CEFPROZIL powder, for suspension

Cefprozil by

Drug Labeling and Warnings

Cefprozil by is a Prescription medication manufactured, distributed, or labeled by NorthStar Rx LLC, Aurobindo Pharma Limited. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

SPL UNCLASSIFIED SECTION

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

DESCRIPTION

Cefprozil is a semi-synthetic broad-spectrum cephalosporin antibiotic.

Cefprozil is a cis and trans isomeric mixture (≥90% cis). The chemical name for the monohydrate is (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, and the structural formula is:

Cefprozil, USP is a white to yellowish powder with a molecular formula for the monohydrate of C18H19N3O5SH2O and a molecular weight of 407.45.

Cefprozil for oral suspension, USP is intended for oral administration.

Cefprozil for oral suspension, USP contains cefprozil USP equivalent to 125 mg or 250 mg anhydrous cefprozil per 5 mL constituted suspension. In addition, the oral suspension contains the following inactive ingredients: aspartame, microcrystalline cellulose, carboxymethylcellulose sodium, citric acid monohydrate, colloidal silicon dioxide, FD&C Red No.3, glycine, polysorbate 80, simethicone emulsion, sodium benzoate, sodium chloride, bubble gum flavor and sucrose.

CLINICAL PHARMACOLOGY

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. (See Table.) 

*Data represent mean values of 12 healthy volunteers.
Dosage (mg)	Mean Plasma Cefprozil; Concentrations; (mcg/mL)*			8-hour; Urinary; Excretion (%)
	Peak; appx. 1.5 h	4 h	8 h
250 mg	6.1	1.7	0.2	60%
500 mg	10.5	3.2	0.4	62%
1000 mg	18.3	8.4	1	54%

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 tablet or suspension formulations 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).

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.

In patients with reduced renal function, the plasma half-life may be prolonged up to 5.2 hours depending on the degree of the renal dysfunction. In patients with complete absence of renal function, the plasma half-life of cefprozil has been shown to be as long as 5.9 hours. The half-life is shortened during hemodialysis. Excretion pathways in patients with markedly impaired renal function have not been determined. (See PRECAUTIONS and DOSAGE AND ADMINISTRATION.)

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.

Healthy geriatric volunteers (≥65 years old) who received a single 1-g dose of cefprozil had 35% to 60% higher AUC and 40% lower renal clearance values compared with healthy adult volunteers 20 to 40 years of age. The average AUC in young and elderly female subjects was approximately 15 to 20% higher than in young and elderly male subjects. The magnitude of these age- and gender-related changes in the pharmacokinetics of cefprozil is not sufficient to necessitate dosage adjustments.

Adequate data on CSF levels of cefprozil are not available.

Comparable pharmacokinetic parameters of cefprozil are observed between pediatric patients (6 months to 12 years) and adults following oral administration of selected matched doses. The maximum concentrations are achieved at 1 to 2 hours after dosing. The plasma elimination half-life is approximately 1.5 hours. In general, the observed plasma concentrations of cefprozil in pediatric patients at the 7.5, 15, and 30 mg/kg doses are similar to those observed within the same time frame in normal adult subjects at the 250, 500, and 1000 mg doses, respectively. The comparative plasma concentrations of cefprozil in pediatric patients and adult subjects at the equivalent dose level are presented in the table below.

an=11; bn=5; cn=9; dn=11.
		Mean (SD) Plasma Cefprozil Concentrations (mcg/mL)
Population	Dose	1 h	2 h	4 h	6 h	TT1/2 (h)
children; (n=18)	7.5 mg/kg	4.7; (1.57)	3.99; (1.24)	0.91; (0.3)	0.23a; (0.13)	0.94; (0.32)
adults; (n=12)	250 mg	4.82; (2.13)	4.92; (1.13)	1.7b; (0.53)	0.53; (0.17)	1.28; (0.34)
children; (n=19)	15 mg/kg	10.86; (2.55)	8.47; (2.03)	2.75; (1.07)	0.61c; (0.27)	1.24; (0.43)
adults; (n=12)	500 mg	8.39; (1.95)	9.42; (0.98)	3.18d; (0.76)	1d; (0.24)	1.29; (0.14)
children; (n=10)	30 mg/kg	16.69; (4.26)	17.61; (6.39)	8.66; (2.7)	–	2.06; (0.21)
adults; (n=12)	1000 mg	11.99; (4.67)	16.95; (4.07)	8.36; (4.13)	2.79; (1.77)	1.27; (0.12)

Microbiology

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. Cefprozil has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

• Aerobic gram-positive microorganisms: Aerobic gram-negative microorganisms:
• Staphylococcus aureus (including β-lactamase-producing strains): Haemophilus influenzae (including β-lactamase-producing strains)
• NOTE: Cefprozil is inactive against methicillin-resistant staphylococci.: Moraxella (Branhamella) catarrhalis ; (including β-lactamase-producing strains)

The following in vitro data are available; however, their clinical significance is unknown. Cefprozil exhibits in vitro minimum inhibitory concentrations (MICs) of 8 mcg/mL or less against most (≥90%) strains of the following microorganisms; however, the safety and effectiveness of cefprozil in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Aerobic gram-positive microorganisms:

        Enterococcus durans                                                    Staphylococcus warneri 
        Enterococcus faecalis                                                  Streptococcus agalactiae
        Listeria monocytogenes                                               Streptococci (Groups C,D,F, and G)
        Staphylococcus epidermidis                                        viridans group Streptococci
        Staphylococcus saprophyticus

        NOTE: Cefprozil is inactive against Enterococcus faecium.

Aerobic gram-negative microorganisms:

        Citrobacter diversus                                                    Proteus mirabilis 
        Escherichia coli                                                           Salmonella spp.
        Klebsiella pneumoniae                                                Shigella spp.
        Neisseria gonorrhoeae                                                Vibrio spp.
        (including β-lactamase-producing strains)

        NOTE: Cefprozil is inactive against most strains of Acinetobacter, Enterobacter, Morganella morganii, Proteus vulgaris, Providencia, Pseudomonas, and Serratia.

Anaerobic microorganisms:

Prevotella (Bacteroides) melaninogenicus                  Fusobacterium spp.
Clostridium difficile                                                     Peptostreptococcus spp.
Clostridium perfringens                                              Propionibacterium acnes

        NOTE: Most strains of the Bacteroides fragilis group are resistant to cefprozil.

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefprozil  and other antibacterial drugs, cefprozil should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Cefprozil for oral suspension is 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

Pharyngitis/tonsillitis caused by Streptococcus pyogenes.

NOTE: The usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever, is penicillin given by the intramuscular route. Cefprozil is generally effective in the eradication of Streptococcus pyogenes from the nasopharynx; however, substantial data establishing the efficacy of cefprozil in the subsequent prevention of rheumatic fever are not available at present.

Otitis Media caused by Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (including β-lactamase-producing strains). (See CLINICAL STUDIES.)

NOTE: In the treatment of otitis media due to β-lactamase producing organisms, cefprozil had bacteriologic eradication rates somewhat lower than those observed with a product containing a specific β-lactamase inhibitor. In considering the use of cefprozil, lower overall eradication rates should be balanced against the susceptibility patterns of the common microbes in a given geographic area and the increased potential for toxicity with products containing β-lactamase inhibitors.

Acute Sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (including β-lactamase-producing strains).

LOWER RESPIRATORY TRACT

Acute Bacterial Exacerbation of Chronic Bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase-producing strains), and Moraxella (Branhamella) catarrhalis (including β-lactamase-producing strains).

SKIN AND SKIN STRUCTURE

Uncomplicated Skin and Skin-Structure Infections caused by Staphylococcus aureus (including penicillinase-producing strains) and Streptococcus pyogenes. Abscesses usually require surgical drainage.

CONTRAINDICATIONS

Cefprozil for oral suspension is 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.

PRECAUTIONS

General

Prescribing cefprozil in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

In patients with known or suspected renal impairment (see DOSAGE AND ADMINISTRATION), careful clinical observation and appropriate laboratory studies should be done prior to and during therapy. The total daily dose of cefprozil 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, should be given with caution to patients receiving concurrent treatment with potent diuretics since these agents are suspected of adversely affecting renal function.

Prolonged use of cefprozil may result in the overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Cefprozil should be prescribed with caution in individuals with a history of gastrointestinal disease particularly colitis.

Positive direct Coombs’ tests have been reported during treatment with cephalosporin antibiotics.

Information for Patients

Phenylketonurics: Cefprozil for oral suspension contains 8.4 mg of phenylalanine per 5 mL (1 teaspoonful) constituted suspension for both the 125 mg/5 mL and 250 mg/5 mL dosage forms.

Patients should be counseled that antibacterial drugs including cefprozil should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefprozil is 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 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.

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.

Drug/laboratory Test Interactions

Cephalosporin antibiotics may produce a false positive reaction for glucose in the urine with copper reduction tests (Benedict’s or Fehling’s solution or with Clinitest® tablets1), but not with enzyme-based tests for glycosuria (e.g., Clinistix®). 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.

1 Clinitest ® and Clinistix ® are registered trademarks of Bayer Healthcare LLC.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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.

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.

Pregnancy

Teratogenic Effects: Pregnancy Category 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.

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 is administered to a nursing woman, since the effect of cefprozil on nursing infants is unknown.

Pediatric Use

(See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION.)

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 for the treatment of otitis media is supported by evidence from adequate and well-controlled studies of cefprozil in pediatric patients. (See CLINICAL STUDIES.)

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.

Geriatric Use

Of the more than 4500 adults treated with cefprozil 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 cannot be excluded (see CLINICAL PHARMACOLOGY).

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. See DOSAGE AND ADMINISTRATION for dosing recommendations for patients with impaired renal function.

ADVERSE REACTIONS

The adverse reactions to cefprozil are similar to those observed with other orally administered cephalosporins. Cefprozil was usually well tolerated in controlled clinical trials. Approximately 2% of patients discontinued cefprozil therapy due to adverse events.

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%).

The following adverse events, regardless of established causal relationship to cefprozil, 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.

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. (See DOSAGE AND ADMINISTRATION and OVERDOSAGE.) If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

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.

DOSAGE AND ADMINISTRATION

Cefprozil for oral suspension is administered orally. 

a In the treatment of infections due to Streptococcus pyogenes, cefprozil should be administered for at least 10 days.; b Not to exceed recommended adult doses.
Population/Infection	Dosage; (mg)	Duration; (days)
ADULTS (13 years and older)
UPPER RESPIRATORY TRACT
Pharyngitis/Tonsillitis	500 q24h	10a
Acute Sinusitis; (For moderate to severe infections, the higher dose should be; used)	250 q12h or; 500 q12h	10
LOWER RESPIRATORY TRACT
Acute Bacterial Exacerbation of Chronic Bronchitis	500 q12h	10
SKIN AND SKIN STRUCTURE
Uncomplicated Skin and Skin Structure Infections	250 q12h or; 500 q24h or; 500 q12h	10
CHILDREN (2 years to 12 years)
UPPER RESPIRATORY TRACTb
Pharyngitis/Tonsillitis	7.5 mg/kg q12h	10a
SKIN AND SKIN STRUCTURE
Uncomplicated Skin and Skin Structure Infections	20 mg/kg q24h	10
INFANTS & CHILDREN (6 months to 12 years)
UPPER RESPIRATORY TRACTb
Otitis Media; (See INDICATIONS AND USAGE and CLINICAL; STUDIES)	15 mg/kg q12h	10
Acute Sinusitis; (For moderate to severe infections, the higher dose should be; used)	7.5 mg/kg q12h or; 15 mg/kg q12h	10

Renal Impairment

Cefprozil may be administered to patients with impaired renal function. The following dosage schedule should be used.

Creatinine Clearance (mL/min)	Dosage (mg)	Dosing Interval
* Cefprozil is in part removed by hemodialysis; therefore, cefprozil should be administered after the completion of   hemodialysis.
30 to 120; 0 to 29*	standard; 50% of standard	standard; standard

Hepatic Impairment

No dosage adjustment is necessary for patients with impaired hepatic function.

HOW SUPPLIED

Cefprozil for Oral Suspension, USP 125 mg/5 mL: Each 5 mL of reconstituted suspension contains cefprozil USP equivalent to anhydrous cefprozil 125 mg.

                    50 mL Bottle                         NDC: 16714-396-01 
                    75 mL Bottle                         NDC: 16714-396-02
                  100 mL Bottle                         NDC: 16714-396-03

Cefprozil for Oral Suspension, USP 250 mg/5 mL: Each 5 mL of reconstituted suspension contains cefprozil USP equivalent to anhydrous cefprozil 250 mg.

                    50 mL Bottle                          NDC: 16714-397-01
                    75 mL Bottle                          NDC: 16714-397-02
                  100 mL Bottle                          NDC: 16714-397-03

All powder formulations for oral suspension contain cefprozil in light pink granular powder with bubble-gum flavored mixture.

Reconstitution Directions for Oral Suspension

Prepare the suspension at the time of dispensing; for ease in preparation, add water in two portions and shake well after each aliquot. 

Total Amount of Water Required for Reconstitution

Bottle Size	Final Concentration    125 mg/5 mL	Final Concentration    250 mg/5 mL
50 mL	35 mL	35 mL
75 mL	52 mL	52 mL
100 mL	70 mL	70 mL

After mixing, store at 2° to 8°C [36° to 46° F] in a refrigerator and discard unused portion after 14 days.

Store dry powder at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature] prior to constitution.

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:

U.S. Acute Otitis Media Study Cefprozil vs β-lactamase inhibitor-containing control drug

EFFICACY:
Pathogen	% of Cases with Pathogen  (n=155)	Outcome
S. pneumoniae	48.4%	cefprozil success rate 5% better than control
H. influenzae	35.5%	cefprozil success rate 17% less than control
M. catarrhalis	13.5%	cefprozil success rate 12% less than control
S. pyogenes	2.6%	cefprozil equivalent to control
Overall	100%	cefprozil success rate 5% less than control

SAFETY:

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

Age Group	Cefprozil	Control
* The majority of these involved the diaper area in young; children.
6 months to 2 years	21%	41%
3 to 12 years	10%	19%

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:

European Acute Otitis Media Study Cefprozil Vs β-lactamase inhibitor-containing control drug

EFFICACY:
Pathogen	% of Cases with Pathogen  (n=47)	Outcome
S. pneumoniae	51%	cefprozil equivalent to control
H. influenzae	29.8%	cefprozil equivalent to control
M. catarrhalis	6.4%	cefprozil equivalent to control
S. pyogenes	12.8%	cefprozil equivalent to control
Overall	100%	cefprozil equivalent to control

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).

Manufactured for: Northstar Rx LLC
                                 Memphis, TN 38141.

Manufactured by: Aurobindo Pharma Limited
                                Chitkul (V)-502 307, India.

M.L.No.: 78/MD/AP/96/F/B/R

Revised: 09/2018

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 125 mg/5 mL (50 mL Bottle)

Rx only
NDC: 16714-396-01
Cefprozil for Oral
Suspension, USP
125 mg/5 mL
50 mL
when reconstituted
NORTHSTARTM

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 250 mg/5 mL (50 mL Bottle)

Rx only
NDC: 16714-397-01
Cefprozil for Oral
Suspension, USP
250 mg/5 mL
50 mL
when reconstituted
NORTHSTARTM

INGREDIENTS AND APPEARANCE

CEFPROZIL 
cefprozil powder, for suspension

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 16714-396
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
CEFPROZIL (UNII: 4W0459ZA4V) (CEFPROZIL ANHYDROUS - UNII:1M698F4H4E)	CEFPROZIL ANHYDROUS	125 mg  in 5 mL

Inactive Ingredients
Ingredient Name	Strength
ASPARTAME (UNII: Z0H242BBR1)
MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
CARBOXYMETHYLCELLULOSE SODIUM (UNII: K679OBS311)
CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP)
FD&C RED NO. 3 (UNII: PN2ZH5LOQY)
GLYCINE (UNII: TE7660XO1C)
POLYSORBATE 80 (UNII: 6OZP39ZG8H)
DIMETHICONE (UNII: 92RU3N3Y1O)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
SODIUM BENZOATE (UNII: OJ245FE5EU)
SODIUM CHLORIDE (UNII: 451W47IQ8X)
SUCROSE (UNII: C151H8M554)

Product Characteristics
Color	PINK (Light Pink)	Score
Shape		Size
Flavor	BUBBLE GUM	Imprint Code
Contains

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 16714-396-01	50 mL in 1 BOTTLE; Type 0: Not a Combination Product	01/30/2007
2	NDC: 16714-396-02	75 mL in 1 BOTTLE; Type 0: Not a Combination Product	01/30/2007
3	NDC: 16714-396-03	100 mL in 1 BOTTLE; Type 0: Not a Combination Product	01/30/2007

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA065381	01/30/2007

CEFPROZIL 
cefprozil powder, for suspension

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 16714-397
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
CEFPROZIL (UNII: 4W0459ZA4V) (CEFPROZIL ANHYDROUS - UNII:1M698F4H4E)	CEFPROZIL ANHYDROUS	250 mg  in 5 mL

Inactive Ingredients
Ingredient Name	Strength
ASPARTAME (UNII: Z0H242BBR1)
MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
CARBOXYMETHYLCELLULOSE SODIUM (UNII: K679OBS311)
CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP)
FD&C RED NO. 3 (UNII: PN2ZH5LOQY)
GLYCINE (UNII: TE7660XO1C)
POLYSORBATE 80 (UNII: 6OZP39ZG8H)
DIMETHICONE (UNII: 92RU3N3Y1O)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
SODIUM BENZOATE (UNII: OJ245FE5EU)
SODIUM CHLORIDE (UNII: 451W47IQ8X)
SUCROSE (UNII: C151H8M554)

Product Characteristics
Color	PINK (Light Pink)	Score
Shape		Size
Flavor	BUBBLE GUM	Imprint Code
Contains

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 16714-397-01	50 mL in 1 BOTTLE; Type 0: Not a Combination Product	01/30/2007
2	NDC: 16714-397-02	75 mL in 1 BOTTLE; Type 0: Not a Combination Product	01/30/2007
3	NDC: 16714-397-03	100 mL in 1 BOTTLE; Type 0: Not a Combination Product	01/30/2007

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA065381	01/30/2007

Labeler - NorthStar Rx LLC (830546433)

Registrant - Aurobindo Pharma Limited (650082092)

Establishment
Name	Address	ID/FEI	Business Operations
Aurobindo Pharma Limited		918917639	ANALYSIS(16714-396, 16714-397) , MANUFACTURE(16714-396, 16714-397)