance is cefotaxime sodium: one bottle of powder contains 2.096 g of cefotaxime sodium corresponding to 2 g of cefotaxime.
  • The other component of the solvent vial is water for injections.

What Cefotaxime Hospira looks like and contents of the pack

  • Cefotaxime Hospira "500 mg / 2 ml powder and solvent for solution for injection": pack containing 1 bottle of powder + 1 solvent ampoule of 2 ml.
  • Cefotaxime Hospira "1000 mg / 4 ml powder and solvent for solution for injection" and Cefotaxime Hospira "1000 mg / 4 ml powder and solvent for solution for injection for intramuscular use": pack containing 1 bottle of powder + 1 solvent ampoule of 4 ml.
  • Cefotaxime Hospira "2000 mg / 10 ml powder and solvent for solution for injection for intravenous use": pack containing 1 bottle of powder + 1 solvent ampoule of 10 ml.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Cefotaxime can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT - 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION - 03.0 PHARMACEUTICAL FORM - 04.0 CLINICAL PARTICULARS - 04.1 Therapeutic indications - 04.2 Posology and method of administration - 04.3 Contraindications - 04.4 Special warnings and appropriate precautions for use - 04.5 Interactions with other medicinal products and other forms of interaction - 04.6 Pregnancy and lactation - 04.7 Effects on the ability to drive and use machines - 04.8 Undesirable effects - 04.9 Overdose - 05.0 PHARMACOLOGICAL PROPERTIES - 05.1 "Pharmacodynamic properties - 05.2 Pharmacokinetic properties" - 05.3 Preclinical safety data - 06.0 PHARMACEUTICAL PARTICULARS - 06.1 Excipients - 06.2 Incompatibility "- 06.3 Shelf life" - 06.4 Special precautions for storage - 06.5 Nature of the primary packaging and contents of the package - 06.6 Instructions for use and handling - 07.0 AUTHORIZATION HOLDER ALL "PLACING ON THE MARKET - 08.0 MARKETING AUTHORIZATION NUMBER - 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION - 10.0 DATE OF REVISION OF THE TEXT - 11.0 FOR RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY - 12.0 INSTRUCTIONS FOR RADIOPHONES ON EXTEMPORARY PREPARATION AND QUALITY CONTROL -

01.0 NAME OF THE MEDICINAL PRODUCT -

CEFOTAXIME HOSPIRA POWDER AND SOLVENT FOR SOLUTION FOR INJECTION

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -

Cefotaxime Hospira "500 mg / 2ml powder and solvent for solution for injection" 1 bottle powder + 1 solvent vial 2ml

One bottle contains: Active ingredient: cefotaxime sodium 524 mg (equivalent to 500 mg of cefotaxime)

Cefotaxime Hospira "1000 mg / 4ml powder and solvent for solution for injection" 1 bottle powder + 1 solvent vial 4ml

One bottle contains: Active ingredient: 1.048 g cefotaxime sodium (equivalent to 1 g of cefotaxime)

Cefotaxime Hospira "1000 mg / 4ml powder and solvent for solution for injection for intramuscular use" 1 vial powder + 1 solvent vial 4ml

One bottle contains: Active ingredient: - cefotaxime sodium 1.048 g (equal to 1 g of cefotaxime)

One solvent ampoule contains: Active ingredient: 40 mg lidocaine.

Cefotaxime Hospira "2000 mg / 10 ml powder and solvent for solution for injection for intravenous use" 1 vial of powder + 1 vial of solvent 10 ml

One bottle contains: Active ingredient: 2.096 g cefotaxime sodium (equivalent to 2 g of cefotaxime)

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM -

Powder and solvent for solution for injection

Powder and solvent for solution for injection for intravenous use

04.0 CLINICAL INFORMATION -

04.1 Therapeutic indications -

Of elective and specific use in serious bacterial infections of ascertained or presumed origin from "difficult" Gram-negative germs or from mixed flora with the presence of Gram-negative bacteria resistant to the most common antibiotics.

In these infections the product is indicated, in particular, in defied and / or immunosuppressed patients.

It is also indicated in the prophylaxis of surgical infections.

04.2 Posology and method of administration -

The dose and route of administration should be chosen according to the type of infection, its severity, the degree of sensitivity of the pathogen, the condition and body weight of the patient.

The duration of treatment with cefotaxime varies according to the therapeutic response; however, therapy should be continued at least up to 3 days after the breakdown.

In the case of intermittent intravenous administration, the solution should be injected over 3-5 minutes. During post-marketing surveillance of the drug, cases of potentially life-threatening arrhythmia have been reported in a few patients who received rapid intravenous administration of cefotaxime through a central venous catheter.

Adults: the basic dosage is 2 g per day (1 g every 12 hours) to be administered intramuscularly or intravenously and if necessary it can be increased to 3-4 g and in very severe cases up to 12 g intravenously, appropriately reducing the interval between administrations at 8-6 hours.

As regards the intravenous administration of the lowest doses, direct injection is used, to be performed in 3-5 minutes (in case a venous infusion is already in progress, the tube can be pinched about 10 cm above the needle and inject the cefotaxime into the tube below the tweezers).

At higher doses, cefotaxime can be administered by short intravenous infusion (20 minutes) after dissolving 2 g in 40 ml of water for injections, isotonic saline or glucose solution, or by continuous intravenous infusion (50-60 minutes) afterwards. having dissolved 2 g in 100 ml of solvent, plasma expanders.

It is recommended not to mix cefotaxime with sodium bicarbonate solutions or with aminoglycosides.

When the intravenous route is used, it is still advisable to start therapy by administering cefotaxime directly into a vein.

Particularly sensitive patients may complain of pain after intramuscular injection; for the treatment of these subjects we recommend the use, up to 2 times a day, of a solvent containing 1% lidocaine hydrochloride solution (except for subjects hypersensitive to lidocaine). This solution should only be used intramuscularly and therefore you must absolutely avoid intravascular administration.

Children: under 12 years, 50-100 mg / kg can be administered to be divided into 2-4 daily administrations.

In some extremely serious and life-threatening cases, doses of 200 mg / kg / day have been reached without signs of intolerance.

In premature babies, the posology should not exceed 50 mg / kg / day since renal function is not yet fully developed.

The solvent containing lidocaine hydrochloride should not be used in children under 12 years of age, in whom intramuscular administration should be carried out with the solution in water alone for injections.

04.3 Contraindications -

Hypersensitivity to cephalosporins.

Cefotaxime Hospira is contraindicated in patients with a history of hypersensitivity to cefotaxime and / or its excipients.

There may be cross-allergic reactions between penicillins and cephalosporins (see section 4.4).

- Cefotaxime Hospira reconstituted with solvent containing lidocaine must never be used:

• intravenously;

• in infants under the age of 30 months;

• in patients with a history of hypersensitivity to lidocaine and other local anesthetics of the amide type;

• in patients with rhythm disturbances;

• in patients with severe heart failure.

- Generally contraindicated in pregnancy and lactation (See section 4.6 Pregnancy and lactation)

04.4 Special warnings and appropriate precautions for use -

As with other antibiotics, the use of cefotaxime, especially if prolonged, may result in increased growth of non-sensitive microorganisms. Careful examination of the patient's condition is essential. If superinfections occur during therapy, appropriate measures should be taken.

Third generation cephalosporins, like other beta-lactamines, can induce microbial resistance and this occurrence is greater towards opportunistic organisms, especially Enterobacteriaceae and Pseudomonas, in immunosuppressed subjects and probably by associating more beta-lactamines with each other.

Anaphylactic reactions

Before initiating therapy with cefotaxime, a careful medical history is required in order to detect previous hypersensitivity reactions to cefotaxime, cephalosporins, penicillin or other drugs.

Clinical and laboratory tests have shown partial cross-allergicity between penicillin and cephalosporins.

The use of cefotaxime is strongly contraindicated in subjects with a history of immediate type hypersensitivity to cephalosporins.

Some patients receiving cefotaxime have experienced serious reactions including hypersensitivity reactions with fatal outcome (see sections 4.3 and 4.8).

Cefotaxime should therefore be administered with caution to those patients who have experienced type 1 hypersensitivity reactions to penicillin.

Patients with allergies, especially to drugs, should be given antibiotics, including cefotaxime, with caution.

In the event of an allergic reaction, therapy must be interrupted and appropriate treatment instituted (vasopressor amines, antihistamines, corticosteroids) or, in the presence of anaphylaxis, immediate treatment with adrenaline or other appropriate emergency measures.

Severe bullous eruptions

Cases of severe bullous eruptions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with cefotaxime (see section 4.8). Patients should be advised that if skin and / or mucosal reactions occur they should contact their physician immediately before continuing treatment.

Pathologies associated with Clostridium difficile.

Diarrhea, particularly severe and / or persistent, occurring during treatment or the first few weeks after treatment, may be symptomatic of a disease associated with the Clostridium difficile (CDAD). CDAD can range in intensity from mild to life-threatening; the most severe form is pseudomembranous colitis.

It is important to consider this diagnosis in patients who present with diarrhea during therapy with cefotaxime.

The diagnosis of this rare but possible fatal condition can be confirmed with endoscopy and / or a histological examination.

If a diagnosis of pseudomembranous colitis is suspected, treatment with cefotaxime should be discontinued immediately and appropriate therapy with a specific antibiotic initiated immediately. Clostridium difficile it can be favored by fecal stasis. Drugs that inhibit peristalsis should not be given.

Treatment with broad-spectrum antibiotics alters the normal flora of the colon and this can allow the growth of clostridia.

Some studies have shown that a toxin produced by Clostridium difficile it is the main cause of colitis associated with antibiotic therapy.

Cases of pseudomembranous colitis have been described in conjunction with the use of cephalosporins (and other broad spectrum antibiotics); it is important to consider this diagnosis in patients who present with diarrhea during therapy.

Mild cases of colitis may regress upon discontinuation of treatment. Electrolyte and protein solutions are recommended when moderate to severe colitis occurs. If colitis does not regress upon discontinuation of treatment or if it is severe, oral vancomycin must be administered, which is the antibiotic of choice in case of pseudomembranous colitis caused by Clostridium difficile.

Cefotaxime should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Hematological reactions

During treatment with cefotaxime, especially when administered for long periods, leukopenia, neutropenia and, more rarely, agranulocytosis may develop. For treatment cycles longer than 7-10 days, the white blood cell count should be monitored and in the event of neutropenia the treatment should be discontinued.

A few cases of eosinophilia and thrombocytopenia, rapidly reversible after discontinuation of treatment, have been reported. Cases of haemolytic anemia have also been reported (see section 4.8).

Patients with renal insufficiency

Dosage should be adjusted based on creatinine clearance. In patients with creatinine clearance pharmacokinetics of cefotaxime, dose reduction is only necessary in cases of marked renal insufficiency.

The concomitant use of aminoglycosides or other nephrotoxic drugs (see section 4.5) should be done with caution. Renal function should be monitored in these patients, in the elderly and in pre-existing renal insufficiency.

Neurotoxicity

High doses of beta-lactam antibiotics, including cefotaxime, especially in patients with renal insufficiency, may lead to encephalopathies (e.g. loss of consciousness, abnormal movements and convulsions) (see section 4.8).

Patients should be advised to contact their physician immediately before continuing treatment if such reactions occur.

Precautions for administration

During post-marketing surveillance of the drug, life-threatening arrhythmias have been reported in very few patients who received rapid intravenous administration of cefotaxime through a central venous catheter. The recommended time for injection or infusion should be followed (see section 4.2).

See section 4.3 for contraindications related to formulations containing lidocaine.

Tissue irritation at the intravenous injection site is rare; it can be avoided by injecting the drug very slowly (3-5 minutes).

Effects on laboratory tests

As with other cephalosporins, false positive Coombs' tests have been reported in some patients being treated with cefotaxime. This phenomenon can interfere with blood compatibility tests.

Administration of cephalosporins can interfere with some laboratory tests causing false positivity of glycosuria with methods conducted with non-specific reducing agents (such as Benedict, Fehling, "Clinitest" methods), but this phenomenon does not occur when enzymatic methods are used (such as the specific glucose oxidase method).

Sodium intake

There amount of sodium contained in cefotaxime sodium (48.2 mg / g) must be taken into account.

04.5 Interactions with other medicinal products and other forms of interaction -

Cefotaxime must not be mixed in the same syringe with other antibiotics and other drugs.

In progress of infection with Pseudomonas aeruginosa it may be indicated to associate with cefotaxime another antibiotic which is also active against this particular pathogen.

Uricosurics:

Probenecid interferes with the renal tubular passage of cefotaxime, thereby increasing exposure to cefotaxime by approximately 2-fold and reducing renal clearance by approximately half at therapeutic doses. Due to the high therapeutic index of cefotaxime, no adjustment is necessary. of the dose in patients with normal renal function. Dosage adjustment may be necessary in patients with renal insufficiency (see sections 4.4 and 4.2).

The volume of distribution of the drug does not appear to be affected by the concomitant administration of oral probenecid.

Aminoglycoside antibiotics and diuretics:

Like other cephalosporins, cefotaxime can potentiate the nephrotoxic effects of nephrotoxic drugs such as aminoglycosides or potent diuretics (e.g. furosemide).

The "simultaneous use of aminoglycosides, an association that" in vitro "gives rise to a synergistic or at least additive effect, can be indicated in particularly serious infections: the two antibiotics must in any case be administered in separate syringes; in these cases, constant monitoring of functionality is recommended. renal.

The administration of high doses of cefotaxime, concomitantly with highly effective saluretics (furosemide), has not so far been shown to affect renal function. As a precaution, however, it should be noted that renal function may be compromised by the simultaneous administration of high doses of effective cephalosporins and saluretics.

Renal function should be monitored in these patients (see section 4.4).

04.6 Pregnancy and breastfeeding -

Pregnancy:

Cefotaxime crosses the placental barrier. Studies conducted in various animal species have shown no direct or indirect teratogenic or embryotoxic effects. However, the safety of cefotaxime has not been established in human pregnancy and therefore the drug should not be used during pregnancy unless the anticipated benefit outweighs the potential risks.

Feeding time:

Cefotaxime passes into breast milk, therefore it is advisable to stop breastfeeding in case of administration of the drug.

Effects on the physiological intestinal flora of the breastfed infant leading to diarrhea, colonization by similar yeast fungi and sensitization of the infant cannot be excluded.

However, a decision to continue or not therapy must be made taking into account the benefit to the infant of breastfeeding and to the mother of the therapy.

04.7 Effects on ability to drive and use machines -

There is no evidence that cefotaxime directly affects the ability to drive and use machines.

High doses of cefotaxime, especially in patients with renal insufficiency, may cause encephalopathies (e.g. loss of consciousness, abnormal movements and convulsions) (see section 4.8). Patients should be advised not to drive or use machines if any of these symptoms occur.

04.8 Undesirable effects -

System and organ classification Very common (≥1 / 10) Common (≥1 / 100 to Uncommon (≥1 / 1000 to Rare (≥1 / 10,000 to Very rare ( Not known (frequency cannot be estimated from the available data) Infections and infestations Superinfection, (see section 4.4), candida vaginitis Disorders of the blood and lymphatic system Leukopenia, eosinophilia, thrombocytopenia Neutropenia, agranulocytosis (see section 4.4), haemolytic anemia, granulocytopenia Disorders of the immune system Jarisch-Herxheimer reaction Anaphylactic reactions, angioedema, bronchospasm, anaphylactic shock Nervous system and psychiatric disorders Convulsions (see section 4.4) Headache, dizziness, encephalopathy (loss of consciousness, abnormal movements) (see section 4.4), agitation and confusion, headache and dizziness Cardiac pathologies Arrhythmia following a rapid bolus infusion through a central venous catheter Gastrointestinal disorders Diarrhea Glossitis, heartburn, nausea, vomiting, abdominal pain, pseudomembranous colitis (see section 4.4) Hepatobiliary disorders Increased levels of liver enzymes (ALAT, ASAT, LDH, gamma-GT, alkaline phosphatase) and / or bilirubin ** Hepatitis * (sometimes with jaundice) Skin and subcutaneous tissue disorders Rash, itching, hives Night sweats, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (see section 4.4) Renal and urinary disorders Decreased kidney function / increased creatinine (especially when prescribed with aminoglycosides) Interstitial nephritis, increased azotemia General disorders and administration site conditions Pain at the injection site (IM administration) Fever, inflammatory reactions at the injection site, including phlebitis / thrombophlebitis Systemic reactions to lidocaine (IM administration, as the solvent contains lidocaine), chest tightness, asthenia Metabolism and nutrition disorders Anorexia Musculoskeletal and connective tissue disorders Arthralgia

* Post-marketing experience

** These elevated values ​​may rarely exceed twice the upper limit of the normal range and cause liver damage, usually cholestatic and very often asymptomatic.

Other gastrointestinal diseases: anorexia, glossitis and gastric heartburn. The occurrence of severe and prolonged diarrhea has been related to the use of different classes of antibiotics. In this case, the possibility of enterocolitis must be considered, which can sometimes be accompanied by the presence of blood in the stool. A particular form of enterocolitis. that occurs with the use of antibiotics is pseudomembranous colitis (in most cases due to Clostridium difficile). In the event that the colonoscopic investigation confirms the diagnosis, the antibiotic in use must be discontinued immediately and treatment with oral vancomycin initiated. Peristalsis inhibitor drugs are contraindicated.

Other reactions reported were injection site induration and brittleness, Candida vaginitis, agitation, confusion, asthenia, night sweats.

Jarisch-Herxheimer reaction

A Jarisch-Herxheimer reaction may develop during the first few days of treatment for borreliosis.

The appearance of one or more of the following symptoms has been reported after a few weeks of treatment for borreliosis: skin rash, itching, fever, leukopenia, increased liver enzyme levels, difficulty in breathing, feeling of joint discomfort.

Hepatobiliary disorders

Increased levels of liver enzymes (ALAT, ASAT, LDH, gamma-GT and / or alkaline phosphatase) and / or bilirubin have been observed. These laboratory abnormalities can rarely exceed even twice the upper limit of the range. normality, compatible with a pattern of liver damage, usually cholestatic and very often asymptomatic.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address http://www.agenziafarmaco.gov.it/it/responsabili

04.9 Overdose -

Symptoms of overdose may largely correspond to the undesirable effect profile.

There is a risk of reversible encephalopathy when high doses of β-lactam antibiotics, including cefotaxime, are administered. In the event of an overdose, cefotaxime should be discontinued and supportive treatment initiated, including measures to accelerate elimination, and symptomatic treatment of undesirable effects (eg convulsions). There is no specific antidote. Serum levels. of cefotaxime can be reduced by hemodialysis or peritoneal dialysis.

05.0 PHARMACOLOGICAL PROPERTIES -

05.1 "Pharmacodynamic properties -

Pharmacotherapeutic group: Antiinfectives, cephalosporins, ATC code: J01DD01

Cefotaxime is a broad spectrum antibiotic, particularly active even in the presence of bacterial β-lactamases. Cefotaxime is active "in vitro" on both Gram-negative and Gram-positive bacteria, both aerobic and anaerobic.

05.2 "Pharmacokinetic properties -

Cefotaxime is not appreciably absorbed from the gastrointestinal tract, so it must be administered parenterally.

After i.m. administration of cefotaxime the blood peaks are reached in about 30 minutes and correspond to the following values: 24 mcg / ml after 1 g, 12 mcg / ml after 500 mg, 5 mcg / ml after 250 mg; the mean plasma half-life is 70-80 minutes.

After direct intravenous administration the blood peaks are reached in 5 "-10" and correspond to the following values: 214 mcg / mL after 2 g; 110 mcg / mL after 1 g; 40 mcg / mL after 500 mg, with mean plasma half-life of 40 ".

After i.m. administration and e.v. at the usual dose, cefotaxime is distributed in tissues and body fluids; aqueous humor, bronchial secretion, saliva, middle ear, bone tissue, bile, ascitic, pleural, prostatic and cerebrospinal fluid.

Cefotaxime is partially metabolised in the liver to desacetylcefotaxime which has antibacterial activity.

Cefotaxime and its metabolites are mainly excreted in the urine. In adults with normal renal function, approximately 40-60% of the single IM dose. or i.v. is excreted unchanged in the urine and approximately 24% is excreted as desacetylcefotaxime over 24 hours.

05.3 Preclinical safety data -

The LD50 of cefotaxime administered intravenously is between 9,000 and 10,000 mg / kg body weight in mice and rats and is greater than 1,500 mg / kg in dogs; via i.p. and s.c.is, in the mouse, respectively of 12,060 and 18,700 mg / kg, while by the i.m. in rats it is greater than 7,000 mg / kg.

The administration for 6 months of cefotaxime doses up to 250 mg / kg s.c. to rats and i.m. in dogs did not induce significant changes in the parameters examined.

Studies carried out on rats and rabbits have shown that cefotaxime is devoid of teratogenic effects; neither fertility nor peri- and postnatal development were compromised.

06.0 PHARMACEUTICAL INFORMATION -

06.1 Excipients -

Solvent ampoule for all preparations contains: water for injections.

06.2 Incompatibility "-

It is recommended not to mix Cefotaxime Hospira with sodium bicarbonate solutions, antibiotics and other drugs.

06.3 Period of validity "-

In intact packaging, properly stored: 36 months

The reconstituted product (solubilization of the contents of the bottle with the contents of the corresponding solvent vial) can be stored in the refrigerator at +2 / + 8 ° C for 24 hours (protected from light).

06.4 Special precautions for storage -

Keep away from light.

The solutions prepared including those diluted with aseptic technique with perfusion solutions remain chemically stable for 24 hours at room temperature, but in compliance with good pharmaceutical practice it is recommended to use the solutions, where possible, within 3 hours of their constitution.

ATTENTION: The product does not contain preservatives. After use it should be thrown away even if used only partially.

06.5 Nature of the immediate packaging and contents of the package -

Type III colorless glass bottles, bromobutyl rubber closure with flip cap; colorless type I glass vials

Cefotaxime Hospira "500 mg / 2ml powder and solvent for solution for injection" 1 bottle powder + 1 solvent vial 2ml

Cefotaxime Hospira "1000 mg / 4ml powder and solvent for solution for injection" 1 bottle powder + 1 solvent vial 4ml

Cefotaxime Hospira "1000 mg / 4ml powder and solvent for solution for injection for intramuscular use" 1 vial powder + 1 solvent vial 4ml

Cefotaxime Hospira "2000 mg / 10 ml powder and solvent for solution for injection for intravenous use" 1 vial of powder + 1 vial of solvent 10 ml

06.6 Instructions for use and handling -

Solvent vial opening: Withdraw the contents of the solvent vial by syringe and pour it into the powder vial.

When completely dissolved, withdraw the contents of the vial and proceed with the injection.

Attention: the solution for intramuscular use should never be used for intravenous administration.

The dissolved product, from the beginning, has a yellow hue, this does not affect the efficacy and tolerability of the drug.

07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -

Hospira Italia S.r.l.

Via Orazio, 20/22

80122 Naples

08.0 MARKETING AUTHORIZATION NUMBER -

AIC 034992026 Cefotaxime Hospira "500 mg / 2ml powder and solvent for solution for injection" 1 powder bottle + 1 2ml solvent ampoule

AIC 034992038 Cefotaxime Hospira "1000 mg / 4ml powder and solvent for solution for injection" 1 bottle powder + 1 solvent vial 4ml

AIC 034992040 Cefotaxime Hospira "1000 mg / 4ml powder and solvent for solution for injection for intramuscular use" 1 bottle powder + 1 solvent vial 4ml

AIC 034992053 Cefotaxime Hospira "2000 mg / 10 ml powder and solvent for solution for injection for intravenous use" 1 vial of powder + 1 vial of solvent 10 ml

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -

December 2001

10.0 DATE OF REVISION OF THE TEXT -

11/2014

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY -

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL -

none:  toxicity-and-toxicology legumes baby-health