Cefprozil

J01D - Other beta-lactam antibacterials ATC J01DC10 Small molecule Prodrug First-in-class Natural product Orphan

🧬 Cross-allergy: Cephalosporins

JFDA label: Quzil 500mg

Mechanism of Action

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Indications

Approved

Acute bacterial exacerbation of chronic bronchitis
Otitis media
Pharyngitis/tonsillitis
Skin and skin-structure infections, uncomplicated

Off-label

Community-acquired pneumonia treatment in children 3 months to younger than 12 years caused by S. pneumoniae
Urinary tract infections in children (empiric)

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: openfda-label.

Bacteria

Organism	Activity	MIC
Bacteroides fragilis	Active	—
Citrobacter diversus	Active	—
Clostridium difficile	Active	—
Clostridium perfringens	Active	—
Enterococcus durans	Active	—
Enterococcus faecalis	Active	—
Enterococcus faecium	Active	—
Escherichia coli	Active	—
Haemophilus influenzae	Active	—
Klebsiella pneumoniae	Active	—
Listeria monocytogenes	Active	—
Morganella morganii	Active	—
Neisseria gonorrhoeae	Active	—
Proteus mirabilis	Active	—
Proteus vulgaris	Active	—
Staphylococcus aureus	Active	—
Staphylococcus epidermidis	Active	—
Staphylococcus saprophyticus	Active	—
Staphylococcus warneri	Active	—
Streptococcus agalactiae	Active	—
Streptococcus pneumoniae	Active	—
Streptococcus pyogenes	Active	—

Class profile

gramStatus	Both
spectrumBreadth	Moderate
atypicalCoverage	No
isBactericidal	1
moaCategory	Cell wall synthesis inhibitor (beta-lactam, 2nd generation cephalosporin)
pdIndex	Time-dependent
postAntibioticEffect	None
mrsaCoverage	0
resistanceMechanisms	Beta-lactamase production,PBP mutations

Contraindications

Source: Lexicomp

Hypersensitivity to cefprozil, any component of the formulation, or other cephalosporins Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (1)

Common Dizziness

Hepatobiliary disorders (1)

Common Increased serum transaminases

Renal and urinary disorders (1)

Common Vaginitis

Gastrointestinal disorders (4)

Common abdominal pain · diarrhea · Nausea · vomiting

Skin and subcutaneous tissue disorders (2)

Common Diaper rash · genital pruritus

Infections and infestations (1)

Common Superinfection

Dosing

Source: Lexicomp

Acute bacterial exacerbation of chronic bronchitis: Oral: 500 mg every 12 hours for 10 days Pharyngitis/tonsillitis: Oral: 500 mg every 24 hours for 10 days (administer for ≥10 days if due to S. pyogenes) Skin and skin-structure infections, uncomplicated: Oral: 250 to 500 mg every 12 hours, or 500 mg every 24 hours for 10 days

(For additional information see "Cefprozil: Pediatric drug information") Acute bacterial exacerbation of chronic bronchitis: Children >12 years and Adolescents: Refer to adult dosing. Otitis media: Oral: Infants ≥6 months and Children: 15 mg/kg/dose every 12 hours for 10 days (maximum: 500 mg/dose) Pharyngitis/tonsillitis: Children 2 to 12 years: Oral: 7.5 mg/kg/dose every 12 hours for 10 days (administer for ≥10 days if due to S. pyogenes) (maximum: 500 mg/day) Children >12 years and Adolescents: Refer to adult dosing. Skin and skin-structure infections, uncomplicated: Children 2 to 12 years: Oral: 20 mg/kg/day once every 24 hours for 10 days (maximum: 1,000 mg/day) Children >12 years and Adolescents: Refer to adult dosing. Urinary tract infection (off-label use): Infants and Children 2 to 24 months: Oral: 15 mg/kg/dose twice daily for 7 to 14 days (AAP, 2011)

Refer to adult dosing.

Manufacturer's labeling: Infants, Children, Adolescents, and Adults: Oral: CrCl ≥30 mL/minute: No dosage adjustment necessary. CrCl End-stage renal disease (ESRD) on hemodialysis: Give dose after dialysis on dialysis days. Alternative recommendations (Aronoff, 2007): Adults: Oral: CrCl >50 mL/minute: No dosage adjustment necessary CrCl Intermittent hemodialysis (IHD): Supplement with 250 mg after dialysis on dialysis days Peritoneal dialysis: Administer 50% of usual dose every 12 hours Infants, Children, and Adolescents: Oral: Recommendations based on 30 mg/kg/day divided every 12 hours in patients with normal renal function: GFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary. GFR 2: 7.5 mg/kg/dose every 12 hours ESRD on hemodialysis: 7.5 mg/kg/dose every 12 hours; supplement with 5 mg/kg/dose after dialysis on dialysis days Peritoneal dialysis: 7.5 mg/kg/dose every 12 hours

No dosage adjustment necessary.

Warnings & Precautions

Source: Lexicomp

Hypersensitivity

If a serious hypersensitivity reaction occurs, discontinue and institute emergency supportive measures, including airway management and treatment (eg, epinephrine, antihistamines and/or corticosteroids).

Penicillin allergy

Use with caution in patients with a history of penicillin allergy.

Superinfection

Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Disease-related concerns:

Gastrointestinal disease

Use with caution in patients with a history of gastrointestinal disease, particularly colitis.

Renal impairment

Use with caution in patients with renal impairment; modify dosage in severe impairment. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Benzyl alcohol and derivatives

Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982). Some data suggest that benzoate displaces bilirubin from protein-binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Phenylalanine

Some products may contain phenylalanine.

Polysorbate 80

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade, 1986; CDC, 1984). See manufacturer's labeling.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events were not observed in animal reproduction studies.

Lactation

Small amounts of cefprozil are excreted in breast milk. The manufacturer recommends that caution be exercised when administering cefprozil to nursing women. Nondose-related effects could include modification of bowel flora.

Monitoring

Efficacy	Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin)
Toxicity	Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea)
Clinical pearl	Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship).
Counseling	Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h.

Chemistry & Properties

Formula	C18H19N3O5S
Molecular weight	389.43 g/mol
IUPAC name	(6R,7R)-7-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-prop-1-enyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
CAS	92665-29-7
PubChem CID	62977
InChIKey	`WDLWHQDACQUCJR-PBFPGSCMSA-N`
logP	0.71 (XLogP -1.4)
Polar surface area	132.96 Å²
H-bond acceptors / donors	6 / 4
Drug-likeness (QED)	0.55
Lipinski violations	0

SMILES

CC=CC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)[C@H](N)c3ccc(O)cc3)[C@H]2SC1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	1.152 h
Volume of distribution	0.224 L/kg
Protein binding	44.0%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2D6	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (14, DDInter)

Interacting drug	Severity	Management
Amikacin	moderate
Amikacin (liposome)	moderate
Balsalazide	moderate
Chloramphenicol	moderate
Dicoumarol	moderate
Ethinylestradiol	moderate
Gentamicin	moderate
Kanamycin	moderate
Mycophenolic acid	moderate
Neomycin	moderate
Pemetrexed	moderate
Picosulfuric acid	moderate
Streptomycin	moderate
Warfarin	moderate

Registered Products (6)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Quzil Suspension	Suspension 125 mg/5 ml	75 ml	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	6.430
Aurozil	Tablet 250 mg	10 tab	AL Rahma Drug Store	8.790
Quzil	Tablet 250 mg	10 tab	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	8.790
Quzil	Suspension 250 mg/5 ml	75 ml	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	11.030
Aurozil	Tablet 500 mg	10 tab	AL Rahma Drug Store	14.420
Quzil	Tablet 500 mg	10 tab	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	14.840