Active ingredients: Ceftazidime
Starcef 250 mg / 1ml powder and solvent for solution for injection
Starcef 500 mg / 1.5 ml powder and solvent for solution for injection
Starcef 1 g / 3 ml powder and solvent for solution for injection
Indications Why is Starcef used? What is it for?
Starcef is an antibiotic used in adults and children (including newborn babies). It works by killing the bacteria that cause infections and belongs to a group of medicines called cephalosporins.
Starcef is used to treat severe bacterial infections of:
- lungs or chest
- lungs and bronchi in patients suffering from cystic fibrosis
- brain (meningitis)
- ear
- urinary tract
- skin and soft tissues
- abdomen and abdominal wall (peritonitis)
- bones and joints.
Starcef can also be used:
- to prevent infections during prostate surgery in men
- to treat patients with low white blood cell counts (neutropenia) who have a fever due to a 'bacterial infection.
Contraindications When Starcef should not be used
You should not be given Starcef:
- if you are allergic to ceftazidime or any of the other ingredients of this medicine.
- if you have had a severe allergic reaction to any other antibiotic (penicillins, monobactams and carbapenems) as you may also be allergic to Starcef.
- Tell your doctor before starting treatment with Starcef if you think this applies to you. You must not be given Starcef.
Precautions for use What you need to know before taking Starcef
Take special care with Starcef
Look out for some symptoms such as allergic reactions, nervous system disorders and gastrointestinal disorders such as diarrhea while being treated with Starcef. This will reduce the risk of possible problems. See (Conditions you need to look out for) in section 4. If you have had an allergic reaction to other antibiotics you may also be allergic to Starcef.
If you need blood or urine tests
Starcef can affect the results of tests for the presence of sugar in the urine and a blood test known as the Coombs test. If you are having these tests:
- Tell the person taking the sample that you are being treated with Starcef.
Interactions Which drugs or foods may change the effect of Starcef
Tell your doctor if you are taking, have recently taken or might take any other medicines. This also includes medicines without a prescription.
You should not be given Starcef without consulting your doctor if you are taking:
- an antibiotic called chloramphenicol
- a type of antibiotics called aminoglycosides eg gentamicin, tobramycin
- diuretic tablets called furosemide
- Tell your doctor if this applies to you.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
Ask your doctor for advice before you are given Starcef:
- if you are pregnant, if you suspect, or are planning to become pregnant
- if you are breast-feeding
Your doctor will weigh the benefit of treatment with Starcef against the risk to the baby.
Driving and using machines
Starcef can cause side effects that affect the ability to drive such as dizziness. Do not drive or use machines unless you are sure you are not experiencing any effects.
Starcef contains sodium
You need to take the following into consideration if you are on a controlled sodium diet.
Dose, Method and Time of Administration How to use Starcef: Posology
Starcef is usually given by a doctor or nurse. It can be given as an "intravenous infusion or as an injection" directly into a vein or muscle.
Starcef is prepared by your doctor, pharmacist or nurse using water for injections or appropriate infusion fluids.
Recommended dose
The appropriate dose of Starcef will be decided by your doctor and depends on: the severity and type of infection; if you are being treated with other antibiotics; your body weight and age, the condition of your kidneys.
Newborn babies (0-2 months): for each kg of the baby's body weight, 25 to 60 mg of Starcef will be administered per day divided into two doses.
Babies (over 2 months) and babies weighing less than 40 kg: for each kg of the infant or child's body weight, 100 to 150 mg of Starcef per day will be administered in three doses. The maximum dose is 6 g per day.
Adults and adolescents weighing 40 kg or more: 1 to 2 g of Starcef three times a day. The maximum dose is 9 g per day.
Patients over 65 years of age: The daily dose should generally not exceed 3 g per day especially if you are over 80 years of age.
Patients with kidney problems: You may be given a different dose than usual. Your doctor or nurse will decide how much Starcef you need based on the severity of your kidney disease. Your doctor will monitor you closely and may have kidney function tests at more regular intervals.
If you forget to use Starcef: If you forget an injection, you must have it as soon as possible. Do not take a double dose (two injections at the same time) to make up for a forgotten dose, just take the next dose at the usual time.
Do not stop taking Starcef: Do not stop taking Starcef unless your doctor tells you to. If you have any further questions on the use of this medicine, ask your doctor or nurse.
Overdose What to do if you have taken too much Starcef
If you are given more Starcef than you should: If you accidentally use a higher dose than prescribed, contact your doctor or the nearest hospital immediately.
Side Effects What are the side effects of Starcef
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Conditions you need to look out for The following serious side effects have occurred in a small number of people, but their exact frequency is not known:
- severe allergic reaction. The signs include raised itchy rash, swelling, sometimes on the face or mouth causing difficulty in breathing.
- skin rash with small target-like blistering formations (a dark spot in the center surrounded by a "light area with a black ring around the edge).
- widespread rash with blisters and peeling of the skin (these may be signs of Stevens-Johnson syndrome or toxic epidermal necrolysis).
- nervous system disorders: tremors, convulsions and, in some cases, coma. These have occurred in people whose dose they were given was too high, especially in people with kidney disease.
- there have been rare reports of severe hypersensitivity reactions with severe skin rash, which may be accompanied by fever, tiredness, swelling of the face or lymph nodes, increased eosinophils (a type of white blood cell), effects on the liver, kidney or lung ( a reaction called DRESS, Drug Reaction with Eosinophilia and Systemic Symptoms).
Contact your doctor or nurse urgently if you get any of these symptoms
Common side effects
These may affect up to 1 in 10 patients:
- diarrhea
- swelling and redness along the vein
- raised red rash that may be itchy
- pain, burning, swelling or inflammation at the injection site.
- Tell your doctor if any of these conditions worry you.
Common side effects that may show up in blood tests are:
- an increase in a type of white blood cell (eosinophilia)
- an increase in the number of cells that help blood clot
- an increase in liver enzymes.
Uncommon side effects
These may affect up to 1 in 100 patients:
- inflammation of the intestines which may cause pain or diarrhea which may contain blood
- candidiasis - fungal infections in the mouth or vagina
- headache
- dizziness
- stomach pain
- nausea or vomiting
- fever and chills.
- Tell your doctor if you have any of these conditions.
Uncommon side effects that may show up in blood tests are:
- a reduction in the number of white blood cells
- a reduction in the number of platelets (cells that help blood clot)
- an increase in the blood level of urea, BUN or serum creatinine.
Very rare side effects
These may affect up to 1 in 10,000 patients:
- Inflammation or kidney failure
Other side effects
Other side effects have occurred in a small number of people, but their exact frequency is not known:
- feeling of needles and pins
- unpleasant taste in the mouth
- yellowing of the whites of the eyes or skin.
Other side effects that may show up in blood tests are:
- too fast destruction of red blood cells
- an increase in some types of white blood cells
- severe decrease in the number of white blood cells.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the reporting system at: www.agenziafarmaco.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the vial and outer carton after the expiry date. The expiry date refers to the last day of that month. Store below 25 ° C.
Reconstituted solution
Your doctor, pharmacist or nurse will prepare the medicine in water for injections or in compatible fluids. Once prepared, the medicine should be used within 6 days if stored in the refrigerator (at 4 ° C) or within 9 hours if stored at 4 ° C. ambient temperature (below 25? C).
Keep the vials in the original carton in order to protect them from light.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other Information
What Starcef contains
- Starcef is available in the following strengths: 250mg / 1ml, 500mg / 1.5ml and 1g / 3ml. The active substance is ceftazidime (present as ceftazidime pentahydrate).
Starcef 250 mg / 1 ml powder and solvent for solution for injection contains 250 mg of ceftazidime
Starcef 500 mg / 1.5 ml powder and solvent for solution for injection contains 500 mg of ceftazidime
Starcef 1 g / 3 ml powder and solvent for solution for injection contains 1 g of ceftazidime
- The only other component is sodium carbonate (sterile anhydrous).
- See section 2 for other important information on sodium, one of the components of Starcef.
What Starcef looks like and contents of the pack
Starcef 250 mg / 1 ml powder and solvent for solution for injection:
- 1 vial of sterile white to cream powder of 250 mg, contained in a glass vial of 17 ml with a bromobutyl rubber stopper and flip-off aluminum seal + 1 solvent vial of 1 ml of glass
Starcef 500 mg / 1.5 ml powder and solvent for solution for injection:
- 1 vial of sterile white to cream colored powder of 500 mg, contained in a glass vial of 17 ml with a bromobutyl rubber stopper and flip-off aluminum seal + 1 solvent vial of 1.5 ml of glass
Starcef 1 g / 3 ml powder and solvent for solution for injection:
- 1 vial of sterile white to cream colored powder of 1 g, contained in a glass vial of 17 ml with a bromobutyl rubber stopper and flip-off aluminum seal + 1 solvent vial of 3 ml of glass
Your doctor, pharmacist or nurse will prepare the injection or infusion in water for injections or a suitable infusion fluid. Once prepared, Stacef changes color from light yellow to amber. This is perfectly normal.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
STARCEF POWDER AND SOLVENT FOR SOLUTION FOR INJECTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Starcef 250 mg / 1 ml powder and solvent for solution for injection
Each vial contains 250 mg of ceftazidime (as pentahydrate) with sodium carbonate (118 mg per gram of ceftazidime).
Excipient with known effects
Each vial contains 13 mg (0.58 mmol) sodium per vial.
Starcef 500 mg / 1.5 ml powder and solvent for solution for injection
Each vial contains 500 mg of ceftazidime (as pentahydrate) with sodium carbonate (118 mg per gram of ceftazidime).
Excipient with known effects
Each vial contains 26 mg (1.15 mmol) sodium per vial.
Starcef 1 g / 3 ml powder and solvent for solution for injection
Each vial contains 1 g of ceftazidime (as pentahydrate) with sodium carbonate (118 mg per gram of ceftazidime).
Excipient with known effects
Each vial contains 52 mg (2.3 mmol) sodium per vial.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
250 mg / 1 ml powder and solvent for solution for injection
Powder for solution for injection
Vial containing sterile white to cream powder.
1 ml colorless glass type I solvent vial.
500 mg / 1.5 ml powder and solvent for solution for injection
Powder for solution for injection
Vial containing sterile white to cream powder.
Type I colorless glass solvent vial of 1.5 ml.
1 g / 3 ml powder and solvent for solution for injection
Powder for solution for injection
Vial containing sterile white to cream powder.
Type I colorless glass 3 ml solvent vial.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Starcef is indicated for the treatment of the infections listed below in adults and children including neonates (from birth).
• Nosocomial pneumonia
• Bronchopulmonary infections in cystic fibrosis
• Bacterial meningitis
• Chronic suppurative otitis media
• Malignant external otitis
• Complicated urinary tract infections
• Complicated skin and soft tissue infections
• Complicated intra-abdominal infections
• Bone and joint infections
• Dialysis-associated peritonitis in patients with continuous ambulatory peritoneal dialysis (Continuous ambulatory peritoneal dialysis-CAPD).
Treatment of patients with bacteraemia that occurs or is suspected to be associated with any of the infections listed above.
Ceftazidime can be used in the management of neutropenic patients with fever suspected to be caused by a "bacterial infection."
Ceftazidime can be used in the peri-operative prophylaxis of urinary tract infections of patients undergoing transurethral resection of the prostate (trans-urethral resection of the prostate-TURP).
The choice of ceftazidime must take into account its antibacterial spectrum which is restricted mainly to Gram negative aerobic bacteria (see sections 4.4 and 5.1).
Ceftazidime should be administered together with other antibacterial agents whenever bacteria considered to be potentially responsible for infections are outside its spectrum of activity.
Official guidelines on the appropriate use of antibacterial agents should be considered.
04.2 Posology and method of administration
Dosage
Table 1: adults and children ≥ 40 kg
Table 2: children
Pediatric population
The safety and efficacy of Starcef administered as a continuous infusion in infants and children aged ≤ 2 months have not been established.
Senior citizens
In view of the age-related reduced clearance of ceftazidime in elderly patients, the daily dose should normally not exceed 3 g in patients over 80 years of age.
Hepatic insufficiency
Available data do not indicate the need for dose adjustment for patients with mild to moderate hepatic impairment. There are no data from studies in patients with severe hepatic impairment (see also section 5.2). Close clinical monitoring for safety and efficacy is advised.
Kidney failure
Ceftazidime is excreted unchanged by the kidney. Therefore, in patients with impaired renal function the dosage should be reduced (see also section 4.4).
An initial loading dose of 1 g should be administered. Maintenance doses should be based on creatinine clearance:
Table 3: Recommended maintenance doses of Starcef in renal insufficiency - intermittent infusion
Adults and children ≥ 40 kg
In patients with severe infections the unit dose should be increased by 50% or the dosing frequency increased.
In children, the creatinine clearance estimate should be calculated as a function of body surface area or lean body mass.
Children
Close clinical monitoring for safety and efficacy is advised.
Table 4: Recommended maintenance doses of Starcef in renal insufficiency - continuous infusion
Adults and children ≥ 40 kg
Caution is advised in dose selection. Close clinical monitoring for safety and efficacy is advised.
Children
The safety and efficacy of Starcef given as a continuous infusion in children of weight
If continuous infusion is used in children with renal insufficiency, creatinine clearance should be calculated as a function of body surface area or lean body mass.
Hemodialysis
The serum half-life values during hemodialysis range from 3 to 5 hours.
After each hemodialysis period, the maintenance dose of ceftazidime recommended in Tables 5 and 6 should be repeated.
Peritoneal dialysis
Ceftazidime can be used in peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD).
In addition to intravenous use, ceftazidime can be added to dialysis fluid (usually 125 to 250 mg per 2 liters of dialysis solution).
For patients with renal insufficiency on continuous arteriovenous hemodialysis or high-flow haemofiltration in intensive care units: 1 g per day either as a single dose or in divided doses. For low-flow haemofiltration follow the recommended dosage in renal insufficiency.
For patients in veno-venous hemofiltration and veno-venous hemodialysis, follow the recommended dosage in Tables 5 and 6 below.
Table 5: Continuous veno-venous haemofiltration dosage guidelines
Table 6: Continuous veno-venous hemodialysis dosing guidelines
p> Method of administration
The dose depends on the severity, sensitivity, site and type of infection and the age and renal function of the patient.
Starcef 500 mg and 250 mg should be administered by intravenous injection or by deep intramuscular injection. Recommended intramuscular injection sites are the outer upper quadrant of the gluteus maximus or lateral part of the thigh. Starcef solutions can be administered directly into a vein. The standard recommended route of administration is by intermittent intravenous injection. Intramuscular administration should only be considered when the intravenous route of administration is not possible or is less appropriate for the patient. Starcef 1 g should be administered by intravenous injection or by infusion or by deep intramuscular injection. Recommended intramuscular injection sites are the outer upper quadrant of the gluteus maximus or lateral part of the thigh. Starcef solutions can be administered directly into a vein or introduced through an infusion set if the patient is receiving fluids by injection.
The standard recommended route of administration is by intermittent intravenous injection or continuous intravenous infusion). Intramuscular administration should only be considered when the intravenous route of administration is not possible or is less appropriate for the patient.
04.3 Contraindications
Hypersensitivity to ceftazidime, to any other cephalosporin or to any of the excipients listed in section 6.1.
History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems).
04.4 Special warnings and appropriate precautions for use
Hypersensitivity
As with all beta-lactam antibacterial agents, severe and sometimes fatal hypersensitivity reactions have been reported. In the event of severe hypersensitivity reactions, treatment with ceftazidime should be discontinued immediately and appropriate emergency measures undertaken.
Before starting treatment, it should be ensured that the patient does not have a history of severe hypersensitivity reactions to ceftazidime or other cephalosporins or any other type of beta-lactam agent. Particular caution should be exercised if ceftazidime is administered to patients with a history of non-severe hypersensitivity to other beta-lactam agents.
Activity spectrum
Ceftazidime has a limited spectrum of antibacterial activity. It is not suitable for use as a single antibacterial agent for the treatment of certain types of infections unless the pathogen is already documented and known to be sensitive or there is a high suspicion that the most likely pathogen may be sensitive. treatment with ceftazidime. This applies particularly when considering the treatment of patients with bacteraemia and when treating bacterial meningitis, skin and soft tissue infections, and bone and joint infections. Furthermore, ceftazidime is sensitive to the hydrolysis of several broad spectrum beta lactamases (extended-spectrum beta-lactamases-ESBLs).
Therefore information on the prevalence of ESBL producing organisms should be considered when choosing ceftazidine treatment.
Pseudomembranous colitis
Colitis associated with antibacterial agents and pseudo-membranous colitis have been reported with almost all antibacterial agents, including ceftazidime and can range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea during or following the administration of ceftazidime (see section 4.8). The discontinuation of ceftazidime therapy and the administration of a specific treatment for the Clostridium difficile must be taken into account. Medicinal products that inhibit peristalsis should not be given.
Renal function
Concomitant treatment with high doses of cephalosporins and nephrotoxic medicinal products such as aminoglycosides or potent diuretics (e.g. furosemide) may have an adverse effect on renal function.
Ceftazidime is eliminated by the kidney, therefore the dose should be reduced according to the degree of renal impairment. Patients with renal insufficiency should be carefully monitored for both efficacy and safety. Neurological sequelae have occasionally been reported when the dose has not been reduced in patients with renal insufficiency (see sections 4.2 and 4.8).
Overgrowth of non-sensitive microorganisms
Prolonged use may lead to an overgrowth of non-sensitive microorganisms (eg Enterococci, fungi) which may require treatment discontinuation or other appropriate measures. Repeated monitoring of the patient's condition is essential.
Interactions with tests / assays
Ceftazidime does not interfere with enzymatic tests for the determination of glycosuria, but slight interference (false-positive) may occur with methods based on copper reduction (Benedict, Fehling, Clinitest).
Ceftazidime does not interfere with the alkaline picrate assay for the determination of creatinine. The development of a positive Coombs test associated with the use of ceftazidime in approximately 5% of patients may interfere with blood compatibility tests.
Sodium content
Important information about an excipient of Starcef:
250 mg / 1 ml powder and solvent for solution for injection
Starcef 250 mg contains 13 mg (0.58 mmol) sodium per vial.
500 mg / 1.5 ml powder and solvent for solution for injection
Starcef 500 mg contains 26 mg (1.15 mmol) sodium per vial.
1 g / 3 ml powder and solvent for solution for injection
Starcef 1 g contains 52 mg (2.3 mmol) sodium per vial.
This should be considered for patients who are on a controlled sodium diet.
04.5 Interactions with other medicinal products and other forms of interaction
Only interaction studies with probenecid and furosemide have been performed.
Concomitant use of high doses with nephrotoxic medicinal products may have adverse effects on renal function (see section 4.4).
Chloramphenicol is an antagonist in vitro ceftazidime and other cephalosporins. The clinical relevance of this observation is not known, but if concomitant administration of ceftazidime and chloramphenicol is proposed, the possibility of antagonism between the two antibiotics should be considered.
04.6 Pregnancy and breastfeeding
Pregnancy
There is a limited amount of data on the use of ceftazidime in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo / fetal development, parturition or postnatal development (see section 5.3).
Starcef should only be prescribed to pregnant women if the benefit outweighs the risk.
Feeding time
Ceftazidime is excreted in breast milk in small amounts but at therapeutic doses of ceftazidime no effects on breastfed infants are anticipated. Ceftazidime can be used during breastfeeding.
Fertility
No data available.
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed. However, undesirable effects (eg dizziness) may occur which may impair the ability to drive or use machines (see section 4.8).
04.8 Undesirable effects
The most common adverse reactions are eosinophilia, thrombocytosis, phlebitis or thrombophlebitis with intravenous administration, diarrhea, transient increases in liver enzymes, maculopapular or urticarial rash, pain and / or inflammation following intramuscular injection, and positive Coombs test.
Data from sponsored and non-sponsored clinical trials were used to determine the frequency of common and uncommon side effects. The frequencies assigned to all other undesirable effects were determined primarily on the basis of post-marketing pharmacovigilance data and refer to the reporting frequency rather than the actual frequency. Within each frequency class, the undesirable effects are reported in descending order of severity. The following convention was used for frequency classification:
Very common (≥ 1/10)
Common (≥1 / 100 y
Uncommon (≥1 / 1000 y
Rare (≥1 / 10,000 y
Very rare (
Not known (cannot be estimated from the available data)
1 There have been reports of neurological sequelae including tremors, myoclonus, convulsions, encephalopathy and coma in patients with renal insufficiency in whom the dose of Starcef was not adequately reduced.
2 Diarrhea and colitis may be associated with the presence of Clostridium difficile and present in the form of pseudomembranous colitis.
3ALT (SGPT), AST (SOGT), LHD, GGT, alkaline phosphatase.
4 There have been rare cases where DRESS has been associated with ceftazidime.
5 A positive Coombs test develops in approximately 5% of patients and may interfere with blood compatibility tests.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address: http://www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Overdose can lead to neurological sequelae including encephalopathy, seizures and coma.
Symptoms of overdose may occur if the dose is not reduced appropriately in patients with renal insufficiency (see sections 4.2 and 4.4).
Serum levels of ceftazidime can be reduced by hemodialysis or peritoneal dialysis.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antibacterials for systemic use. Third generation cephalosporins - ATC code: J01DD02.
Mechanism of action
Ceftazidime inhibits bacterial cell wall synthesis following adhesion to penicillin-binding proteins (penicillin binding proteins - PBP). This involves disruption of cell wall biosynthesis (peptidoglycan) which leads to bacterial cell lysis and death.
Pharmacokinetic / pharmacodynamic relationship
For cephalosporins, the most important pharmacokinetic-pharmacodynamic index correlated with efficacy in vivo has been shown to be the percentage of time within the dosage range during which the non-protein bound drug concentration remains above the minimum inhibitory concentration (MIC) of ceftazidime for individual target bacterial species (i.e. T% > MIC).
Resistance mechanism
Bacterial resistance to ceftazidime may be due to one or more of the following mechanisms:
• hydrolysis by beta lactamases. Ceftazidime can be effectively hydrolyzed by broad-spectrum beta-lactamases (extended-spectrum beta-lactamases-ESBLs) including the SHV family of ESBLs and AmpC enzymes that can be induced or de-repressed stably in some species of aerobic Gram-negative bacteria
• reduced affinity of penicillin binding proteins for ceftazidime
• impermeability of the outer membrane that limits the access of ceftazidime to penicillin-binding proteins in Gram-negative organisms
• bacterial efflux pumps.
Breakpoints
The breakpoints of the Minimum Inhibitory Concentration (MIC) established by the European Committee on Antibacterial Sensitivity Tests (European Committee on Antimicrobial Susceptibility Testing - EUCAST) are the following:
S = sensitive, I = intermediate, R = resistant.
1 Breakpoints related to high dose therapy (2 g x 3).
2 Non-species related breakpoints were mostly determined based on PK / PD data and are independent of the MIC distribution of specific species. They are for use only for species not mentioned in the table or notes below.
Microbiological sensitivity
The prevalence of acquired resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, when the local prevalence of resistance is such that the utility of ceftazidime in some types of infections is questionable, expert advice should be sought.
Commonly sensitive species
Gram-positive aerobes:
Streptococcus pyogenes
Streptococcus agalactiae
Gram-negative aerobes:
Citrobacter koseri
Haemophilus influenzae
Moraxella catarrhalis
Neisseria meningitidis
Pasteurella multocida
Proteus mirabilis
Proteus spp. (others)
Providencia spp.
Species for which acquired stamina could be a problem
Gram-negative aerobes:
Acinetobacter baumannii £+
Burkholderia cepacia
Citrobacter freundii
Enterobacter aerogenes
Enterobacter cloacae
Escherichia coli
Klebsiella pneumoniae
Klebsiella spp. (others)
Pseudomonas aeruginosa
Serratia spp.
Morganella morganii
Gram-positive aerobes:
Staphylococcus aureus £
Streptococcus pneumonitis ££
Viridans group streptococcus
Gram-positive anaerobes:
Clostridium perfringens
Peptostreptococcus spp.
Gram-negative anaerobes:
Fusobacterium spp.
Inherently resistant organisms
Gram-positive aerobes:
Enterococcus spp. included Enterococcus faecalis and Enterococcus faecium
Listeria spp.
Gram-positive anaerobes:
Clostridium difficile
Gram-negative anaerobes:
Bacteroides spp. (many species of Bacteroides fragilis are resistant).
Others:
Chlamydia spp.
Mycoplasma spp.
Legionella spp.
£S. aureus which is methicillin-sensitive is considered to have inherently low sensitivity to ceftazidime. All the S. aureus methicillin-resistant are resistant to ceftazidime.
££S. pneumoniae who demonstrates intermediate susceptibility or is resistant to penicellin can be expected to demonstrate at least reduced susceptibility to ceftazidime.
+High rates of resistance have been observed in one or more areas / countries / regions within the European Union.
05.2 Pharmacokinetic properties
Absorption
After intramuscular administration of 500 mg and 1 g of ceftazidime, peak plasma levels of 18 and 37 mg / l, respectively, are reached rapidly. Five minutes after intravenous bolus administration of 500 mg, 1 g or 2 g the plasma levels are 46, 87 and 170 mg / l, respectively. The kinetics of ceftazidime are linear within the single dose range of 0.5 to 2 g following intravenous or intramuscular administration.
Distribution
Serum protein binding of ceftazidime is low and approximately 10%. Concentrations that exceed the MICs for common pathogens can be obtained in tissues such as bone, heart, bile, sputum, aqueous humor, synovial, pleural and peritoneal fluids. Ceftazidime rapidly crosses the placenta and is excreted in breast milk. Penetration into the intact blood brain barrier is poor resulting in low levels of ceftazidime in the CSF in the absence of inflammation. However, concentrations of 4 to 20 mg / l or more are found in the CSF when the meninges are inflamed.
Biotransformation
Ceftazidime is not metabolised.
Elimination
After parenteral administration, plasma levels decrease with a half-life of approximately 2 hours. Ceftazidime is excreted unchanged in the urine by glomerular filtration. About 80-90% of the dose is recovered in the urine within 24 hours. Less than 1% is excreted via the bile.
Special patient populations
Kidney failure
Elimination of ceftazidime is decreased in patients with impaired renal function and the dose should be reduced (see section 4.2).
Hepatic insufficiency
The presence of mild to moderate hepatic dysfunction had no effect on the pharmacokinetics of ceftazidime in individual doses of 2 g intravenously every 8 hours for 5 days provided that renal function was not impaired (see section 4.2).
Senior citizens
The reduced clearance observed in elderly patients was mainly due to the age-related decrease in clearance of ceftazidime. The mean elimination half-life ranged from 3.5 to 4 hours after single or repeated doses for 7 days twice daily, of 2 g by intravenous bolus injection in elderly patients aged 80 years or older.
Pediatric population
The half-life of ceftazidime is prolonged in preterm and full-term infants from 4.5 to 7.5 hours after doses of 25 to 30 mg / kg. However, at the age of 2 months the half-life is within the values for adults.
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, reproductive toxicity. Carcinogenicity studies have not been conducted with ceftazidime.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Powder vials: sodium carbonate (sterile anhydrous).
Solvent ampoule: water for injections.
06.2 Incompatibility
Starcef in sodium bicarbonate solution for injection is less stable than other fluids for intravenous administration. This solution is not recommended for dilution. Starcef must not be mixed in the same infusion set or syringe with aminoglycosides.
Formations of precipitates have been reported by adding vancomycin to ceftazidime solutions.
Therefore, it is advisable to allow an adequate amount of fluid to flow into the infusion set and infusion lines between the two administrations.
06.3 Period of validity
3 years
After reconstitution
Chemical and physical in-use stability has been demonstrated for 6 days at 4 ° C and 9 hours at 25 ° C. From a microbiological point of view, the reconstituted solution should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8 ° C, unless reconstitution has taken place under aseptic conditions. checked and validated.
After dilution
Chemical and physical in-use stability has been demonstrated for 6 days at 4 ° C and 9 hours at 25 ° C.
From a microbiological point of view, the reconstituted and diluted solution should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8 ° C, unless reconstitution has taken place under aseptic conditions. checked and validated.
06.4 Special precautions for storage
Store below 25 ° C.
Keep the vials in the outer carton to protect from light.
For storage conditions after reconstitution see section 6.3.
06.5 Nature of the immediate packaging and contents of the package
Starcef 250 mg / 1 ml powder and solvent for solution for injection: - 1 vial of powder of 250 mg in colorless glass Ph.Eur.Type III of 17 ml with a bromobutyl rubber stopper and flip-off aluminum seal + 1 ampoule of solvent 1 ml in colorless type I glass
Starcef 500 mg / 1.5 ml powder and solvent for solution for injection:
- 1 vial of powder of 500 mg in colorless glass Ph.Eur.Type III of 17 ml with a bromobutyl rubber stopper and flip-off aluminum seal + 1 solvent vial of 1.5 ml in type I colorless glass
Starcef 1 g / 3 ml powder and solvent for solution for injection:
- 1 vial of powder of 1 g in colorless glass Ph.Eur.Type III of 17 ml with a bromobutyl rubber stopper and flip-off aluminum seal + 1 solvent vial of 3 ml in type I colorless glass
06.6 Instructions for use and handling
All types of Starcef vials are supplied under reduced pressure. As the product dissolves, carbon dioxide is released and a positive pressure develops. Small bubbles of carbon dioxide in the reconstituted solution can be ignored.
Instructions for reconstitution
See table for addition of solution volumes and concentrations which may be useful if fractional doses are required.
* Note: The resulting volume of the ceftazidime solution in the reconstitution medium increases due to the drug displacement factor resulting in the concentrations listed in mg / ml shown in the table above.
The color of the solutions can vary from pale yellow to amber depending on the concentration, type of diluent and storage conditions used. Within the framework of the established recommendations, the activity of the product is not affected by such color variations. Ceftazidime at concentrations between 1 mg / ml and 40 mg / ml is compatible with:
• sodium chloride 9 mg / ml (0.9%) for injections
• sodium lactate M / 6 for injections
• sodium lactate compound for injections (Hartmann's solution)
• 5% dextrose for injections
• 0.225% sodium chloride and 5% dextrose for injections
• 0.45% sodium chloride and 5% dextrose for injections
• 0.9% sodium chloride and 5% dextrose for injections
• 0.18% sodium chloride and 4% dextrose for injections
• 10% dextrose for injections
• Dextran 40 10% for injections in 0.9% sodium chloride for injections
• Dextran 40 10% for injections in 5% dextrose for injections
• Dextran 70 6% for injections in 0.9% sodium chloride for injections
• Dextran 70 6% for injections in 5% dextrose for injections
Ceftazidime at concentrations ranging from 0.05 mg / ml to 0.25 mg / ml is compatible with the lactate solution for intra-peritoneal dialysis.
Ceftazidime at the concentrations listed in the table above can be reconstituted for intramuscular use with 0.5% or 1% lidocaine hydrochloride for injections.
The contents of a 500 mg vial of ceftazidime for injection, reconstituted with 1.5 ml of water for injections, can be added to solutions of metronidazole (500 mg in 100 ml) and both retain their activity.
250 mg, 500 mg 1 g powder for solution for injection
Preparations for bolus injection solutions
1. Insert the syringe needle through the vial closure and inject the recommended amount of diluent. The absence of air may make it easier for the diluent to enter. Remove the syringe needle.
2. Shake to dissolve: Carbon dioxide is released and a clear solution will be obtained in 1-2 minutes.
3. Turn the vial. With the plunger of the syringe fully lowered, insert the needle through the opening of the vial and draw the total volume of the solution into the syringe (the pressure in the vial may help aspiration). Make sure that the needle stays inside the solution and does not enter the upper space. The aspirated solution may contain small bubbles of carbon dioxide, these can be ignored.
These solutions can be administered directly into a vein or introduced through an infusion set if the patient is receiving fluids parenterally. Ceftazidime is compatible with the used infusion fluids listed above.
Any remaining antibiotic solution should be discarded.
For single use only.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
SIGNATURE. S.p.A. - Via di Scandicci, 37 - Florence.
08.0 MARKETING AUTHORIZATION NUMBER
STARCEF 250 mg / 1 ml Powder and solvent for solution for injection "1 vial of powder + 1 vial of 1 ml solvent" A.I.C .: 025859012
STARCEF 500 mg / 1.5 ml Powder and solvent for solution for injection "1 vial powder + 1 solvent vial of 1.5 ml" A.I.C .: 025859024
STARCEF 1 g / 3 ml Powder and solvent for solution for injection "1 vial of powder + 1 vial of 3 ml solvent" A.I.C .: 025859036
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 6 July 1985
Date of most recent renewal: May 2010
10.0 DATE OF REVISION OF THE TEXT
September 2016
