Active ingredients: Cefepime
Maxipime 2000 mg / 10 ml powder and solvent for solution for injection
Maxipime package inserts are available for pack sizes:- Maxipime 2000 mg / 10 ml powder and solvent for solution for injection
- Maxipime 500 mg / 1.5 ml powder and solvent for solution for injection, Maxipime 1000 mg / 3 ml powder and solvent for solution for injection
Indications Why is Maxipime used? What is it for?
Maxipime contains cefepime and belongs to the category of beta-lactam antibiotics, drugs capable of causing the death of bacteria or preventing their growth.
Maxipime can be used alone, as a drug of first choice, after obtaining the results of the test that assesses whether a bacterium is sensitive to the action of this antibiotic (sensitivity test) or, if necessary, it can be used safely in combination. with other antibiotics.
Maxipime is indicated
- in adults:
- for the treatment of moderate and severe infections caused by bacteria that respond to the action of this antibiotic, including:
- respiratory tract infections
- complicated (i.e. associated with serious diseases) and uncomplicated infections of the lower urinary tract (bladder and urethra) and upper (kidney and ureters)
- skin and soft tissue infections
- infections that occur inside the abdomen, including inflammation of the peritoneum (membrane that surrounds the internal walls of the abdomen and the organs it contains) and infections of the biliary tract (the transport system of the bile produced by the liver)
- bacteremia (presence of bacteria in the blood) which is due to, or is suspected to be due to, any of the above infections, including episodes of fever in patients with poor immune defenses
- empirical treatment of fever episodes in neutropenic patients, used as the sole drug. Patients with neutropenia have a low number of neutrophils, a type of white blood cell (febrile neutropenia) in their blood. In neutropenic patients who have a high risk of contracting serious infections, therapy with Maxipime alone may not be appropriate.
- infections caused by one or more groups of bacteria, which respond to the action of this antibiotic
- in abdominal surgical prophylaxis, ie before the patient undergoes abdominal surgery
- for the treatment of moderate and severe infections caused by bacteria that respond to the action of this antibiotic, including:
- in infants over 1 month of age:
- for the treatment of cerebrospinal meningitis (inflammatory disease of the membranes lining the brain and cerebrospinal fluid) caused by bacteria that respond to the action of this antibiotic.
Contraindications When Maxipime should not be used
You will not be given Maxipime
- If you are allergic to cefepime or any of the other ingredients of this medicine (listed in section 6).
- If you are allergic to cephalosporins or other beta-lactam antibiotics (same class of antibiotics to which Maxipime belongs) such as penicillins, monobactams and carbapenems.
Precautions for use What you need to know before taking Maxipime
Talk to your doctor or pharmacist before you are given Maxipime. Tell your doctor:
- if you have kidney problems or other conditions that affect how it works. In this case, especially if you are elderly, your doctor will need to change the recommended dose, reduce the maintenance dose and check your kidney function. The administration of repeated doses should be determined based on the functioning of the kidneys, the severity of the infection and the sensitivity of the bacterium to the antibiotic (see section 3 "How Maxipime is given to you");
- if you suffer from asthma;
- if you are predisposed to having allergic reactions (allergic diathesis);
- if you have ever had an allergic reaction to other beta-lactam antibiotics or other medicines, as your doctor will give you Maxipime with caution.
This active ingredient is not suitable for the treatment of some types of infections unless the bacterium is, with appropriate tests, sensitive to the action of this antibiotic.
Possible consequences of using Maxipime
Like other antibiotics, Maxipime may cause uncontrolled growth of bacteria that are not sensitive to this antibiotic. Should you develop a new infection in addition to the one already in progress, your doctor will take appropriate measures.
Pay special attention
- Maxipime can alter the results of a blood test used to detect the presence of antibodies on red blood cells (Coombs test). If you have to take this test, tell your doctor that you are taking this drug.
- Maxipime can also alter the results of tests to check for sugar in the urine (glycosuria). If you are diabetic and regularly undergo such tests, please tell your doctor: other types of tests may be used to monitor your diabetes while being treated with this medicine.
Children and adolescents
In the case of children and adolescents, the physician should carefully evaluate the dose to be administered based on the age, weight, severity and type of infection and the functioning of the patient's kidneys.
Interactions Which drugs or foods may change the effect of Maxipime
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Talk to your doctor if you are taking:
- antibiotics such as bacteriostatic antibiotics or aminoglycoside antibiotics
- potent diuretics (medicines that increase urine production) as they can potentially cause kidney problems.
In this case, your doctor will advise you to carefully check the functioning of your kidneys.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before being given this medicine.
The safety of Maxipime during pregnancy has not been established, therefore it is recommended to use the drug only in cases of real need and under close medical supervision.
If you are breast-feeding, your doctor will give you Maxipime with caution, as small amounts of the drug pass through your breast milk.
Driving and using machines
Maxipime may affect the ability to drive and use machines, as some side effects such as altered consciousness, dizziness, confusion or hallucinations may occur.
Dosage and method of use How to use Maxipime: Dosage
The dose will be determined by your doctor based on the type of bacterium, the severity of your infection, the functioning of your kidneys and your general condition.
Maxipime will be given to you into a vein in your body by a doctor or healthcare professional.
Use in children and adolescents
Your doctor will work out the recommended dose based on your child's age, weight, severity and type of infection and how your child's kidneys are functioning.
Duration of treatment
Your doctor will work out the duration of treatment based on the age, weight, severity and type of infection and the functioning of your / your baby's kidneys.
Overdose What to do if you have taken too much Maxipime
It is unlikely that you will be given an overdose of Maxipime.
If you are inadvertently given an overdose of Maxipime, the symptoms of overdose may include:
- encephalopathy (disease characterized by a widespread lesion of the brain tissue)
- myoclonus (rapid involuntary muscle jerk)
- convulsions (violent and involuntary contractions of some muscles).
Side Effects What are the side effects of Maxipime
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Use of Maxipime generally causes mild and transient side effects which rarely require discontinuation of treatment.
If during the administration of Maxipime you experience any of the following serious side effects, which can lead to death, contact your doctor immediately, who will STOP the treatment and will give you an appropriate and specific treatment:
- severe allergic reactions, including anaphylactic shock;
- diarrhea associated with Clostridium difficile, a bacterium normally found in the digestive system and which, with prolonged use of antibiotics, can cause abdominal cramps or other diseases. This side effect can range in severity: from mild diarrhea to colitis (inflammation of the colon), fatal. You may also experience this undesirable effect in the two months following the end of Maxipime-based therapy;
- reversible encephalopathy (disease characterized by a diffuse lesion of the brain tissue) which can cause disturbances in the state of consciousness such as confusion, hallucinations, stupor (dizziness that almost removes the ability to speak and act) and coma;
- convulsions (violent and involuntary contractions of some muscles) including non-convulsive status epilepticus (disorder of the brain, without motor manifestations, caused by the excessive activity of certain nerve cells in the brain);
- myoclonus (rapid involuntary muscle jerk);
- kidney failure (reduced ability of the kidneys to perform their function). The assessment of undesirable effects is based on the following frequency data.
Very common (may affect more than 1 in 10 people):
- positive direct Coombs test (test that evaluates the presence of antibodies capable of attacking and destroying red blood cells)
Common (may affect up to 1 in 10 people):
- reduction in the amount of hemoglobin in the blood (anemia)
- high concentration of eosinophils in the blood, a type of white blood cell (eosinophilia)
- inflammation of a vein (phlebitis) where the infusion was given
- diarrhea
- appearance of red patches on the skin (rash)
- reaction, pain and inflammation where the infusion / injection was given
- increased blood concentration of alkaline phosphatase (a protein found mainly in the liver, biliary tract and bone) which may indicate skeletal or liver disease
- increase in alanine aminotransferase (ALT, a protein found especially in the liver) which may indicate liver problems
- increased aspartate aminotransferase (AST, a protein found especially in muscles, liver and heart) which can mainly indicate liver and heart problems
- increased concentration of bilirubin (a substance produced by aged or damaged red blood cells) in the blood, indicating a liver problem
- increase in the time it takes for the blood to clot (prolonged prothrombin time or prolonged activated partial thromboplastin time)
Uncommon (may affect up to 1 in 100 people):
- infection of the mouth caused by fungi of the genus Candida (oral candidiasis)
- infection of the vagina
- reduction in the number of platelets in the blood (thrombocytopenia)
- reduction in the number of white blood cells in the blood (leukopenia)
- reduction in the number of neutrophils in the blood, type of white blood cells (neutropenia)
- headache
- inflammation of the colon associated with the use of antibiotics (pseudo-membranous colitis)
- inflammation of the colon (colitis)
- nausea
- He retched
- skin irritation (erythema)
- appearance of red (swelling of the skin) or white bumps of various sizes (hives)
- itch
- fever (raised body temperature)
- inflammation where the infusion was given
- increase in blood levels of urea, which indicates reduced kidney function
- increased blood levels of creatinine, which indicates kidney damage
Rare (may affect up to 1 in 1000 people):
- infection caused by the fungus Candida albicans (candidiasis)
- severe rapid allergic reaction which can cause death (anaphylactic reaction)
- swelling of the face, eyes, lips, tongue and throat with possible difficulty in breathing and swallowing (angioedema)
- change in feeling in the limbs or other parts of the body (paraesthesia)
- taste disturbance (dysgeusia)
- dizziness
- increase in the diameter of blood vessels (vasodilation)
- shortness of breath (dyspnoea)
- pain in the abdomen
- constipation (constipation)
- itching in the genitals
- chills
Frequency not known (frequency cannot be estimated from the available data):
- reduction in the amount of hemoglobin in the blood caused by insufficient production of red blood cells in the bone marrow (aplastic anemia)
- reduction in the amount of hemoglobin in the blood caused by the formation of antibodies that destroy red blood cells (haemolytic anemia)
- almost total destruction and detachment of the skin and mucous membranes (toxic epidermal necrolysis)
- destruction and detachment of the skin and mucous membranes following an allergic reaction (Stevens Johnson syndrome)
- appearance of bright red rosette lesions (erythema multiforme or polymorphic)
- blood loss from vessels (haemorrhage)
- kidney disease caused by chemicals, physical factors, or drugs (toxic nephropathy)
- false positive result in the measurement of glucose in urine (glucosuria test) by methods using reducing agents
- severe decrease in the number of granulocytes (type of white blood cells) in the blood (agranulocytosis)
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor. 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.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Do not store above 30 ° C. Keep away from light.
Do not store the reconstituted solution above 25 ° C for 24 hours or, alternatively, store at 2 to 8 ° C for 7 days.
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 carton after EXP.
The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Other information
What Maxipime contains
Maxipime 2000 mg / 10 ml powder and solvent for solution for injection Vial:
- The active ingredient is cefepime dihydrochloride monohydrate equivalent to 2000 mg of cefepime
- The other component is: L-arginine.
Solvent vial:
Each solvent vial contains water for injections
Description of what Maxipime looks like and contents of the pack
Powder and solvent for solution for injection for intravenous use.
Maxipime 2000 mg / 10 ml powder and solvent for solution for injection is available in a carton containing:
- 1 vial with a purple plastic cap engraved with "Read Insert" (= "Read the Package Leaflet") and 1 solvent vial with 10 ml of water for injections.
The following information is intended for medical or healthcare professionals only
HOW TO USE MAXIPIME
Maxipime can be administered intravenously and intramuscularly.
The dosage and route of administration vary according to the susceptibility of the organism involved, the severity of the infection, the renal function and the general condition of the patient.
Adults and children over 12 years of age (> 40 kg)
A guide to the dosage of cefepime for adults and children over 12 years of age (> 40 kg) with normal renal function is provided in Table 1.
The intravenous route of administration is preferable for those patients with severe infections, especially those that endanger the patient's life, especially if septic shock is present.
Table 1
Adults and children over 12 years of age (> 40 kg) with normal renal function *
* The duration of therapy normally varies between 7 and 10 days.
More severe infections may require longer treatment; Empirical treatment of febrile neutropenia (immunocompromised patient) should last 7 days or until the neutropenia resolves.
Surgical prophylaxis (adults): the dosages recommended for the prevention of bacterial infections during and after surgery are as follows:
- A single dose of 2 g i.v. of Maxipime (30 minute infusion, see "Instructions for Use") to be started 60 minutes before surgery. A single 500 mg iv dose of metronidazole, if deemed appropriate, can be administered immediately after the end of the Maxipime infusion. The dose of metronidazole should be prepared and administered in accordance with the product technical information. Due to the incompatibility Maxipime and metronidazole should not be mixed in the same container; it is recommended to flush the set with a compatible liquid prior to administration of metronidazole.
- If the duration of surgery exceeds 12 hours, a second dose of Maxipime followed by metronidazole, if appropriate, should be administered 12 hours after the initial prophylactic dose.
Children aged 1 month to 12 years with normal kidney function
Bacterial meningitis
Recommended dosage: Patients over two months of age and weighing ≤ 40 kg: 50 mg / kg every 8 hours for 7 - 10 days.
Experience with the use of Maxipime in patients under two months of age is limited. While this experience was obtained at 50 mg / kg, pharmacokinetic data obtained in individuals over 2 months suggest that a dose of 30 mg / kg every 12 or 8 hours can be considered adequate for pediatric patients between the first and second month of age. Doses of 30 mg / kg between 1 and 2 months and those of 50 mg / kg between 2 months and 12 years are comparable with the 2 g of the adult. The administration of Maxipime in these patients should be carefully monitored.
Adult schemes may be applied for pediatric patients weighing more than 40 kg (see Table 1). For patients over 12 years of age and weighing ≤ 40 kg, the younger age scheme weighing ≤ 40 kg should be used.
The pediatric dosage should not exceed the adult dosage (2 g every 8 hours). Experience with intramuscular administration in pediatric patients is limited.
Senior citizens
No dosage modification is required, except in cases of concomitant renal insufficiency (See "Precautions for use").
Reduced Hepatic Function
No dosage modification is required except in cases of concomitant renal insufficiency.
Reduced Kidney Function
In patients with renal dysfunction, the dosage of cefepime should be adjusted to compensate for the decreased renal elimination.
The recommended starting dose of cefepime in patients with mild to moderate renal dysfunction should be the same as in patients with normal renal function (Table 1).
The recommended maintenance dose of cefepime in adult patients with renal impairment is shown in the table below (Table 2).
TABLE 2
Maintenance dose in adults with renal insufficiency *
* The pharmacokinetic model indicates that a reduced dosage is required for these patients.
Patients undergoing hemodialysis
In patients undergoing hemodialysis, approximately 68% of the total amount of cefepime present in the body at the start of dialysis will be eliminated over a 3 hour period. For these patients, the pharmacokinetic model indicates that a dose reduction is required. Patients receiving cefepime and undergoing hemodialysis at the same time should receive the following dosage: a 1 g loading dose on the first day of therapy and thereafter 500 mg of cefepime per day for all infections except febrile neutropenia requiring 1 g per day. On dialysis days, cefepime should be administered immediately after dialysis. Whenever possible, cefepime should be administered at the same time each day.
Patients undergoing continuous peritoneal dialysis
In continuous peritoneal dialysis, Maxipime can be administered at the doses normally recommended for patients with normal renal function (ie 500 mg, 1 g or 2 g depending on the severity of the infection) but with an interval of 48 hours between one dose and the next. .
Pediatric patients with impaired renal function
Since urinary excretion is the predominant route of elimination of cefepime, dosage adjustments are recommended in pediatric patients and patients with impaired renal function. As recommended in Table 2, the same dose intervals and / or dose intervals should be used. a reduction of the latter.
Duration of treatment
The duration of therapy depends on the course of the infection and must, therefore, be established by the doctor.
Instructions for Use
Intravenous administration
To prepare a Maxipime solution for intravenous administration, the following diluents should be used:
- Water for injections F.U.
- Physiological solution (0.9% sodium chloride solution), with or without 5% glucose
- Ringer's solution with or without 5% glucose
- 5% or 10% glucose solution
- 6 M sodium lactate solution
Maxipime can be injected slowly into a vein over a period of 3-5 minutes. The drug can also be administered directly into perfusion tubes or via continuous intravenous infusion. If administered by infusion, inject the drug over approximately 30 minutes.
Intramuscular administration
Maxipime 0.5 g must be diluted with 1.5 ml of sterile water for injections (provided in the pack).
Maxipime 1 g must be diluted with 3 ml of sterile water for injections (provided in the package).
Volumes of reconstitution
Maxipime reconstitution volumes for intravenous and intramuscular administration are summarized in the following table:
TABLE 3
Instructions for reconstitution
The solution must be reconstituted at the time of use.
It is preferable to administer the drug immediately after its reconstitution.
Maxipime can be administered simultaneously with other antibiotics or other drugs as long as they are not mixed in the same syringe or perfusion liquid.
Like other cephalosporins, Maxipime solutions may vary in color depending on the storage period. This characteristic does not influence the efficacy and tolerability of the drug.
OVERDOSE
Symptoms of overdose include encephalopathy, myoclonus, and seizures.
In cases of severe overdose, especially in patients with impaired renal function, serum levels of Maxipime can be reduced by hemodialysis. Peritoneal dialysis is not helpful. Accidental overdose can occur when patients with renal dysfunction take high doses of the drug (see "How to use Maxipime", "Warnings and precautions", and "Undesirable effects").
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.
01.0 NAME OF THE MEDICINAL PRODUCT
MAXIPIME POWDER AND SOLVENT FOR INJECTABLE SOLUTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
MAXIPIME 500 mg / 1.5 ml powder and solvent for solution for injection
Each bottle contains
Active ingredient: cefepime dihydrochloride monohydrate, equal to 500 mg of cefepime.
MAXIPIME 1000 mg / 3 ml powder and solvent for solution for injection
Each bottle contains
Active ingredient: cefepime dihydrochloride monohydrate, equal to 1000 mg of cefepime.
MAXIPIME 2000 mg / 10 ml powder and solvent for solution for injection
Each bottle contains
Active ingredient: cefepime dihydrochloride monohydrate, equal to 2000 mg of cefepime.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Powder and solvent for solution for injection.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
MAXIPIME is indicated in adults for the treatment of moderate and severe infections caused by susceptible bacteria, including respiratory tract infections and infections (complicated and uncomplicated) of the lower and upper urinary tract, skin and soft tissue infections , intra-abdominal infections, including peritonitis and biliary infections, septicemia / bacteraemia including febrile episodes in immunocompromised patients.
Empirical treatment of febrile episodes in neutropenic patients.
Cefepime monotherapy is indicated for the empirical treatment of febrile episodes in neutropenic patients.
In neutropenic patients at high risk for severe infections (eg, patients with recent bone marrow transplantation, with onset hypotension, with underlying haematological malignancy, or with severe and prolonged neutropenia), antimicrobial monotherapy may not be appropriate. there is insufficient data to support the efficacy of cefepime alone in such patients.
MAXIPIME is indicated in children for the treatment of cerebrospinal meningitis caused by sensitive germs.
MAXIPIME is indicated for the treatment of infections caused by one or more susceptible, aerobic and anaerobic bacterial strains.
Due to the broad antibacterial spectrum, after obtaining susceptibility test results, MAXIPIME can be used alone as a drug of first choice. When appropriate, MAXIPIME can be used safely in combination with aminoglycoside or other antibiotics.
MAXIPIME is indicated for surgical prophylaxis in patients undergoing intra-abdominal surgery.
04.2 Posology and method of administration
Administration
MAXIPIME can be administered intravenously and intramuscularly. When administered intramuscularly alone, MAXIPIME does not generally cause pain.
The dosage and route of administration vary according to the susceptibility of the organism involved, the severity of the infection, the renal function and the general condition of the patient.
Adults
A guide to cefepime dosing for adults and children over 12 years of age with normal renal function is provided in Table 1.
The intravenous route of administration is preferable for those patients with severe infections, especially those that endanger the patient's life, especially if septic shock is present.
Table 1
Adults and Children over 12 years of age with normal renal function *
* The duration of therapy normally varies between 7 and 10 days; more severe infections may require longer treatment. Empirical treatment of febrile neutropenia (immunocompromised patients) should last 7 days or until the neutropenia resolves.
Surgical prophylaxis (adults): the recommended dosages for the prevention of bacterial infections during and after surgery are as follows:
A single 2 g iv dose of MAXIPIME (30 minute infusion, see 6.6) to be started 60 minutes before surgery. A single 500 mg iv dose of metronidazole, if deemed appropriate, may be given immediately after the end of the surgery. infusion of MAXIPIME. The dose of metronidazole must be prepared and administered in accordance with the technical information of the product. Due to the incompatibility, MAXIPIME and metronidazole must not be mixed in the same container; it is recommended to wash the set with a compatible liquid before administration of metronidazole.
If the duration of surgery exceeds 12 hours, a second dose of MAXIPIME followed by metronidazole, if appropriate, should be administered 12 hours after the initial prophylactic dose.
Children aged 1 month to 12 years with normal kidney function
Meningitis bacterial
Recommended dosage: patients over two months of age and weighing 40 kg: 50 mg / kg every 8 hours for 7 - 10 days.
Experience with the use of MAXIPIME in patients under 2 months of age is limited. While this experience was obtained at 50 mg / kg, pharmacokinetic data obtained in individuals over 2 months suggest that a dosage of 30 mg / kg every 12 or 8 hours may be considered adequate for pediatric patients between the first and second month of age. Doses of 30 mg / kg between 1 and 2 months and those of 50 mg / kg between 2 months months and 12 years are comparable with the 2 g of the adult. The administration of MAXIPIME in these patients should be carefully monitored.
Adult schemes may be applied for pediatric patients weighing more than 40 kg (see Table 1). For patients over 12 years of age and weighing 40 kg the scheme for younger people weighing 40 kg should be used.
The pediatric dosage should not exceed the adult dosage (2 g every 8 hours). Experience with intramuscular administration in pediatric patients is limited.
Senior citizens
No dosage modification is required, except in case of concomitant renal insufficiency (see 4.4).
Reduced Hepatic Function
No dosage modification is required except in cases of concomitant renal insufficiency.
Reduced Kidney Function
In patients with renal dysfunction, the dosage of cefepime should be adjusted to compensate for the decreased renal elimination. The recommended starting dose of cefepime in patients with mild to moderate renal dysfunction should be the same as in patients with normal renal function. The recommended maintenance dose of cefepime in adult patients with renal insufficiency can be seen in the table below.
TABLE 2
Maintenance dose in adults with renal insufficiency *
Patients undergoing hemodialysis
In patients undergoing hemodialysis, approximately 68% of the total amount of cefepime present in the body at the start of dialysis is eliminated over a 3 hour period. At the end of each dialysis session, a dose equivalent to the starting dose should be administered.
In continuous peritoneal dialysis, MAXIPIME can be administered at the doses normally recommended for patients with normal renal function (ie 500 mg, 1 g or 2 g depending on the severity of the infection) but every 48 hours.
Pediatric patients with impaired renal function
Since urinary excretion is the predominant route of elimination of cefepime, dosage adjustments are recommended in pediatric patients and patients with impaired renal function.
As recommended in Table 2, the same increases in the intervals between doses and / or a reduction of the latter should be used.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients, to cephalosporins, penicillins or other beta-lactam antibiotics.
04.4 Special warnings and appropriate precautions for use
In patients with renal dysfunction, such as decreased diuresis due to renal insufficiency (creatinine clearance ≤ 50 ml / min) or other conditions that may impair renal function, the dosage of MAXIPIME should be adjusted to compensate for the decreased renal elimination. Due to prolonged and elevated serum concentrations of the antibiotic at usual dosages in patients with renal insufficiency or other conditions that may impair renal function, maintenance dosage should be reduced when cefepime is administered to these patients. Repeated dosing should be determined based on the degree of renal dysfunction, the severity of the infection and the sensitivity of the causative agent (see 4.2 and 5). The following serious adverse events have been reported during post-marketing surveillance: reversible encephalopathy (disturbances of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures (including non-convulsive status epilepticus) and / or renal failure ( see point 4.8). Most cases have been reported in patients with renal dysfunction who received doses of MAXIPIME above those recommended. In general, the symptoms of neurotoxicity disappeared after discontinuation of cefepime and / or after hemodialysis; however, some cases have been fatal.
As with other beta-lactam antibiotics, before initiating therapy with MAXIPIME, it should be carefully assessed that the patient has not previously been hypersensitive to penicillins or other drugs; in this case MAXIPIME should be administered with extreme caution.
In the event of an allergic reaction to MAXIPIME, therapy should be discontinued and the patient treated appropriately. Severe hypersensitivity reactions may require adrenaline and supportive measures.
With the use of nearly all antibacterial agents including MAXIPIME, associated diarrhea has been reported Clostridium difficile which can range in severity from mild diarrhea to fatal colitis. The diagnosis of C. difficult associated with diarrhea in all patients who present with diarrhea following antibiotic therapy. A careful medical history is required as it has been reported that onset of diarrhea is associated with C. difficult it can also occur in the two months following the administration of antibacterial agents. In case of C. difficult, suspected or known, it may be necessary to discontinue antibiotic therapy not prescribed for this condition.
In case of concomitant use of potentially nephrotoxic drugs such as aminoglycosides and potent diuretics, renal function should be carefully monitored.
Senior citizens
Of the more than 6400 adult patients treated with MAXIPIME in clinical trials, 35% were 65 years or older while 16% were 75 or older.
In clinical studies, elderly patients being treated at commonly recommended adult doses have shown clinical efficacy and safety comparable to that of adult patients, unless the patients have renal insufficiency. The differences are limited to a modest lengthening of the half-life and a lower renal clearance than in younger patients. If renal function is impaired, dosage adjustment is recommended (see 4.2).
Cefepime is known to be substantially excreted via the kidney and the risk of toxic reactions to this drug may be higher in patients with renal dysfunction. As elderly patients are more prone to decline in renal function, caution should be exercised in dosage selection and renal function monitoring (see 4.8 and 5). Serious adverse events including reversible encephalopathy (disturbances of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures (including non-convulsive status epilepticus) have occurred in geriatric patients with renal insufficiency given usual doses of cefepime. ) and / or renal insufficiency (see section 4.8).
04.5 Interactions with other medicinal products and other forms of interaction
Direct Coombs test positive, without evidence of haemolysis, was observed in 12.3% of patients who received MAXIPIME every 12 hours in clinical trials.
False positive reactions of glycosuria may be observed in patients treated with MAXIPIME when reducing agents are used. False positive reactions have not been observed with methods including glucose oxidase.
04.6 Pregnancy and breastfeeding
The safety of MAXIPIME in pregnant women has not been established as adequate and well-controlled studies have not been conducted in these patients.
Reproduction studies performed on animals with doses up to 8-10 times the maximum daily dose do not indicate direct or indirect harmful effects on reproduction, on embryonic or fetal development, on the period of gestation, and on peri- and postnatal development. Since animal reproduction studies are not always predictive of human response, it is recommended to use the drug during pregnancy only when clearly needed.
Cefepime is excreted in very low concentrations in breast milk and therefore caution is advised when administering the drug to breastfeeding women.
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed.
04.8 Undesirable effects
MAXIPIME is generally well tolerated.
In clinical studies (N = 5598) the most common adverse events were gastrointestinal symptoms and hypersensitivity reactions.
Adverse reactions rarely required discontinuation of treatment and were generally mild and transient in nature. Adverse reactions during therapy with MAXIPIME considered drug related are listed below:
Adverse reactions reported with an incidence ranging from 0.1 to 1% (unless otherwise specified)
Hypersensitivity: skin rash (1.8%), itching, hives.
Digestive system: nausea, vomiting, oral candidiasis, diarrhea (1.2%), colitis (including pseudomembranous colitis)
Central nervous system: headache
Other: fever, vaginitis, erythema.
Adverse reactions reported with an incidence ranging from 0.05 to 0.1%: abdominal pain, constipation, vasodilation, dyspnoea, dizziness, paraesthesia, genital itching, taste disturbances, chills, unspecified candidiasis.
Clinically significant events occurring in less than 0.05% of cases included anaphylaxis and convulsions.
Local reactions
In the IV infusion site (5.2%): phlebitis (2.9%) and inflammation (0.1%), In the intramuscular injection site: pain and inflammation (2.6%).
Changes in laboratory parameters that developed during clinical trials in patients with normal baseline values were transient and were transient. Those that occurred with 1-2% incidence (unless otherwise specified) were: anemia, eosinophilia, thrombocytopenia (0.5-1%), positive Coombs test without haemolysis (18.7%), increased transaminase (ALT 3.6%; AST 2.5%), alkaline phosphatase, total bilirubin, BUN (0.5-1%), creatinine (0.5-1%), prothrombin time and partial thromboplastin time (2.8%). Rare cases of transient leukopenia and neutropenia have been observed.
The following events have been reported from post-marketing clinical experience, but the causal link with the drug could not be determined: as with other drugs in this class, encephalopathy (disturbances of consciousness including confusion, hallucinations, stupor and coma ), seizures, myoclonus, and / or renal failure Most cases have been reported in patients with renal dysfunction who received doses above those recommended (see section 4.4).
In addition, anaphylaxis (including anaphylactic shock), transient leukopenia, neutropenia, agranulocytosis, and thrombocytopenia have been reported.
Pediatric patients: the safety profile in children is similar to that seen in adults, with rash being the most frequently reported event in clinical trials.
04.9 Overdose
In the event of severe overdose, especially in patients with impaired renal function, the serum levels of MAXIPIME can be reduced with hemodialysis. Peritoneal dialysis is not helpful. Accidental overdose may occur when patients with renal dysfunction take high doses of the drug (see sections 4.2, 4.4 and 4.8).
Symptoms of overdose include encephalopathy, myoclonus, seizures, and neuromuscular excitability.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: beta-lactam antibacterials.
ATC code: J01DE01.
Bacteriology
Cefepime is a new generation cephalosporin with a broad spectrum of action, which exerts its bactericidal action by inhibiting cell wall synthesis. Cefepime presents in vitro activity against a "wide range of gram-positive and gram-negative bacteria, including some forms resistant to aminoglycoside antibiotics, ceftazidime and other third generation cephalosporins. It has a low affinity for chromosomal beta-lactamases and is very resistant to" hydrolytic action of most of them. It exhibits rapid penetration into the cell wall of gram-negative bacteria.
Cefepime was active, in vitro, against the following bacterial strains: Gram-positive aerobes: Staphylococcus aureus (including beta-lactamase producing strains), Staphylococcus epidermidis (including beta-lactamase producing strains), Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Staphylococcus warnocceri pyogenes (Group A streptococci), Streptococcus agalactiae (Group B streptococci), Group C streptococci, Group D streptococci (S.bovis), Group F streptococci, Group G streptococci, Streptococcus pneumoniae (including intermediate penicillin-resistant strains with MIC for penicillin between 0.1 and 1 mcg / ml), Viridans streptococci. Many strains of enterococci, e.g. Enterococcus faecalis, and methicillin-resistant staphylococci are resistant to most cephalosporins including cefepime. Gram-negative aerobes: Pseudomonas spp. (including P. aeruginosa, P. fluorescens, P. cepacia, P. stutzeri, P. putida, P. testosteroni, P. acidovorans, P. paucimobilis and P. pseudomallei), Escherichia coli, Klebsiella spp. (including K. pneumoniae, K. oxytoca and K. ozaenae), Enterobacter spp. (including E. cloacae, E. aerogenes, E. agglomerans and E. sakazakii), Citrobacter spp. (including C. diversus, C. freundii, C.amalonaticus, and C.aerogenes), Proteus spp. (including P. mirabilis, P. vulgaris and P. penneri), Serratia spp. (including Serratia marcescens and S.liquefaciens), Providencia spp. (including P. stuartii, P. rettgeri and P. alcalifaciens), Morganella morganii, Haemophilus influenzae (including beta-lactamase producing strains), Haemophilus parainfluenzae, Haemophilus ducreyi, Hafnia alvei, Kluvyera spp., Salmonella spp., Shigella spp. , Aeromonas hydrophila, Yersinia enterocolitica, Campylobacter jejuni, Vibrio spp. (including V. cholerae), Flavobacterium spp., Alcaligenes spp., Capnocytophaga spp., Acinetobacter calcoaceticus (subspp. anitratus and lwoffi), Moraxella catarrhalis (formerly Branhamella catarrhalis - including beta-lactamase producing strains), Neisseria gonorrhoe beta-lactamase producing strains), Neisseria meningitidis, Gardnerella vaginalis, Legionella spp. Cefepime is inactive against many strains of Pseudomonas pickettii and Xanthomonas maltophilia.
Anaerobes: Peptostreptococcus spp., Fusobacterium spp., Clostridium perfringens, Veillonella spp., Mobiluncus spp., Bacteroides spp., (B. Melaninogenicus, and other Bacteroides of oral origin). Cefepime is inactive on Bacteroides fragilis and Clostridium difficile.
Synergy has been observed with aminoglycoside antibiotics.
05.2 Pharmacokinetic properties
The pharmacokinetics of MAXIPIME were linear in the range of 250 mg - 2 g intravenously and in the range 500 mg - 2 g intramuscularly, and did not vary according to the duration of treatment.
Absorption: Following intramuscular administration, MAXIPIME is completely absorbed.
Distribution: The mean plasma concentrations of cefepime at various time intervals in healthy adult male volunteers following single intravenous administrations of 250 mg, 500 mg, 1 g and 2 g and following single intramuscular administrations of 500 mg, 1 g 2 g, are shown in table 3.
TABLE 3
Mean plasma concentrations of cefepime (mcg / ml) in healthy adult males
The mean elimination half-life of cefepime is approximately 2 hours.
Cefepime achieves therapeutic concentrations for sensitive pathogens in biological fluids and body tissues as listed in Table 4.
The relative tissue distribution of cefepime does not vary with dose in the range of 250 mg - 2 g.
Metabolism
The mean steady state volume of distribution is 18 liters. There is no evidence of accumulation of cefepime in healthy subjects receiving doses of up to 2 g intravenously every 8 hours for a period of 9 days. The binding of cefepime to serum proteins is less than 19% and is independent of its concentration. in the serum.
Cefepime is not extensively metabolised. The major metabolite in the urine is N-methylpyrrolidine which is rapidly converted to N-oxide; this accounts for approximately only 6.8% of the dose.
TABLE 4
Average concentrations of cefepime in various biological fluids and body tissues in healthy adults
Excretion
The mean total clearance of the drug from the organism is 120 ml / min. The mean renal clearance is 110 ml / min, demonstrating that elimination occurs almost exclusively via the kidney, mainly by glomerular filtration. The urinary concentration of unchanged cefepime constitutes approximately 85% of the dose. After a dose of 500 mg intravenously, concentrations of MAXIPIME were not detectable after 12 hours in plasma and after 16 hours in urine. The mean urine concentration in urine. "12 - 16 hour post-dose range was 17.8 mcg / mL. After a 1 or 2 g intravenous dose, urinary concentrations averaged 26.5 mcg / mL and 28.8 mcg / mL, respectively, in the 12-24 hour range. No plasma levels of drug 24 hours after administration.
Senior citizens:
The pharmacokinetics of MAXIPIME in both sexes over 65 years of age are well known. Patients with normal renal function in relation to age do not require modification of the dosage, which must instead be adjusted when renal function is impaired (see section 4.2 and 4.4).
Abnormal liver function
The pharmacokinetics of cefepime in patients with hepatic impairment receiving a single 1 g dose remain unaffected. Therefore, dose adjustment is not required for patients with hepatic dysfunction, unless there is concomitant renal insufficiency.
Alteration of renal function
Studies in patients with varying degrees of renal impairment have shown a significant prolongation in the elimination half-life of the drug. C "is a linear relationship between total body clearance and creatinine clearance in patients with impaired renal function (see 4.2 Reduced Renal Function). The mean elimination half-life in patients requiring dialysis or hemodialysis or continuous peritoneal dialysis is 13-17 hours.
Pediatric patients
The mean plasma concentrations of cefepime after the first dose are similar to those observed at steady state, with very little accumulation after repeated administration.
The mean bioavailability is 82% after IM administration. There are no substantial differences in children between the first dose and steady state, regardless of the regimen (BID or TID), nor between ages or between males and females. The elimination half-life is 1.7 hours, the excretion of unchanged cefepime in urine is 60% of the administered dose, and the renal route and routes of elimination preferential. Table 5 shows the concentrations of cefepime in the CSF in comparison. with plasma concentrations.
TABLE 5
Mean concentrations of cefepime in plasma and cerebrospinal fluid *
* Patient ages ranged from 3.1 months to 14.7 years, with a mean age of 2.9 years (SD 3.9). Patients with suspected CNS infection were treated with cefepime, 50 mg / kg, administered by IV infusion for 5-20 minutes every 8 hours. Plasma and CSF samples were collected from selected patients approximately 0.5, 1, 2, 4 and 8 hours after the end of the infusion, on the 2nd or 3rd day of therapy.
05.3 Preclinical safety data
No clinically relevant effects were observed.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
L-arginine (approximately 725 mg of L-arginine per g of cefepime active substance).
06.2 Incompatibility
There are currently no data on physical / chemical stability of MAXIPIME in combination with other drugs. It is advisable not to combine MAXIPIME in the same solution with other drugs when it is administered intravenously (see 6.6).
06.3 Period of validity
3 years.
The solution must be reconstituted at the time of use and can be stored at a temperature not exceeding 25 ° C for 24 hours or, alternatively, at a temperature between 2 ° C - 8 ° C for 7 days.
06.4 Special precautions for storage
Store at a temperature not exceeding 30 ° C. Keep the medicine protected from light.
The reconstituted solution should be stored at a temperature not exceeding 25 ° C for 24 hours or, alternatively, at a temperature between 2 ° C - 8 ° C for 7 days.
06.5 Nature of the immediate packaging and contents of the package
MAXIPIME 500 mg / 1.5 ml powder and solvent for solution for injection
A glass bottle of 500 mg with attached solvent ampoule of 1.5 ml of water for injections (usable for intramuscular administration).
MAXIPIME 1000 mg powder and solvent for solution for injection
One 1000 mg glass bottle with attached 3 ml solvent ampoule of water for injections (usable for intramuscular administration).
MAXIPIME 2000 mg powder and solvent for solution for injection
A 2000 mg glass bottle with a 10 ml solvent ampoule of water for injections (usable for intravenous administration).
06.6 Instructions for use and handling
Intravenous administration
To prepare the MAXIPIME solution to be administered intravenously, the following diluents should be used:
- Water for injections F.U.
- Physiological solution (0.9% sodium chloride solution), with or without 5% glucose
- Ringer's solution with or without 5% glucose
- 5% or 10% glucose solution
- 6 M sodium lactate solution
MAXIPIME can be injected slowly into a vein over a period of 3-5 minutes. The drug can also be administered directly into perfusion tubes or via continuous intravenous infusion. If administered by infusion, inject the drug over approximately 30 minutes. Intramuscular administration
MAXIPIME 0.5 g must be diluted with 1.5 ml of water for injections (provided in the pack).
MAXIPIME 1 g must be diluted with 3 ml of water for injections (provided in the pack). Volumes of reconstitution
MAXIPIME reconstitution volumes for intravenous and intramuscular administration are summarized in the following table:
TABLE 6
Instructions for reconstitution
It is preferable to administer the drug immediately after its reconstitution.
MAXIPIME can be administered simultaneously with other antibiotics or other drugs as long as they are not mixed in the same syringe or perfusion liquid.
Like other cephalosporins, MAXIPIME solutions may vary in color depending on the storage period. This characteristic does not influence the efficacy and tolerability of the drug.
07.0 MARKETING AUTHORIZATION HOLDER
BRISTOL-MYERS SQUIBB S.r.l. Via Virgilio Maroso, 50 - Rome
08.0 MARKETING AUTHORIZATION NUMBER
MAXIPIME 500 mg / 1.5 ml powder and solvent for solution for injection - A.I.C. N ° 028899019
MAXIPIME 1000 mg / 3 ml powder and solvent for solution for injection - A.I.C. N ° 028899021
MAXIPIME 2000 mg / 10 ml powder and solvent for solution for injection - A.I.C. N ° 028899033
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Last renewal date: November 2009.
10.0 DATE OF REVISION OF THE TEXT
August 2011
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