Cefprozil Information
Cefprozil ()
Cefprozil () 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 (6,7)-7-[()-2-amino-2-(-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:
CHNOS•HO M.W. 407.45
Cefprozil () is a white to yellowish powder.
Cefprozil () for oral suspension USP is intended for oral administration.
Cefprozil () for oral suspension USP contains Cefprozil () 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, FD&C Red No. 3, flavors (natural and artificial) gum fruit, glycine, hypromellose, microcrystalline cellulose/carboxymethylcellulose sodium, silicon dioxide, sodium benzoate, sodium chloride, and sucrose.
Cefprozil () 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.)
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 (C) of Cefprozil () . However, there was an increase of 0.25 to 0.75 hours in the time to maximum plasma concentration of Cefprozil () (T).
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.
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 and .)
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.
Cefprozil () Indications And Usage
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.
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 from the nasopharynx; however, substantial data establishing the efficacy of Cefprozil () in the subsequent prevention of rheumatic fever are not available at present.
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.
Secondary Bacterial Infection of Acute Bronchitis and Acute Bacterial Exacerbation of Chronic Bronchitis
Streptococcus pneumoniae, Haemophilus influenzae
Moraxella (Branhamella) catarrhalis
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefprozil () for oral suspension and other antibacterial drugs, Cefprozil () for oral suspension 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 () Contraindications
Cefprozil () is contraindicated in patients with known allergy to the cephalosporin class of antibiotics.
Cefprozil () Warnings
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of , and surgical evaluation should be instituted as clinically indicated.
Cefprozil () Precautions
Prescribing Cefprozil () for oral suspension in the absence of a 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 ), 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.
Phenylketonurics: Cefprozil () for oral suspension contains phenylalanine 10.1 mg 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 () for oral suspension should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Cefprozil () for oral suspension 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 () for oral suspension 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.
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.
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 tablets), 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.
Clinitest and Clinistix are registered trademarks of the Bayer HealthCare LLC.
Long term studies have not been performed to evaluate the carcinogenic potential of Cefprozil () .
Cefprozil () was not found to be mutagenic in either the Ames or 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 . 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/m.
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/m.
(See and .)
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 .)
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.
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 ).
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 for dosing recommendations for patients with impaired renal function.
Cefprozil () 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:
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.
Cefprozil () 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.
Cefprozil () Dosage And Administration
Cefprozil () for oral suspension is administered orally.
Cefprozil () How Supplied
Cefprozil () for oral suspension USP is available as follows:
125 mg/5 mL: Each 5 mL of constituted suspension contains the equivalent of 125 mg anhydrous Cefprozil () in bottles of 50 mL, 75 mL, and 100 mL.
250 mg/5 mL: Each 5 mL of constituted suspension contains the equivalent of 250 mg anhydrous Cefprozil () in bottles of 50 mL, 75 mL, and 100 mL.
All light pink powder formulations for oral suspension contain Cefprozil () in a fruit-gum flavored mixture.
Cefprozil () Clinical Studies
In a controlled clinical study of 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:
EFFICACY:
SAFETY:
The incidences of adverse events, primarily diarrhea and rash, were clinically and statistically significantly higher in the control arm versus the Cefprozil () arm.
The majority of these involved the diaper area in young children.
In a controlled clinical study of 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:
EFFICACY:
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).
Cefprozil () References
Manufactured By:
Sellersville, PA 18960
Rev. B 9/2007
Cefprozil () Principal Display Panel
Cefprozil () for
Oral Suspension USP
125 mg/5 mL*
*
according to directions, contains
125 mg anhydrous Cefprozil () .
Rx only
50 mL (when mixed)
TEVA
Cefprozil () Principal Display Panel
Cefprozil () for
Oral Suspension USP
250 mg/5 mL*
*
according to directions, contains
250 mg anhydrous Cefprozil () .
Rx only
50 mL (when mixed)
TEVA
