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| Velosef Pamphlet |
VELOSEF
CEPHRADINE ORAL
DESCRIPTION
VELOSEF (Cephradine) is a semisynthetic cephalosporin antibiotic.
VELOSEF contains cephradine a semisynthetic cephalosporin antibiotic intended for oral administration.
Cephradine is designated chemically as (6R, 7R-7- [(R)-2. amino-2-(1 ,4-cyclohexidien-1 yl)acetamidoj-3-methyl-8- oxo-5-thia- 1 -azabicyclo-[4 .2 .O]oct-2-ene-2-carboxylic acid its molecular formula is CH19NO4S and has a molecular weight of 349.40.
VELOSEF is available in the following dosage forms and strengths:
Capsules, 250 and 500 mg. Inert ingredients Include lactose, magnesium stearate, talc, titanium dioxide, gelatin, and colorants.
Tablets, 1 g. Inert ingredients include corn starch, magnesium stearate, microcrystalline cellulose, silicon dioxide and lactose.
Powder for Oral Suspension, 125 and 250 mg / 5 ml after constitution. Inert ingredients include citric acid, guar gum, methylcellulose, sodium citrate, sucrose, flavoring agents and colorants.
CLINICAL PHARMACOLOGY
Cephradine is acid stable and is rapidly absorbed following oral administration in the fasting state. Following doses of 250 mg, 500 mg, and 1 gm in normal adult volunteers, average peak serum levels of approximately 9, 16.5 and 24.2 pg/mI, respectively, were obtained at one hour. 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. Fourty eight hours after administration of 100 mg/kglday of cephradine for the treatment of otitis media, cephradine was present in the middle ear exudate at an average level of 3.6 .ig/ml. Cephradine does not pass across the blood-brain barrier to any appreciable extent.
Over 90% of the drug is excreted unchanged in the urine within 6 hours. Peak urine concentrations are approximately 1600 pg/mI following a 250 mg dose. 3200 pg/mi following a 500 mg dose, and 4000 pg/mI following a 1 gm dose.
MICROBIOLOGY
Cephradine is a broad-spectrum, bactericidal antibiotic
active against both gram-positive and gram-negative
bacteria. Cephradine is active against the following
organisms in vitro:
• Group A beta-hemolytic streptococci.
• Staphylococci, including coagulase-positive, coagulasenegative, and penicillinase-producing strains.
• Streptococci pneumon iae (formerly Diplococcus
pneumoniae).
• Escherlchia coli.
• Proteus mirabilis
CEPHRADINE ORAL
DESCRIPTION
VELOSEF (Cephradine) is a semisynthetic cephalosporin antibiotic.
VELOSEF contains cephradine a semisynthetic cephalosporin antibiotic intended for oral administration.
Cephradine is designated chemically as (6R, 7R-7- [(R)-2. amino-2-(1 ,4-cyclohexidien-1 yl)acetamidoj-3-methyl-8- oxo-5-thia- 1 -azabicyclo-[4 .2 .O]oct-2-ene-2-carboxylic acid its molecular formula is CH19NO4S and has a molecular weight of 349.40.
VELOSEF is available in the following dosage forms and strengths:
Capsules, 250 and 500 mg. Inert ingredients Include lactose, magnesium stearate, talc, titanium dioxide, gelatin, and colorants.
Tablets, 1 g. Inert ingredients include corn starch, magnesium stearate, microcrystalline cellulose, silicon dioxide and lactose.
Powder for Oral Suspension, 125 and 250 mg / 5 ml after constitution. Inert ingredients include citric acid, guar gum, methylcellulose, sodium citrate, sucrose, flavoring agents and colorants.
CLINICAL PHARMACOLOGY
Cephradine is acid stable and is rapidly absorbed following oral administration in the fasting state. Following doses of 250 mg, 500 mg, and 1 gm in normal adult volunteers, average peak serum levels of approximately 9, 16.5 and 24.2 pg/mI, respectively, were obtained at one hour. 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. Fourty eight hours after administration of 100 mg/kglday of cephradine for the treatment of otitis media, cephradine was present in the middle ear exudate at an average level of 3.6 .ig/ml. Cephradine does not pass across the blood-brain barrier to any appreciable extent.
Over 90% of the drug is excreted unchanged in the urine within 6 hours. Peak urine concentrations are approximately 1600 pg/mI following a 250 mg dose. 3200 pg/mi following a 500 mg dose, and 4000 pg/mI following a 1 gm dose.
MICROBIOLOGY
Cephradine is a broad-spectrum, bactericidal antibiotic
active against both gram-positive and gram-negative
bacteria. Cephradine is active against the following
organisms in vitro:
• Group A beta-hemolytic streptococci.
• Staphylococci, including coagulase-positive, coagulasenegative, and penicillinase-producing strains.
• Streptococci pneumon iae (formerly Diplococcus
pneumoniae).
• Escherlchia coli.
• Proteus mirabilis
• Kiebsiella species.
• Hemophilus influénzae,
Cephradlne is not active against most strains of Enterobacter species. Mon.aneIia morganii (formerly proteus morganii), and proteus vulgaris. Most strains of Enterococci (Enteroccus faecalis) are resistant to cephradine. It has no activity against Pseuclomonas or Herellea species, When tested by in vitro methods, staphylococci exhibit cross-resistance between cephradine and methicillin-type antibiotics.
Cephalosporin-class discs are used in disc susceptibility testing.
INDICATIONS
VELOSEF (cephradine) is indicated in the treatment of the following infections due to susceptible organisms:
• Respiratory tract infections, eg., tonsillitis, pharyngitis, lobar pneumonia.
• Otitis media.
• Skin and skin structure infections.
• Urinary tract infections including prostatitis. Bacteriological studies to determine the causative organisms and their sensitivity to cephradine should be performed. Therap’ may be instituted prior to receiving results of sensitivity tests.
CONTRAINDICATIONS
Cephradine is cotraindicated in patients with known hypersensitivity to any cephalosporin antibiotic or to any component of the formulation.
PRECAUTIONS
There is evidence of partial cross-allergenicity between the penicillins and the ephaIosporins. Therefore. cephradine should be used with penicillins. There have been instances of patients who have had reactions to both drug classes, including anaphyIais (see ADVERSE REACTIONS).
Pseudomembranot.s colitis has been reported with the use of cephalosporins and other broad spectrum antibiotics), including cephradirie; therefore, it is important to consider this diagnosis in patients who develop diarrhea in association with antibiotic use. Mild cases of colitis may respond to drug discontinuance alone: moderate to severe cases should be managed as indicated.
In patients with known or suspected renal impairment, careful clinical observation and appropriate laboratory studies should be performed since cephradine accumulates in the serum and tissues unless dosage is suitably reduced )see DOSAGE AND ADMINISTRATION). After treatment witi cephradine, a false-positive reaction for glucose in the utine may occur with Benedict’s solution, Fehlings solution, or with Clinitest’ tablets, but not with enzyme-based tets suh as Clinistix tablets, and Tes-Tape.
As with other cephalosporins, positive direct Coombs’ tests have been infrequently reported.
As with all antibiotics, prolonged use may result in overgrowth of nonsisceptible organisms.
Pregnancy:
This drug should b used during pregnancy only if clearly needed.
Cephradlne is not active against most strains of Enterobacter species. Mon.aneIia morganii (formerly proteus morganii), and proteus vulgaris. Most strains of Enterococci (Enteroccus faecalis) are resistant to cephradine. It has no activity against Pseuclomonas or Herellea species, When tested by in vitro methods, staphylococci exhibit cross-resistance between cephradine and methicillin-type antibiotics.
Cephalosporin-class discs are used in disc susceptibility testing.
INDICATIONS
VELOSEF (cephradine) is indicated in the treatment of the following infections due to susceptible organisms:
• Respiratory tract infections, eg., tonsillitis, pharyngitis, lobar pneumonia.
• Otitis media.
• Skin and skin structure infections.
• Urinary tract infections including prostatitis. Bacteriological studies to determine the causative organisms and their sensitivity to cephradine should be performed. Therap’ may be instituted prior to receiving results of sensitivity tests.
CONTRAINDICATIONS
Cephradine is cotraindicated in patients with known hypersensitivity to any cephalosporin antibiotic or to any component of the formulation.
PRECAUTIONS
There is evidence of partial cross-allergenicity between the penicillins and the ephaIosporins. Therefore. cephradine should be used with penicillins. There have been instances of patients who have had reactions to both drug classes, including anaphyIais (see ADVERSE REACTIONS).
Pseudomembranot.s colitis has been reported with the use of cephalosporins and other broad spectrum antibiotics), including cephradirie; therefore, it is important to consider this diagnosis in patients who develop diarrhea in association with antibiotic use. Mild cases of colitis may respond to drug discontinuance alone: moderate to severe cases should be managed as indicated.
In patients with known or suspected renal impairment, careful clinical observation and appropriate laboratory studies should be performed since cephradine accumulates in the serum and tissues unless dosage is suitably reduced )see DOSAGE AND ADMINISTRATION). After treatment witi cephradine, a false-positive reaction for glucose in the utine may occur with Benedict’s solution, Fehlings solution, or with Clinitest’ tablets, but not with enzyme-based tets suh as Clinistix tablets, and Tes-Tape.
As with other cephalosporins, positive direct Coombs’ tests have been infrequently reported.
As with all antibiotics, prolonged use may result in overgrowth of nonsisceptible organisms.
Pregnancy:
This drug should b used during pregnancy only if clearly needed.
Nursing Mothers:
Since .ephradine is excreted into breast miik during lactatioi caution should be exercised when cephradine is administered to a nursing woman.
ADVERSE REACTIONS
As with other cephalosporins, untoward reactions are limited essentially to gastrointestinal disturbances and, on occasion, to hypersensitivity phenomena, the latter are more likely to occur in individuals who have previously demonstrated hypersensitivity and those with a history of allergy, asthma, hay fever or urticaria.
The following adverse reactions have been reported following the use of cephradine:
Gastrointestinal: Glossitis, nausea, vomiting, heartburn, diarrhea or loose stools, abdominal pain, colitis, and pseudomembranous colitis.
Hypersensitivity: Mild urticaria or skin rash, pruritus, and joint pains. As with other cephalosporins. there have been rare reports of anaphylaxis, erythema multiforme, Stevens- Johnson syndrome, and toxic epidermal necrolysis.
Hematologic: Mild, transient eosinophilia, leukopenia and neutropenia.
Liver: Isolated instances of elevated SGOT, SGPT, total bilirubin and alkaline phosphatase have been observed with no evidence of hepatocellular damage.
Renal: Transitory rises in BUN have been observed in some patients treated with cephalosporins; their frequency increases in patients over 50 years old. In adults for whom serum creatinine determinations were performed, the rise in BUN was not accompained by a rise in serum creatinine. Otler adverse reactions have included dizziness, tightness in the chest and candidal vaginitis.
DQSAGE AND ADMINISTRATION
Cehradine may be given without regard to meals.
Acilt:
• Respiratory tract infections (other than lobar pn and skin and soft tissue Infections - The usqal dose is 250 mg every 6 hours or 500 mg every 12 hoirs. Severe infections may require larger doses.
• Lobar pneumonia - The usual dose is 500 mg every 6 hours or 1 gm every 12 hours.
• Uncomplicated urinary tract infections - The usual dose for uncomplicated infections is 500 mg every 12 hours. For more serious infections including prostatitis, 500 mg every 6 hours or 1 gm every 12 hours is recommended. Prolonged intensive therapy Is recommended for rostatitis and epididymitis.
Children:
In mild to moderately severe infections the usual daily dose is from 25 to 50 mg/kg administered in equally divided doses every 6 or 12 hours.
For otitis media due to H. influenzae. daily doses from 75 to 100 mg/kg administered in equally divided dopes every 6 or 12 hours is recommended. The maximum ddse should ot exceed 4 gm per day.
In all patients, regardless of age and weight, doss up to 1 gm every 6 hours may be given for severe 4r chronic infections.
Since .ephradine is excreted into breast miik during lactatioi caution should be exercised when cephradine is administered to a nursing woman.
ADVERSE REACTIONS
As with other cephalosporins, untoward reactions are limited essentially to gastrointestinal disturbances and, on occasion, to hypersensitivity phenomena, the latter are more likely to occur in individuals who have previously demonstrated hypersensitivity and those with a history of allergy, asthma, hay fever or urticaria.
The following adverse reactions have been reported following the use of cephradine:
Gastrointestinal: Glossitis, nausea, vomiting, heartburn, diarrhea or loose stools, abdominal pain, colitis, and pseudomembranous colitis.
Hypersensitivity: Mild urticaria or skin rash, pruritus, and joint pains. As with other cephalosporins. there have been rare reports of anaphylaxis, erythema multiforme, Stevens- Johnson syndrome, and toxic epidermal necrolysis.
Hematologic: Mild, transient eosinophilia, leukopenia and neutropenia.
Liver: Isolated instances of elevated SGOT, SGPT, total bilirubin and alkaline phosphatase have been observed with no evidence of hepatocellular damage.
Renal: Transitory rises in BUN have been observed in some patients treated with cephalosporins; their frequency increases in patients over 50 years old. In adults for whom serum creatinine determinations were performed, the rise in BUN was not accompained by a rise in serum creatinine. Otler adverse reactions have included dizziness, tightness in the chest and candidal vaginitis.
DQSAGE AND ADMINISTRATION
Cehradine may be given without regard to meals.
Acilt:
• Respiratory tract infections (other than lobar pn and skin and soft tissue Infections - The usqal dose is 250 mg every 6 hours or 500 mg every 12 hoirs. Severe infections may require larger doses.
• Lobar pneumonia - The usual dose is 500 mg every 6 hours or 1 gm every 12 hours.
• Uncomplicated urinary tract infections - The usual dose for uncomplicated infections is 500 mg every 12 hours. For more serious infections including prostatitis, 500 mg every 6 hours or 1 gm every 12 hours is recommended. Prolonged intensive therapy Is recommended for rostatitis and epididymitis.
Children:
In mild to moderately severe infections the usual daily dose is from 25 to 50 mg/kg administered in equally divided doses every 6 or 12 hours.
For otitis media due to H. influenzae. daily doses from 75 to 100 mg/kg administered in equally divided dopes every 6 or 12 hours is recommended. The maximum ddse should ot exceed 4 gm per day.
In all patients, regardless of age and weight, doss up to 1 gm every 6 hours may be given for severe 4r chronic infections.
As with antibiotic treatment in general, 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 infections caused by group A beta-hemolytic streptococci, a minimum of 10 days of treatment is recommended to guard against the risk of rhematic fever or glomerulonephritis. In the treatment of chronic urinary tract infections, frequent bacteriologic and clinical appraisal is necessary during therapy and may be necessary for several months afterwards. Persistent infections may require treatment for several weeks. Doses smaller than those indicated above should not be used. Doses for children should not exceed doses recommended for adults,
Oral cephradine may be utilized following clinical
improvement achieved with parenteral therapy for the continuation of therapy for persistent or severe infections where prolonged therapy is indicated.
Dosage in patients with renal impairment:
Not on Dialysis: The following dosage schedule based on a dosage of 500 mg Q6H 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.
Oral cephradine may be utilized following clinical
improvement achieved with parenteral therapy for the continuation of therapy for persistent or severe infections where prolonged therapy is indicated.
Dosage in patients with renal impairment:
Not on Dialysis: The following dosage schedule based on a dosage of 500 mg Q6H 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.
Creatinine clearance
|
Dose
|
Time interval
|
> 20 mI/mm
5 - 20 mI/mm <5ml/min |
500 mg
250 mg 250mg |
6 hours
6 hours 12 hours |
On Chronic, Intermittent Hemodialysis:
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.
HOW SUPPLIED
Capsules, 250 and 500 mg: Boxes of 12 capsules.
Tablets, I gm: Boxes of 8 tablets.
Powder for Oral Suspension: Bottles of 60 ml and 100 ml
125 mg I 5 ml or 250 mg I 5 ml after reconstitution.
STORAGE
Capsules and Tablets: Store at temperature not exceeding 30° C. Avoid excessive heat and protect from light and humidity.
Powder for Oral Suspension: Prior to reconstitution, store at temperature below 25° C, in tightly closed containers. Avoid excessive heat and protect from light. After constitution as directed on the container label, keep tightly closed, store under refrigeration (2° - 8° C), and discard any unused portion after 14 days. If stored at temperature 2° C, after constitution, discard any unused portion after 7
days
SmithKline Beechm Egypt L.L.C.
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.
HOW SUPPLIED
Capsules, 250 and 500 mg: Boxes of 12 capsules.
Tablets, I gm: Boxes of 8 tablets.
Powder for Oral Suspension: Bottles of 60 ml and 100 ml
125 mg I 5 ml or 250 mg I 5 ml after reconstitution.
STORAGE
Capsules and Tablets: Store at temperature not exceeding 30° C. Avoid excessive heat and protect from light and humidity.
Powder for Oral Suspension: Prior to reconstitution, store at temperature below 25° C, in tightly closed containers. Avoid excessive heat and protect from light. After constitution as directed on the container label, keep tightly closed, store under refrigeration (2° - 8° C), and discard any unused portion after 14 days. If stored at temperature 2° C, after constitution, discard any unused portion after 7
days
SmithKline Beechm Egypt L.L.C.
An affiliated co. to GiaxoSmithKline
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