Piperacillin/Tazobactam Actavis
SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
Piperacillin/Tazobactam Actavis 2 g / 0.25 g powder for solution for infusion
Piperacillin/Tazobactam Actavis 4 g / 0.5 g powder for solution for infusion
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each vial contains 2 g piperacillin (as sodium salt) and 0.25 g tazobactam (as sodium salt).
One vial of powder for solution for infusion contains 4.7 mmol (108 mg) of sodium.
Each vial contains 4 g piperacillin (as sodium salt) and 0.5 g tazobactam (as sodium salt).
One vial of powder for solution for infusion contains 9.4 mmol (216 mg) of sodium.
3. PHARMACEUTICAL FORM
Powder for solution for infusion.
White to off-white powder.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Piperacillin/Tazobactam Actavis is indicated for the treatment of the following infections in adults and children over 2 years of age (see sections 4.2 and 5.1):
Adults and adolescents
- Severepneumoniaincluding hospital-acquired and ventilator-associated pneumonia
- Complicated urinary tract infections (including pyelonephritis)
- Complicated intra-abdominal infections
- Complicated skinand soft tissue infections(including diabetic footinfections)
Treatment of patients with bacteraemia that occursin association with, or is suspected to be associated with, any of the infections listed above.
Piperacillin/Tazobactam Actavis may be used in the management of neutropenic patientswith fever suspected to be due to a bacterial infection.
Children 2 to 12 yearsof age
- Complicated intra-abdominalinfections
Piperacillin/Tazobactam Actavis may be usedin the management of neutropenic childrenwith fever suspected to be due to a bacterial infection.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
4.2 Posology and method of administration
Posology
The dose and frequency of Piperacillin/Tazobactam Actavis depends on the severity and localisation of the infection and expected pathogens.
Adult and adolescent patients
Infections
The usual dose is 4 g piperacillin / 0.5 g tazobactam given every 8 hours.
For nosocomial pneumonia and bacterial infections in neutropenic patients, the recommended dose is 4 g piperacillin / 0.5 g tazobactam administered every 6 hours. This regimen may also be applicable to treat patients with other indicated infections when particularly severe.
The following table summarises the treatment frequency and the recommended dose for adult and adolescent patients by indication or condition:
|
Treatment frequency |
Piperacillin/Tazobactam Actavis 4 g / 0.5 g |
|
Every 6 hours |
Severe pneumonia |
|
Neutropenic adults with fever suspected to be due to a bacterial infection. |
|
|
Every 8 hours |
Complicated urinary tract infections (including pyelonephritis) |
|
Complicated intra-abdominal infections |
|
|
Skin and soft tissue infections (including diabetic foot infections) |
Renal impairment
The intravenous dose should be adjusted to the degree of actual renal impairment as follows (each patient must be monitored closely for signs of substance toxicity; medicinal product dose and interval should be adjusted accordingly):
|
Creatinine clearance (ml/min) |
Piperacillin/Tazobactam Actavis (recommended dose) |
|
> 40 |
No dose adjustment necessary |
|
20-40 |
Maximum dose suggested: 4 g / 0.5 g every 8 hours |
|
< 20 |
Maximum dose suggested: 4 g / 0.5 g every 12 hours |
For patientson haemodialysis, one additionaldose of piperacillin / tazobactam2 g / 0.25 g should be administered following each dialysis period, because haemodialysis removes 30%-50% of piperacillin in 4hours.
Hepatic impairment
No dose adjustment is necessary (see section 5.2).
Dose in elderly patients
No dose adjustment is required for the elderly with normal renal function or creatinine clearance values above 40 ml/min.
Paediatric population (2-12 years of age)
Infections
The following table summarises the treatment frequency and the dose per body weight for paediatric patients 2-12 years of age by indication or condition:
|
Dose per weight and treatment frequency |
Indication / condition |
|
80 mg Piperacillin / 10 mg Tazobactam per kg body weight / every 6 hours |
Neutropenic children with fever suspected to be due to bacterial infections* |
|
100 mg Piperacillin / 12.5 mg Tazobactam per kg body weight / every 8 hours |
Complicated intra-abdominal infections* |
* Not to exceed the maximum 4 g / 0.5 g per dose over 30 minutes.
Renal impairment
The intravenous dose should be adjusted to the degree of actual renal impairment as follows (eachpatient must be monitored closely for signs of substancetoxicity; medicinal productdose and interval should be adjusted accordingly):
|
Creatinine clearance (ml/min) |
Piperacillin/Tazobactam Actavis (recommended dose) |
|
> 50 |
No dose adjustment needed. |
|
≤ 50 |
70 mg piperacillin / 8.75 mg tazobactam / kg every 8 hours. |
For children on haemodialysis, one additional dose of 40 mg piperacillin / 5 mg tazobactam / kg should be administered following each dialysis period.
Use in children aged below 2 years
The safety and efficacy of Piperacillin/Tazobactam Actavis in children 0- 2 years of age has not been established.
Nodata from controlled clinical studies are available.
Treatmentduration
The usual duration of treatment for most indications is in the range of 5-14 days. However, the duration of treatment should be guided by the severity of the infection, the pathogen(s)and the patient's clinical and bacteriological progress.
Route of administration
Piperacillin/Tazobactam Actavis 2 g / 0.25 g is administered by intravenous infusion (over 30 minutes).
Piperacillin/Tazobactam Actavis 4 g / 0.5 g is administered by intravenous infusion (over 30 minutes).
For reconstitution instructions, see section 6.6.
4.3 Contraindications
Hypersensitivity to the active substancesor any other penicillin-antibacterial agent or to any of the excipients listed in section 6.1.
History of acute severe allergic reaction to any other beta-lactam active substances (e.g. cephalosporin, monobactam or carbapenem).
4.4 Special warnings and precautions for use
The selection of piperacillin / tazobactam to treat an individual patient should take into account the appropriateness of using a broad-spectrum semi-synthetic penicillin based on factors such as the severity of the infection and the prevalence of resistance to other suitable antibacterial agents.
Before initiating therapy with Piperacillin/Tazobactam Actavis, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, other beta-lactam agents (e.g. cephalosporin, monobactam or carbapenem) and other allergens. Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid [including shock]) reactions have been reported in patients receiving therapy with penicillins,including piperacillin / tazobactam. These reactions are more likely to occur in persons with a history of sensitivity to multiple allergens. Serious hypersensitivity reactions require the discontinuation of the antibiotic, and may require administration of epinephrine and other emergency measures.
Antibiotic-induced pseudomembranous colitis may be manifested bysevere, persistent diarrhoeawhich may be life-threatening. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment. In these cases Piperacillin/Tazobactam Actavis should be discontinued.
Therapy with Piperacillin/Tazobactam Actavis may result in the emergence of resistant organisms, which might cause super-infections.
Bleeding manifestations have occurred in some patients receiving beta-lactam antibiotics. These reactions sometimes have been associated with abnormalities of coagulation tests,such as clotting time, platelet aggregation and prothrombin time, and are more likely to occur in patients with renal failure. If bleeding manifestations occur, the antibiotic should be discontinued and appropriate therapy instituted.
Leukopenia and neutropenia may occur, especially during prolonged therapy; therefore, periodic assessment of haematopoietic function should be performed.
As with treatment with other penicillins, neurological complications in the form of convulsions may occur when high doses are administered, especially in patients with impaired renal function.
Each vial of Piperacillin/Tazobactam Actavis 2 g / 0.25 gcontains 4.7 mmol (108 mg) of sodium and Piperacillin/Tazobactam Actavis 4 g / 0.5 gcontains 9.4 mmol (216 mg) of sodium. This should be takeninto consideration forpatients who are on a controlled sodium diet.
Hypokalaemia may occur in patients with low potassium reserves or thosereceiving concomitant medicinal products that may lower potassium levels; periodic electrolyte determinations maybe advisablein such patients.
4.5 Interaction with other medicinal products and other forms of interaction
Non-depolarising muscle relaxants
Piperacillin when used concomitantly with vecuronium has been implicated in the prolongation of the neuromuscular blockade of vecuronium. Due to their similar mechanismsof action, it is expected that the neuromuscular blockade produced by any of the non-depolarising muscle relaxants could be prolonged in the presence of piperacillin.
Oral anticoagulants
During simultaneous administration of heparin, oral anticoagulants and other substances that may affect the blood coagulation system including thrombocyte function, appropriate coagulation tests should be performed more frequently and monitored regularly.
Methotrexate
Piperacillin may reduce the excretion of methotrexate; therefore, serumlevels of methotrexate should be monitored in patients to avoid substance toxicity.
Probenecid
Aswith other penicillins, concurrentadministration of probenecid and piperacillin / tazobactam produces a longer half-life and lower renal clearance for both piperacillin and tazobactam; however, peak plasma concentrations of either substances are unaffected.
Aminoglycosides
Piperacillin, either alone or with tazobactam, did not significantly alter the pharmacokinetics of tobramycin in subjects with normal renal function and with mild or moderate renal impairment. The pharmacokinetics of piperacillin, tazobactam, and the M1 metabolite were also not significantly altered by tobramycin administration.
The inactivation of tobramycin and gentamicin by piperacillin has been demonstrated in patients with severe renal impairment.
For information related to the administration of piperacillin / tazobactam with aminoglycosides please refer to sections 6.2 and 6.6.
Vancomycin
No pharmacokinetic interactions have been noted between piperacillin / tazobactam and vancomycin.
Effects on laboratory tests
Non-enzymatic methods of measuring urinary glucose may lead to false-positive results, as with other penicillins. Therefore, enzymatic urinary glucose measurement is required under Piperacillin/Tazobactam Actavis therapy.
A number of chemicalurine protein measurement methods may lead to false-positive results. Protein measurement with dip sticks is not affected.
The direct Coombs test may be positive.
Bio-Rad Laboratories Platelia AspergillusEIA tests may lead to false-positive results forpatients receiving Piperacillin/Tazobactam Actavis.Cross-reactions with non-Aspergilluspolysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia AspergillusEIA test have been reported.
Positive test results for the assays listed above in patients receiving Piperacillin/Tazobactam Actavis should be confirmed by other diagnostic methods.
4.6 Fertility, pregnancyand lactation
Pregnancy
There are no or a limited amount of data from the use ofpiperacillin andtazobactam in pregnant women.
Studies in animals have shown developmentaltoxicity, but no evidence of teratogenicity, at doses that are maternally toxic(see section 5.3).
Piperacillin and tazobactam cross the placenta. Piperacillin/ tazobactam should only be used during pregnancy if clearly indicated, i.e. only if the expected benefit outweighs the possible risks to the pregnant woman and foetus.
Breast-feeding
Piperacillin is excreted in low concentrations in humanmilk; tazobactamconcentrations in human milk have not been studied. Women who are breast-feeding should be treated only if the expected benefit outweighs the possible risks to the woman and child.
Fertility
A fertility study in rats showed no effect on fertility and mating after intraperitoneal administration of tazobactam or the combination piperacillin / tazobactam (see section 5.3).
4.7 Effects on ability to drive and use machines
No studies on the effecton the ability to drive and use machines have been performed.
4.8 Undesirable effects
The most commonly reported adverse reactions (occurring in 1 to 10 patients in 100) are diarrhoea, vomiting, nausea and rash.
In the following table, adverse reactions are listed by system organ class and MedDRA-preferred term. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
|
System Organ Class |
Common ≥ 1/100 to < 1/10 |
Uncommon ≥ 1/1,000 to < 1/100 |
Rare ≥ 1/10,000 to < 1/1,000 |
Very rare (< 1/10,000) |
|
Infections and infestations |
|
candidal superinfection |
|
|
|
Blood and lymphatic system disorders |
|
leukopenia, neutropenia, thrombocytopenia |
anaemia, haemolytic anaemia, purpura, epistaxis, bleeding time prolonged, eosinophilia |
agranulocytosis, pancytopenia, activated partial thromboplastin time prolonged, prothrombin time prolonged, Coombs direct test positive, thrombocythaemia |
|
Immune system disorders |
|
hypersensitivity |
anaphylactic/ anaphylactoid reaction (including shock) |
|
|
Metabolism and nutrition disorders |
|
|
|
hypokalaemia, blood glucose decreased, blood albumin decreased, blood protein total decreased |
|
Nervous system disorders |
|
headache, insomnia |
|
|
|
Vascular disorders |
|
hypotension, thrombophlebitis, phlebitis |
flushing |
|
|
Gastrointestinal disorders |
diarrhoea, vomiting, nausea |
jaundice, stomatitis, constipation, dyspepsia |
pseudo-membranous colitis, abdominal pain |
|
|
Hepatobiliary disorders |
|
alanine aminotransferase increased, aspartate aminotransferase increased |
hepatitis, blood bilirubin increased, blood alkaline phosphatase increased, gamma- glutamyltrans- ferase increased |
|
|
Skin and subcutaneous tissue disorders |
rash, including maculopapular rash |
urticaria, pruritus |
erythema multiforme, dermatitis bullous, exanthema |
toxic epidermal necrolysis, Stevens-Johnson syndrome |
|
Musculoskeletal and connective tissue disorders |
|
|
arthralgia, myalgia |
|
|
Renal and urinary disorders |
|
blood creatinine increased |
renal failure, tubulointerstitial nephritis |
blood urea increased |
|
General disorders and administration site conditions |
|
pyrexia, injection-site reaction |
chills |
|
Piperacillin therapy has been associated with an increased incidence of fever and rash in cysticfibrosis patients.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued 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 listed in Appendix V.
4.9 Overdose
Symptoms
There have been post-marketing reports of overdose with piperacillin/ tazobactam. The majority of those events experienced,including nausea, vomiting, and diarrhoea,have also been reported with the usual recommended dose. Patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given intravenously (particularly in the presence of renal failure).
Treatment
In the event of an overdose, piperacillin / tazobactam treatment should be discontinued.No specific antidote is known.
Treatment should be supportive and symptomatic according to the patient’sclinical presentation.
Excessive serum concentrations of either piperacillin or tazobactam may be reduced by haemodialysis (see section 4.4).
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antibacterials for systemic use, Combinations of penicillinsincl.beta-lactamase inhibitors; ATC code: J01C R05
Mechanism of action
Piperacillin, a broad-spectrum, semisynthetic penicillin exerts bactericidal activity by inhibition of both septum and cell-wall synthesis.
Tazobactam, a beta-lactam structurally related to penicillins, is aninhibitor of many beta-lactamases, which commonly cause resistance to penicillins and cephalosporinsbut it does not inhibit AmpC enzymes or metallo beta-lactamases. Tazobactumextends the antibiotic spectrum of piperacillin to include many beta-lactamase-producing bacteria that have acquired resistance to piperacillin alone.
Phamacokinetic / Pharmacodynamicrelationship
The time abovethe minimum inhibitoryconcentration (T>MIC) is consideredto be the major pharmacodynamic determinant of efficacyfor piperacillin.
Mechanism of resistance
The two main mechanismsof resistance to piperacillin / tazobactam are:
- Inactivation of the piperacillin component by those beta-lactamases that are not inhibited by tazobactam: beta-lactamases in the Molecular class B, C and D. In addition, tazobactam does not provide protection against extended-spectrum beta-lactamases (ESBLs) in the Molecular class A and D enzyme groups.
- Alterationof penicillin-binding proteins (PBPs), which results in the reductionof the affinity of piperacillin for the molecular target in bacteria.
Additionally, alterations in bacterial membrane permeability, as well as expression of multi-drug efflux pumps, may cause or contribute to bacterial resistanceto piperacillin / tazobactam, especially in Gram-negative bacteria.
Breakpoints
|
EUCAST Clinical MIC Breakpoints for Piperacillin / Tazobactam (2009-12-02, v 1). For Susceptibility Testing Purposes, the Concentration of Tazobactam is Fixed at 4 mg/l |
|
|
Pathogen |
Species-related breakpoints (S ≤ / R >) |
|
Enterobacteriaceae |
8/16 |
|
Pseudomonas |
16/16 |
|
Gram-negative and Gram-positive anaerobes |
8/16 |
|
Non-species related breakpoints |
4/16 |
The susceptibility of streptococciis inferred from the penicillin susceptibility.
The susceptibility of staphylococciis inferred from the oxacillin susceptibility.
Susceptibility
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, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
|
Groupings of relevant species according to piperacillin / tazobactam susceptibility |
|
COMMONLY SUSCEPTIBLE SPECIES |
|
Aerobic Gram-positive micro-organisms Enterococcus faecalis Listeria monocytogenes Staphylococcus aureus, methicillin-susceptible£ Staphylococcus species, coagulase negative, methicillin-susceptible Streptococcus pyogenes Group B streptococci |
|
Aerobic Gram-negative micro-organisms Citrobacter koseri Haemophilus influenza Moraxella catarrhalis Proteus mirabilis |
|
Anaerobic Gram-positive micro-organisms Clostridium species Eubacterium species Peptostreptococcus species |
|
Anaerobic Gram-negative micro-organisms Bacteroides fragilis group Fusobacterium species Porphyromonas species Prevotella species |
|
SPECIES FOR WHICH ACQUIRED RESISTANCE MAY BE A PROBLEM |
|
Aerobic Gram-positive micro-organisms Enterococcus faecium$,+ Streptococcus pneumonia Streptococcus viridans group |
|
Aerobic Gram-negative micro-organisms Acinetobacter baumannii$ Burkholderia cepacia Citrobacter freundii Enterobacter species Escherichia coli Klebsiella pneumonia Morganella morganii Proteus vulgaris Providencia ssp. Pseudomonas aeruginosa Serratia species |
|
INHERENTLY RESISTANT ORGANISMS |
|
Aerobic Gram-positive micro-organisms Corynebacterium jeikeium |
|
Aerobic Gram-negative micro-organisms Legionella species Stenotrophomonas maltophilia+,$ |
|
Other microorganisms Chlamydophilia pneumonia Mycoplasma pneumonia |
|
$ Species showing natural intermediate susceptibility. + Species for which high-resistance rates (more than 50%) have been observed in one or more areas/countries/regions within the EU. £ All methicillin-resistant staphylococci are resistant to piperacillin / tazobactam. |
5.2 Pharmacokinetic properties
Absorption
The peakpiperacillin and tazobactam concentrations after 4 g / 0.5 g administered over 30 minutes byintravenous infusion are 298 µg/mland 34 µg/ml respectively.
Distribution
Both piperacillin and tazobactam are approximately30% bound to plasma proteins. The protein binding of either piperacillin or tazobactam is unaffected by the presence of the other compound. Protein binding of the tazobactam metabolite is negligible.
Piperacillin /tazobactam iswidely distributed in tissuesand body fluids including intestinal mucosa, gallbladder, lung, bile,and bone.Mean tissue concentrations are generally 50 to 100% of those in plasma. Distribution into cerebrospinal fluid is low in subjects with non-inflamed meninges, as with other penicillins.
Biotransformation
Piperacillin is metabolised to a minor microbiologically active desethyl metabolite. Tazobactam is metabolised to a single metabolitethathas been found to be microbiologicallyinactive.
Elimination
Piperacillin and tazobactam are eliminated viathe kidney byglomerular filtration and tubular secretion.
Piperacillin is excreted rapidly as unchanged substance,with 68% of the administered dose appearing in the urine. Tazobactam and its metabolite are eliminated primarily by renal excretion,with 80% of the administered dose appearing as unchanged substanceand the remainder as the single metabolite. Piperacillin, tazobactam, and desethyl piperacillin are also secreted into the bile.
Following single or multiple doses of piperacillin / tazobactam to healthy subjects, the plasma half-life of piperacillin and tazobactam ranged from 0.7 to 1.2 hours and was unaffected by dose or duration of infusion. The elimination half-lives of both piperacillin and tazobactam are increased with decreasing renal clearance.
There are no significant changes in piperacillin pharmacokinetics due to tazobactam. Piperacillin appears to slightly reduce the clearanceof tazobactam.
Special populations
The half-life of piperacillin and of tazobactam increases by approximately 25% and 18%, respectively, in patients with hepatic cirrhosis compared to healthy subjects.
The half-life of piperacillinand tazobactam increases with decreasing creatinine clearance. The increase in half-life is two-fold and four-fold for piperacillin and tazobactam,respectively, at creatinine clearance below 20 ml/min compared to patients with normal renal function.
Haemodialysis removes 30% to 50%of piperacillin/ tazobactam, with an additional 5% of the tazobactam dose removed as the tazobactam metabolite. Peritoneal dialysis removes approximately 6% and 21% of the piperacillin and tazobactam doses, respectively, with up to 18% of the tazobactam dose removed as the tazobactam metabolite.
Paediatric population
In a population PK analysis, estimated clearance for 9 month-old to 12 year-old patients was comparable to adults, with a population mean (SE) valueof 5.64 (0.34) ml/min/kg. The piperacillin clearance estimate is 80% of this value for paediatric patients 2-9 months of age. The population mean (SE) for piperacillin volume of distribution is 0.243 (0.011) l/kg and is independent ofage.
Elderly patients
The mean half-life for piperacillin and tazobactam were 32% and 55% longer, respectively, in the elderly compared with younger subjects. This difference may be due to age-related changes in creatinine clearance.
Race
No difference in piperacillin or tazobactam pharmacokinetics was observed between Asian (n=9) and Caucasian (n=9) healthy volunteers who received single 4 g / 0.5 g doses.
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity and genotoxicity. Carcinogenicity studies have not been conducted with piperacillin/ tazobactam.
A fertility and general reproduction study in rats using intraperitoneal administration of tazobactam or the combination piperacillin/ tazobactam reported a decrease in litter size and an increase in fetuses with ossification delays and variations of ribs, concurrent with maternal toxicity.Fertility of the F1 generation and embryonic development of F2 generation werenot impaired.
Teratogenicity studies using intravenous administration of tazobactam or the combination piperacillin / tazobactam in mice and rats resulted in slight reductions in rat fetal weights at maternally toxic doses but did not show teratogenic effects.
Peri/postnatal development was impaired (reduced pup weights, increase in stillbirths, increase in pup mortality) concurrent with maternal toxicity after intraperitoneal administration of tazobactam or the combination piperacillin / tazobactam in the rat.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
None.
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
Whenever Piperacillin/Tazobactam Actavisis used concurrently with another antibiotic (e.g. aminoglycosides), the substancesmust be administered separately. The mixing of beta-lactam antibioticswith an aminoglycoside in vitrocan result in substantial inactivation of the aminoglycoside.
Piperacillin/Tazobactam Actavisshould not be mixed with other substancesin a syringe or infusion bottle since compatibility has not been established.
Due to chemical instability, Piperacillin/Tazobactam Actavis should not be used with solutions that contain sodium bicarbonate.
Lactated Ringer’s (Hartmann´s) solution is not compatible with piperacillin/tazobactam.
Piperacillin/Tazobactam Actavisshould not be added to blood products or albumin hydrolysates.
6.3 Shelf life
Vial before opening:2 years
After reconstitution (and dilution):
Reconstituted and/or diluted Piperacillin/Tazobactam Actavisshould be used immediately.
From a microbiological point of view, the product should be used immediately.
Unused solution should be discarded.
6.4 Special precautions for storage
Unopened: Store in the original package in order to protect from light.
Store below 250C.
For storage conditions of the reconstituted and diluted medicinal product, see section 6.3.
6.5 Nature and contents of container
Piperacillin/Tazobactam Actavis2g/0..25 g powder for solution for infusion:
Clear glass vials of 30 ml stoppered with grey colour bromo butyl rubber stopper and sealed with violet colour PP/Al flip off seal.
Pack sizes: 1 and 12 vials per carton.
Piperacillin/Tazobactam Actavis4g/0.5 g powder for solution for infusion:
Clear glass vials of 48 ml stoppered with grey colour bromo butyl rubber stopper and sealed with red colour PP/Al flip off seal.
Pack sizes: 1 and 12 vials per carton.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
The reconstitution and dilution is to be made under aseptic conditions. The solution is to be inspected visually for particulate matter and discolourationprior to administration. The solution should only be used if the solution is clear and free from particles.
Intravenous use
Reconstitute each vial with the volume of solvent shown in the table below, using one of the compatible solvents for reconstitution.Swirl until dissolved.
|
Content of vial |
Volume of solvent* to be added to vial |
|
2 g / 0.25 g (2 g piperacillin and 0.25 g tacobactam) |
10 ml |
|
4 g / 0.5 g (4 g piperacillin and 0.5 g tacobactam) |
20 ml |
* Compatible solvents for reconstitution:
- 0.9% (9 mg/ml) sodium chloride solution for injection
- Sterile water for injections
- Glucose 5%
- Glucose 5% in sodium chloride 0.9% (9 mg/ml) solution
The reconstituted solutions may be further diluted to the desired volume (e.g. 50 ml to150 ml) with one of the following compatible solvents:
- 0.9% (9 mg/ml) sodium chloride solution for injection
- Sterile water for injections
- Glucose 5%
- Glucose 5% in sodium chloride 0.9% (9 mg/ml) solution
- Dextran 6% in 0.9% sodium chloride
See section 6.2 for incompatibilities.
Any unused product or waste material should be disposed of in accordance with local requirements.
For single use only. Discard any unused solution.
7. MARKETING AUTHORISATION HOLDER
[To be completed nationally]
{Name and address}
<{tel}>
<{fax}>
<{e-mail}>
8. MARKETING AUTHORISATION NUMBER(S)
[To be completed nationally]
9. DATE OF FIRSTAUTHORISATION/RENEWAL OF THE AUTHORISATION
[To be completed nationally]
10. DATE OF REVISION OF THE TEXT
10 October 2014