VELOSEF®
NAME OF THE MEDICINAL PRODUCT :
VELOSEF Cephradine Oral
Oral forms:
Cephradine, 250 mg, capsules
Cephradine, 500 mg, capsules
Cephradine, 19, tablets
Cephradine, 125 mq, powder for oral suspension , 250 mg, powder for oral suspension
Excipients :
Cephradine, 250 mg, 500 mg, capsules lactose, magnesium stearate, talc, titanium dioxide, gelatin. and colorants
Cephradine, tablets Corn starch, magnesium stearate. microcrystalline cellulose,
silicon dioxide and lactose
Cephradine, 125 mg, 250 mg, powder for oral suspension Citric acid. guar gum, methylcellulose, sodium citrate. sucrose, flavoring agents and colorants
PHARMACEUTICAL FORM CLINICAL INFORMATION :
Capsules: light blue capsules filled with off white granular powder
Tablets: off white, slightly mottled, capsule shaped with bisect bar on one side
Powder for oral suspension: homogenous fine free flowing powder
Indications :
Capsules, tablets, oral suspension For the treatment of:
-intections of the urinary, respiratory tracts and skin and soft tissues, these include:
-Upper respiratory infections: pharyngitis, sinusitis, otitis media, tonsillitis, laryngo-tracheo bronchitis .
– Lower respiratory infections acute and chronic bronchitis, lobar and bronchopneumonia.
– Urinary tract infections: cystitis, urethritis, pyelonephritis.
– Skin and soft tissue infections: abscess, cellulitis, furunculosis, impetigo.
– Bacteriological 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.
Dosage and Administration :
All patients, regardless of age and weight In all patients, regardless of age and weight, doses up to 1 gm every 6 hours may be given for severe or 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 rheumatic 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 dinical improvement achieved with parenteral therapy for the continuation of therapy for persistent or severe infections where prolonged therapy is indicated.
Capsules, tablets, oral suspension Cephradine may be given without regard to meals.
Adults:
Capsules, tablets, oral suspension
Respiratory tract infections (other than lobar pneumonia) and skin and soft tissue infections – The usual dose is 250 mg every 6 hours or 500 mg every 12 hours. Severe infections may require larger doses.
Lobar pneumonia- The usual dose is 500 rng every 6 hours or 1 gm every 12 hours.
Uncomplicated urinary tract infections – The usual dose for uncomplicated infections is SOD mg every 12 hours. For more serious infections including prostatitis. 500 mg every 6 hours or 1 gm every 12 hours is recommended.
Children
Capsules, tablets, oral suspension
In mild to moderately severe infections the usual daily dose is from 25 to 50 mgttc;g administered in equally divided doses every 6 or 12 hours. For otitis media due to H. influenzae, daily doses from 75 to 100 mglkg administered in equally divided doses every 6 or 12 hours is recommended. The maximum dose should not exceed 4 g per
day.
Renal impainnent
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 mVmin 500mg 6 hours
5 – 20 mUmin 250mg 6 hours
<5mVmin 250mg 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.
Elderly
There are no specific dosage recommendations or precautions for use in the elder1y except, as with other drugs, to monitor those patients with impaired renal or hepatic function.
Hepatic impairment
There are no relevant data available.
Contra indications
Cephradine is contraindicated in:
·Hypersensitivity to the cephalosporin antibiotics or any component of the formulation
Warnings and Precautions
Renal Impairment
Dosage: Use of this antibiotic in patients with renal dysfunction should be monitored intensively. A modified dosage schedule in patients with decreased renal function is necessary (see section Dosage and Administration). False positive reaction for glucose
Atter treatment with cephradine, a false positive reaction for glucose in the urine may occur with Benedict’s or Fehling’ solution or with reagent tablets such as Clinitest, but not with enzyme-based tests such as Clinistix or Diastix. Prolonged use
As with all antibiotics, prolonged use may result in overgrowth of non-susceptible organisms.
Hypersensitivity phenomena
Hypersensitivity phenomena are more likely to occur in
individuals who have previously demonstrated hypersensitivity and those with a history of allergy, asthma, hay fever or urticaria (see section Adverse Reactions).
Excipients
oTablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. OOral suspension contains sucrose, patients with rare
hereditary problems of fructose intolerance, glucose galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Interactions
Penicillins
There is evidence of partial cross-allergenicity between peniciUins and cephalosporins. Therefore cephradine should be used with caution in those patients with known hypersensitivity to peniciltins. There have been instances of patients who have had reactions to both drug classes (including anaphylaxis) – see section Adverse Reactions. Loop diuretics Loop diuretics may increase nephrotoxicity of cephalosporins. Probenecid
Probenecid has been seen to raise serum concentrations of cephradine, by reducing renal clearance of the cephalosporins.
Pregnancy and Lactation
Fertility
There are no relevant data available.
Pregnancy
Although animal studies have not demonstrated any teratogenic- ity, safety in pregnancy has not been established. Therefore this antibiotic should not be used during pregnancy or lactation unless considered essential by the physician.
Lactation
Cephradine is excreted in breast milk and should be used with caution in lactating mothers (see also section Warnings and Precautions).
Ability to perform tasks that require judgement, motor or cognitive skills
Since this medicine may cause dizziness, patients should be cautioned about operating hazardous machinery, including automobiles.
Adverse Reactions
Post Mar1<eting Data
Adverse reactions are ranked under headings of frequency using the following convention:
Very common 2:1/10
Common 2::11100 to <1110
Uncommon 2:1/1000 to <1/100
Rare 2:1/10000 to <1/1000
Very rare <1/10000
Not known (cannot be estimated from the available data).
Infections and infestations
Rare: vaginitis, candidosis
Not known: pseudomembranous colitis
Blood and lymphatic system disorders
Not known: eosinophilia, leucopenia and neutropenia. positive
direct Coombs tests, elevation~ of I?I~ urea nitrogen (BUN) and serum creatinine
Immune system disorders
Rare: anaphylaxis see Skin and subcutaneous tissue disorders
Nervous system disorders
Rare: dizziness
Respiratory, thoracic and mediastinal disorders
Rare: tightness in the chest
Gastrointestinal disorders
Rare: glossitis, heartburn, nausea, vomiting, diarrhoea, abdominal pain
Not known: gastro-intestinal disturbances
Hepatobifiary disorders
Very rare: hepatitis, cholestatic jaundice
Not known: elevations of alanine amino-transferase (ALT),
aspartate amino-transferase (AST), total bilirubin and alkaline
phosphatase
Skin and subcutaneous tissue disorders
Rare: erythema multifonne, Stevens Johnson Syndrome, toxic
epidermal necrolysis
Not known: urticaria, skin rashes
Musculoskeletal and connective tissue disorders
Not known: joint pains
General disorders and administration site conditions
Not known: oedema
Overdosage
None known
Clinical Pharmacology
Pharmacodynamics
Pharmacotherapeutic group
Antibacterial for systematic use, first generation cephalosporins
Mechanism of Action and Pharmacodynamic effects
Cephradine is a broad-spectrum, bactericidal antibiotic active against both Gram-positive and Gram-negative bacteria. It is also highly active against most strains of penicillinase-producing
Staphylococci.
Microbiology:
The following organisms have shown in vitro sensitivity to cephradine.
Gram-positive – Staphylococci (both penicillin sensitive and resistant strains), Streptococci, Streptococcus pyogenes (beta haemolytic) and Streptococcus pneumoniae. Gram-negative – Escherichia coli, Klebsiella spp, Proteus mirabilis, Haemophilus influenzae, Shigella spp., Salmonella spp. (including Salmonella typhi) and Neisseria spp. Because cephradine is unaffected by penicillinase, many strains
of Escherichia coli and Staphylococcus aureus which produce this enzyme are susceptible to cephradine but resistant to ampicillin.
Pharmacokinetics
Cephradine is acid stable and is rapidly absorbed following oral administration in the fasting state. Following doses of 250 mg, SOO mg, and 1 g in normal adult volunteers, average peak serum levels of approximately 9, 16.5 and 24.2 IJg/ml, 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 mglkglday of cephradine for treatment of otitis media, average concentration of cephradine in middle ear exudate was 3.6 lJglml. 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 jJglml following a 250 mg dose, 3200 IJglml following a 500 mg
Use and Handling
Capsules, tablets, oral suspension There are no special requirements for use or handling of this product.
Package and storage:
Capsules, 250 mg Boxes of 12 capsules.
Capsules, 500 mg: Boxes of 8 capsules & 16 capsules
Tablets, 1 gm: Boxes of 8 tablets.
Powder for Oral Suspension: Bottles of 60 ml and 100 ml125 mg /5 ml or 250 mg /5 m! 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 250 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 (20 – 80 C), and discard any unused portion after 14 days. If stored at temperature 250 C, after constitution, discard any unused portion after 7 days.
Patient instructions:
Keep out of reach of children.
Manufactured by:
Smithkline Beecham, el Haram , Giza.
Smithkline Beecham Egypt L.L.C.
