INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
PROZEF 125 mg/5 mL Suspension
PROZEF 250 mg/5 mL Suspension
PROZEF 250 mg Tablets
PROZEF 500 mg Tablets


SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

PROZEF 125 mg/5 mL Suspension
PROZEF 250 mg/5 mL Suspension
PROZEF 250 mg Tablets
PROZEF 500 mg Tablets

COMPOSITION
PROZEF (Cefprozil) is a semi-synthetic broad-spectrum cephalosporin antibiotic intended for oral administration.
PROZEF tablets contain Cefprozil monohydrate equivalent to 250 mg or 500 mg of anhydrous Cefprozil.
PROZEF for oral suspension contains Cefprozil monohydrate equivalent to 125 mg or 250 mg Cefprozil per 5 mL reconstituted suspension and sodium benzoate 0,1% w/v as preservative.
Phenylketonurics: PROZEF for oral suspension contains phenylalanine (from aspartame) 28 mg per 5 mL reconstituted suspension for both the 125 mg/5 mL and 250 mg/5 mL dosage forms.

PHARMACOLOGICAL CLASSIFICATION
Category A 20.1.1 Broad and Medium Spectrum Antibiotics.

PHARMACOLOGICAL ACTION
Cefprozil is approximately 96% absorbed following oral administration in both fasting and non-fasting subjects. Average plasma concentrations after administrations of Cefprozil to fasting subjects are shown in the following table. Urinary recovery accounts for approximately 60% of the administration dose.

Dosage	Mean Plasma Cefprozil Concentrations (mcg/mL)		8-hour Urinary Excretion
	Peak approx. 1.5 hour	4 hour	8 hour	Percentage
250 mg 500 mg 1g	6.1 10.5 18.3	1.7 3.2 8.4	0.2 0.4 1.0	60% 62% 54%

During the first four-hour period after drug administration, the average urine concentrations following the 250 mg, 500 mg and 1g doses are approximately 700 mcg/mL, 1000 mcg/mL and 2900 mcg/mL.
Plasma protein binding is approximately 36% and is independent of concentration in the range of 2 mcg/mL to 20 mcg/mL. The average plasma half-life in normal subjects is 1.3 hours.
Cefprozil does not accumulate in the plasma in individuals with normal renal function.
In patients with reduced renal function, the plasma half-life prolongation is related to 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 to 2.1 hours. Excretion pathways in patients with markedly impaired renal function have not been determined. (See PRECAUTIONS and DOSAGE AND DIRECTIONS FOR USE).
The average AUC observed in elderly subjects ( 65 years of age) is approximately 35-60% higher than that of young adults and the average AUC in females is approximately 15-20% higher than in males. The magnitude of these age and gender-related variations in the pharmacokinetics of Cefprozil are not sufficient to necessitate dosage adjustments.
In patients with impaired hepatic function, no significant differences in pharmacokinetic parameters are observed, when compared to normal control subjects.
Adequate data on CSF levels of Cefprozil are not available.

MICROBIOLOGY
Cefprozil has in vitro activity against the following organisms. (In vitro activity does not necessarily imply in vivo efficacy). The bactericidal action of Cefprozil results from inhibition of cell-wall synthesis.
Aerobes, gram-positive
Staphylococci including Staphylococcus aureus (including penicillinase-producing strains); NOTE: Cefprozil is inactive against methicillin-resistant staphylococci.
Streptococcus pyogenes (Group A streptococci); S. pneumoniae.
Enterococci including E faecalis; NOTE: Cefprozil is inactive against E. faecium.
Other: Listeria monocytogenes.
Aerobes, gram-negative
Branhamella catarrhalis
Haemophilus influenzae (including penicillinase-producing strains)
Citrobacter diversus
Escherichia coli
Klebsiella pneumoniae
Neisseria gonorrhoeae (including penicillinase-producing strians)
Proteus mirabilis
Salmonella spp.
Shigella spp.
Vibrio spp.
NOTE: Cefprozil is inactive against most strains of Acinetobacter, Enterobacter, Morganella morganii, Proteus vulgaris, Providencia, Pseudomonas and Serratia.
Anaerobes
NOTE: Most strains of the Bacteroides fragilis group are resistant to Cefprozil.
Clostridium difficile; C perfringens
Fusobacterium spp.
Peptostreptococcus spp.
Prevotella melaninogenica
(formerly) known as Bacteroides melaninogenicus.
Propionibacterium acnes.
In vitro sensitivity does not necessarily imply clinical efficacy.

INDICATIONS
PROZEF is indicated for the treatment of patients with mild to moderately severe infections caused by susceptible strains of the designated microorganisms listed below:
Upper respiratory tract:
Pharyngitis/tonsilitis caused by Streptococcus pyogenes. Note: The usual agent 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:
Otitis media caused by Streptococcus pneumoniae, Haemophilus influenza and Branhamella catarrhalis.
Note: In the treatment of otitis media due to beta-lactamase producing organisms, cefprozil had bacteriologic eradication rates somewhat lower than those observed with a product containing a specific beta-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 beta-lactamase inhibitors.
Sinusitis
Lower respiratory tract:
Secondary bacterial infection of acute bronchitis, and acute bacterial exacerbation of chronic bronchitis caused by Streptococcus pneumonia, Haemophilus influenza (beta-lactamase positive and negative strains) and Branhamella catarrhalis.
Skin and skin structure:
Uncomplicated skin and skin structure infections caused by Staphylococcus aureus (including penicillinase-producing strains) and Streptococcus pyogenes.
Urinary tract:
Uncomplicated urinary tract infections including acute cystitis in women caused by Escherichia coli, Klebsiella pneumonia and Proteus mirabilis.
Culture and susceptibility testing should be performed when appropriate to determine susceptibility of the causative organism to Cefprozil.

CONTRA-INDICATIONS
PROZEF is contraindicated in patients with known allergy to the cephalosporin class of antibiotics or any component of the formulation.

Use in Pregnancy and Lactation
Safety of use in pregnancy and lactation has not been established.

WARNINGS
Before therapy with PROZEF is instituted, careful inquiry should be made to determine whether the patients has had previous hypersensitivity reactions to PROZEF, cephalosporins, penicillins, or other medicine. If this product is to be given to penicillin-sensitive patients, caution should be exercised because cross-sensitivity among beta-lactam antibiotics has been documented. If an allergic reaction to PROZEF occurs, discontinue the medication. Serious acute hypersensitivity reactions may require emergency treatment measures.
Pseudomembranous colitis can occur.

DOSAGE AND DIRECTIONS FOR USE
Adults and children over 12 years
PROZEF is administered orally for a period of 10 days in the treatment of infections due to susceptible bacteria in the following:

Upper respiratory infections	500 mg every 24 hours
Lower respiratory infections	500 mg every 12 hours
Sinusitis	250 mg every 12 hours or
	500 mg every 12 hours
Uncomplicated urinary tract infections	500 mg every 24 hours
Skin & skin structure infections	250 mg every 12 hours or
	500 mg every 12 or 24 hours

Children
In children between 1 year and 12 years of age with upper respiratory tract infections, pharyngitis, or tonsillitis, 7,5 mg/kg every 12 hours is recommended. In otitis media, a 15 mg/kg dose administered every 12 hours is recommended. In skin and skin structure infections 20 mg/kg once daily is recommended.
In sinusitis: 7.5 - 15 mg/kg every 12 hours
In the treatment of beta-hemolytic streptococcal infections, a therapeutic dosage of PROZEF should be administered for at least 10 days.
Renal Impairment
Cefprozil may be administered to patients with impaired renal function. No dosage adjustment is necessary for patients with creatinine clearance values > 30 mL/min. For those with creatinine clearance values < 30 mL/min, 50% of the standard dose should be given at the standard dosing interval. Cefprozil is in part removed by hemodialysis; therefore, Cefprozil should be administered after the completion of hemodialysis.       
Hepatic Impairment
No dosage adjustment is necessary for patients with impaired hepatic function.

SIDE-EFFECTS AND SPECIAL PRECAUTION
Side-Effects
The most common adverse effects in patients treated with Cefprozil are:
Gastrointestinal:Diarrhoea, nausea, vomiting and abdominal pain.
Hepatobiliary: Elevations of AST (SGOT), ALT (SGPT), alkaline phosphatase, and bilirubin values. Cholestatic jaundice has been reported.
Hypersensitivity:Rash and urticaria. Such reactions have been reported more frequently in children than in adults.
CNS:Dizziness, hyperactivity, headache, nervousness, insomnia, confusion and somnolence have been reported.
Hematopoietic:Decreased leukocyte count, eosinophilia. Prolonged prothrombin time has also been observed.
Renal:Elevations in blood urea and serum creatinine.
Other: Nappy rash and superinfection, genital pruritus and vaginitis. Anaphylaxis, angioedema, fever, erythema multiforme, Stevens Johnson Syndrome, thrombocytopenia, serum sickness and colitis including pseudomembranous colitis have occurred.

PRECAUTIONS
General
Evaluation of renal status before and during therapy is recommended, especially in seriously ill patients. In patients with known or suspected renal impairment (see DOSAGE and DIRECTIONS for USE), careful clinical observation and appropriate laboratory studies should be done prior to and during therapy. The total daily dose of PROZEF should be reduced in these patients because high and/or prolonged plasma antibiotic concentrations can occur in such individuals from usual doses. Cephalosporins, including PROZEF, 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 PROZEF 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.
Positive direct Coombs tests have been reported during treatment with cephalosporin antibiotics.
Interactions
Cephalosporin can inhibit vitamin K synthesis by supressing gut flora. Prophylactic vitamin K therapy is recommended when cephalosporins are used for long periods in malnourished or seriously ill patients.
Nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and cephalosporin antibiotics.
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 (glucose oxidase) for glycosuria. A false negative reaction may occur in the ferricyanide test for blood glucose. The presence of Cefprozil in the blood does not interfere with the assay of plasma or urine creatinine by the alkaline picrate method.
Paediatric Use
Safety and effectiveness in children below the age of 1 year have not been established. Accumulation of other cephalosporin antibiotics in newborn infants (resulting from prolonged drug half-life in this age group) has been reported.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Single doses as high as 5000 mg/kg administered in animal toxicology studies were without serious or lethal consequences.
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.

IDENTIFICATION

PROZEF 125 mg/5 mL:	Powders for oral suspension. Off-white to pale yellow gritty powder. Reconstitution with water as per label instructions produces a orange suspension.
PROZEF 250 mg/5 mL:	Powders for oral suspension. Off-white to pale yellow gritty powder. Reconstitution with water as per label instructions produces an orange suspension.
PROZEF 250 mg Tablets:	A light orange film-coated, rounded caplet shaped, plain standard biconvex tablet, embossed with "7720" on one side and "250" on the other side.
PROZEF 500 mg Tablets:	A white film-coated rounded caplet shaped, plain standard biconvex tablet, embossed with "7721" on one side and "500" on the other side.

PRESENTATION
TABLETS: Blister packs with 10 tablets.
POWDERS FOR ORAL SUSPENSIONS: Powders in plastic bottles providing 60 mL or 100 mL of each strength when reconstituted.

STORAGE INSTRUCTIONS
PROZEF (Cefprozil) for oral suspension.
All powder formulations for oral suspension contain Cefprozil in a pleasantly flavoured mixture. Directions for mixing are included on the label. After mixing, store in a refrigerator, and discard unused portion after 14 days. Shake well before using. Keep container tightly closed
Store at room temperature not exceeding 25°C prior to reconstitution.
PROZEF (Cefprozil) Tablets.
Store at room temperature not exceeding 25°C.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS

PROZEF 125 mg/5 mL Suspension:	28/20.1.1/0519
PROZEF 250 mg/5 mL Suspension:	28/20.1.1/0520
PROZEF 250 mg Tablets:	28/20.1.1/0517
PROZEF 500 mg Tablets:	28/20.1.1/0518

NAME AND BUSINESS ADDRESS OF APPLICANT
Bristol-Myers Squibb (Pty) Ltd *
47 van Buuren Road
Bedfordview
2008

DATE OF PUBLICATION OF THIS PACKAGE INSERT
April 1999

* Authorised user of the TM PROZEF

Updated on this site: October 2005
Source: Pharmaceutical Industry
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