Cefprozil

Class: Second Generation Cephalosporins
Chemical Name: (6R, 7R) - 7 - [(R) - 2 - amino - 2 - (p - hydroxyphenyl)acetamido] - 8 - oxo - 3 - propenyl - 5 - thia - 1 - azabicyclo[4.2.0]oct - 2 - ene - 2 - carboxylic acid monohydrate
CAS Number: 92665-29-7
Brands: Cefzil

Introduction

Antibacterial; β-lactam antibiotic; second generation cephalosporin.^{1 a}

Uses for Cefprozil

Acute Otitis Media (AOM)

Treatment of AOM caused by S. pneumoniae, H. influenzae (including β-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains).^{1 3 4 12 21 30 36 37 43 44 45 62 80 81}

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci).¹ Generally effective in eradicating S. pyogenes from the nasopharynx, but efficacy in prevention of subsequent rheumatic fever has not been established to date.^{1 80 81}

CDC, AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice;^{48 49 50 59 76} oral cephalosporins and oral macrolides considered alternatives.^{48 49 50 59 76} Amoxicillin sometimes used instead of penicillin V, especially for young children.^{48 50}

Respiratory Tract Infections

Treatment of acute sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase-producing strains), or Moraxella catarrhalis (including β-lactamase-producing strains).^{1 34 65 80 81}

Treatment of secondary bacterial infections of acute bronchitis caused by susceptible S. pneumoniae, H. influenzae (including β-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains).^{1 16 38 80 81}

Treatment of acute bacterial exacerbation of chronic bronchitis caused by susceptible S. pneumoniae, H. influenzae (including β-lactamase producing strains), or M. catarrhalis (including β-lactamase producing strains).^{1 16 38 80 81}

Treatment of mild to moderate community-acquired pneumonia† (CAP).²⁰ If an oral cephalosporin is used as an alternative to penicillin G or amoxicillin for treatment of CAP caused by penicillin-susceptible S. pneumoniae, ATS and IDSA recommend cefpodoxime, cefprozil, cefuroxime, cefdinir, or cefditoren.²⁰

Skin and Skin Structure Infections

Treatment of uncomplicated skin and skin structure infections caused by Staphylococcus aureus (including penicillinase-producing strains) or S. pyogenes.^{1 10 35 63 80 81}

Also has been used for treatment of uncomplicated skin and skin structure infections caused by S. epidermidis†, S. saprophyticus†, group B or G streptococci†, E. coli†, or K. pneumoniae†.^{10 35}

Cefprozil Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals.^{1 80 81}

Dosage

Available as cefprozil monohydrate; dosage expressed as anhydrous cefprozil.^{1 80 81}

Pediatric Patients

Acute Otitis Media (AOM)

Oral

Children 6 months to 12 years of age: 15 mg/kg every 12 hours for 10 days.^{1 80 81}

Pharyngitis or Tonsillitis

Oral

Children 2–12 years of age: 7.5 mg/kg every 12 hours for 10 days.^{1 80 81}

Children ≥13 years of age: 500 mg once daily for 10 days.^{1 80 81}

Respiratory Tract Infections

Acute Sinusitis

Oral

Children 6 months to 12 years of age: 7.5 mg/kg every 12 hours for 10 days.^{1 80 81} For moderate to severe infections, 15 mg/kg every 12 hours for 10 days.^{1 80 81}

Children ≥13 years of age: 250 mg every 12 hours for 10 days.^{1 80 81} For moderate to severe infections, 500 mg every 12 hours for 10 days.^{1 80 81}

Secondary Bacterial Infections of Acute Bronchitis

Oral

Children ≥13 years of age: 500 mg every 12 hours for 10 days.^{1 80 81}

Acute Exacerbations of Chronic Bronchitis

Oral

Children ≥13 years of age: 500 mg every 12 hours for 10 days.^{1 80 81}

Skin and Skin Structure Infections

Oral

Children 2–12 years of age: 20 mg/kg once every 24 hours for 10 days.^{1 80 81}

Children ≥13 years of age: 250 or 500 mg every 12 hours for 10 days or 500 mg once daily for 10 days.^{1 80 81}

Adults

Pharyngitis or Tonsillitis

Oral

500 mg once daily for 10 days.^{1 80 81}

Respiratory Tract Infections

Acute Sinusitis

Oral

250 mg every 12 hours for 10 days.^{1 80 81} For moderate to severe infections, 500 mg every 12 hours for 10 days.^{1 80 81}

Secondary Bacterial Infections of Acute Bronchitis

Oral

500 mg every 12 hours for 10 days.^{1 80 81}

Acute Exacerbations of Chronic Bronchitis

Oral

500 mg every 12 hours for 10 days.^{1 80 81}

Skin and Skin Structure Infections

Oral

250 or 500 mg every 12 hours for 10 days or 500 mg once daily for 10 days.^{1 80 81}

Special Populations

Hepatic Impairment

No dosage adjustments required.^{1 80 81}

Renal Impairment

No dosage adjustments required in patients with Cl_cr ≥30 mL/minute.^{1 7 80 81}

Patients with Cl_cr <30 mL/minute: administer 50% of the usual dose using the usual dosing intervals.^{1 80 81}

Hemodialysis patients: administer cefprozil doses after dialysis sessions.^{1 80 81}

Geriatric Patients

No dosage adjustments required except those related to renal impairment.^{1 80 81} Cautious dosage selection because of age-related decreases in renal function.^{1 80 81} See Renal Impairment under Dosage and Administration.

Cautions for Cefprozil

Contraindications

• 
  

  Known allergy to cefprozil or other cephalosporins.^{1 80 81}

  
  

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Diarrhea and Colitis

Possible emergence and overgrowth of nonsusceptible bacteria or fungi with prolonged use.^{1 80 81} Careful observation of the patient is essential.^{1 80 81} Institute appropriate therapy if superinfection occurs.^{1 80 81}

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.^{1 80 81} C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including cefprozil, and may range in severity from mild diarrhea to fatal colitis.¹ Hypertoxin producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.¹

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.^{1 80 81} Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.¹

If CDAD is suspected or confirmed, the anti-infective may need to be discontinued.¹ Some mild cases may respond to discontinuance alone.^{1 69 70 71 72 73} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.^{1 69 70 71 72}

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (anaphylaxis,¹ serum-sickness-like reactions,^{1 14} erythema,^{9 12} Stevens-Johnson syndrome^{1 14} ) have been reported.¹

If a hypersensitivity reaction occurs, discontinue cefprozil immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).¹

Cross-hypersensitivity

Partial cross-sensitivity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.¹

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.¹ Cautious use recommended in patients with a history of hypersensitivity to penicillins:¹ avoid use in those who have had an immediate-type (anaphylactic) hypersensitivity reaction ^a and administer with caution in those who have had a delayed-type (e.g., rash, fever, eosinophilia) reaction.^a

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of cefprozil and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.^{1 80 81}

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.^{1 80 81} In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.^{1 80 81}

Phenylketonuria

Oral suspensions containing 125 or 250 mg of cefprozil/5 mL contain aspartame (NutraSweet), which is metabolized in the GI tract to provide 28 mg of phenylalanine/5 mL.^{1 3 81}

Other commercially available preparations do not contain aspartame;¹ these other preparations should be used in individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine.¹

History of GI Disease

Cephalosporins should be used with caution in patients with a history of GI disease, particularly colitis.^{1 80 81} (See Superinfection/Clostridium difficile-associated Diarrhea and Colitis under Cautions.)

Coombs' Test Results

Positive direct Coombs’ test results reported with some cephalosporins.^{1 a} This may interfere with certain hematologic studies or transfusion cross-matching procedures.^a May also cause positive Coombs’ tests in neonates whose mothers received a cephalosporin prior to delivery.^a

Specific Populations

Pregnancy

Category B.^{1 80 81}

Lactation

Distributed into milk; use with caution.^{1 80 81}

Pediatric Use

Safety and efficacy not established in infants <6 months of age for the treatment of AOM or acute sinusitis.^{1 80 81}

Safety and efficacy not established in children <2 years of age for the treatment of pharyngitis or tonsillitis or for uncomplicated skin and skin structure infections.^{1 80 81}

Geriatric Use

Safety and efficacy in those ≥65 years of age similar to that in younger adults, but possibility exists of greater sensitivity to the drug in some geriatric patients.^{1 80 81}

Cefprozil is substantially eliminated by kidneys and risk of toxicity may be greater in patients with impaired renal function.^{1 80 81} Assess renal function periodically since geriatric patients are more likely to have renal impairment.^{1 80 81}

Hepatic Impairment

Half-life only slightly prolonged.¹ No dosage adjustments required.¹

Renal Impairment

Decreased clearance.^{1 80 81}

Use with caution in those with known or suspected renal impairment.^{1 80 81} Monitor closely and assess renal function prior to and during therapy.^{1 80 81}

Reduce dosage in those with Cl_cr <30 mL/minute.^{1 80 81} See Renal Impairment under Dosage and Administration.

Common Adverse Effects

Diarrhea, nausea, vomiting, rash, genital pruritus or vaginitis, dizziness.^{1 9}

Interactions for Cefprozil

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Aminoglycosides	Nephrotoxicity has been reported when aminoglycosides used concomitantly with some cephalosporins1
Antacids	Study using capsules (not commercially available) indicate bioavailability not affected when given 5 minutes after an antacid1
Diuretics		Caution if used concomitantly with potent diuretics since such drugs may adversely affect renal function1
Probenecid	Increased cefprozil AUC1
Tests for glucose	Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution1 False-negative reaction possible in blood glucose tests using ferricyanide	Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)1

Cefprozil Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed from GI tract.¹ Bioavailability is 90–95% in fasting adults;^{1 21 24} peak plasma concentrations attained within 1.5 hours.^{1 61}

Tablets and oral suspension are bioequivalent under fasting conditions.¹

Food

Food does not affect absorption or peak plasma concentrations, but time to peak plasma concentrations may be prolonged by 15–45 minutes.¹ Not considered clinically important.¹

Distribution

Extent

Distributed into various body tissues and fluids including blister fluid,^{21 22} middle ear fluid,²⁶ and tonsillar and adenoidal tissue.^{21 27}

Distributed into milk in low concentrations.^{1 5}

Plasma Protein Binding

35–45%.^{1 23}

Elimination

Metabolism

Not appreciably metabolized.^{21 22 23 24 28}

Elimination Route

Eliminated principally in urine by glomerular filtration and tubular secretion.^{21 22 23 24 28}

54–70% of a single dose eliminated unchanged in urine within 24 hours.^{1 21 22 23 24 28}

Half-life

Adults with normal renal function: 1–1.4 hours.^{1 21 22 23 28}

Children 6 months to 12 years of age: 0.94–2.1 hours.^{1 13 21}

Special Populations

In geriatric patients, clearance decreased and AUC increased.¹

Plasma half-life increased slightly in patients with hepatic impairment (about 2 hours).^{1 21}

Prolonged plasma half-life (up to 5.2–5.9 hours) in patients with renal impairment.^{1 7}

Stability

Storage

Oral

Tablets

15–30°C.^{1 80}

For Suspension

15–25°C.^{1 81} After reconstitution, store in a refrigerator and discard after 14 days.^{1 81}

Actions and SpectrumActions

• 
  

  Second generation cephalosporin active against some aerobic gram-negative bacteria that generally are resistant to first generation cephalosporins, but has a narrower spectrum of activity than third generation cephalosporins.^{1 3 11}

  
  


• 
  

  Usually bactericidal.^{1 a}

  
  


• 
  

  Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.^{1 a}

  
  


• 
  

  In vitro spectrum of activity includes many gram-positive aerobic bacteria, some gram-negative aerobic bacteria, and some anaerobic bacteria.¹ Inactive against fungi and viruses.^a

  
  


• 
  

  Gram-positive aerobes: active in vitro and in clinical infections against Staphylococcus aureus (including β-lactamase-producing strains), Streptococcus pneumoniae, and S. pyogenes (group A β-hemolytic streptococci).¹ Also active in vitro against Enterococcus durans, E. faecalis, Listeria monocytogenes, Staphylococcus epidermidis, S. saprophyticus, S. warneri, Streptococcus agalactiae (group B streptococci), and groups C, D, F, and G streptococci.¹ E. faecium and oxacillin-resistant (methicillin-resistant) staphylococci are resistant.¹

  
  


• 
  

  Gram-negative aerobes: active in vitro and in clinical infections against Haemophilus influenzae (including β-lactamase producing strains) and Moraxella catarrhalis (including β-lactamase-producing strains).^{1 21 a} Also active in vitro against Citrobacter diversus, Escherichia coli, Klebsiella pneumonia, Neisseria gonorrhoeae, (including β-lactamase-producing strains), Proteus mirabilis, Salmonella, Shigella, and Vibrio.¹ Inactive against most strains of Acinetobacter, Enterobacter, Morganella morganii, P. vulgaris, Providencia, Pseudomonas, and Serratia.¹

  
  


• 
  

  Anaerobes: active in vitro against Prevotella melaninogenicus, Clostridium difficile, C. perfringens, Fusobacterium, Peptostreptococcus, and Propionibacterium acnes.¹ Most strains of Bacteroides fragilis are resistant.¹

  
  


• 
  

  Strains of staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant staphylococci) should be considered resistant to cefprozil, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.¹⁹ In addition, β-lactamase-negative, ampicillin-resistant (BLNAR) strains of H. influenzae should be considered resistant to cefprozil despite the fact that results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.¹⁹

  
  

Advice to Patients

• 
  

  Advise patients that antibacterials (including cefprozil) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).^{1 80 81}

  
  


• 
  

  Importance of completing full course of therapy, even if feeling better after a few days.^{1 80 81}

  
  


• 
  

  Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with cefprozil or other antibacterials in the future.^{1 80 81}

  
  


• 
  

  Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.¹ Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.¹

  
  


• 
  

  Advise individuals with phenylketonuria and other individuals who must restrict their intake of phenylalanine that cefprozil oral suspensions contain aspartame (NutraSweet), which is metabolized in the GI tract to phenylalanine.^{1 81}

  
  


• 
  

  Importance of notifying clinician of persistent or worsening symptoms of infection.^{1 80 81}

  
  


• 
  

  Importance of informing clinician if history includes allergy or sensitivity to cephalosporins or penicillins.^{1 80 81 a}

  
  


• 
  

  Importance of discontinuing cefprozil and informing clinician if an allergic or hypersensitivity reaction occurs.^{1 80 81 a}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 80 81 a}

  
  


• 
  

  Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.^a

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Cefprozil

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	For suspension	125 mg (of anhydrous cefprozil) per 5 mL*	Cefprozil for Suspension
			Cefzil	Bristol-Myers Squibb
		250 mg (of anhydrous cefprozil) per 5 mL*	Cefprozil for Suspension
			Cefzil	Bristol-Myers Squibb
	Tablets, film-coated	250 mg (of anhydrous cefprozil)*	Cefprozil Film-coated Tablets
			Cefzil	Bristol-Myers Squibb
		500 mg (of anhydrous cefprozil)*	Cefprozil Film-coated Tablets
			Cefzil	Bristol-Myers Squibb

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Cefzil 250MG/5ML Suspension (B-M SQUIBB U.S. (PRIMARY CARE)): 100/$73.99 or 300/$212.97

Cefzil 250MG/5ML Suspension (B-M SQUIBB U.S. (PRIMARY CARE)): 50/$45.99 or 150/$115.97

Cefzil 250MG Tablets (B-M SQUIBB U.S. (PRIMARY CARE)): 20/$109.99 or 60/$305.96

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions December 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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2. Bristol-Myers Squibb US Pharmaceutical Division, Princeton, NJ: Personal communication.

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29. Thornsberry C. Review of the in vitro antibacterial activity of cefprozil, a new oral cephalosporin. Clin Infect Dis. 1992; 14(Suppl 2):S189-94. [IDIS 297196] [PubMed 1617037]

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36. Blumer JL, Forti WP, Summerhouse TL. Comparison of the efficacy and tolerability of once-daily ceftibuten and twice-daily cefprozil in the treatment of children with acute otitis media. Clin Ther. 1996; 18:811-20. [IDIS 376625] [PubMed 8930425]

37. Kafetzis DA. Multi-investigator evaluation of the efficacy and safety of cefprozil, amoxicillin-clavulanate, cefixime and cefaclor in the treatment of acute otitis media. Eur J Clin Microbiol Infect Dis. 1994; 13:857-65. [PubMed 7889960]

38. Ball P. Efficacy and safety of cefprozil versus other beta-lactam antibiotics in the treatment of lower respiratory tract infections. Eur J Clin Microbiol Infect Dis. 1994; 13:851-6. [PubMed 7889959]

39. McCarty JM. Comparative efficacy and safety of cefprozil versus penicillin, cefaclor and erythromycin in the treatment of streptococcal pharyngitis and tonsillitis. Eur J Clin Microbiol Infect Dis. 1994; 13:846-50. [PubMed 7889958]

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41. Shyu WC, Shah VR, Campbell DA et al. Oral absolute bioavailability and intravenous dose-proportionality of cefprozil in humans. J Clin Pharmacol. 1992; 32:798-803. [IDIS 303254] [PubMed 1430299]

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