Cefprozil

Half-Life: 1.3 hr

Peak Plasma Time: 1.5 hr

Protein Bound: 35-45%

Absorption: oral 94%

Metabolism: liver

Excretion: unchanged in urine: 61%

Mechanism of Action

Second-generation cephalosporin that binds to one or more of the penicillin-binding proteins, which in turn inhibits cell wall synthesis and results in bactericidal activity. Has gram-positive activity that first-generation cephalosporins have and adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store the tablets at room temperature and away from excess heat and moisture (not in the bathroom). Keep liquid medicine in the refrigerator, closed tightly, and throw away any unused medication after 14 days.

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, stop taking cefprozil and call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

Other drugs may interact with cefprozil, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Cefzil

Probenecid (Benemid) may increase the blood concentration of cefprozil by decreasing excretion of cefprozil by the kidney. This interaction is sometimes used to enhance the effect of cephalosporins.

Combining cefprozil with aminoglycosides (for example, tobramycin) produces additive bacterial killing effects but also may increase the risk of harmful effects to the kidney.

Exenatide (Byetta) may delay or reduce the absorption of cephalosporins. Cephalosporins should be administered one hour before exenatide.

CCefprozil may cause false test results with some tests for sugar in the urine.

Take the medication as soon as you remember the missed dose. If it is almost time for your next dose, skip the missed dose and use the medicine at your next regularly scheduled time. Do not use extra medicine to make up the missed dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Contraindications

• Known allergy to cefprozil or other cephalosporins.80 81

Warnings/Precautions

Warnings

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

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.80 81 142 C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including cefprozil, and may range in severity from mild diarrhea to fatal colitis.80 81 142 C. difficile produces toxins A and B which contribute to development of CDAD;142 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.80 81

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.80 81 142 Obtain careful medical history since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.80 81 142

If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.142 Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.71 72 80 81 142

Sensitivity Reactions

Hypersensitivity reactions (anaphylaxis,80 81 serum-sickness-like reactions,14 80 81 erythema,9 12 Stevens-Johnson syndrome14 80 81 ) have been reported.

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).80 81

Partial cross-sensitivity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.46 80 81

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.80 81 Cautious use recommended in patients with a history of hypersensitivity to penicillins:80 81 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

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.80 81

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

Depending on the manufacturer, 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 per 5 mL.3 81 101 102 103 104 105

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

Specific Populations

Category B.80 81

Distributed into milk; use with caution.80 81

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

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

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.80 81

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.80 81 Select dosage with caution and consider renal function monitoring since geriatric patients are more likely to have renal impairment.80 81

Half-life only slightly prolonged.80 81 Dosage adjustments not required.80 81

Decreased clearance.80 81

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

Reduce dosage in those with Clcr <30 mL/minute.80 81 See Renal Impairment under Dosage and Administration.

Common Adverse Effects

Diarrhea, nausea, vomiting, abdominal pain, rash, genital pruritus or vaginitis, dizziness.9 80 81

Take cefprozil only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

Shake the oral liquid well before each use. Measure the medicine with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.

Keep using cefprozil for the full treatment time, even if you feel better after the first few doses. Your infection may not clear up if you stop using the medicine too soon.

Dosing

The dose of cefprozil will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of cefprozil. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage forms (tablets or suspension):
  • For bronchitis:
    • Adults and teenagers—500 milligrams (mg) every 12 hours, taken for 10 days.
    • Children younger than 13 years of age—Use and dose must be determined by your doctor.
  • For ear infections:
    • Children 6 months to 12 years of age—Dose is based on body weight and must be determined by your doctor. The dose is usually 15 milligrams (mg) per kilogram (kg) of body weight every 12 hours, taken for 10 days.
    • Infants younger than 6 months of age—Use and dose must be determined by your doctor.
  • For sinusitis:
    • Adults and teenagers—250 or 500 milligrams (mg) every 12 hours for 10 days.
    • Children 6 months to 12 years of age—Dose is based on body weight and must be determined by your doctor. The dose is usually 7.5 to 15 milligrams (mg) per kilogram (kg) of body weight every 12 hours, taken for 10 days.
    • Infants younger than 6 months of age—Use and dose must be determined by your doctor.
  • For skin infections:
    • Adults and teenagers—250 to 500 milligrams (mg) every 12 hours or 500 mg once a day, taken for 10 days.
    • Children 2 to 12 years of age—Dose is based on body weight and must be determined by your doctor. The dose is usually 20 milligrams (mg) per kilogram (kg) of body weight per day, taken for 10 days.
    • Children younger than 2 years of age—Use and dose must be determined by your doctor.
  • For sore throat and tonsillitis:
    • Adults and teenagers—500 milligrams (mg) once a day for 10 days.
    • Children 2 to 12 years of age—Dose is based on body weight and must be determined by your doctor. The dose is usually 7.5 milligrams (mg) per kilogram (kg) of body weight every 12 hours, taken for 10 days.
    • Children younger than 2 years of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of cefprozil, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the oral liquid in the refrigerator. Throw away any unused medicine after 14 days.

Store the tablets in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

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 phenylalanine 9.5 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 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® 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.

1Clinitest® 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.

Refer to adult dosing.

No dosage adjustment necessary.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Refrigerate suspension after reconstitution; discard after 14 days.

Positive direct Coombs, false-positive urinary glucose test using cupric sulfate (Benedict's solution, Clinitest, Fehling's solution), but not with enzyme-based tests for glycosuria (eg, Clinistix). A false-negative reaction may occur in the ferricyanide test for blood glucose.

Concerns related to adverse effects:

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

• Penicillin allergy: Use with caution in patients with a history of penicillin allergy.

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

Disease-related concerns:

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

• Renal impairment: Use with caution in patients with renal impairment; modify dosage in severe impairment.

Concurrent drug therapy issues:

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

Dosage form specific issues:

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

• Phenylalanine: Some products may contain phenylalanine.

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

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea or diarrhea. Have patient report immediately to prescriber bruising, bleeding, severe loss of strength and energy, seizures, urinary retention, change in amount of urine passed, vaginitis, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Uncomplicated: 500 mg orally every 12 to 24 hours for 14 days

500 mg orally every 12 to 24 hours for 10 to 14 days

2 to 12 years: 20 mg/kg orally every 24 hours for 10 days; do not exceed 1 g/day
13 years or older: Adult dose

Cefprozil is in part removed by hemodialysis. The dose should be administered after the completion of hemodialysis.

Summary of Use during Lactation

Cefprozil is acceptable to use during breastfeeding. Limited information indicates that maternal doses of cefprozil up to 1 gram produce low levels in milk that are not expected to cause adverse effects in breastfed infants. Occasionally, disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush, has been reported with cephalosporins, but these effects have not been adequately evaluated.

Drug Levels

Maternal Levels. Nine healthy women were given a single 1 gram dose of cefprozil orally 6 to 12 months postpartum. Milk levels of cis-cefprozil (which accounts for 90% of cefprozil) ranged from 0.7 to 1.3 mg/L during the 12 hours after the dose. The peak level averaged 3.4 mg/L at 6 hours after the dose. By 24 hours after the dose, milk cefprozil levels were 0.3 mg/L.[1][2] Using the peak milk level value and assuming that the trans-isomer adds an additional 10% to the peak, an exclusively breastfed infant would receive a maximum of 3.3% of the weight-adjusted maternal dosage.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

References

1. Shyu WC, Shah VR, Venitz J et al. The excretion of cefprozil (CPR) into breast milk. Clin Pharmacol Ther. 1992;51:182. Abstract. DOI: doi:10.1038/clpt.1992.14

2. Shyu WC, Shah VR, Campbell DA et al. Excretion of cefprozil into human breast milk. Antimicrob Agents Chemother. 1992;36:938-41. PMID: 1510416