VELOSEF

VELOSEF 

VELOSEF TM 
Capsules, tablets, oral suspension, vials QUALITATIVE AND QUANTITATIVE COMPOSITION Velosef 250 mg, 500mg capsules hard Each hard capsule contains 250 mg or 500 mg of Cephradine. Veloset 1 g tablets Each tablet contains 1 g of Cephradine Velosef 250 mg/5 ml powder for oral suspension Each 5 ml of oral suspension after constitution contains 250 mg of Cephradtne. Velosef250mg,500 mg 19 powder for solution for injection. Each vial contains 250 mg, 500 mg , 1 gm of Cephradine. Excipients Veloset 250 mg,500 mg capsules, hard Talc, Magnesium stearate, Lactose Velosef 1 g, tablets Micr.rystalline cellulose, Magnesium steante, talc. Velosef 250 mg, powder for oral suspension Sucrose. Sodium citrate anhydrous, Citric acid anhydrous, Guar gum, Methylcellulose, FD&C Red NO 40, Flavour blood orange, Flavour imitation orange banana, colloidal silicon dioxide. Velosef, 250 mg. 500 mg, 1 g powder for solution for inject or L-arginine CLINICAL INFORMATION Indications Cephradine is indicated for the treatment of infections of the urinary and respiratory tracts and of skin and soft tissues, these include, • upper respiratory infections pharyngitis, sinusitis orss media, tonsillitis. laryngo-tracheo bronchitis, • lower respiratory 'Macrons : acute and chronic bronchitis, lobar and bronchopneumonia, • urinary tract infections: cystitis. urethrtas, pyelonephritis, • skin and soft tissue infections: abscess, cellulitis, furunculosis, impetigo. Cephradine has been shown to be effective in reducing the incidence of post-operative infections in patients undergoing surgical procedures associated with a high risk of infection. It Is also of value where post-operative infections would be disastrous and where patients have a reduced host resistance to bacterial infection. Protection is best ensured by achieving adequate local tissue concentrations at the time contamination is likely to occur. Thus. cephradine should be administered immediately prior to surgery and treatment should be continued during the post-operative period. 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. C_ephqadane parenteral forrnulatiorre For the treatment of; • bone and joint infections, • septicaemia and endocardrts. Stenle cephradine for injection Is indicated pnmanly for those petals unable to tolerate oral medication It is also indicated or intravenous use either by direct injection or by intravenous infusion for the treatment of serious and life threatening infections. Dosage and Administration 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 streptococP a minimum of 10 days of treatment is recommended to guard against the risk of rheumatic fever or glorrierulonephritis. In the treatment of chronic pinery tract infectipre, frequent bacteriologic and clinical appraisal is nemssary 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 Gooftaldnaorp tgm4rets In all patents regardless of age and weight, doses up to 1 g every 6 hours may be given for severe or chronic infections. Oral cephradine may be utilised following clinical improvement achieved with parenteral therapy for the continuation of therapy for persistent or severe infections where prolonged therapy is indicated. Cephradine may be given without regard to meals. Cephradineepttearn f muktions Paienteral therapy may be followed by oral cephradine either as capsules, tablets or oral suspension. Route of Administration Cephradine oral formulations For oral use Ceohradinadrerenteral formulatinre For intramuscular use For intravenous use Cephradine may be given intravenously or by deep intramuscular injechon. To minimize pain and induration, intramuscular injections should be made into a large muscle mass, such as the gluteus or lateral aspect of the thigh. Reference is made to the use of local anaesthetics in the section on Use and Handling. Since sterile abscesses have been reported following accidental subcutaneous infection, the preparation should be administered by deep intramuscular injection (see section Adverse Reactions). Intravenously cephradine may be administered by either direct intravenous erection or by intravenous infusion. For direct intravenous injection, the solution may be slowly injected directly into a vein over a 3 to 5 minute period or may be given as a supplementary injection through the injection site on an administration set when the infusion solution is compatible with cephradine. For usage instructions see Section Use and Handling. Adults cRegospryiadna fremc tioIn ratoy tract bl sn  (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. Lobarpneumonia The usual dose is 500 mg every 6 hours or 1 g every 12 hours. Uncomplicated unary tract infections The usual dose for uncomplicated infections is 500 mg every 12 hours. For more serious elections including prostatitis. 500 mg every 6 hours or 1 g every 12 hours recommended. Prolonged intensive therapy's recommended for prostates and epididymitis. CrePhradine parerepalore daily The usual daily dose is 2 to 4 g daily in four equally divided doses intramuscularly or intravenously rep, 500 mg to 1 g four times a day). A dosage of 500 mg four times a day em adequate in uncomplicated pneumonia, skin and skin structure Infections, and most urinary tract
infections. In bone infections the usual dosage is 1 g four tunes a day administered Intravenously In severe infections such as endocaniitis, 2 g four times a day given intravenously is recommended. Alternatively, in severe infections, the dose may be increased by giving silences every four hours. The maximum dose should not exceed 8 g per day Prophylaxis To prevent postoperative infection in contaminated or potentially contaminated surgery recommended doses are as follows: • 1-2 g intravenously or intramuscularly • 1 g every 4 to 6 hours after the first dose for one to two doses, or for up to 24 hours postoperatively, Prophylaxis in caesarean section The first dose of 1 g is administered intravenously as soon as the umbilical Gerd is clamped. The second and third doses should be given as 1 g Intravenously or intramuscularly at 6 and 12 hours her the first dose. Children C_ep_hradtrmoral foureirri jr;re.s In mild to moderately severe infections the usual daily dose from 25 to 50 mg/kg/day administered in equally divided doses every 6 or 12 hours. For otitis media due to H inf benne. daily doses from 75 to 100 mg/kg administered in equally divided doses every 6 or 12 hours is recommended The maximum dose should not exceed 4 g per day. Doses for children should not exceed doses recommended for adults. capLiracont f smnflrost The usual dose range is 50 to 100 mg/kg/day (approximately 23-45 mg/lb/day) in equally divided doses four times a day and should be regulated by age, weight of the patient, and severity of the infection being treated The maximum paediatric daily dose should not exceed the dose recommended for adults (see Section Warnings and Precautions). There are no specific dosage recommendations or precautions for use in the elderly except, as with other drugs, to monitor those patients with Impaired renal or hepatic function. Renal impairment Patients not on dialysis The following dosage schedule based on a dosage of 500 mg every 6 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 venation.
Crearnine clearance Dose lime interval >20 ml/min 500 mg 6 hours 5-20 mVren 250 mg 6 hours <5 mVmn 250 mg 12 hours
Patients on chronic, intermittent haemodialysis • 250 nig start. • 250 mg at 12 hours, • 250 mg 36-48 hours (after start). Children may require dosage modification proporttonat to their weight and severity of infection. See also Section Warnings and Precautions. Hepatic impairment There are no relevant data available. Contraindications Cephradine is contraindicated in Hypersensitivity to the active substance, to other cephalospcens or to any of the exopents.
Previous immediate and/or severe hypersensitivity reaction to a penicillin or to any other beta-lactam medicinal products. Wamings and Precautions Renal impairment Use of cephradine in patents with renal dysfunction should be monitored intensively. A modified dosage schedule n patients with decreased renal function is necessary (see Section Dosage and Administration). False positive reaction for glucose Following administration of cephradine, a false positive reaction for glucose in the unne may occur with Benedict s or Fehling's solution m with reagent tablets such as (atest, but not with enzyme-based tests such as Clinist x 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 flee Section Adverse Reactions). Special caution is required to determine any other type of previous hypersensitivity reactions to penicillin or to other beta-lactam medicinal products because patients hypersensitive to these medicines may be hypersensitive to (Cephradine) as well (cross- allergy). History of colitis/gastrointestinal disorders Cephradine should be used with caution in those patients with a known history of colitis/ gastrointestinal disorders. ffeloseL.250 tablets Lactose This product contains Lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take these medicines. Velosef 250 mg/ 5 ml oral suspension: Sucrose; Patients with intolerance to some sugars have to contact their physician before taking these medicines especially patients was diabetes mellitus. Geolarnaeral formulations n Paechatnc use As these products contain arginine they should be used with caution In paediatric population. Interactions pins There is evidence of partial cross-allergenicity between penicillins and cephalosporins. Therefore cephradine should be used with caution in those patients with known nypersensitivity to penicillin, 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 nephrotosicity 01 cephalosporins. Probenecid Probenecid has been seen to rause seem conceetrations of cephradine. by reducing renal clearance of the cephalosponns. Active drug substances of high molecular weight are incompatible with cephalosponns In parenteral mixtures. Oral contraceptives In common with other antibiotics, cephradine may affect the gut ffora, leading to lower oestrogen reabsorbtron and reduced efficacy of combined oral contraceptives. Warfarin The Concomitant use of cephradine with warfann may result In increased INR and thereby increase
the dsk for bleeding. The mechanism of the Interaction appears to involve alterations in intestinal flora that synthesise vitamin K In a nested case-control study, there was an association between cephalosporin use in patents on warlarin therapy and en increased risk of bleeding. When possible, substitute an antibiotic with a low-risk profile for bleeding. If concomitant useis deemed necessary, more frequent monitoring of INS s recommended especially during initiation and discontinuation of the antibiotic. Live typhoid vaccine Cephradine, like other antibiotics with antibacterial activity against Salmonella lyptu organtsms, may interfere with the immunological response to the live typhoid vaccine. The appropriate period of time (24 hours w more should elapse between the administration of the last dose of the antibiotic and the INe typhoid vaccine. Pregnancy and Lactation Fertility There are no relevant data available. Pregnancy Cephradine should not be used during pregnancy unless considered essential by the physician. Although an studies have not demonstrated any teratogenqity, safety in pregnancy has not been established. Lactation Cephradine should not be used during breast-feeding unless considered essential by the physician. Cephradine is excreted in breast milk. (see Section Warnings and Precautions). Ability to perform tasks that require judgement, motor or cognitive skills Since this mene may cause dizziness, pat hate be cautioned about operatng hazardous machinery, including automobiles. Adverse Reactions Clinical Trial Data Not relevant for this product. Post Marketing Data Adverse reactions are ranked under headings of frequency using the following convention. Very common 21/10 Common 21/100 to 01/10 Uncommon 21/1000 to <1/100 Rare 21/10000 to <1/1000 Very rare <1/10000 Not known (cannot be estimated from the available data). Infections and infestations Not known: vaginal infection. candroliasis, pseudomembranous colffis Blood and lymphatic system disorders Not known: eosinophilia, leukopenia, neutropenia, Coombs direct test positive Immune system disorders Not known: hypersensitivity (see Skin and subcutaneous tissue disorders), anaphylactic reaction Nervous system disorders Not known: dimness. headache Gastrointestinal disorders Not known: glossitis, dyspepsia nausea, vomiting, diant.a, abdominal pain, gastrointestinal disorder Hepatobiliary disorders Not known: hepatitis, jaundice cholestatic. alanine aminotransferase increased, aspartate aminotransferase increased, blood biliftrsin increased, blood alkaline phosphatase increased Renal and urinary disorders Not known: tubulanterstitrel nephritis, blood urea increased, blood creatinne Increased
Skin and subcutaneous tissue disorders Not known: erythema multiforme, Stevens-Johnson syndrome, toxic et:le:lama necrolysis, trsticana, rash, punt. Musculoskeletal and connective tissue disorders Nat known: arthralgia Genera/ disorders and administration site conditions Not known: chest discomfort, oedema, pyrexia cepladne parenteral form atrons Vascular disorders Not known: thrombophlebers General disorders and administration site candidNot blown: inaction site pain Overdosage There are no relevant data available. Clinical Pharmacology Pharmacodynamics Pharmacotherapeutic group Antenfectives for systemic use, first generation cephalospotins Mechanism of Action and PhamlacodynamIc effects Cephradine is a broad-spectrum, bactenctdal antibiotic active against both Gram-positive and Gram-negative bactina. 11 is also highly active against most strains of pencitinase-producing Staphylococci, Microbiology The following organisms have shown In vitro sensitivity to cephradine. Gra_nnie Staphylococci (both penicillin sensitive and resistant strains), Streptococci, Streptococcus pyogenes (beta haemolytic) and Streptococcus pneumonia°. Gyarnre Escherichia call, Nebsiella spp„ Proteus Haemophilus influenme, Shigella spp., Salmonella spp. (including Salmonella lye/Mend Neisseria spp. Because cephradine is unaffected by perscillinase, many strains of Escherichia coh and Staphylococcus aunaus which produce this enzyme are susceptible to cephradine but resistant to arnproillin. Phannacokinetic• Absorption cephradinestajtrefftriatom Cephradine is acid stable and is rapidly absorbed following oral administration in the fasting state. Following doses of 250 mg, 500 mg, and 1 gin normal adult volunteers, average peak serum levels of approximately 9, 16.5 and 242 pg/ml, respectively, were obtained at one hour, T. presence of food in the gastrointestinal tract delays the absorption but does not affect the total amount of cephradine absorbed. Ceptodjr_et J:kirggefiactr_rnula Following intramuscular administration of a angle 1 g dose of cephradine to normal volunteers, the average peak serum concentration was 15.1 pg/ml at approximately 1 hour, and declined to 6.2 pg/ml at 3 hours and 1.5 pg/ml at 6 hours. A single 1 g intravenous dose resulted in serum concentrations of 66 pg/ml at 5 minutes and declined to 12 pg/ml at 1 hour and 1 (giro! at 4 hours. Cenfinuous infusion of 500 mg per hour in a 70 kg man maintained a concentration of about 21 A pg/ml cephradine activity. A serum concentration of approximately 3 pg/ml can be obtained for each milligram of cephradine administered per kg of body weight per hour of infusion. Distilbution Measurable serum levels are present 6 hours atter administration. 48 hours after the administration of 100 mg/kg/day of cephradine
for treatment of otitis media, the average concentration of cephradine in middle ear exudate was 3,6 pg/ml. Cephradine does not cross the blood-brain barrier to any appreciable extent. Cephradine is minimally bound to serum proteins (8 to 17%). Assays of bone and cardiac tissue (atrial appendage) obtained at surgery have shown that cephradine penetrates these trssues. Elimination icm_trartim oral formulations Over 90% of the drug is excreted unchanged in the urine within 6 hours. Peak unne concentrations are approximately 1600 pg/ml following a 250 mg dose, 3200 pg/ml following a 500 mg dose, and 4000 pg/ml following a 1 g dose. 13hradinestarenteral formulations Cephradine is excreted unchanged in the urine. The kidneys excrete 57% to 80% of an Intramuscular dose in the first six Nage this results et a high unne concentration. Clinical Studies Not relevant for this product. NON CLINICAL INFORMATION There are no relevant data avatlable. PHARMACEUTICAL INFORMATION Storage See outer pack. Nature and Contents of Container Velosef 250 mg capsules: pack containing 2 strips each of 6 capsules and inner  leaflet. Velosef 500 mg capsules: pack containing 2 stops each of 6 or 8 capsules and Inner leaflet. Velosef 250ing./5rnl oral suspension: pack containing bottle of 100 ml containing powder for oral suspensqn and timer leaflet. Velosef 1 g tablets: pack containing 1 or 2 strips each of 4 or 8 tablets and inner leaflet. Velosef 250 mg, 500 mg injection: pack containing vial of 250 mg or 500 mg powder and 1 solvent ampoule ( 5 ml water for infectton), and Inner leaflet. Velosef 1g injection: pack containing vial of 1 g powder and 2 solvents ampouleaeach of 5 mil water for injection and inner leaflet. Incompatibilities There are no relevant data available. Use and Handling Ofetiyartimitral forrnpaSows There are no special requirements for use or handling of these products. CAphradine. abrenIeral formulatiOnS For intramuscular use Asepticalry add sterile Water fp Injection or Bactenostatic Water for Injects.' according to the following table Mot for use in neonates if benryl alcohol is the bacteriostat present).
Single Volume Volume after Approximate dose vial of diluent to be added reconstitution concentration 250 mg 1,2 ml 1.2 ml 208 mg/ml 500 mg 2.0 ml 2.2 ml 227 mg/m1 1 g 4.0 ml 4.5 ml 222 mg/.
Shake to effect solution and withdraw the equired amount Cephradine con ains no bacteriostat and is eel intended to multiple dose use Solutions should he used within 2 hours if held at room temperature; it stored in the refrigerator (5°C). solutions retain full potency for 24 hours. Reconstituted solutions may valy in colour from light to straw yellow; however, this does not affect the potency.

It a local anaesthetic is considered desirable, for intramuscular use only 0.5%1rolccaine hydrochlonde injection is recommended as the diluent in place of the above-mentioned volumes of Water for Injection. Other diluents also suitable for intramuscular use are tidocaine hydrochloride injection 1% or procaine hydrochlonde injection 1% or 2%. For direct intravenous inject'Suitable intravenous injection diluents are • Steele Water For !election, • 5% Dextrose Injection, • Sodium Gironde Injectors. Aseptically add 5 ml of diluent to the 250 mg or 500 mg vials. 10 ml to the 1 g vial. Shake to effect solution and withdraw the ens re contents. These solutions should be used within 2 hour, when held at room temperature; if stored at 5 C. solutions retain full potency for 24 hours. For continuous or intermittent rotravenous inNsion Suitable intravenous infusion solutions for cephradne are • 5% or 10% Dextrose Injection, • Sodium Chloride Injection, • Sodium Lactate Injection (M/6 sodium lactate), • Dextrose and Sodium Chloride Injection (5%40.9%) or (5%:0.45%), • 10% Invert Sugar in Water for Injection, • Normosol-R, • lonosol B with Dextrose 5%. Sterile Water for Injection may be used as an intravenous infusion solution for a cepreadete concentration of 30 to 50 mg/rel (30 mg/mi Is approxtmately isotonic) To prepare cephradine for transfer into an intravenous infusion container, asepticaIN add 10 ml of Stehle Water for Injection, or a salable infusion solution, to the 1 g vial, and shake to effect solution. Aseptically transfer the entire contents to the intravenous infusion container. Intravenous infusion solutions containing cephradine rematri potent for 10 hours at room temperature or 48 hours at 5°C at concentrations up to 50 mg of cephradine per ml. For prolonged infusions, replace the tnfusion every 10 hours with a freshly prepared solution. Infusion solutions of cephradine In Sterile Water for Injection that are frozen immediately after reconstitution in the original container are stable for as long as six weeks when stored at -20°C. Extemporaneous mixtures of cephradine With other antibiotics are not recommended. Manufactured by SruthK1Ine Beecham - El Harem - Giza. Version number 03 Version date: 05 July 2013
S3
SmithKline Beecham Egypt L.L.C. An affiliated co. ta GlaxoSmithKline
72014F