Julphacef is used in the treatment of bacterial infections of the respiratory and urinary tracts and of the skin and soft tissues.

These include the following:

§ Upper respiratory tract infections - sinusitis, pharyngitis, tonsillitis, laryngo-tracheo bronchitis and otitis media.

§ Lower respiratory tract infections - acute and chronic bronchitis, lobar and bronchopneumonia.

§ Urinary tract infections - cystitis, urethritis and pyelonephritis.

§ Skin and soft tissue infections - impetigo, abscess, cellulitis, furunculosis.

Julphacef is also used in the prophylaxis of postoperative infections following surgical procedures associated with a high risk of infection and for patients with a reduced host resistance to bacterial infection. Cefradine should be administered immediately prior to surgery in order to ensure sufficient local tissue concentrations at the time that contamination is likely to occur. Treatment should be continued during the post-operative period.

Laboratory testing should be carried out to determine the causative agents and their sensitivity to cefradine. However, therapy may commence prior to receipt of the sensitivity test results.

Adults: Generally, the usual daily dosage of Julphacef for injection is 2 - 4g daily in 4 equally divided doses intramuscularly or intravenously (e.g., 500mg to 1g q.i.d). 

Uncomplicated pneumonia, skin and soft tissue infections, and most urinary tract infections: 500mg q.i.d.

Bone infections: 1g q.i.d. given intravenously.

Severe infections such as endocarditis: 2g q.i.d. given intravenously. Alternatively, in severe infections, the dose may be increased by giving injections every four hours, not exceeding 8g per day.

Prophylaxis, to prevent postoperative infection in contaminated or potentially contaminated surgery: 1g IV or IM is to be administered 30 - 90 minutes prior to surgery, followed by 1g every 4 - 6 hours after the first dose; for one to two doses or for up to 24 hours postoperatively.

Prophylaxis in caesarean section: 1g IV is to be administered as soon as the umbilical cord is clamped followed by 1g IV or IM at 6 and 12 hours after the first dose.

Infants and Children: 50 - 100mg/kg/day in equally divided doses 4 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.

In general, as with antibiotic therapy, treatment should be continued for a minimum of 48 - 72 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. In infections caused by group A b-haemolytic streptococci, a minimum of 10 days of treatment is recommended as a prophylaxis against rheumatic fever or glomerulonephritis. In the treatment of chronic urinary tract infection, frequent bacteriologic and clinical evaluation is necessary during therapy and may be necessary for several months afterwards. Persistent infections may require treatment for several weeks. Parenteral therapy may be followed by oral Julphacef either as capsules or oral suspension.

Julphacef may be given intravenously or by deep intramuscular injection. 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.

Dosage in patients with impaired renal function

Adults with impaired renal function may require dosage reduction as follows:

Patients not on dialysis:

Patients on chronic intermittent haemodialysis:

250mg at the start of dialysis, then 250mg after 12 hours, and 250mg 6 - 48 hours after the start.

Children with renal function impairment may require a reduction in dose proportional to their weight and severity of infection.

Following administration of cefradine, a false positive reaction for glucose in the urine may occur with Benedict's or Fehling's solution or with reagent tablets such as Clinitest. This does not occur with enzyme based tests such as Clinistix or Diastix.

Prolonged use of antibiotics may result in overgrowth of non-susceptible organisms.

There is evidence of partial allergenicity between the penicillins and the cephalosporins. Therefore, cefradine 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).

Dosage should be reduced in renal failure (see section 4.2).

As with other cephalosporins, cefradine may have the following drug interactions upon concurrent use with the following drugs:

Aminoglycosides: The risk of nephrotoxicity of aminoglycosides may be increased.

Coumarins: The anticoagulant effect of coumarins may possibly be enhanced.

Probencid: Probencid reduces the excretion of cefradine, increasing thereby its plasma concentration.

Typhoid vaccine (oral): As with other antibacterials, cefradine inactivates oral typhoid vaccine. It should be avoided for 3 days before and after oral typhoid vaccination.

Although animal studies have shown no teratogenic effects, safety in pregnancy has not been established. As with all medicines, use should be avoided in pregnancy especially in the first trimester, unless considered essential by the physician. Cefradine is excreted in breast milk and therefore should be used with caution in lactating mothers.

Since this medicine may cause dizziness, patients should be cautioned about operating hazardous machinery, including automobiles.

Undesirable effects are uncommon and mainly mild in nature. They are limited essentially to gastrointestinal disturbances and on occasion to hypersensitivity phenomena.

To report any side effect(s):

The National Pharmacovigilance and Drug Safety Centre (NPC)

Fax: +966-11-205-7662

Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.

Toll free phone: 8002490000

E-mail: npc.drug@sfda.gov.sa

Website: www.sfda.gov.sa/npc

None known

Cefradine is an antibiotic agent with a broad spectrum of activity 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 cefradine:

§ Gram-positive

Staphylococci (both penicillin sensitive and resistant strains),  Streptococci, Streptococcus pyogenes (beta haemolytic) andStreptococcus pneumoniae.

§ Gram-negative

Escherichia coli, Klebsiella spp., Proteus mirabilis, Haemophilus influenza, Shigella spp., Salmonella spp. (includingSalmonella typhi) and Neisseria spp.

Because cefradine is unaffected by penicillinase, many strains of Escherichia coli and Staphylococcus aureus which produce this enzyme are susceptible to cefradine but resistant to ampicillin.

Cefradine has a high degree of stability to many beta-lactamases. It has a low degree of protein binding and a large volume of distribution. Therefore, tissue levels are generally found to be high.

Following intramuscular injection, peak plasma concentrations of about 6 and 14 micrograms per mL have been obtained within 1 - 2 hours of doses of 500mg and 1 g respectively. Only about 6 - 20% is reported to be bound to plasma proteins. A plasma half-life of about 1 hour has been reported; this is prolonged in patients with renal impairment. Cephradine is widely distributed to body tissues and fluids, but does not enter the CSF in significant quantities. Therapeutic concentrations may be found in the bile. It crosses the placenta into the fetal circulation and is distributed in small amounts into breast milk. Cephradine is excreted unchanged in the urine, 60 to 80% of an intramuscular dose being recovered within 6 hours. Probenecid delays excretion. Cephradine can be removed by haemodialysis and peritoneal dialysis.

There are no preclinical safety data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

Inactive Ingredients:

1.      Arginine, sterile

Not applicable.

Store below 30^oC. After reconstitution, use within 2 hours.

Clear glass vial with a printed label, 1 vial packed in a printed carton along with a leaflet.

Reconstitution of Solutions and storage:

For Intramuscular Use: Aseptically add sterile Water for Injection or Bacteriostatic Water for Injection (not for use in neonates if benzyl alcohol is the bacteriostat present) according to the following table:

Shake to effect solution and withdraw the required amount. Julphacef contains no bacteriostat and is not intended for multiple-dose use. Solutions should be used within 2 hours if held at a temperature below 30^oC, but if stored in the refrigerator (5^oC), these solutions retain full potency for 24 hours. Reconstituted solutions may vary in colour from light to straw yellow, however, this does not affect the potency.

If a local anaesthetic is considered desirable, for intramuscular use only, 0.5% lidocaine hydrochloride injection is recommended as the diluent in the place of the above-mentioned volumes of Water for Injection. Other diluents also suitable for intramuscular use are lidocaine hydrochloride injection 1% or procaine hydrochloride injection 1% or 2%.

For Intravenous use: Julphacef may also be administered by direct intravenous injection or by intravenous infusion

For Direct Intravenous Injection: Suitable intravenous injection diluents are Sterile Water for Injection, 5% Dextrose Injection, or Sodium Chloride Injection.

Aseptically add 5mL of diluent to the 500mg vials, 10 mL to the 1g vial. Shake to effect solution and withdraw the entire contents. 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. These solutions should be used within 2 hours when held at a temperature below 30^oC, but if stored at 5^oC, these solutions retain full potency for 24 hours.

For continuous or intermittent IV infusion: Suitable intravenous infusion solutions for Julphacef are 5% or 10% Dextrose Injection, Sodium Chloride Injection, Sodium Lactate Injection (M/6 sodium lactate), Dextrose and Sodium Chloride Injection (5%:0.9%) or (5%:0.45%), 10% Invert Sugar in Water for Injection, Normosol^®-R, and lonosol^® B with Dextrose 5%. Sterile Water for Injection may be used as an IV infusion solution for Julphacef at cephradine concentration of 30 - 50mg/mL (30mg/mL is approximately isotonic).

To prepare Julphacef for transfer into an IV infusion container, aseptically add 10mL of Sterile Water for Injection, or a suitable infusion solution, to the 1g vial, and shake to effect solution. Aseptically transfer the entire contents to the IV infusion container. Intravenous infusion solutions containing Julphacef remain potent for 10 hours at room temperature or 48 hours at 5°C at concentrations up to 50mg of cephradine per mL. For prolonged infusions, replace the infusion every 10 hours with a freshly prepared solution. Infusion solutions of Julphacef 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.

Protect solutions of Julphacef from concentrated light or direct sunlight.