药品名称
【别名】头孢丙烯 , 施复捷
【外文名】Cefprozil

药理作用
本品为第二代头孢菌素类抗生素，具有广谱抗菌作用，其杀菌的作用机理是阻碍细菌细胞壁的合成。

药代动力学
健康受试者空腹口服头孢丙烯，约95％的给药量可被吸收。空腹服用250mg、500mg或1g后，平均血药浓度为6.1，10.5，和18.3μg/ml，达峰时间为1.5小时。食物与本品同服不影响头孢丙烯的血药峰浓度，但达峰时间可延长0.25-0.75小时。本品的消除半衰期为1.3小时，稳态分布容积约0.23L/kg，蛋白结合率为36％。肾功能减退者，本品的血浆半衰期可处长至5.2小时。血液透析可清除头孢丙烯。肝功能损害者的血浆半衰期可增至2小时左右，但这种改变并不说明肝功能损害者需要调整剂量。

适应症
用于敏感菌所致的下列轻、中度感染：上呼吸道感染（化脓性链球菌性咽炎/扁桃体炎、中耳炎、急性鼻窦炎）。下呼吸道感染（急性支气管炎继发细菌感染和慢性支气管炎急性发作）。皮肤和软组织感染。

用法用量
成人上呼吸道感染，500mg qd,下呼吸道感染500mg bid，皮肤或皮肤软组织感染，250mg bid或500mg qd,严重病例500mg bid.2-12岁的儿童上呼吸道感染，每次7.5mg/kg体重 bid;皮肤或皮肤软组织感染，每次20mg/kg体重 qd；6个月婴儿至2岁儿童中耳炎，每次15mg/kg体重 bid；急性鼻窦炎，一般每次7.5mg/kg体重 bid；严重病例可服用每次15mg/kg体重 bid。疗程一般7-14天，但β-溶血性链球菌所致急性扁桃体炎、咽炎的疗程至少10天。肾功能不全者误码根据肌酐清除率调整剂量：肌酐清除率在30-120ml/分者，按常用剂量、常规时间间隔服药；肌酐清除率为0-29ml/分者，按50％常用剂量，常规时间间隔服药。肝功能受损者无需调整剂量。任何疑问，请遵医嘱！

不良反应
与其他口服头孢菌素相似，主要为胃肠道反应，如腹泻、恶心、呕吐和腹痛。过敏反应，常见为皮疹、荨麻疹。儿童过敏反应较成人多见，多在开始治疗后几天内出现，停药后几天内消失。

注意事项
对头孢菌素类抗生素过敏者禁用。有青霉素过敏史者服用本品应谨慎。凡以往有青霉素所致过敏性休克史或其他严重过敏反应者不宜使用核武器中。同时报用强利尿剂治疗的患者使用本品应谨慎。

规格
头孢丙烯片剂：250mg/片；500mg/片。
头孢丙烯口服混悬液：125mg/5ml; 250mg/5ml。

〖原产地英文商品名〗CEFPROZIL for oral suspension 250mg/5ml 100mls/bottle
〖原产地英文药品名〗CEFPROZIL
〖中文参考商品译名〗头孢丙烯口服混悬液 250毫克/5毫升 100毫升/瓶
〖中文参考药品译名〗头孢丙烯
〖生产厂家中文参考译名〗lupin pharmaceuticals
【生产厂家英文名〗lupin pharmaceuticals

Cefzil® Tablets
(cefprozil) 250 mg and 500 mg

Cefzil® for Oral Suspension
(cefprozil) 125 mg/5 mL and 250 mg/5 mL

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

DRUG DESCRIPTION
CEFZIL (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.

Cefprozil is a white to yellowish powder with a molecular formula for the monohydrate of C18H19N3O5S•H2O and a molecular weight of 407.45.

CEFZIL Tablets and CEFZIL for Oral Suspension are intended for oral administration.

CEFZIL Tablets contain cefprozil equivalent to 250 mg or 500 mg of anhydrous cefprozil. In addition, each tablet contains the following inactive ingredients: cellulose, hypromellose, magnesium stearate, methylcellulose, simethicone, sodium starch glycolate, polyethylene glycol, polysorbate 80, sorbic acid, and titanium dioxide. The 250 mg tablets also contain FD&C Yellow No. 6.

CEFZIL for Oral Suspension 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, cellulose, citric acid, colloidal silicone dioxide, FD&C Red No. 3, flavors (natural and artificial), glycine, polysorbate 80, simethicone, sodium benzoate, sodium carboxymethylcellulose, sodium chloride, and sucrose.

INDICATIONS
CEFZIL 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
Secondary Bacterial Infection of Acute Bronchitis and 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.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of CEFZIL and other antibacterial drugs, CEFZIL 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.

SIDE EFFECTS
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 CEFZIL, 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.

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 (eg, 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.

WARNINGS
BEFORE THERAPY WITH CEFZIL IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFZIL, 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 CEFZIL 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 CEFZIL, 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 CEFZIL 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 CEFZIL (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 CEFZIL, 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 CEFZIL 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.

Carcinogenesis, Mutagenesis, and 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 µg/mL. Caution should be exercised when CEFZIL 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 CEFZIL 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 CEFZIL 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 CEFZIL 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 CEFZIL 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 CEFZIL cannot be excluded (see CLINICAL PHARMACOLOGY).

CEFZIL 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.

OVERDOSE
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.

CONTRAINDICATIONS
CEFZIL (cefprozil) is contraindicated in patients with known allergy to the cephalosporin class of antibiotics.