Cefepime

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications: 

• Nosocomial and community-acquired pneumonia caused by Staphylococcus aureus (methicillin-susceptible strains), Pseudomonas aeruginosa, Klebsiella species (including Klebsiella pneumoniae), Enterobacter species, Escherichia coli, Proteus mirabilis, Streptococcus pneumoniae (including intermediate penicillin resistant strains), Haemophilus influenzae (including beta-lactamase producing strains), Haemophilus parainfluenzae and Moraxella (Branhamella) catarrhalis (including beta-lactamase producing strains), including cases associated with bacteremia
• Acute bacterial exacerbation of chronic bronchitis and acute bronchitis due to Streptococcus pneumoniae (including intermediate penicillin resistant strains), Haemophilus influenzae (including beta-lactamase producing strains), Moraxella (Branhamella) catarrhalis (including beta-lactamase producing strains)
• Complicated urinary tract Infections caused by Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis and Enterobacter species, including cases associated with bacteremia
• Uncomplicated urinary tract infections due to Escherichia coli, Proteus mirabilis, Klebsiella species and Enterobacter species
• Skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible strains), Streptococcus pyogenes (Group A streptococci), Streptococcus agalactiae (Group B streptococci), other beta-haemolytic Streptococcus species, Enterobacter species, Klebsiella species, Proteus mirabilis, Morganella morganii, Escherichia coli, Serratia marcescens and Acinetobacter calcoaceticus
• Complicated intra-abdominal Infections Including peritonitis and biliary tract infections caused by Escherichia coli, sensitive Pseudomonas aeruginosa
• Febrile neutropenia

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other cephalosporins
• History of severe hypersensitivity to any other type of beta-lactam antibiotics (penicillins, monobactams and carbapenems)

Cautions

• History of non-severe hypersensitivity to other beta-lactam agents
• Pregnancy
• Breastfeeding
• Moderate to severe renal impairment
• Elderly patients with renal failure
• History of asthma or allergic diathesis
• Patients that have shown some form of allergy, particularly to medicines
• May impair ability to drive or operate machinery

Forms avail. in SA and covered in this monograph: inj

Adult dosages below include:

• General dosing range
• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages 
• Indications and dosages registered in other jurisdictions

Infections caused by: Gram-positive aerobes such as Staphylococcus aureus and coagulase-negative staphylococci including beta-lactamase producing strains; Streptococci; Gram-positive aerobes such as Pneumococci; Acinetobacteria;  Aeromonas spp; Citrobacter; Enterobacteriae; Escherichia coli; Haemophilus influenzae including beta-lactamase producing stains; Klebsiella; Moraxella catarrhalis including beta-lactamase-producing stains; Morganella morganii; Proteus; Providencia; Pseudomonas; Serratia; C. freundii; C. koseri; Y. enterocolitica 

General dosing range

• IV: 1-2g, 8-12hrly

---

See additional prescribing points for administration directions

---

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Febrile neutropenia (Additional agent required)
- If fever develops after 48hrs of admission

• IV: 2g, 12hrly; If neutrophil count increases to >0.5X10⁹/L: Treatment duration: Continue for 2 days after fever has settled; If neutrophil count remains ≤0.5X10⁹/L: Treatment duration: Continue for 7 days after fever has settled
  (STG, Adult 2019)

Hospital-acquired pneumonia (Additional agent required)
- With prior intravenous antibiotic use within 90 days and ventilator-associated pneumonia (VAP)

• IV: 2g, 12hrly; Treatment duration: 10 days
  (STG, Adult 2019)

---

South African registered indications and dosages

Mild to moderate urinary tract infections
- Uncomplicated and complicated

• IV/IM: 500mg-1g, 12hrly; Max dose: 2g/8hrly; Treatment duration: 7-10 days

Mild to moderate infections
- Bronchitis
- Skin and skin structure infections

• IV/IM: 1g, 12hrly; Max dose: 2g/8hrly; Treatment duration: 7-10 days

---

When P. aeruginosa is isolated or suspected, combination therapy with an aminoglycoside should be used

---

Severe infections
- Pneumonia
- Urinary tract infections
- Complicated intra-abdominal infections, including cases with associated bacteraemia

• IV: 2g, 12hrly; Max dose: 2g/8hrly; Treatment duration: 7-10 days - more severe infections may require longer treatment

---

In patients who are at risk of mixed aerobic-anaerobic infection, including infections in which Bacteroides fragilis may be present, concurrent therapy with an anti-anaerobic agent is recommended

---

Empiric treatment of fever in neutropenic patients

• IV: 2g, 8hrly; Max dose: 2g/8hrly; Treatment duration: 7 days or until resolution of neutropenia

---

Combination of cefepime with other appropriate antimicrobial agents should be considered in patients at high risk for severe infection (including patients with a history of recent bone marrow transplantation, hypotension at presentation, an underlying haematologic malignancy, or severe or prolonged neutropenia) or when called for by host or local epidemiological factors

---

Doses above relate to patients weighing >40kg

---

In the treatment of beta-haemolytic streptococcal infections, a therapeutic dose must be administered for at least 10 days

---

Indications and dosages registered in other jurisdictions

Lower respiratory tract infections, including:
- Nosocomial pneumonia
- Community-acquired pneumonia
- Acute bacterial exacerbation of chronic bronchitis
- Secondary bacterial infection of acute bronchitis
Skin and subcutaneous infections
Intra-abdominal infections
- Peritonitis
- Biliary tract infections
Gynaecological infections
Management of neutropenic patients with fever that is suspected to be due to a bacterial infection (additional agents required)
Treatment of bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above

Mild to moderate infections (non-urinary tract infections)

• IV/IM: 1g, 12hrly; Max dose: 2g/8hrly; Treatment duration: 7-10 days

Severe infections

• IV: 2g, 12hrly; Max dose: 2g/8hrly; Treatment duration: 7-10 days - more severe infections may require longer treatment

Very severe or life-threatening infections

• IV: 2g, 8hrly; Max dose: 2g/8hrly; Treatment duration: 7-10 days - more severe infections may require longer treatment

---

More severe infections can require a more prolonged treatment

---

In the empirical treatment of febrile neutropenia, the usual treatment duration should not be less than 7 days or until resolution of the neutropenia

---

In patients weighing ≤40kg, the posology indicated for children is recommended

---

Mild to moderate urinary tract infections
- Uncomplicated and complicated urinary tract infections, including pyelonephritis

• IV/IM: 500mg-1g, 12hrly; Max dose: 2g/8hrly; Treatment duration: 7-10 days

Paed. forms avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• General dosing range
• South African registered indications and dosages 
• Indications and dosages registered in other jurisdictions

Infections caused by: Gram-positive aerobes such as Staphylococcus aureus and coagulase-negative staphylococci including beta-lactamase producing strains; Streptococci; Gram-positive aerobes such as Pneumococci; Acinetobacteria;  Aeromonas spp; Citrobacter; Enterobacteriae; Escherichia coli; Haemophilus influenzae including beta-lactamase producing stains; Klebsiella; Moraxella catarrhalis including beta-lactamase-producing stains; Morganella morganii; Proteus; Providencia; Pseudomonas; Serratia; C. freundii; C. koseri; Y. enterocolitica 

General dosing range

Older than 28 days 

Non-pseudomonal

• IV/IM: 100mg/kg/day, in 3 divided doses

Pseudomonal

• IV/IM: 150mg/kg/day, in 3 divided doses

---

See additional prescribing points for administration directions

---

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African registered indications and dosages

Pneumonia
Urinary tract infections
Skin structure infections

Younger than 2 months

• Not established for use
  Experience in this age group is limited and administration of cefepime in these patients should be carefully monitored

Between 2 months - 12 years and <40kg

• IV: 50mg/kg, 12hrly; Max dose: 2g/8hrly; Max duration: 10 days - more severe infections may require 8hrly dosing to be used

Children >40kg

• See adult dosage  

Empiric treatment of febrile neutropenia

Younger than 2 months

• Not established for use
  Experience in this age group is limited and administration of cefepime in these patients should be carefully monitored

Between 2 months - 12 years and <40kg

• IV: 50mg/kg; 8hrly; Max dose: 2g/8hrly; Max duration: 7-10 days

Children >40kg

• See adult dosage  

---

Children with renal impairment: Caution; dose adjustment recommended

---

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 (2g/8hrly)

---

Experience with intramuscular administration in paediatric patients is limited

---

Indications and dosages registered in other jurisdictions

Pneumonia
Urinary tract infection
Skin and subcutaneous tissue infection 

Younger than 1 month

• No information available

Between 1-2 months

• 30mg/kg, 8-12hrly

---

Experience in this age group is limited and administration of cefepime in these patients must be carefully monitored. The dosage above is based on data extrapolated from pharmacokinetic models obtained from children aged >2 months old on a 50mg/kg dosage

---

Older than 2 months and ≤40kg ₁₁

• IV: 50mg/kg, 12hrly; Max dose: 2g/8hrly; Treatment duration 10 days - more severe infections may require 8hrly dosing to be used

Children >40kg

• See adult dosage

---

The maximum recommended dose for adults (2g, 8hrly) should not be exceeded

---

Bacteraemia that occurs in association with infections, bacterial meningitis and empirical treatment of febrile neutropenia

Younger than 1 month

• No information available

Between 1-2 months

• 30mg/kg, 8-12hrly

---

Experience in this age group is limited and administration of cefepime in these patients must be carefully monitored. The dosage above is based on data extrapolated from pharmacokinetic models obtained from children aged >2 months old on a 50mg/kg dosage

---

Older than 2 months and ≤40kg

• IV: 50mg/kg, 8hrly; Max dose: 2g/8hrly; Treatment duration: 7-10 days  

Children >40kg

• See adult dosage

---

The maximum recommended dose for adults (2g, 8hrly) should not be exceeded

---

The experience with intramuscular use in children is limited

---

Children with renal impairment: Caution; dose adjustment recommended

Pregnancy

• Caution
• There is insufficient data on exposure during pregnancy
• Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, labour or post-natal development
• Cefepime should only be prescribed to pregnant women with great caution

Breastfeeding

• Caution
• Cefepime is excreted in human milk in very low quantities, so caution is recommended when administered to the breastfeeding woman

Fertility

• There are no data on the use of cefepime in human fertility. Reproductive studies in animals did not reveal any effects on fertility

Renal Impairment

• Mild: No dose adjustment recommended
• Moderate to severe: Caution; dose adjustment recommended

eGFR (ml/min/1.73m2)	Adult maintenance doses
Loading dose: No adjustment necessary and should be administered in full as calculated mg/kg if needed
≥60- 89	No adjustment necessary
≥19- 59	Administer normal dose, 24hrly
<19	Reduce daily dose by 50%; Administer 24hrly
<10 Haemodialysis	Reduce daily dose by 50%; Administer after dialysis session

 

eGFR (ml/min/1.73m2)	Paediatric maintenance dose
Loading dose: No adjustment necessary and should be administered in full as calculated mg/kg if needed
>50	No adjustment necessary
10-50	50mg/kg, 24hrly
<10	50mg/kg, 48hrly
Intermittent haemodialysis	50mg/kg, 24hrly
Peritoneal dialysis (PD)	50mg/kg, 24hrly
Continuous renal replacement therapy (CRRT)	50mg/kg, 12hrly

Hepatic Impairment

• No dose adjustment recommended

Elderly

• No dose adjustment recommended
  Dose adjustment needed in impaired renal function

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• State of confusion
• Hallucination
• Headaches
• Seizures
• Paraesthesia
• Dizziness
• Coma
• Stupor
• Encephalopathy
• Altered state of consciousness
• Myoclonus

Cardiovascular Disorders

• Infusion site phlebitis
• Vasodilation
• Haemorrhage

Respiratory Disorders

• Dyspnoea

Gastrointestinal Disorders

• Diarrhoea
• Pseudomembranous colitis
• Colitis
• Nausea and vomiting
• Abdominal pain
• Constipation

Hepatobiliary Disorders

• Increased alkaline phosphatase
• Increased alanine aminotransferase
• Increased aspartate aminotransferase
• Increased blood bilirubin

Genitourinary Disorders

• Increased blood urea
• Increased blood creatinine
• Renal failure
• Toxic nephropathy
• Genital pruritis
• False-positive glycosuria

Skin and Subcutaneous Tissue Disorders

• Rash
• Erythema
• Urticaria
• Pruritis
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Erythema multiforme
• Infusion site reaction
• Injection site inflammation and pain

Immune, Blood and Lymphatic System Disorders

• Oral candidiasis
• Vaginal infection
• Candidiasis
• Anaemia
• Eosinophilia
• Thrombocytopenia
• Leukopenia
• Neutropenia
• Aplastic anaemia
• Haemolytic anaemia
• Agranulocytosis
• Anaphylactic reaction
• Angioedema
• Anaphylactic shock  
• Fever
• Chills
• Prolonged prothrombin time
• Prolonged partial thromboplastin time

Sensory Disorders

• Dysgeusia

Others

• Positive Coombs test

• Bacteriostatic antibiotics
• Nephrotoxic agents
• Aminoglycosides
• Potent diuretics
• Coumarin anticoagulants

Other interactions

• Interference with serological tests (See additional prescribing points)
  - Coombs test
  - Copper reduction tests (Benedict's or Fehling's solution or with Clinitest tablets)
• Physical-chemical incompatibilities (See additional prescribing points)

None routine. Specific cases may require

• Renal function

Additional observations

• Signs and symptoms of anaphylaxis during first dose

Injection 1g, Injection 2g - EML (Hospital)

---

Administration directions

Cefepime should be dissolved in:

• water for injection;
• sodium chloride 0.9% solution;
• sodium chloride 0.9% with glucose 5% solution;
• glucose 5% or 10% solution;
• Ringer lactate solution;
• Ringer lactate with glucose 5% solution;
• sodium lactate 1/6M solution

For intravenous injection, the volume of the solvent to be added to each vial and the resulting concentration of cefepime are:

Quantity of cefepime per vial	Volume of solvent added (ml)	Approximate final volume (ml)	Approximate concentration of cefepime (mg/ml)
1.0g IV	10.0	11.4	90
2.0g IV	10.0	12.8	160

For intravenous infusion, the volume f solvent for infusion to be used for reconstitution and the resulting concentration of cefepime are:

Quantity of cefepime per vial	Volume of solvent added (ml)	Approximate final volume (ml)	Approximate concentration of cefepime (mg/ml)
1.0g IV	50.0	51.4	19
2.0g IV	50.0	52.8	38

The resulting solution should be administered over approximately 30mins

For intramuscular injection, reconstitute the 1g vial by using 3.0ml of water for injections

Interaction with diagnostic tests

• A positive Coombs test, without evidence of haemolysis has been described in patients treated with cefepime twice daily
• Cephalosporin antibiotics may produce a false-positive reaction for glucose in the urine with copper reduction tests (Benedict's or Fehling's solution or with Clinitest tablets), but not with enzyme-based tests (glucose oxidase) for glycosuria. Therefore, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be used

Physical-chemical incompatibilities

• There is a physical-chemical incompatibility with:
  - Metronidazole
  - Vancomycin
  - Gentamicin
  - Tobramycin
  - Netilmicin
  - Aminophylline
• In the cases where a concomitant intravenous administration is indicated, these active substances should not be administered together with cefepime or through the same intravenous route

Cefepime is a broad-spectrum, bactericidal antibiotic, with activity against a wide range of gram-positive and gram-negative bacteria, including many strains resistant to aminoglycosides or third generation cephalosporins. It is highly resistant to hydrolysis caused by most beta-lactamases. It has a reduced affinity for beta-lactamases changed via chromosomes and has a rapid penetration in the cells of the gram-negative bacteria. It acts by inhibition of bacterial cell wall synthesis.

Spectrum of activity: Gram-positive aerobes such as Staphylococcus aureus and coagulase-negative staphylococci including beta-lactamase producing strains; Streptococci; Gram-negative aerobes such as Pneumococci; Acinetobacteria;  Aeromonas spp; Citrobacter; Enterobacteriae; Escherichia coli; Haemophilus influenzae including beta-lactamase producing stains; Klebsiella; Moraxella catarrhalis including beta-lactamase producing stains; Morganella morganii; Proteus; Providencia; Pseudomonas; Serratia; C. freundii; C. koseri; Y. enterocolitica

 

 

 

 

Injection (per vial) 500mg

• Maxipime (Bristol-Myers) originator

Injection (per vial) 1g

• Auro-Cefepime (Aurobindo)
• Cefect (Actor)
• Cefepime Actor 1 (Actor)
• Cefepime 1g Fresenius (Fresenius Kabi)
• Cefepime Safeline 1g (Safeline Pharmaceuticals)
• Critipeme (Sandoz)
• Maxipime (Bristol-Myers) originator

Injection (per vial) 2g

• Auro-Cefepime (Aurobindo)
• Cefect (Actor)
• Cefepime Actor 2 (Actor)
• Cefepime 2g Fresenius (Fresenius Kabi)
• Cefepime Safeline 2g (Safeline Pharmaceuticals)
• Critipeme (Sandoz SA)
• Maxipime (Bristol-Myers) originator