SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET 1 SUMMARY OF PRODUCT CHARACTERISTICS 2 1. NAME OF THE MEDICINE {(Invented) name} 1 g powder for solution for injection/infusion 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each vial contains cefazolin sodium equivalent to 1 g cefazolin. Excipient(s) with known effect: Each vial of {(Invented) name} 1 g contains 50.56 mg (2.2 mmol) sodium. 3. PHARMACEUTICAL FORM Powder for solution for injection/infusion. White or almost white powder. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Cefazolin is indicated in adults, adolescents, children and infants older than one month for the treatment of the following infections caused by cefazolin-sensitive microorganisms: • skin and soft tissue infections • bone and joint infections Perioperative prophylaxis: Perioperative administration of cefazolin may reduce the incidence of postoperative infections in contaminated or potentially contaminated surgery. Susceptibility of causative organism to the treatment should be tested (if possible), although therapy may be initiated before the results are available. Consideration should be given to official guidance on the appropriate use of antibacterial agents. 4.2 Dosage and method of administration Dosage The dosage depends on the susceptibility of the micro-organisms and the severity of the disease. • Adults and adolescents (above 12 years of age and ≥ 40 kg bodyweight). In infections caused by very sensitive gram-positive micro-organisms the usual dosage in adults and adolescents is 1 to 2 g/day in two or three equal doses. • In infections caused by less sensitive gram-positive organisms and gram-negative organisms, the usual dosage is 3 to 4 g/day in three or four equal doses. {(Invented) name} has been administered up to doses of a maximum 6 g/day in cases of severe infections, such as endocarditis. In adult and adolescent patients with renal insufficiency a lower dosage should be adhered to, in order to avoid accumulation. This lower dose can be determined by assessing the blood levels. Should this not be possible, the dosage can be determined by BUN and/or creatinine clearance. After an initial dose of 500 mg the following guidelines can be used as guide for the maintenance 3 dosage. Maintenance therapy with {(Invented) name} in patients with reduced renal function. Dose Kidney BUN Creatinine Gram- Gram- Serum half- function (mg %) clearance positive negative life-time (ml/min) infections infections (hours) Mild 20-34 70-40 250-500 mg 500 mg-1 g 3-5 impairment every 8 hours every 8 hours Moderate 35-49 40-20 125-250 mg 250-600 mg 6-12 impairment every 12 hours every 12 hours Severe 50-75 20-5 75-150 mg 150-400 mg 15-30 impairment every 24 hours every 24 hours Also see section 4.4 “Special warnings and precautions for use” Perioperative prophylaxis In order to avoid a postoperative infection in (possibly) infectious surgeries, these are the recommended dosages: a. 1 g administered 30 minutes to 1 hr prior to surgery. b. For longer operations (2 hours or more), 500 mg to 1 g administered intravenously during the surgery (administration to be amended depending on the duration of the surgery). c. 500 mg to 1 g administered intravenously, every 6 to 8 hours during 24 hours postoperative. It is important that (1) the perioperative dose is administered shortly prior to the start of the operation (30 mins to 1 hr), so that adequate levels of antibiotic are reached in the serum and tissues at the time of the first surgical incisions; and (2) cefazolin, if need be, is administered at set times during the surgery - at moments of increased exposure to micro-organisms - in order to reach sufficiently high antibiotic levels. The prophylaxis with cefazolin should reasonably be terminated within 24 hours after the end of the surgery. In surgeries where the risk of infections poses a particularly great risk (open heart surgery or prosthetic arthroplasty) the prophylaxis should be continued up to 3 to 5 days postoperative. Paediatric population Children and infants older than one month In infections caused by very sensitive gram-positive micro-organisms a dosage of 25 to 50 mg/kg of body weight divided in two or four doses a day will be efficient. In infections caused by less sensitive gram-positive micro-organisms and by the gram-negative causative agent, a dosage of max 100 mg/kg is recommended in three or four equal doses. In children and infants older than one month with renal insufficiency a lower dose may be recommended in order to avoid accumulation. This lower dose can be determined by assessing the blood levels. Should this not be possible, the dosage can be determined by the creatinine clearance according to the following guidelines. In children and infants older than one month with moderate renal insufficiency (creatinine clearance of 40-20 ml/min) 25 % of the normal daily dosage, divided in doses every 12 hours, will be sufficient. In children and infants older than one month with severe renal insufficiency (creatinine clearance 20-5 ml/min) 10 % of the normal daily dosage, administered every 24 hours, will be sufficient. All these guidelines apply after an initial starting dose. Also see section 4.4 “Special warnings and precautions for use” 4 Prematures and infants below the age of 1 month As the safety of use in premature babies and infants younger than one month has not been established, the use of {(Invented) name} in these patients is not recommended. Also see section 4.4 “Special warnings and precautions for use”. Guidelines for paediatric dosage 1 g vial to be prepared with 4 ml of diluent. Dilution = 225 mg/ml. Weight in kg 25 mg/kg/day in 3 doses 25 mg/kg/day in 4 doses doses in mg every volume in ml doses in mg every volume in ml 8 hours needed 6 hours needed 5 42 0.2 31 0.15 10 85 0.4 62 0.3 15 125 0.5 94 0.4 20 167 0.7 125 0.5 25 208 0.9 156 0.7 Weight in kg 50 mg/kg/day in 3 doses 50 mg/kg/day in 4 doses doses in mg every volume in ml doses in mg every volume in ml 8 hours needed 6 hours needed 5 83 0.4 63 0.3 10 166 0.7 125 0.6 15 250 1.1 188 0.8 20 333 1.5 250 1.1 25 417 1.9 313 1.4 Elderly patients No dose adjustments are needed in elderly patients with normal renal function. Duration of treatment Depends on the course of the disease. In keeping with the general principles of antibiotic therapy, treatment with {(Invented) name} should be continued for at least 2 to 3 days after the fever has subsided or proof has been obtained for the eradication of the causative agent. Method of administration {(Invented) name} may be administered intramuscular as well as intravenous. Intramuscular injection Dissolved in sterile water for injection, according to the following dilution table. Shake well until all the powder has been dissolved. Product after reconstitution is clear, almost colourless solution. {(Invented) name} must be injected into a major muscle mass. A reconstituted {(Invented) name} solution remains stable for 24 hours in the refrigerator (2°C - 8°C). Dilution table Content of the vial to be added diluent obtained volume Average concentration 1 g 2.5 ml 3.0 ml 330 mg/ml Intravenous administration: {(Invented) name} may be administered directly into a vein, either as a continuous or an intermittent 5 drip. The total daily dose is the same as for intramuscular administration. Intermittent and continuous infusion {(Invented) name} can be administered in combination with an existing intravenous therapy, either in the primary drip or in the secondary infusion drip. 1 g {(Invented) name} may be dissolved in 100 ml 9 ml/ml (0.9 %) sodium chloride intravenous solution. In these intravenous solutions {(Invented) name} remains stable for 24 hours in the refrigerator (2°C - 8°C). Direct intravenous injection: Dilute 1 g {(Invented) name} solution further with at least 10 ml water for injection, inject slowly during 3 to 5 minutes. In no case should the injection be shorter than 3 minutes. This should be done straight into the vein or into the tube in which the patient is administered the abovementioned intravenous solution. CAUTION: One-off doses of more than 1g need to be administered over thirty to sixty minutes. 4.3 Contraindications • Hypersensitivity to the active substance or to any other cephalosporins. • Prior severe allergic reactions to penicillin or any other type of β-lactam antibiotics. • When administered to children younger than 1 year, cefazolin should not be dissolved in a lidocaine solution. 4.4 Special warnings and precautions for use • Before the administration of cefazolin, previous hypersensitivity reactions to cephalosporins and penicillins should be investigated. Cephalosporins should not be used in patients known to develop an immediate allergic reaction to cephalosporins. In case of doubt, a doctor should be present during the initial administration in order to be able to treat any anaphylactic reactions. There is a cross- allergy between penicillin and cephalosporin. • When an allergic reaction occurs caused by {(Invented) name}, the administration of the product must be stopped immediately and appropriate treatment for the patient must be sought. • Although cefazolin seldom causes kidney function impairments, it is recommended to examine the kidney function, especially in seriously ill patients, who get maximum amounts administered and in patients who get other potentially nephrotoxic drugs administered at the same time, such as amino glycosides or powerful diuretics (e.g. furosemide or etacrynic acid).