CEFRIL 250 CAPSULES
CEFRIL 500 CAPSULES
CEFRIL 125 SUSPENSION
CEFRIL 250 SUSPENSION
(and dosage form)
CEFRIL 250 CAPSULES
CEFRIL 500 CAPSULES
CEFRIL 125 SUSPENSION
CEFRIL 250 SUSPENSION
CEFRIL products contain Cephradine which is a semi-synthetic cephalosporin chemically designated as 7-[D-2-amino-2-(1,4-cychlohexadien-1-yl) acetamido]-3-methyl-8-oxo- 5- thia-1- azabicyclo [4.2.0]oct-2-ene-2-carboxylic acid. CEFRIL 250 CAPSULES and CEFRIL 500 CAPSULES contain 250 mg and 500 mg cephradine respectively. CEFRIL 125 SUSPENSION and CEFRIL 250 SUSPENSION provide 125 mg and 250 mg cephradine per 5 mL respectively after reconstitution to 100 mL of suspension.
Category A 20.1.1 Broad Spectrum Antibiotics
Cephradine is a broad spectrum, bactericidal antibiotic active against both Gram positive and Gram negative bacteria.
Microbiology: The following organisms have shown in vitro sensitivity to cephradine.
Gram positive: Staphylococci (both penicillin sensitive and resistant strains), Group A Beta-haemolytic Streptococci, and Streptococcus pneumoniae.
Gram negative: Escherichia coli, Klebsiella species, Proteus mirabilis, Haemophilus influenzae and Neisseria species. Pseudomonads are uniformly resistant.
Because cephradine is unaffected by penicillinase, many strains of E. coli and Staphylococcus aureus that produce this enzyme are susceptible to cephradine. Methicillin-resistant staphylococci are not sensitive to cephradine.
Human Pharmacology: Cephradine is acid stable and is rapidly absorbed following oral administration in the fasting state. Following doses of 250 mg and 500 mg, average peak serum levels of approximately 9 and 16,5 micrograms/mL, respectively, were obtained at one hour in adult volunteers. The presence of food in the gastrointestinal tract delays the absorption but does not affect the total amount of cephradine absorbed.
Measurable serum levels are present six hours after administration. Over 90% of the drug is excreted unchanged in the urine within 6 hours. Peak urine concentrations are approximately 1600 micrograms/mL following a 250 mg dose and 3200 micrograms/mL following a 500 mg dose. After 48 hours administration of 100 mg/kg/day of cephradine for the treatment of otitis media, cephradine has been measured in the middle ear exudate at an average level of 3,6 micrograms/mL.
Cephradine is indicated for use primarily in the treatment of infections of the genitourinary and respiratory tracts and in the skin and soft tissue caused by susceptible organisms as listed below:
Staphylococcal infections (including infections caused by both penicillinase-producing and non-penicillinase-producing strains): Abscess, furunculosis, bronchitis and impetigo.
Streptococcal infections (beta-haemolytic): Cellulitis, pneumonia, follicular tonsillitis, otitis media, pharyngitis, sinusitis, scarlet fever, septic sore throat and urinary tract infections.
Pneumococcal infections: Lobar pneumonia, bronchitis, cellulitis and otitis media.
Haemophilus influenzae infections: Otitis media and laryngo-tracheo-bronchitis.
E. coli infections: Abscess and urinary tract infections.
Klebsiella infections: Lobar pneumonia and urinary tract infections.
Bacteriology studies to determine the causative organisms and their sensitivity to cephradine should be performed. Therapy may be instituted prior to receiving the results of the sensitivity test.
Cephradine is contra-indicated in patients with known sensitivity to the cephalosporin family of antibiotics or to any component of the formulation.
Safety in pregnancy and lactation has not been established.
Cephradine is secreted in breast milk.
DOSAGE AND DIRECTIONS FOR USE
Cephradine may be given without regard to meals.
Adults: For respiratory tract infections (other than lobar pneumonia) the usual dose is 250 mg four times a day in equally spaced doses. Mild or moderately severe upper respiratory tract infections and skin and/or soft tissue infections can be treated with capsules, 500 mg twice a day. For genitourinary tract infections and lobar pneumonia the usual dose is 500 mg four times a day in equally spaced doses; severe or chronic infections may require larger doses. Mild or moderately severe urinary tract infections can be treated with capsules, 1 000 mg twice a day. Prolonged intensive therapy is recommended for prostatitis and epididymitis.
Children: The usual dose is from 25 to 50 mg/kg/day total, given every 6 hours in equally divided doses. For otitis media due to H. influenzae, doses from 75 to 100 mg/kg/day in equally divided doses every 6 hours are recommended. The maximum dose should not exceed 4 grams per day. The recommended duration of treatment is 14 days for urinary tract infections and 10 days for other infections.
All patients, irrespective of age and weight: Larger doses (up to 1 gram four times a day) may be given for severe chronic infections. Therapy should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. In the treatment of beta-haemolytic streptococcal infections a therapeutic dose must be administered for at least 10 days to guard against the risk of rheumatic fever and glomerulo-nephritis. In the treatment of chronic urinary infections, frequent bacteriologic and clinical appraisal is necessary during therapy and may be necessary for several months afterwards. Stubborn infections may require treatment for several weeks. Smaller doses than those indicated above should not be used. Doses for children should not exceed doses recommended for adults.
Renal Impairment Dosage:
The following dosage schedule based on a dosage of 500 mg every six hours and on creatinine clearance is suggested as a guideline. Further modification in the dosage schedule may be required because of the dosage selected and individual variation.
On Chronic, Intermittent Haemodialysis:
|| TIME INTERVAL|
|> 20 mL/min
|| 500 mg
|| 6 hours|
|5 - 20 mL/min
|| 250 mg
|| 6 hours|
|< 5 mL/min
|| 250 mg
|| 12 hours|
250 mg start
250 mg at 12 hours
250 mg 36-48 hours (after start)
Children may require dosage modification proportional to their weight and severity of infection.
SIDE EFFECTS AND SPECIAL PRECAUTIONS
As with other cephalosporins, untoward reactions will be limited essentially to gastrointestinal disturbances and, on occasion, to hypersensitivity phenomena. The latter are more likely to occur in individuals who previously have demonstrated hypersensitivity phenomena and those with a history of allergy, asthma, hay fever, or urticaria.
Adverse reactions reported following the use of cephradine include:
Gastrointestinal: Glossitis, nausea, vomiting, diarrhoea or loose stools, abdominal pain, heartburn, colitis and pseudomembranous colitis.
Hypersensitivity reactions: A mild urticaria or skin rash, pruritus and joint pains were reported. Less frequent reports of anaphylaxis, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Hematologic: Mild, transient eosinophilia, leucopenia, and neutrophilia.
Liver: Cases of elevated SGOT, SGPT, total bilirubin and alkaline phosphatase have been observed; in most patients the values were only mildly elevated and tended to return to normal at the end of therapy. No consistent pattern was observed that would suggest hepatocellular damage.
Renal: Mild elevations of blood urea have been reported. In most cases, however, the values tended to return to normal. In adults for whom serum creatinine determinations were performed, the rise in blood urea was not accompanied by a rise in serum creatinine, which would suggest an extrarenal mechanism for the elevation of blood urea.
Other adverse reactions reported were dizziness and tightness in the chest and candidal vaginitis.
There is evidence of partial cross-allergenicity between the penicillins and the cephalosporins. Therefore, cephradine should be used with caution in those patients with known hypersensitivity to penicillins.
There have been instances of patients who have had reactions to both drug classes (including anaphylaxis).
Pseudomembranous colitis has been reported with the use of cephalosporins (and other broad spectrum antibiotics) including cephradine; therefore, it is important to consider this diagnosis in patients who develop diarrhoea in association with antibiotic use.
Patients with known or suspected renal impairment should receive careful clinical observation and appropriate laboratory studies since cephradine may accumulate in the serum and tissues unless the dosage is suitably reduced (see DOSAGE AND DIRECTIONS FOR USE).
As with all antibiotics, prolonged use may result in overgrowth of non-susceptible organisms.
After treatment with cephradine, a false positive reaction for glucose in the urine may occur with Benedict's or Fehling's solution or with Clinitest tablets, but not with enzyme based tests such as Clinistix, and Tes-Tape. As with other cephalosporins, a false positive Coombs' test has been reported.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Treatment of overdosage should be symptomatic and supportive.
CEFRIL 250 CAPSULES are two piece gelatine capsules with opaque blue cap and opaque orange body imprinted SQUIBB. CEFRIL 500 CAPSULES are two piece gelatine capsules body and cap opaque blue in colour imprinted SQUIBB. When prepared, CEFRIL 125 SUSPENSION is an orange flavoured suspension and CEFRIL 250 SUSPENSION is an aromatic fruity flavoured suspension, both with an off-white to yellowish colour.
Cephradine is available for oral administration as 250 mg and 500 mg capsules stripped in blister packs of 20 capsules. It is also available for oral administration as two powders for suspension which provide after reconstitution to 100 mL, pleasantly flavoured suspensions containing the equivalent of 125 mg and 250 mg of cephradine per 5 mL medicine measure.
Sterile Cefril for injection is also available for those patients unable to tolerate oral medication, and it is also indicated for intravenous use either by direct intravenous injection or by intravenous infusion for the treatment of serious and life threatening infections.
CEFRIL CAPSULES: Store at room temperature not exceeding 25°C.
CEFRIL SUSPENSION: Store at room temperature not exceeding 25°C in dry form.
When the prepared suspension is stored at room temperature (not exceeding 25°C), discard unused portion after 7 days. When stored in a refrigerator (5°C), discard unused portion after 14 days. Keep tightly closed. Protect prepared suspensions from light.
KEEP OUT OF REACH OF CHILDREN.
|CEFRIL 250 CAPSULES
|CEFRIL 500 CAPSULES
|CEFRIL 125 SUSPENSION
|CEFRIL 250 SUSPENSION
NAME AND BUSINESS ADDRESS OF APPLICANT:
BRISTOL-MYERS SQUIBB (PTY) LTD*
47 Van Buuren Road
DATE OF PUBLICATION OF THIS PACKAGE INSERT
*Authorised user of the TM CEFRIL
Updated on this site: June 2005
Source: Pharmaceutical Industry
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