INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo DURACEF suspension 250 mg/5 mL
DURACEF suspension 500 mg/5 mL
DURACEF capsules 500 mg
DURACEF 1 g dispersible tablet

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

DURACEF suspension 250 mg/5 mL
DURACEF suspension 500 mg/5 mL
DURACEF capsules 500 mg
DURACEF 1 g dispersible tablet

COMPOSITION:
POWDERS FOR ORAL SUSPENSION:
Powders providing
cefadroxil monohydrate equivalent to 250 mg and 500 mg cefadroxil per 5 mL respectively when reconstituted, containing approximately 0,1% m/v sodium benzoate as preservative.

CAPSULES:
Capsules containing cefadroxil monohydrate equivalent to 500 mg cefadroxil.

TABLETS:
Each dispersible tablet contains cefadroxil monohydrate equivalent to 1 g cefadroxil.

PHARMACOLOGICAL CLASSIFICATION:
A 20.1.1 Broad and medium spectrum antibiotic.

PHARMACOLOGICAL ACTION:
CLINICAL PHARMACOLOGY:
DURACEF (cefadroxil monohydrate) is a semisynthetic antibiotic with a broad spectrum of bactericidal activity. It is chemically designated as 7-[[D-2-amino-2-(4-hydroxyphenyl) acetyl]amino]-3-methyl-8-oxo-5-tia-1-azabicyclo {4.2.0}oct-2-ene-2-carboxylic acid monohydrate. DURACEF is stable in the presence of acid and is rapidly absorbed after oral administration. Following single oral doses of 250, 500 and 1000 mg, average peak serum concentrations are approximately 9, 16 and 28 µg/mL respectively. Measurable levels are present 12 hours after administration. DURACEF is approximately 20% bound to serum proteins. DURACEF has been shown to be widely distributed in most body tissues, including tonsils, bronchial secretions, pleural fluid, liver and bile and prostate. Approximately 80% of the medicine is excreted unchanged in the urine within eight hours. Peak urine concentrations reach approximately 1800 µg/mL following a single 500 mg dose.
Urine DURACEF concentration was maintained well above MIC of susceptible urinary pathogens for 20 to 22 hours following a single one gram dose.
Increase in dosage generally produces a proportional increase in DURACEF serum and urinary concentrations.

MICROBIOLOGY:
DURACEF is bactericidal in vitro against a wide range of Gram-positive and Gram-negative micro-organisms. Sensitive Gram-positive organisms include penicillinase and non-penicillinase producing staphylococci, ß-haemolytic streptococci, Streptococcus pneumoniae and Streptococcus pyogenes. Strains of sensitive Gram-negative organisms include Escherichia coli, Klebsiella pneumoniae and some strains of Proteus mirabilis, Haemophilus influenzae, and Shigella spp. In vitro sensitivity does not necessarily imply in vivo efficacy.

NOTE:
MOST STRAINS OF ENTEROCOCCI (STREP. FAECALIS AND S. FAECIUM) ARE RESISTANT TO DURACEF. DURACEF HAS NO ACTIVITY AGAINST PSEUDOMONAS SPECIES AND ACINETOBACTER CALCOACETICUS (FORMERLY MIMA AND HERELLEA SPECIES).

DISC SUSCEPTIBILITY TESTS:
The most practical applicable estimate of antibiotic sensitivity is the measurement of zone diameters on disc testing. Interpretations correlate zone diameters of disc test with minimum inhibitory concentration values for DURACEF. With this procedure, a report of "resistant" from the laboratory indicates that the infecting organism is not likely to respond to therapy. A report of "intermediate susceptibly" suggests that the organism would be susceptible if the infection is confined to the urinary tract, as DURACEF produces high antibiotic levels in the urine.

INDICATIONS:
DURACEF is indicated in the treatment of the following infections when due to susceptible micro-organisms:
Respiratory tract infections, urinary tract infections and skin and soft tissue infections.

CONTRA-INDICATIONS:
DURACEF is contra-indicated in patients with known allergy to the cephalosporin group of antibiotics. The safe use of DURACEF during pregnancy and lactation has not been established. Safety in premature infants and neonates has not been established.

WARNINGS:
IN PENICILLIN-SENSITIVE PATIENTS, CEPHALOSPORIN ANTIBIOTICS SHOULD BE USED WITH GREAT CAUTION. THERE IS CLINICAL AND LABORATORY EVIDENCE OT PARTIAL CROSS-SENSITIVITY OF THE PENICILLINS AND CEPHALOSPORINS, AND THERE ARE INSTANCES OF PATIENTS WHO HAVE HAD REACTIONS TO BOTH DRUGS (INCLUDING FATAL ANAPHYLAXIS AFTER PARENTERAL USE).

Any patient who has demonstrated a history of some form of allergy, particularly to medicines, should receive DURACEF cautiously and then only when absolutely necessary.

Pseudomembranous colitis has been reported. Therefore it is important to consider its diagnosis in patients who develop diarrhoea in association with the use of DURACEF.

DOSAGE AND DIRECTIONS FOR USE:
DURACEF administered orally is well absorbed. Administration of the antibiotic may be made without regard to food as meals have no significant effect on absorption. Administration with food may be helpful in diminishing gastro-intestinal complaints occasionally associated with oral cephalosporin therapy.

Adults and children having a mass of more than 40 g
Urinary Tract Infections:
For acute uncomplicated lower urinary tract infections (e.g. cystitis), the usual daily dosage is 1 or 2 grams per day in a single dose. In complicated or chronic urinary tract infections, the usual dosage is 1 g every 12 hours for a minimum of 7-10 days.

Skin and Skin Structure Infections:
For skin and skin structure infections the usual dosage is 1 gram per day in a single dose.

Upper Respiratory Tract Infections:
In upper respiratory infections the usual dosage is 500 mg every 12 hours. For Group A ß-haemolytic streptococcal pharyngitis and tonsillitis, 1 g DURACEF may be given as a single, daily dose. For any infections caused by Group A ß-haemolytic streptococcus, treatment should be administered for 10 days.

Lower Respiratory Tract Infections:
For lower respiratory tract infections the recommended dosage is 500 mg to 1,0 g every 12 hours.

Children having a mass of less than 40 kg:
The following dosage chart is a useful guide* to DURACEF therapy in children:

% of Adult
Dose
Age and Mass Total daily dosage
(Based on range of
1-2 g for adults)
75% 12 years (40 kg) 750 mg to 1,5 g
50% 7 years (23 kg) 500 mg to 1,0 g
25% 1 year (10 kg) 250 mg to 500 mg
12,5% Full-term (3,2 kg) 125 mg to 250 mg
* using the Percentage Method based on formula:

Surface area of Child X 100 = Percentage of Adult dose
Surface area of Adult

Urinary Tract Infections:
In acute uncomplicated urinary tract infections (e.g. cystitis)the recommenmded daily dose for children is 12,5 mg to 25 mg/kg every 12 hours. In complicated or chronic urinary tract infections the recommended dose for children is 25 mg/kg every 12 hours administered for 7-10 days.

Skin and Skin Structure Infections:
For skin and skin structure infections the recommended dose for children is 25 mg/kg given once daily or 25 mg/kg every 12 hours depending on the sensitivity of the organism.

Upper and Lower Respiratory Tract Infections:
In respiratory tract infections the recommended dose for children is 25 mg/kg every 12 hours. For Group A ß-haemolytic streptococcal pharyngitis and tonsillitis. DURACEF may be given as a single daily dose at 30 mg/kg/day. In infections caused by the Group A ß-haemolytic streptococcus, treatment should be administered for 10 days.

Dosage in Renal Impairment:
A modified dosage schedule is unnecessary in patients with creatinine clearance rates of greater than 50 mL/min. In those patients with creatinine clearance rates of 50 mL/min or less, the following reduced schedule is recommended as a guideline, based creatinine clearance rate (mL/min/1,73 m2). Each patient should be considered individually. Patients with renal insufficiency may be treated with an initial dose equal to that chosen for a patient with normal renal function (see above). Subsequent doses may be administered according to the following table:

Creatinine clearance Dose Dose Interval
0-10 mL/min/1,73 m2 500 mg 36 hours
10-25 mL/min/1,73 m2 500 mg 24 hours
25-50 mL/min/1,73 m2 500 mg 12 hours
Further modifications of the dosage schedule may be necessary in children.

Treatment should be continued for a minimum of 46 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. A MINIMUM OF 10 DAYS TREATMENT IS RECOMMENDED FOR ANY INFECTION CAUSED BY GROUP A BETA-HAEMOLYTIC STREPTOCOCCI. Chronic urinary tract infections may require prolonged intensive therapy with continued bacteriologic and clinical follow-up.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Cefadroxil may have the potential for producing allergic reactions. Rash, pruritus, urticaria and angioedema may be observed infrequently. Should an allergic reaction to DURACEF occur, the medicine should be discontinued and the patient treated with adrenaline, corticosteroids and/or antihistamines. CAUTION SHOULD BE EXERCISED WHEN DURACEF IS ADMINISTERED TO A NURSING MOTHER.

Side-effects including nausea, vomiting, diarrhoea, dyspepsia and abdominal discomfort, dizziness, headache and monilial vaginitis may also occur. Reversible neutropenia, leukopenia and minor elevations in serum transaminase may occur.

A false-positive Coombs' reaction may occur in some patients receiving DURACEF therapy. Patients treated with DURACEF may have a false-positive glycosuria reaction when Benedict’s or Fehling’s solutions, copper sulphate or Clinitest tablets are used in testing. This does not occur with enzyme-based tests such as Clinistix.

Use of DURACEF may result in the overgrowth of non-susceptible organisms. If superinfection occurs during therapy, appropriate measures should be taken.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See side-effects and special precautions. Treatment is symptomatic and supportive.

IDENTIFICATION:
POWDER FOR ORAL SUSPENSION:
Off-white powder. Reconstitution with water as per label directions produces off-white, fruit-flavoured suspension.

CAPSULES:
Hard gelatine capsules comprising opaque, white caps and bodies overprinted 7244.

DISPERSIBLE TABLETS:
White to creamy-white, scored round tablets, 24,5 mm in diameter. Tablets are embossed CDX and have a slightly fruity odour.

PRESENTATION:
POWDERS FOR ORAL SUSPENSION:
Powders in plastic bottles providing 60 mL of each strength when reconstituted.

CAPSULES:
Blister packs with 10 capsules.

DISPERSIBLE TABLETS:
Tablets stripped in foil packs of 5 tablets. Tablets to be dispersed as per label instructions.

STORAGE INSTRUCTIONS:
Store in a cool, dry place. Temperatures should not exceed 25°C.

NOTE: Powders for oral suspension: The potency of reconstituted suspensions will be maintained for one week at temperatures that do not exceed 25°C and for two weeks under refrigeration (2-8°C).
Keep out of reach of children.

REGISTRATION NUMBERS:
Suspensions: P/20.l.1/244/5
Capsules: P/20.1.1/247
Dispersible Tablet: 27/20.1.1/277
NAME AND BUSINESS ADDRESS OF APPLICANT:
Bristol-Myers Squibb (Pty) Ltd >
AMR Park,
1 Concorde Road East,
Bedfordview
2008

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
January 1993

** Authorised user of the TM DURACEF

29-0001        02/93

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