MAXIPIME (cefepime hydrochloride) for injection

MAXIPIME (cefepime hydrochloride) for injection

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MAXIPIME (cefepime hydrochloride) for injection

MAXIPIME (cefepime hydrochloride, USP) is a semi-synthetic, cephalosporin antibacterial for parenteral administration. The chemical name is 1-[[(6R,7R)-7-[2-(2-amino-4-thiazolyl)-glyoxylamido]-2-carboxy-8- oxo-5-thia-1-azabicyclo[4.2.0] oct-2-en-3-yl]methyl]-1-methylpyrrolidinium chloride,72 -(Z)-(Omethyloxime), monohydrochloride, monohydrate.

Cefepime hydrochloride is a white to pale yellow powder. Cefepime hydrochloride contains the equivalent of not less than 825 mcg and not more than 911 mcg of cefepime (C19H24N6O5S2) per mg, calculated on an anhydrous basis. It is highly soluble in water.

Indications and usage

MAXIPIME is a cephalosporin antibacterial indicated for the treatment of the following infections caused by susceptible strains of the designated microorganisms:

  • Pneumonia.
  • Empiric therapy for febrile neutropenic patients.
  • Uncomplicated and complicated urinary tract infections (including pyelonephritis).
  • Uncomplicated skin and skin structure infections.
  • Complicated intra-abdominal infections (used in combination with metronidazole) in adults

To reduce the development of drug-resistant bacteria and maintain the effectiveness of MAXIPIME and other antibacterial drugs, MAXIPIME should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Mechanism of Action

Cefepime is a bactericidal drug that acts by inhibition of bacterial cell wall synthesis. Cefepime has a broad spectrum of in vitro activity that encompasses a wide range of Gram-positive and Gram-negative bacteria. Within bacterial cells, the molecular targets of cefepime are the penicillin binding proteins (PBP).

Antimicrobial Activity

Cefepime has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections as described in the Indications and Usage

Gram-negative Bacteria

  • Enterobacter spp.
  • Escherichia coli
  • Klebsiella pneumoniae
  • Proteus mirabilis
  • Pseudomonas aeruginosa

Gram-positive Bacteria

  • Staphylococcus aureus (methicillin-susceptible isolates only)
  • Streptococcus pneumoniae
  • Streptococcus pyogenes
  • Viridans group streptococci

Dosage and administration

Recommended Dosage in Adults with Creatinine Clearance (CrCL) Greater Than 60 mL/min (2.1)
Site and Type of InfectionDoseFrequencyDuration (days)
Moderate to Severe Pneumonia§1-2 g IVEvery 8-12 hours10
Empiric Therapy for Febrile Neutropenic Patients2 g IVEvery 8 hours7*
Mild to Moderate Uncomplicated or Complicated Urinary Tract Infections0.5-1 g IV/IM**Every 12 hours07/10/21
Severe Uncomplicated or Complicated Urinary Tract Infections2 g IVEvery 12 hours10
Moderate to Severe Uncomplicated Skin and Skin Structure Infections2 g IVEvery 12 hours10
Complicated Intra-abdominal Infections§ (used in combination with metronidazole)2 g IVEvery 12 hours07/10/21

§For Pseudomonas aeruginosa, use 2 g IV every 8 hours.

*Or until resolution of neutropenia.

**Intramuscular route of administration is indicated only for mild to moderate, uncomplicated or complicated UTIs due to E. coli

Pediatric Patients (2 months to 16 years)

Recommended dosage in pediatric with CrCL greater than 60 mL/min

  • • The usual recommended dosage in pediatric patients is 50 mg per kg per dose administered every 12 hours (every 8 hours for febrile neutropenia).

Contraindications

Patients with known immediate hypersensitivity reactions to cefepime or other cephalosporins, penicillins or other beta-lactam antibacterial drugs.

Warnings and precautions

  • Hypersensitivity Reactions: Cross-hypersensitivity among beta-lactam antibacterial drugs may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to MAXIPIME occurs, discontinue the drug.
  • Neurotoxicity: May occur especially in patients with renal impairment administered unadjusted doses. If neurotoxicity associated with MAXIPIME therapy occurs, discontinue the drug.
  • Clostridioides difficile-Associated Diarrhea (CDAD): Evaluate if diarrhea occurs.

Adverse reactions

The most common adverse reactions (incidence ≥ 1%) were local reactions, positive Coombs’ test, decreased phosphorous, increased ALT and AST, increased PT and PTT and rash. At the highest dose (2 g every 8 hours), incidence of adverse reactions was ≥1% for rash, diarrhea, nausea, vomiting, pruritis, fever, and headache.

Drug interactions

  • Aminoglycosides: increased potential of nephrotoxicity and ototoxicity. Monitor renal function.
  • Diuretics: nephrotoxicity has been reported following concomitant administration of other cephalosporins with potent diuretics such as furosemide. Monitor renal function.
Us ein specific populations

Pregnancy: There are no cases of MAXIPIME exposure during pregnancy reported from postmarketing experience or from clinical trials. Available data from published observational studies and case reports over several decades with cephalosporin use in pregnant women have not established drug-associated risks of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Lactation: Cefepime is present in human breast milk at low concentrations (approximately 0.5 mcg/mL) following a single intravenous dose of 1000 mg. A nursing infant consuming approximately 1000 mL of human milk per day would receive approximately 0.5 mg of cefepime per day. There is no information regarding the effects of cefepime on the breastfed infant or on milk production.

Pediatric Use: The safety and effectiveness of cefepime in the treatment of uncomplicated and complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, pneumonia, and as empiric therapy for febrile neutropenic patients have been established in the age groups 2 months up to 16 years. Use of MAXIPIME in these age groups is supported by evidence from adequate and well-controlled studies of cefepime in adults with additional pharmacokinetic and safety data from pediatric trials.

Safety and effectiveness in pediatric patients below the age of 2 months have not been established. There are insufficient clinical data to support the use of MAXIPIME in pediatric patients for the treatment of serious infections in the pediatric population where the suspected or proven pathogen is H. influenzae type b. In those patients in whom meningeal seeding from a distant infection site or in whom meningitis is suspected or documented, an alternate agent with demonstrated clinical efficacy in this setting should be used.

Geriatric Use: Of the more than 6400 adults treated with MAXIPIME in clinical studies, 35% were 65 years or older while 16% were 75 years or older. 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.

Serious adverse events have occurred in geriatric patients with renal insufficiency given unadjusted doses of cefepime, including life-threatening or fatal occurrences of the following: encephalopathy, myoclonus, and seizures.

This drug 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.

Renal Impairment: Adjust the dose of MAXIPIME in patients with creatinine clearance less than or equal to 60 mL/min to compensate for the slower rate of renal elimination.

Overdosage

Patients who receive an overdose should be carefully observed and given supportive treatment. In the presence of renal insufficiency, hemodialysis, not peritoneal dialysis, is recommended to aid in the removal of cefepime from the body. Symptoms of overdose include encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, neuromuscular excitability and nonconvulsive status epilepticus.

Storage and Handling

MAXIPIME for injection in the dry state should be stored at 20 to 25° C (68 to 77° F) [see USP controlled room temperature] and protected from light.

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