Consumer medicine information

CEFEPIME-AFT

Cefepime

BRAND INFORMATION

Brand name

Cefepime-AFT

Active ingredient

Cefepime

Schedule

What is in this leaflet

The medicine which your doctor has prescribed for you is called Cefepime-AFT. The information in this leaflet answers some questions you may have about Cefepime-AFT.

This leaflet does not contain all the information about Cefepime-AFT. Your doctor or pharmacist has been provided with full information, and can answer any questions you may have. Follow your doctor's advice, even if it differs from what is in this leaflet.

You should read this leaflet carefully before Cefepime-AFT is given to you. Keep this leaflet in a safe place; you may need to read it again.

What Cefepime-AFT is used for

Cefepime-AFT contains cefepime which belongs to a group of antibiotics called cephalosporins. These antibiotics work by killing the bacteria that are causing the infection.

Cefepime-AFT is an injectable antibiotic used for serious infections in adults caused by bacteria in the lungs (pneumonia and bronchitis), in the kidney and bladder (urinary tract infections), in the skin, inside the abdomen (peritonitis and biliary tract infections), in the womb or vagina, or in the blood (septicaemia). It may be given before surgery or if you have a lack of white blood cells with fever.

Cefepime-AFT is also used for serious infections in children over 2 months of age caused by bacteria in the lungs (pneumonia), in the kidney and bladder (urinary tract infections), or in the skin; or in the blood; or if the child has a lack of white blood cells with fever.

There may be other reasons why your doctor has prescribed Cefepime-AFT. Ask your doctor why Cefepime-A FT has been prescribed for you.

Before you are given Cefepime-AFT

When you must not be given Cefepime-AFT

You should not be given Cefepime-AFT if -

You have an allergy to Cefepime-AFT, or to other cephalosporins or to any ingredient listed at the end of this leaflet. Symptoms of a severe allergic reaction may include chills, fever, fast heart beat, wheezing or coughing. difficulty breathing, dizziness, flushing, sweating and swelling of the face, tongue or other parts of the body.
You have had a serious reaction to cephalosporin, beta-lactam or penicillin antibiotics.

Before you are given Cefepime-AFT

Before you are given Cefepime-AFT your doctor must know -

if you have ever had any type of allergic reaction to antibiotic medicines
if you have any allergies to other medicines or to any other substances such as foods, preservatives or dyes
if you have ever had any other health problems or medical conditions such as -
- kidney disease
- severe bowel conditions or bowel disease
- frequent infections such as fever, severe chills, sore throat or mouth ulcers or lack of white blood cells (neutropenia)
- a recent bone marrow transplant
- cancer of the blood
- low blood pressure
If you have ever suffered diarrhoea as a result of taking medicine.

Pregnancy and breast-feeding

Tell your doctor if

you are pregnant or intend to become pregnant
breast-feeding or plan to breast-feed

Like most medicines Cefepime-AFT is not recommended for women who are pregnant or breast feeding. However your doctor will discuss with you the possible risks and benefits of using Cefepime-AFT during pregnancy.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from your pharmacy or health food shop. Some medicines may interfere with Cefepime-AFT, these include -

any other antibiotic
Fluid tablets (diuretics) such as Lasix (frusemide), Midamor (amiloride), or Moduretic (amiloride and hydrochlorothiazide).

These medicines may be affected by Cefepime-AFT, or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines.

Children

Cefepime-AFT may be given to infants (over 2 months old) and children; Cefepime-AFT is not recommended if the infant is less than 2 months old.

How Cefepime-AFT is given

How much is given

Your doctor will decide what dose you will receive. This dose will be based on your size, as well as the severity and location of your infection.

The usual adult dose is 1 gram given by injection every 12 hours (2 each day) for 7 to 10 days.

The dose of Cefepime-AFT for children aged 2 months to 12 years old will depend on the weight of the child, the severity of the infection and the medical condition of the child.

How it is given

Cefepime-AFT is given as a slow injection (or drip) directly into a vein or as a deep injection into a large muscle.

The injection will be given to you by a nurse or doctor; you will not be giving the injection to yourself.

Laboratory Tests: Cefepime-AFT may cause adverse effects to the blood, liver or kidneys which are detected by laboratory testing. It may be necessary to monitor these effects by having your blood samples analysed regularly. Your doctor will advise if it is necessary for you to have these tests done.

Overdose

Usually you will be in hospital when receiving Cefepime-AFT. Your doctor has information on how to recognise and treat an overdose. Ask your doctor or nurse if you have any concerns when you are receiving Cefepime-AFT.

While you are being given Cefepime-AFT

Things you must do

If the symptoms of your infection do not improve within a few days, or if they become worse, you must tell your doctor.
If you get severe diarrhoea tell your doctor, pharmacist or nurse immediately even if it occurs several weeks after Cefepime-AFT has been stopped. Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care. Do not take any diarrhoea medicine without checking with your doctor first.
If you get a sore white mouth or tongue while receiving or soon after stopping Cefepime-AFT, tell your doctor. Also tell your doctor if you get vaginal itching or discharge. This may mean you have a fungal infection called thrush. Sometimes the use of Cefepime-AFT allows fungi to grow and the symptoms described above to occur. Cefepime-AFT does not work against fungi.
If you become pregnant while you are being given Cefepime-AFT tell your doctor.
If you are about to start taking any new medicine, tell your doctor and pharmacist that you are receiving Cefepime-AFT.
If you have your urine tested for sugar while you are receiving Cefepime-AFT, make sure your doctor knows which test is used. Cefepime-AFT may affect the results of some of these tests.
Tell all the doctors, dentists and pharmacists who are treating you that you are taking Cefepime-AFT.

Things to be careful of

Be careful driving or operating machinery until you know how Cefepime-AFT affects you. Cefepime-AFT generally does not cause any problems with your ability to drive a car or operate machinery. However as with other medicines, Cefepime-AFT may cause dizziness, drowsiness or tiredness in some people. If this happens, do not drive.

Side effects

It is important that you tell a nurse, doctor or pharmacist if you experience any problems when you are being treated with Cefepime-AFT.

Cefepime-AFT helps most people with infections, but it may cause some unwanted side effects in a few people. All medicines have side effects, sometimes they are serious, most of the time they are not. You may need special medical treatment if you get

Call for a nurse or doctor immediately if you experience any of the following -

Signs of a sudden life-threatening allergic reaction such as fast heart beat, feeling faint, wheezing or coughing, difficulty breathing, chills, fever, dizziness, flushing, sweating and swelling of the face, tongue or other parts of the body
Signs of altered mental state such as confusion, hallucinations, lethargy, tremor, twitching muscles or experience a seizure

These are serious side effects. You may need urgent medical attention.

Tell your doctor or nurse if you notice any of the following -

insomnia, anxiety, nervousness, confusion
itching or burning while passing urine, passing little or no urine, drowsiness, nausea, vomiting, poor appetite, headache, weakness, fever, numbness, fluid retention
severe abdominal or stomach cramps, watery and severe diarrhoea (which may be bloody), fever with one or both of the above symptoms
Fevers, chills, sore throat, mouth ulcer

The most common side-effects are:

oral thrush - white, furry, sore tongue and mouth
vaginal thrush - sore and itchy vagina and/or discharge
swelling, pain and inflammation at the site of the injection
skin rash or itchiness, skin redness
nausea, vomiting, diarrhoea, constipation
Headache, fever

After treatment with Cefepime-AFT is finished

Tell your doctor immediately if you notice any of the following side effects, particularly if they occur several weeks after the treatment with Cefepime-AFT has stopped -

severe abdominal or stomach cramps
watery and severe diarrhoea, which may also be bloody
fever with one or both of the above symptoms

These are rare but serious side effects. You may have a serious condition affecting your bowel. Therefore you may need urgent medical attention. Although this side effect is rare, do not take diarrhoea medicine without first checking with your doctor.

The list above is not a complete list of ALL possible side effects. Your doctor can tell you more about the safety of CefepimeAFT. Also, as with any medicine, there are some side effects which are not yet known. Ask your doctor if you have any questions.

Storage

Cefepime-AFT will be stored in the pharmacy or the Ward. The powder for injection is usually kept in a cool dry place where the temperature stays below 25 °C.

Product description

What Cefepime-AFT looks like

Cefepime-AFT is a white to pale yellow powder.

Ingredients

Each vial contains cefepime hydrochloride monohydrate equivalent to cefepime 500 mg, 1 g or 2 g.

The vials also contain the inactive ingredient L-arginine.

The contents of each vial are dissolved in sterile water, 5% glucose or saline for injection before the injection is given.

Sponsor

AFT Pharmaceuticals Pty. Ltd
P.O. Box 748 , North Ryde, NSW 1670
113 Wicks Road, North Ryde, NSW 2113

Australian Registration Numbers:

500 mg vial AUST R 196281
1 g vial AUST R 196279
2 g vial AUST R 196280

This leaflet was prepared on 24 August 2015

Please note that knowledge about the safety of all medicines may change over time. You should, therefore, see your doctor if you have any questions about Cefepime-AFT at any time.

Published by MIMS June 2017

BRAND INFORMATION

Brand name

Cefepime-AFT

Active ingredient

Cefepime

Schedule

1 Name of Medicine

Cefepime hydrochloride monohydrate.

2 Qualitative and Quantitative Composition

Cefepime hydrochloride monohydrate is a semi-synthetic, broad spectrum cephalosporin antibiotic for parenteral administration.
Cefepime hydrochloride monohydrate is a white to pale yellow powder. It is highly soluble in water.
Cefepime-AFT powder for injection is a sterile dry mixture of Cefepime hydrochloride monohydrate and L-arginine. It is supplied in vials containing cefepime hydrochloride monohydrate equivalent to Cefepime 500 mg, 1 g and 2 g.
For the full list of excipients, see Section 6.1.

3 Pharmaceutical Form

Powder for injection.
Cefepime-AFT powder for injection containing cefepime (as hydrochloride monohydrate) 500 mg AUST R 196281.
Cefepime-AFT powder for injection containing cefepime (as hydrochloride monohydrate) 1 g AUST R 196279.
Cefepime-AFT powder for injection containing cefepime (as hydrochloride monohydrate) 2 g AUST R 196280.

4 Clinical Particulars

4.1 Therapeutic Indications

Adults.

Cefepime-AFT is indicated in the treatment of the following infections when caused by susceptible bacteria.
Lower respiratory tract infections, including pneumonia and bronchitis.
Urinary tract infections, both complicated, including pyelonephritis, and uncomplicated infections.
Skin and skin structure infections.
Intra-abdominal infections, including peritonitis and biliary tract infections.
Gynaecological infections.
Septicaemia.
Empiric treatment in febrile neutropenic patients (see Section 4.4 Special Warnings and Precautions for Use).
Cefepime-AFT is also indicated for surgical prophylaxis in patients undergoing intra-abdominal surgery. In this indication it is essential that metronidazole also be administered.

Paediatrics.

Cefepime-AFT is indicated in paediatric patients over 2 months of age for the treatment of the infections listed below when caused by susceptible bacteria.
Pneumonia.
Urinary tract infections, both complicated, including pyelonephritis, and uncomplicated infections.
Skin and skin structure infections.
Septicaemia.
Empiric treatment in febrile neutropenic patients (see Section 4.4 Special Warnings and Precautions for Use).
Culture and susceptibility studies should be performed when appropriate to determine susceptibility of the causative organism(s) to cefepime. Empiric therapy with Cefepime-AFT may be instituted before results of susceptibility studies are known; however, once these results become available, the antibiotic treatment should be adjusted accordingly.
Because of its broad spectrum of bactericidal activity against Gram positive and Gram negative bacteria, Cefepime-AFT can be used appropriately as monotherapy prior to identification of the causative organisms(s). In the treatment of febrile neutropenia, consideration should be given to the need for other antibiotics in combination with Cefepime-AFT. In patients who are at risk of mixed aerobic anaerobic infection, including infections in which Bacterioides fragilis may be present, concurrent initial therapy with an antianaerobic agent is recommended before the causative organism(s) is known.

4.2 Dose and Method of Administration

Dosage.

Cefepime-AFT does not contain any antimicrobial preservative. It should be used in one patient on one occasion only.
Adults. The usual adult dosage and route of administration of cefepime is 1 g administered intravenously or intramuscularly every 12 hours. However, the dosage and route vary according to the susceptibility of the causative organisms, the severity of the infection, and the condition and renal function of the patient. Guidelines for dosage of Cefepime-AFT are provided in Table 1. The usual duration of therapy is 7-10 days; however, more severe infections may require longer treatment.

Surgical prophylaxis.

The dose recommendation for prophylaxis to prevent infection in adults undergoing intra-abdominal surgery is as follows.
A single 2 g I.V. dose of cefepime (as a 30 minute infusion, see above) starting 60 minutes before initial surgical incision. A single 500 mg I.V. dose of metronidazole should be administered immediately following completion of the cefepime infusion. The metronidazole dose should be prepared and administered in accordance with official product labelling. Due to incompatibility, cefepime and metronidazole should not be mixed together in the same container (see Compatibility and stability); flushing of the intravenous line with a compatible fluid before infusion of the metronidazole is recommended.
If the surgical procedure lasts longer than 12 hours from the initial prophylactic dose, a second dose of cefepime followed by metronidazole should be administered 12 hours following the initial prophylactic dose.
Paediatrics (aged 2 months up to 12 years with normal renal function). Usual recommended dosages are as follows.

Pneumonia, urinary tract infections, and skin and skin structure infections.

Patients > 2 months of age with bodyweight ≤ 40 kg: 50 mg/kg q12h. For more severe infections, a dosage schedule of q8h can be used.

Empiric treatment of febrile neutropenia.

Patients > 2 months of age with bodyweight ≤ 40 kg: 50 mg/kg q8h.
The usual duration of therapy is 7-10 days; however, more severe infections may require longer treatment.
For paediatric patients with bodyweights > 40 kg, adult dosing recommendations apply (see Table 5). For patients older than 12 years who are ≤ 40 kg, the dosage recommendations for younger patients ≤ 40 kg should be used. Dosage in paediatric patients should not exceed the maximum recommended dosage in adults (2 g q8h).
Experience with intramuscular administration in paediatric patients is limited and this route is not recommended.

Dosage adjustment.

Impaired hepatic function. No adjustment is necessary for patients with impaired hepatic function.
Impaired renal function. In patients with impaired renal function, the dose of cefepime should be adjusted to compensate for the slower renal elimination. The recommended initial dose of cefepime in patients with mild to moderate renal impairment should be the same as in patients with normal renal function. The recommended maintenance doses of cefepime in patients with renal insufficiency are presented in Table 2.
When only a serum creatinine measurement is available, the following formula (Cockcroft and Gault equation) may be used to estimate creatinine clearance. The serum creatinine should represent a steady-state of renal function.

Children with impaired renal function.

Since urinary excretion is the primary route of elimination of cefepime in paediatric patients (see Section 5 Pharmacological Properties), an adjustment of the dosage of cefepime should also be considered in patients < 12 years of age with renal impairment.
A dose of 50 mg/kg in patients aged 2 months up to 12 years, and a dose of 30 mg/kg in patients aged 1 month up to 2 months, are comparable to a dose of 2 g in an adult. As recommended in Table 2, the same increase in interval between doses and/or reduction in dose should be used.

Dialysis patients.

In patients undergoing haemodialysis, approximately 68% of the total amount of cefepime present in the body at the start of dialysis will be removed during a 3 hour dialysis period. In patients undergoing continuous ambulatory peritoneal dialysis, cefepime may be administered at normally recommended doses, i.e. 500 mg, 1 g or 2 g, depending on infection severity, at a dosage interval of every 48 hours.

Method of administration.

Cefepime-AFT may be given intravenously or by deep intramuscular injection into a large muscle mass (such as the upper quadrant of the gluteus maximus). The dosage and route vary according to the susceptibility of the causative organisms, the severity of the infection, renal function and the overall condition of the patient.
When using cefepime for surgical prophylaxis it is essential that metronidazole also be administered.

Intravenous administration.

The I.V. route of administration is preferable for patients with severe or life threatening infections, particularly if the possibility of shock is present.
For direct I.V. administration, reconstitute Cefepime-AFT with 5 or 10 mL of sterile 5% glucose injection or 0.9% sodium chloride as directed in Table 3. Slowly inject directly into the vein over a period of three to five minutes or inject into the tubing of an administration set while the patient is receiving a compatible I.V. fluid (see Compatibility and stability).
For intravenous infusion, reconstitute the 500 mg, 1 g or 2 g vial as noted above for direct I.V. administration, and add an appropriate quantity of the resulting solution to an I.V. container with one of the compatible I.V. fluids (see Compatibility and stability). The resulting solution should be administered over a period of approximately 30 minutes.

Intramuscular administration.

Cefepime-AFT should be reconstituted with one of the following diluents: sterile water for injections, 0.9% sodium chloride or 5% glucose injection (see Table 3). Although Cefepime-AFT can be reconstituted with 0.5% or 1.0% lignocaine, it is usually not required because cefepime causes little or no pain upon I.M. administration.
Experience with intramuscular administration in paediatric patients is limited and this route is not recommended.

Compatibility and stability.

Intravenous.

Cefepime-AFT is compatible at concentration between 1 and 40 mg/mL with the following I.V. infusion fluids: 0.9% sodium chloride, 5% glucose injection, M/6 sodium lactate injection, 5% glucose and 0.9% sodium chloride injection, lactated Ringers and 5% glucose injection.
Cefepime in 0.9% sodium chloride or 5% glucose injection is compatible when admixed with heparin (10 or 50 units/mL), potassium chloride (10 or 40 mEq/L) and theophylline (0.8 mg/mL in 5% glucose injection). Cefepime at a concentration of 40 mg/mL in 0.9% sodium chloride or 5% glucose injection was found to be compatible with amikacin 6 mg/mL.

Intramuscular.

Cefepime-AFT should be reconstituted with the following diluents: sterile water for injections, 0.9% sodium chloride, 5% glucose injection or 0.5% or 1% lignocaine hydrochloride.

For both routes of administration.

Cefepime-AFT should be reconstituted immediately before use and used as soon as practicable after reconstitution, any residue being discarded. If there is any delay in the use of reconstituted Cefepime-AFT it should be stored at 2-8°C for a maximum of 24 hours.
Solutions of cefepime, like those of most beta-lactam antibiotics, should not be added to solutions of gentamicin, metronidazole, vancomycin, tobramycin sulfate or netilmicin sulfate because of physical or chemical incompatibility. However, if concurrent therapy with cefepime and gentamicin is indicated, each of these antibiotics can be administered separately to the same patient.

Note.

Parenteral drugs should be inspected visually for particulate matter before administration and not used if particulate matter is present.
As with other cephalosporins, the colour of reconstituted Cefepime-AFT may darken on storage. However product potency is not adversely affected.
Reconstituted solutions should be protected from light.

Cefepime-AFT powder for injection is for single use in one patient only.

4.3 Contraindications

Cefepime is contraindicated in patients who have shown immediate hypersensitivity reactions to any component of the formulation (including L-arginine), the cephalosporin class of antibiotics, penicillins or other beta-lactam antibiotics.

4.4 Special Warnings and Precautions for Use

Use in renal impairment.

In patients with impaired renal function, such as reduction of urinary output because of renal insufficiency (creatinine clearance ≤ 50 mL/min) or other conditions that may compromise renal function, the dosage of cefepime should be adjusted to compensate for the slower rate of renal elimination. Because high and prolonged serum antibiotic concentrations can occur from usual doses in patients with renal insufficiency or other conditions that may compromise renal function, the maintenance dosage should be reduced when cefepime is administered to such, severity of infection, and susceptibility of the causative organisms (see Section 4.2 Dose and Method of Administration; Section 5 Pharmacological Properties).

Neurotoxicity.

During postmarketing surveillance, the following serious adverse events have been reported: reversible encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor and coma), myoclonus, seizures (including non-convulsive status epilepticus), and/or renal failure (see Section 4.8 Adverse Effects (Undesirable Effects)). Most cases occurred in patients with renal impairment who received doses of cefepime that exceeded recommendations. In general, symptoms of neurotoxicity resolved after discontinuation of cefepime and/or after haemodialysis however, some cases included a fatal outcome.
Renal function should be monitored carefully if drugs with nephrotoxic potential, such as aminoglycosides and potent diuretics, are administered with cefepime.

Hypersensitivity reactions.

Before therapy with cefepime is instituted, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to cefepime, cephalosporins, penicillins, or other beta-lactam antibiotics. Antibiotics should be administered with caution to any patient who has demonstrated some form of allergy, particularly to drugs. If an allergic reaction to cefepime occurs, discontinue the drug and treat the patient appropriately. Serious immediate hypersensitivity reactions may require adrenalin and other supportive therapy.

Clostridium difficile-associated diarrhea.

Pseudomembranous colitis has been reported with virtually all broad spectrum antibiotics including cefepime; therefore, it is important to consider this diagnosis in patients who develop diarrhoea in association with the use of antibiotics. Treatment with broad spectrum antibiotics alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of antibiotic associated colitis. Mild cases of pseudomembranous colitis may respond to drug discontinuation alone. In moderate to severe cases, management should include fluid, electrolyte and protein supplementation. When colitis does not improve after drug discontinuation or when it is severe, it should be treated with an antibiotic clinically effective against Clostridium difficile. Other causes of colitis should also be considered.

High risk patients.

In patients (adult and paediatric) at high risk for severe infection (including patients with a history of recent bone marrow transplantation, with hypotension at presentation, with an underlying haematologic malignancy, or with severe or prolonged neutropenia), antimicrobial monotherapy may not be appropriate. Insufficient data exist to support the efficacy of cefepime monotherapy in such patients.

Prolonged use.

As with other antibiotics, prolonged use of cefepime may result in overgrowth of nonsusceptible organisms. Should super-infection occur during therapy, appropriate measures should be taken.
If neutropenia occurs as a result of prolonged therapy, cefepime should be discontinued and alternative antibiotic therapy used.

History of gastrointestinal disease.

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

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in patients taking beta-lactam antibiotics. When SCAR is suspected, Cefepime-AFT should be discontinued immediately and an alternative treatment should be considered.

Use in the elderly.

Of the more than 6400 adults treated with cefepime in clinical studies, 35% were 65 years or older while 16% were 75 years or older. In clinical studies, when geriatric patients received the usual recommended adult dose, clinical efficacy and safety were comparable to clinical efficacy and safety in non-geriatric adult patients unless the patients had renal insufficiency. There was a modest prolongation in elimination half-life and lower renal clearance values compared to those seen in younger persons. Dosage adjustments are recommended if renal function is compromised (see Section 4.2 Dose and Method of Administration).
Cefepime is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and renal function should be monitored (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects); Section 5 Pharmacological Properties). Serious adverse events, including encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor and coma), myoclonus, seizures (including nonconvulsive status epileticus), and/or renal failure have occurred in geriatric patients with renal insufficiency given the usual dose of cefepime (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).

Paediatric use.

Experience with the use of cefepime in paediatric patients aged less than 2 months is limited. Safety and effectiveness in paediatric patients below the age of 2 months have not been established. Therefore the administration of cefepime to patients less than 2 months of age is not recommended.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Renal function should be monitored carefully if drugs with nephrotoxic potential, such as aminoglycosides and potent diuretics, are administered with Cefepime. Nephrotoxicity has been reported following concomitant administration of other cephalosporins with aminoglycoside antibiotics or potent diuretics such as frusemide.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Standard tests to assess fertility in rats show no impairment of fertility at exposure levels nearly two-fold higher than the calculated maximal daily human exposure.
(Category B1)
Reproduction studies performed in mice and rats showed no evidence of impaired fertility or harm to the foetus at dose levels equivalent to (mouse) or slightly greater (rat) than the maximum human daily dose when the daily doses are compared to those in man on a mg/m² basis. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Cefepime is excreted in human breast milk in very low concentrations. Although less than 0.01% of a 1 g I.V. dose is excreted in milk, caution should be used when cefepime is administered to a nursing woman.

Labour and delivery.

Cefepime has not been studied for use during labour and delivery. Treatment should only be given if clearly indicated.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Cefepime is generally well tolerated. In clinical trials (n = 5598) the most common adverse events were gastrointestinal symptoms and hypersensitivity reactions. Adverse events considered to be of definite, probable or possible relationship to cefepime are listed below.
Events that occurred at an incidence of > 0.1%-1% (except where noted) were as follows.

Hypersensitivity.

Rash (1.8%), pruritus, urticaria.

Gastrointestinal.

Nausea, vomiting, oral moniliasis, diarrhoea (1.2%), colitis (including pseudomembranous colitis).

Central nervous system.

Headache.

Other.

Fever, vaginitis, erythema.
Events that occurred at an incidence of 0.05%-0.1% were abdominal pain, constipation, vasodilation, dyspnoea, dizziness, paraesthesia, genital pruritus, taste perversion, chills and unspecified moniliasis.
Events that occurred at an incidence of < 0.05% included anaphylaxis and seizures.
Local reactions at the site of I.V. infusions occurred in 5.2% of patients; these included phlebitis (2.9%) and inflammation (0.1%). Intramuscular administration of cefepime was very well tolerated with 2.6% of patients experiencing pain or inflammation at the injection site.
Laboratory test abnormalities that developed during clinical trials in patients with normal baseline values were transient. Those that occurred at a frequency between 1% and 2% (unless noted) were: elevations in alanine aminotransferase (3.6%), aspartate aminotransferase (2.5%), alkaline phosphatase, total bilirubin, anaemia, eosinophilia, prolonged prothrombin time, partial prothrombin time (2.8%), and positive Coombs' test without haemolysis (18.7%). Transient elevations of serum urea, and/or serum creatinine and transient thrombocytopenia were observed in 0.5% to 1% of patients. Transient leucopenia and neutropenia were also seen (< 0.5%).

Skin and other subcutaneous tissue disorders.

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in beta-lactam antibiotics.

Postmarketing experience.

During postmarketing experience, encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor and coma), seizures, myoclonus and/or renal failure have been reported. Most cases occurred in patients with renal impairment who received doses of cefepime that exceeded recommendations (also see Section 4.4 Special Warnings and Precautions for Use).
Anaphylaxis including anaphylactic shock, transient leucopoenia, neutropenia, agranulocytosis and thrombocytopenia have been reported rarely.
Because of the uncontrolled nature of these spontaneous reports, a causal relationship to cefepime has not been determined.
The following adverse reactions and altered laboratory tests have been reported for cephalosporin class antibiotics: urticaria, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, aplastic anaemia, haemolytic anaemia, haemorrhage, hepatic dysfunction including cholestasis, and false positive tests for urinary glucose.