Cefprozil

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Cefprozil
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gloria Picoy [2]

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Overview

Cefprozil is a 2nd generation cephalosporin that is FDA approved for the treatment of mild to moderate infections of upper respiratory tract, lower respiratory tract, and uncomplicated skin and Skin-structure infections. Common adverse reactions include diarrhea, nausea, ALT/SGPT level raised, AST/SGOT level raised and vaginitis.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Cefprozil tablets are indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below:

Upper respiratory tract
  • Dosage: 500 mg daily for 10 days
  • Dosage: 500 mg each 12 hours for 10 days
  • Dosage: 250 mg each 12 hours for 10 days
Lower respiratory tract
  • Dosage: 500 mg each 12 hours for 10 days
Uncomplicated Skin and Skin-Structure Infections
  • 250 mg each 12 hours for 10 days, or
  • 500 mg daily for 10 days, or
  • 500 mg each 12 hours for 10 days

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Cefprozil in adult patients.

Non–Guideline-Supported Use

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Cefprozil tablets are indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below:

Upper respiratory tract
  • Dosage for children between 2-12 years: 7.5 mg/kg daily for 110 days
  • Dosage for 6 month - 12 years: 15 mg/kg each 12 hours for 10 days.
  • Dosage for 6 months - 12 years: 7.5 mg/kg for 10 days or 15 mg/kg each 12 hours for 10 days.
Lower respiratory tract
Uncomplicated Skin and Skin-Structure Infections
  • Dosage for children between 2-12 years: 20 mg/kg daily for 10 days.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Cefprozil in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Cefprozil in pediatric patients.

Contraindications

Cefprozil tablets are contraindicated in patients with known allergy to the cephalosporin class of antibiotics.

Warnings

BEFORE THERAPY WITH CEFPROZIL IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFPROZIL, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-SENSITIVITY AMONG β-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO CEFPROZIL OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefprozil, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Adverse Reactions

Clinical Trials Experience

The most common adverse effects observed in patients treated with cefprozil are:

  • Gastrointestinal: Diarrhea (2.9%), nausea (3.5%), vomiting (1%), and abdominal pain (1%).
  • Hepatobiliary: Elevations of AST (SGOT) (2%), ALT (SGPT) (2%), alkaline phosphatase (0.2%), and bilirubin values (<0.1%). As with some penicillins and some other cephalosporin antibiotics, cholestatic jaundice has been reported rarely.
  • Hypersensitivity: Rash (0.9%), urticaria (0.1%). Such reactions have been reported more frequently in children than in adults. Signs and symptoms usually occur a few days after initiation of therapy and subside within a few days after cessation of therapy.
  • CNS: Dizziness (1%). hyperactivity, headache, nervousness, insomnia, confusion, and somnolence have been reported rarely (<1%). All were reversible.
  • Hematopoietic: Decreased leukocyte count (0.2%), eosinophilia (2.3%).
  • Renal: Elevated BUN (0.1%), serum creatinine (0.1%).
  • Other: Diaper rash and superinfection (1.5%), genital pruritus and vaginitis (1.6%).
Cephalosporin class paragraph

In addition to the adverse reactions listed above which have been observed in patients treated with cefprozil, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics:

Aplastic anemia, hemolytic anemia, hemorrhage, renal dysfunction, toxic epidermal necrolysis, toxic nephropathy, prolonged prothrombin time, positive Coombs’ test, elevated LDH, pancytopenia, neutropenia, agranulocytosis.

Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment, when the dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Postmarketing Experience

The following adverse events, regardless of established causal relationship to cefprozil tablets, have been rarely reported during postmarketing surveillance: anaphylaxis, angioedema, colitis (including pseudomembranous colitis), erythema multiforme, fever, serum-sickness like reactions, Stevens-Johnson syndrome, and thrombocytopenia.

Drug Interactions

  • Nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and cephalosporin antibiotics. Concomitant administration of probenecid doubled the AUC for cefprozil.
  • The bioavailability of the capsule formulation of cefprozil was not affected when administered 5 minutes following an antacid.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): B Reproduction studies have been performed in rabbits, mice, and rats using oral doses of cefprozil of 0.8, 8.5, and 18.5 times the maximum daily human dose (1000 mg) based upon mg/m2, and have revealed no harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Cefprozil in women who are pregnant.

Labor and Delivery

Cefprozil has not been studied for use during labor and delivery. Treatment should only be given if clearly needed.

Nursing Mothers

Small amounts of cefprozil (<0.3% of dose) have been detected in human milk following administration of a single 1 gram dose to lactating women. The average levels over 24 hours ranged from 0.25 to 3.3 mcg/mL. Caution should be exercised when cefprozil tablets are administered to a nursing woman, since the effect of cefprozil on nursing infants is unknown.

Pediatric Use

The safety and effectiveness of cefprozil in the treatment of otitis media have been established in the age groups 6 months to 12 years. Use of cefprozil tablets for the treatment of otitis media is supported by evidence from adequate and well-controlled studies of cefprozil in pediatric patients.

The safety and effectiveness of cefprozil in the treatment of pharyngitis/tonsillitis or uncomplicated skin and skin-structure infections have been established in the age groups 2 to 12 years. Use of cefprozil for the treatment of these infections is supported by evidence from adequate and well-controlled studies of cefprozil in pediatric patients.

The safety and effectiveness of cefprozil in the treatment of acute sinusitis have been established in the age groups 6 months to 12 years. Use of cefprozil in these age groups is supported by evidence from adequate and well-controlled studies of cefprozil in adults.

Safety and effectiveness in pediatric patients below the age of 6 months have not been established for the treatment of otitis media or acute sinusitis, or below the age of 2 years for the treatment of pharyngitis/tonsillitis or uncomplicated skin and skin-structure infections. However, accumulation of other cephalosporin antibiotics in newborn infants (resulting from prolonged drug half-life in this age group) has been reported.

Geriatic Use

Of the more than 4500 adults treated with cefprozil tablets in clinical studies, 14% were 65 years and older, while 5% were 75 years and older. When geriatric patients received the usual recommended adult doses, their clinical efficacy and safety were comparable to clinical efficacy and safety in nongeriatric adult patients. Other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals to the effects of cefprozil tablets cannot be excluded.

Cefprozil 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 it may be useful to monitor renal function.

Gender

There is no FDA guidance on the use of Cefprozil with respect to specific gender populations.

Race

There is no FDA guidance on the use of Cefprozil with respect to specific racial populations.

Renal Impairment

In patients with known or suspected renal impairment, careful clinical observation and appropriate laboratory studies should be done prior to and during therapy. The total daily dose of cefprozil tablets should be reduced in these patients because high and/or prolonged plasma antibiotic concentrations can occur in such individuals from usual doses. Cephalosporins, including cefprozil tablets, should be given with caution to patients receiving concurrent treatment with potent diuretics since these agents are suspected of adversely affecting renal function.

Hepatic Impairment

In patients with impaired hepatic function, the half-life increases to approximately 2 hours. The magnitude of the changes does not warrant a dosage adjustment for patients with impaired hepatic function.

Females of Reproductive Potential and Males

Impairment of fertility was not observed in male or female rats given oral doses of cefprozil up to 18.5 times the highest recommended human dose based upon mg/m2.

Immunocompromised Patients

There is no FDA guidance one the use of Cefprozil in patients who are immunocompromised.

Administration and Monitoring

Administration

Oral

Monitoring

There is limited information regarding Cefprozil Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Cefprozil and IV administrations.

Overdosage

Single 5000 mg/kg oral doses of cefprozil caused no mortality or signs of toxicity in adult, weanling, or neonatal rats, or adult mice. A single oral dose of 3000 mg/kg caused diarrhea and loss of appetite in cynomolgus monkeys, but no mortality.

Cefprozil is eliminated primarily by the kidneys. In case of severe overdosage, especially in patients with compromised renal function, hemodialysis will aid in the removal of cefprozil from the body.

Pharmacology

Cefprozil structure.png
Cefprozil
Systematic (IUPAC) name
7-[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
Identifiers
CAS number 92665-29-7
ATC code J01DC10
PubChem 9887643
DrugBank DB01150
Chemical data
Formula C18H19N3O5S 
Mol. mass 389.427 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 95%
Protein binding 36%
Metabolism ?
Half life 1.3 hours
Excretion ?
Therapeutic considerations
Licence data

US

Pregnancy cat.

B(US)

Legal status

-only(US)

Routes Oral

Mechanism of Action

Cefprozil has in vitro activity against a broad range of gram-positive and gram-negative bacteria. The bactericidal action of cefprozil results from inhibition of cell-wall synthesis.

Structure

The structural formula is:

Cefprozil chemical structure.png

Pharmacodynamics

There is limited information regarding Cefprozil Pharmacodynamics in the drug label.

Pharmacokinetics

The pharmacokinetic data were derived from the capsule formulation; however, bioequivalence has been demonstrated for the oral solution, capsule, tablet, and suspension formulations under fasting conditions.

Following oral administration of cefprozil to fasting subjects, approximately 95% of the dose was absorbed. The average plasma half-life in normal subjects was 1.3 hours, while the steady-state volume of distribution was estimated to be 0.23 L/kg. The total body clearance and renal clearance rates were approximately 3 mL/min/kg and 2.3 mL/min/kg, respectively.

Average peak plasma concentrations after administration of 250 mg, 500 mg, or 1 g doses of cefprozil to fasting subjects were approximately 6.1, 10.5, and 18.3 mcg/mL, respectively, and were obtained within 1.5 hours after dosing. Urinary recovery accounted for approximately 60% of the administered dose.

Cefprozil pharmacokinetic.png

During the first 4-hour period after drug administration, the average urine concentrations following 250 mg, 500 mg, and 1 g doses were approximately 700 mcg/mL, 1000 mcg/mL, and 2900 mcg/mL, respectively.

Administration of cefprozil with food did not affect the extent of absorption (AUC) or the peak plasma concentration (Cmax) of cefprozil. However, there was an increase of 0.25 to 0.75 hours in the time to maximum plasma concentration of cefprozil (Tmax).

The bioavailability of the capsule formulation of cefprozil was not affected when administered 5 minutes following an antacid.

Plasma protein binding is approximately 36% and is independent of concentration in the range of 2 mcg/mL to 20 mcg/mL.

There was no evidence of accumulation of cefprozil in the plasma in individuals with normal renal function following multiple oral doses of up to 1000 mg every 8 hours for 10 days.

Nonclinical Toxicology

Drug/Laboratory Test Interactions

Cephalosporin antibiotics may produce a false positive reaction for glucose in the urine with copper reduction tests, but not with enzyme-based tests for glycosuria. A false negative reaction may occur in the ferricyanide test for blood glucose. The presence of cefprozil in the blood does not interfere with the assay of plasma or urine creatinine by the alkaline picrate method.

Carcinogenesis and Mutagenesis

Long term in vivo studies have not been performed to evaluate the carcinogenic potential of cefprozil.

Cefprozil was not found to be mutagenic in either the Ames Salmonella or E. coli WP2 urvA reversion assays or the Chinese hamster ovary cell HGPRT forward gene mutation assay and it did not induce chromosomal abnormalities in Chinese hamster ovary cells or unscheduled DNA synthesis in rat hepatocytes in vitro. Chromosomal aberrations were not observed in bone marrow cells from rats dosed orally with over 30 times the highest recommended human dose based upon mg/m2.

Clinical Studies

Study One

In a controlled clinical study of acute otitis media performed in the United States where significant rates of β-lactamase-producing organisms were found, cefprozil was compared to an oral antimicrobial agent that contained a specific β-lactamase inhibitor. In this study, using very strict evaluability criteria and microbiologic and clinical response criteria at the 10 to 16 days post-therapy follow-up, the following presumptive bacterial eradication/clinical cure outcomes i.e., clinical success) and safety results were obtained:

Cefprozil Acute Otitis Media Study Cefprozil vs β-lactamase inhibitor-containing control drug.png
Safety

The incidences of adverse events, primarily diarrhea and rash*, were clinically and statistically significantly higher in the control arm versus the cefprozil arm.

Cefprozil safety.png
Study Two

In a controlled clinical study of acute otitis media performed in Europe, cefprozil was compared to an oral antimicrobial agent that contained a specific β-lactamase inhibitor. As expected in a European population, this study population had a lower incidence of β-lactamase-producing organisms than usually seen in U.S. trials. In this study, using very strict evaluability criteria and microbiologic and clinical response criteria at the 10 to 16 days post-therapy follow-up, the following presumptive bacterial eradication/clinical cure outcomes (i.e., clinical success) were obtained:

Cefprozil European Acute Otitis Media Study Cefprozil vs β-lactamase inhibitor-containing control drug.png
Safety

The incidence of adverse events in the cefprozil arm was comparable to the incidence of adverse events in the control arm (agent that contained a specific β-lactamase inhibitor).

How Supplied

  • Cefprozil Tablets 250 mg
  • Bottles of 100
  • NDC 57237-036-01
  • Cefprozil Tablets 500 mg
  • Bottles of 50
  • NDC 57237-037-50
              Bottles of 100                           NDC 57237-037-01

Storage

Store at 20° to 25°C (68° to 77°F)

Images

Drug Images

Cefprozil NDC 00931077.jpg

Drug Name: Cefprozil
Ingredient(s): CEFPROZIL[CEFPROZIL ANHYDROUS]
Imprint: 93;1077
Dosage: 250 mg
Color(s): Orange
Shape: Round
Size (mm): 10
Score: 1
NDC:00931077

Drug Label Author: Teva Pharmaceuticals USA Inc

This pill image is provided by the National Library of Medicine's PillBox.
Cefprozil NDC 00931078.jpg

Drug Name: Cefprozil
Ingredient(s): CEFPROZIL[CEFPROZIL ANHYDROUS]
Imprint: 1078;93
Dosage: 500 mg
Color(s): White
Shape: Oval
Size (mm): 20
Score: 1
NDC:00931078

Drug Label Author: Teva Pharmaceuticals USA Inc

This pill image is provided by the National Library of Medicine's PillBox.
Cefprozil NDC 07815043.jpg

Drug Name: Cefprozil
Ingredient(s): CEFPROZIL[CEFPROZIL ANHYDROUS]
Imprint: 347;250
Dosage: 250 mg
Color(s): White
Shape: Oval
Size (mm): 14
Score: 1
NDC:07815043

Drug Label Author: Sandoz Inc

This pill image is provided by the National Library of Medicine's PillBox.
Cefprozil NDC 07815044.jpg

Drug Name: Cefprozil
Ingredient(s): CEFPROZIL[CEFPROZIL ANHYDROUS]
Imprint: 348;500
Dosage: 500 mg
Color(s): White
Shape: Oval
Size (mm): 18
Score: 1
NDC:07815044

Drug Label Author: Sandoz Inc

This pill image is provided by the National Library of Medicine's PillBox.

Package and Label Display Panel

Cefprozil 250 mg FDA package label.png
Cefprozil 500 mg FDA package label.png
Cefprozil 250 mg.png
This image of the FDA label is provided by the National Library of Medicine.
Cefprozil 500 mg.png
This image of the FDA label is provided by the National Library of Medicine.

Patient Counseling Information

Patients should be counseled that antibacterial drugs including cefprozil tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefprozil tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by cefprozil tablets or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Precautions with Alcohol

Alcohol-Cefprozil interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

There is limited information regarding Cefprozil Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. "FDA LABEL: CEFPROZIL - cefprozil tablet, film coated".









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