Cefepime-Enmetazobactam

Cefepime-Enmetazobactam is a combination medication indicated for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Enterobacter cloacae complex.

• Cefepime-Enmetazobactam is available under the following different brand names: Exblifep

Common side effects of Cefepime-Enmetazobactam include:

• pain and inflammation at the infusion site
• diarrhoea
• skin rash
• headache
• nausea 
• vomiting
• increased transaminases
• increased bilirubin
• anemia

Serious side effects of Cefepime-Enmetazobactam include:

• abdominal pain
• bacterial infection
• hypersensitivity reactions
• chest pain
• eructation
• fungal infection
• gastroenteritis
• insomnia
• pneumonia
• restlessness
• urinary retention

Rare side effects of Cefepime-Enmetazobactam include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms include sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injection, powder for reconstitution

• 2 g/0.5 g (2.5 g/vial)

Complicated Urinary Tract Infection

Adult dosage

• 2.5 g IV every 8 hours  for 7 days; may administer up to 14 days for patients with concurrent bacteremia

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Cefepime-Enmetazobactam has severe interactions with no other drugs
• Cefepime-Enmetazobactam has serious interactions with the following drugs:
  • BCG intravesical live
  • BCG vaccine live
  • cholera vaccine
  • microbiota oral
  • typhoid vaccine live
• Cefepime-Enmetazobactam has moderate interactions with at least 30 other drugs
• Cefepime-Enmetazobactam has minor interactions with the following drug:
  • aminohippurate sodium

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• History of serious hypersensitivity reaction to components of Cefepime-Enmetazobactam or other beta-lactam antibiotics

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Cefepime-Enmetazobactam?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Cefepime-Enmetazobactam?”

Cautions

• Many cephalosporins, including Cefepime, have been associated with decreased prothrombin activity; monitor prothrombin time in patients at risk (eg, renal or hepatic impairment, poor nutritional state, protracted course of antibiotics); administer exogenous vitamin K as indicated
• Prescribing antibiotics in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit and increases the risk of developing drug-resistant bacteria
• Neurotoxicity
  • Neurotoxicity reported, including life-threatening or fatal occurrences of the following: encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), aphasia, myoclonus, seizures, and nonconvulsive status epilepticus
  • Most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment
  • If neurotoxicity occurs, discontinue and institute appropriate supportive measures
• C difficile-associated diarrhea
  • C difficile-associated diarrhea (CDAD) is reported with the use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis
  • Consider CDAD in all patients who present with diarrhea following antibacterial therapy
  • Carefully review the patient’s medical history since CDAD has been reported to occur over 2 months after administration
  • If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C difficile may need to be discontinued
  • Institute appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C difficile, and surgical evaluation as clinically indicated
• Hypersensitivity reactions
  • Hypersensitivity reactions reported
  • Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, and serious skin reactions reported with beta-lactam antibiotics
  • Before initiating, carefully inquire about previous hypersensitivity reactions to cefepime, cephalosporins, penicillins, or other beta-lactams
  • If an allergic reaction occurs, discontinue and institute appropriate supportive measures
• Coombs test
  • Positive direct Coombs tests with or without hemolysis were reported during treatment with cefepime
  • In patients who develop hemolytic anemia, discontinue therapy and institute appropriate therapy
  • Positive Coombs test may be observed in newborns whose mothers have received cephalosporin antibacterial drugs before parturition
• Drug interaction overview
  • Aminoglycosides
    • Monitor renal function
• Cefepime-Enmetazobactam may increase the potential of nephrotoxicity and ototoxicity of aminoglycosides
• Diuretics
  • Monitor renal function
  • Nephrotoxicity was reported following coadministration of other cephalosporins with potent diuretics (eg, furosemide)
• Drug/laboratory tests
  • False-positive urine glucose tests reported
  • Use glucose tests based on enzymatic glucose oxidase reactions
  • Cefepime may cause a false-positive reaction for glucose in the urine when using some methods (eg, Clinitest tablets)

Pregnancy and Lactation

• Data are unavailable regarding the use of Cefepime-Enmetazobactam, or enmetazobactam during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
• Available data from published observational studies and case reports over several decades with cephalosporin use, including cefepime, in pregnant women have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes
• Lactation
  • There is no information regarding the effects of cefepime, enmetazobactam, or their combination on the breastfed infant or milk production
• Cefepime
  • Present in human breast milk at low concentrations (approximately 0.5 mcg/mL) following a single IV 1,000 mg dose
  • A nursing infant consuming approximately 1,000 mL of human milk per day would receive approximately 0.5 mg of cefepime per day
• Enmetazobactam
  • Present in the milk of lactating rats
  • When a drug is present in animal milk, it is likely that the drug will be present in human milk