Tazpen 2.25
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TAZPEN 2.25 TAZPEN 4.5 (TAZPEN 2.25 TAZPEN 4.5)
Composition:
Active substances: piperacillin sodium, tazobactam sodium;
One vial contains piperacillin sodium equivalent to piperacillin 2 g and tazobactam sodium equivalent to tazobactam 0.25 g.
One vial contains piperacillin sodium equivalent to piperacillin 4 g and tazobactam sodium equivalent to tazobactam 0.5 g (for the 4.5 g dose).
Pharmaceutical form. Powder for solution for infusion.
Main physicochemical properties: porous mass or powder, white to almost white.
Pharmacotherapeutic group. Antibacterials for systemic use. Beta-lactam antibiotics, penicillins. Piperacillin and beta-lactamase inhibitor.
ATC code J01CR05.
Pharmacological properties.
Pharmacodynamics.
Mechanism of action.
Piperacillin is a broad-spectrum semisynthetic antibiotic of the penicillin class that inhibits bacterial activity by inhibiting the formation of the cell septum and synthesis of the cell wall.
Tazobactam, a beta-lactam structurally similar to penicillins, is an inhibitor of many beta-lactamases that typically cause resistance to penicillins and cephalosporins, but it does not inhibit AmpC enzymes or metallo-beta-lactamases. Tazobactam extends the antibacterial spectrum of piperacillin to include many bacteria producing beta-lactamases that are resistant to piperacillin alone.
Pharmacokinetic/pharmacodynamic relationship
The time during which the plasma concentration exceeds the minimum inhibitory concentration (% T> MIC) is considered the primary factor determining the pharmacodynamic efficacy of piperacillin.
Mechanisms of resistance.
There are two mechanisms of resistance to piperacillin/tazobactam:
Inactivation of the piperacillin component by beta-lactamases not inhibited by tazobactam: beta-lactamases of molecular classes B, C, and D. Additionally, tazobactam does not protect against extended-spectrum beta-lactamases (ESBLs) of molecular classes A and D.
Modification of penicillin-binding proteins (PBPs), leading to reduced affinity of piperacillin for its molecular target in bacteria.
Furthermore, alterations in bacterial membrane permeability, as well as expression of multidrug efflux pumps, may cause or contribute to bacterial resistance to piperacillin/tazobactam, particularly in Gram-negative bacteria.
Clinical breakpoints.
EUCAST (European Committee on Antimicrobial Susceptibility Testing) has established clinical breakpoints for MIC (minimum inhibitory concentration) values for piperacillin/tazobactam (2009-12-02, v1). For antimicrobial susceptibility testing, a tazobactam concentration of 4 mg/L is used.
| Pathogenic microorganism |
Strain-related breakpoint values, depending on strain (S ≤/R >) |
| Enterobacteriaceae |
8/16 |
| Pseudomonas |
16/16 |
| Gram-negative and gram-positive anaerobes |
8/16 |
| Breakpoints independent of strain |
4/16 |
Sensitivity of streptococci is presumed based on sensitivity to penicillin.
Sensitivity of staphylococci is presumed based on sensitivity to oxacillin.
Susceptibility
The prevalence of acquired resistance in microbial strains may vary geographically and over time for individual species; therefore, local information on resistance should be sought, especially when treating severe infections. If necessary, when local resistance patterns cast doubt on the appropriateness of using the medicinal product for certain infections, refer to official guidelines on the proper use of antibacterial agents.
Microbial strains grouped according to susceptibility to piperacillin/tazobactam
| Primarily susceptible strains Aerobic gram-positive microorganisms: Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, methicillin-susceptible £, Staphylococcus spp., Coagulase-negative, methicillin-susceptible, Streptococcus pyogenes, Streptococci (group B). Aerobic gram-negative microorganisms: Citrobacter koseri, Haemophilus influenzae, Moraxella catarrhalis, Proteus mirabilis. Anaerobic gram-positive microorganisms: Clostridium spp., Eubacterium spp., Peptostreptococcus spp. Anaerobic gram-negative microorganisms: Bacteroides fragilis group, Fusobacterium spp., Porphyromonas spp., Prevotella spp. |
| Strains for which acquired resistance may be a problem Aerobic gram-positive microorganisms: Enterococcus faecium $, +, Streptococcus pneumoniae Streptococcus viridans group Aerobic gram-negative microorganisms: Acinetobacter baumannii $, Burkholderia cepacia, Citrobacter freundii, Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa, Serratia spp. |
| Microorganisms with intrinsic resistance Aerobic gram-positive microorganisms: Corynebacterium jeikeium Aerobic gram-negative microorganisms: Legionella spp., Stenotrophomonas maltophilia +, $ Other microorganisms: Chlamydophila pneumoniae, Mycoplasma pneumoniae |
$ Strains with intermediate intrinsic sensitivity.
- Strains exhibiting a high level of resistance (over 50%).
£ All methicillin-resistant staphylococci are resistant to piperacillin/tazobactam.
Pharmacokinetics.
Absorption.
Peak concentrations after intravenous administration (over 30 minutes) of piperacillin and tazobactam at a dose of 4 g/0.5 g were 298 \µg/mL and 34 \µg/mL, respectively.
Distribution.
Both piperacillin and tazobactam are approximately 30% bound to plasma proteins. Protein binding of piperacillin and tazobactam is not affected by the presence of other compounds. Protein binding of tazobactam metabolites is negligible.
Piperacillin and tazobactam are widely distributed into body tissues and fluids, including intestinal mucosa, gallbladder, lungs, bile, and bones. Tissue concentrations generally range from 50% to 100% compared to plasma concentrations. Drug distribution into cerebrospinal fluid is low, as with other penicillins, unless patients have meningeal inflammation.
Biotransformation.
Piperacillin is metabolized to a desethyl metabolite, which exhibits minimal microbiological activity. Tazobactam is metabolized to a single microbiologically inactive metabolite.
Elimination.
Piperacillin and tazobactam are eliminated by the kidneys via glomerular filtration and tubular secretion. Piperacillin is rapidly excreted unchanged, with 68% of the administered dose recovered in urine. Tazobactam and its metabolite are primarily excreted by the kidneys, with 80% of the dose excreted unchanged and the remainder as a single metabolite. Piperacillin, tazobactam, and desethylpiperacillin are also secreted into bile. After single or multiple doses of piperacillin/tazobactam administered to healthy volunteers, the plasma elimination half-life ranged from 0.7 to 1.2 hours. Dose and infusion duration did not affect this parameter. The elimination half-life of both piperacillin and tazobactam increases with decreased renal clearance. Administration of tazobactam does not significantly affect the pharmacokinetics of piperacillin. Piperacillin reduces the clearance of tazobactam.
Special patient populations.
Elimination half-lives of piperacillin and tazobactam increase by approximately 25% and 18%, respectively, in patients with liver cirrhosis compared to healthy individuals.
The elimination half-life of piperacillin and tazobactam increases with decreased creatinine clearance. When creatinine clearance is below 20 mL/min, the elimination half-life increases by 2-fold for piperacillin and 4-fold for tazobactam compared to patients with normal renal function.
Hemodialysis removes 30% to 50% of piperacillin/tazobactam, and an additional 5% of tazobactam is eliminated as metabolite. Peritoneal dialysis removes approximately 6% and 21% of the dose of piperacillin and tazobactam, respectively, including up to 18% of the tazobactam dose as metabolite.
Children
In pharmacokinetic studies in patients aged 9 months to 12 years, the approximate clearance value was compared to that in adults. The mean value for this age group (standard deviation) was 5.64 (0.34) mL/min/kg. Approximate piperacillin clearance in patients aged 2 to 9 months was 80% of this value. The mean volume of distribution of piperacillin for this age group (standard deviation) was 0.243 (0.011) L/kg and was independent of age.
Elderly patients
The mean elimination half-life of piperacillin and tazobactam in elderly patients was 32% and 55% longer, respectively, compared to younger patients. This difference is likely due to age-related changes in creatinine clearance.
Race
No differences were observed in the pharmacokinetics of piperacillin and tazobactam between Asian (n=9) and European (n=9) healthy volunteers who received a single 4 g/0.5 g dose.
Clinical characteristics.
Indications.
The medicinal product is indicated for the treatment of the following infections in adults and children aged 2 years and older:
Adults and children aged 12 years and older:
- severe pneumonia (including hospital-acquired and ventilator-associated pneumonia);
- complicated urinary tract infections (including pyelonephritis);
- complicated intra-abdominal infections;
- complicated skin and soft tissue infections (including infectious complications in diabetic foot syndrome).
Treatment of patients with bacteremia associated or concurrent with any of the above-mentioned infections.
The medicinal product may be used for the treatment of fever in patients with neutropenia likely caused by bacterial infection.
Children aged 2 to 12 years:
- complicated intra-abdominal infections.
The medicinal product may be used for the treatment of fever in children with neutropenia likely caused by bacterial infection.
It is recommended to follow official guidelines regarding the use of antibacterial agents.
Contraindications.
Hypersensitivity to the active substances or to any other penicillin antibiotics. Severe acute allergic reactions to any other beta-lactam agents in the past (e.g., cephalosporins, monobactams, or carbapenems).
Interaction with other medicinal products and other forms of interaction.
Non-depolarizing muscle relaxants. Concomitant administration of piperacillin with vecuronium leads to prolonged neuromuscular blockade. Due to the similar mechanism of action, neuromuscular blockade caused by any non-depolarizing muscle relaxant may be prolonged when piperacillin is administered.
Oral anticoagulants. When used concomitantly with heparin, oral anticoagulants, and other agents affecting the blood coagulation system, including platelet function, coagulation parameters should be monitored regularly.
Methotrexate. Piperacillin may reduce methotrexate excretion. In patients receiving methotrexate, serum methotrexate levels should be monitored to avoid toxic effects.
Probenecid. As with other penicillin-group drugs, concomitant administration of probenecid and piperacillin/tazobactam results in prolonged elimination half-life and reduced renal clearance of both piperacillin and tazobactam. However, this does not affect the maximum plasma concentration of the active substances.
Aminoglycosides. Piperacillin alone or in combination with tazobactam does not significantly alter the pharmacokinetics of tobramycin in patients with normal renal function or mild to moderate renal impairment. The pharmacokinetics of piperacillin, tazobactam, and metabolite M1 were also not significantly altered when tobramycin was administered.
In patients with severe renal impairment, inactivation of tobramycin and gentamicin by piperacillin has been observed.
Information on the combined use of piperacillin/tazobactam with aminoglycosides is provided in the section "Incompatibility".
Vancomycin. Studies have shown an increased incidence of acute kidney injury in patients receiving piperacillin/tazobactam and vancomycin concomitantly compared to vancomycin alone. In some studies, this interaction was dose-dependent regarding vancomycin.
No pharmacokinetic interactions between piperacillin/tazobactam and vancomycin have been documented.
Effect on laboratory test results. Non-enzymatic methods for glucose determination in urine may yield false-positive results, as with other penicillin-group drugs. Therefore, during therapy with this medicinal product, enzymatic methods for glucose determination in urine are recommended.
Some chemical methods for measuring protein in urine may yield false-positive results. However, test strip methods for protein measurement are not affected.
The direct Coombs test may be positive.
Positive results of the above-mentioned laboratory tests in patients receiving TAZPEN 2.25 or TAZPEN 4.5 should be confirmed by alternative diagnostic methods.
Special precautions for use.
When selecting this medicinal product for the treatment of a specific patient, consideration should be given to the appropriateness of using a broad-spectrum semisynthetic penicillin based on factors such as the severity of infection and the prevalence of resistance to other relevant antibacterial agents.
Prior to initiating therapy with this medicinal product, a thorough patient history should be obtained regarding hypersensitivity reactions to penicillins, other beta-lactam agents (e.g., cephalosporins, monobactams, or carbapenems), and other allergens. Serious, sometimes fatal, hypersensitivity reactions (anaphylactic/anaphylactoid, including shock) have been reported in patients receiving penicillin therapy, including piperacillin/tazobactam. The likelihood of hypersensitivity reactions is increased in individuals with a history of sensitivity to multiple allergens. Serious hypersensitivity reactions require immediate discontinuation of the antibiotic and may necessitate administration of epinephrine and other emergency measures.
The medicinal product may cause severe skin adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). If skin rash develops in patients, they should be closely monitored by a physician, and treatment should be discontinued if the condition progresses.
In cases of severe persistent diarrhea, antibiotic-associated pseudomembranous colitis, which may be life-threatening, should be considered. Symptoms may appear during or after antibacterial therapy. In such cases, the medicinal product should be discontinued immediately.
The risk of emergence of resistant organisms during treatment with this medicinal product may lead to the development of superinfection.
In some patients receiving beta-lactam antibiotics, symptoms of bleeding have been observed. Such reactions were sometimes associated with coagulation disorders, including prolonged bleeding time, platelet aggregation abnormalities, and prothrombin time. These disturbances were most commonly observed in patients with renal impairment. If bleeding occurs, antibiotic administration should be discontinued and appropriate treatment initiated.
Since leukopenia and neutropenia may develop during prolonged therapy, periodic monitoring of blood parameters is recommended.
As with other penicillin-class agents, neurological complications such as seizures may occur with high-dose therapy, particularly in patients with impaired renal function.
This medicinal product contains sodium; therefore, this should be taken into account in patients on a sodium-restricted diet.
Hypokalemia may develop in patients with low body potassium levels or those taking potassium-lowering medications. Periodic monitoring of electrolyte balance is recommended for such patients.
Renal function impairment.
Due to potential nephrotoxicity, piperacillin/tazobactam should be administered with caution in patients with impaired renal function and in those undergoing hemodialysis. Intravenous doses and dosing intervals should be adjusted according to the degree of renal impairment.
Concomitant use of piperacillin/tazobactam and vancomycin may be associated with an increased incidence of acute kidney injury.
Hemophagocytic lymphohistiocytosis (HLH).
Cases of HLH have been reported in patients receiving piperacillin/tazobactam, piperacillin, often after treatment lasting more than 10 days. HLH is a life-threatening syndrome of pathological immune activation characterized by clinical signs and symptoms of excessive systemic inflammation (e.g., fever, hepatosplenomegaly, hypertriglyceridemia, hypofibrinogenemia, elevated serum ferritin, cytopenia, and hemophagocytosis). Patients developing early signs of pathological immune activation should be promptly evaluated. If HLH is diagnosed, treatment with piperacillin/tazobactam or piperacillin should be discontinued.
Use during pregnancy or breastfeeding.
Pregnancy. Currently, there are no or limited data on the use of piperacillin/tazobactam in pregnant women. Animal studies have shown toxic effects on the fetus, but teratogenicity was not observed at doses toxic to the maternal organism. Piperacillin and tazobactam cross the placenta. The medicinal product may be used during pregnancy only if the expected benefit outweighs the potential risk to the woman and the fetus.
Breastfeeding period. Piperacillin passes into breast milk in negligible concentrations. Tazobactam concentrations in breast milk have not been studied. Treatment of women during breastfeeding with this medicinal product is indicated only when the expected benefit outweighs the potential risk to the woman and the infant.
Fertility. Studies in rats showed that intraperitoneal administration of tazobactam or the combination piperacillin/tazobactam had no effect on reproductive function or fertility.
Ability to influence reaction speed when driving or operating machinery.
The effect of the drug on reaction speed when driving or operating machinery has not been established.
Dosage and Administration.
Dosage
The dose and frequency of administration of the medicinal product depend on the severity and location of the infection, as well as the likely causative pathogens.
Adults and children aged 12 years and older
Infections
The usual dose of the medicinal product is 4.5 g (4 g piperacillin / 0.5 g tazobactam) administered every 8 hours.
For hospital-acquired pneumonia and bacterial infections in neutropenic patients, the recommended dose is 4 g piperacillin / 0.5 g tazobactam every 6 hours. This dosing regimen may also be used for treatment of patients with severe forms of other documented infections.
The table below provides the recommended dosing frequency for adult patients and children aged 12 years and older, with indications or conditions specified:
| Dosing frequency |
Indications for use of the medicinal product at a dosage of 4.5 g |
| Every 6 hours |
Severe pneumonia |
| Febrile neutropenia in adults, likely associated with bacterial infection |
|
| Every 8 hours |
Complicated urinary tract infections (including pyelonephritis) |
| Complicated intra-abdominal infections |
|
| Skin and soft tissue infections (including infectious complications in diabetic foot syndrome) |
Patients with renal impairment
The intravenous dose should be adjusted according to the degree of renal impairment as outlined below (each patient should be monitored for signs of drug toxicity; the dose and dosing interval should be appropriately adjusted):
| Creatinine clearance (mL/min) |
Recommended dose of piperacillin/tazobactam |
| > 40 |
No dose adjustment required |
| 20–40 |
Maximum recommended dose: 4 g/0.5 g every 8 hours |
| < 20 |
Maximum recommended dose: 4 g/0.5 g every 12 hours |
Due to hemodialysis removing 30–50% of piperacillin within 4 hours, an additional dose of piperacillin/tazobactam 2 g/0.25 g should be administered after each dialysis session.
Patients with hepatic impairment
Dose adjustment is not required.
Elderly patients
For elderly patients with normal renal function or creatinine clearance values above 40 mL/min, dose adjustment is not required.
Children aged 2 to 12 years.
Infections
The table below provides the recommended dosage and frequency according to body weight for children aged 2 to 12 years, with indications or conditions specified:
| Dose according to body weight and frequency of administration |
Indications or conditions |
| 80 mg piperacillin/10 mg tazobactam per kg body weight/every 6 hours |
Fever in neutropenic children likely caused by bacterial infection* |
| 100 mg piperacillin/12.5 mg tazobactam per kg body weight/every 8 hours |
Complicated intra-abdominal infections* |
* Do not exceed the maximum dose of 4.5 g administered within 30 minutes.
Patients with renal impairment
The intravenous dose should be adjusted according to the degree of renal impairment as indicated below (each patient should be monitored for signs of drug toxicity; the dose and dosing interval should be appropriately adjusted):
| Creatinine clearance (mL/min) |
Recommended dose of piperacillin/tazobactam |
| > 50 |
No dose adjustment required |
| ≤ 50 |
70 mg piperacillin/8.75 mg tazobactam per kg body weight every 8 hours. |
For children undergoing hemodialysis, an additional dose of 40 mg of piperacillin/5 mg of tazobactam per kg of body weight is required after each dialysis session.
Children under 2 years of age.
The efficacy and safety of the medicinal product for treatment of children under 2 years of age have not been established.
Controlled clinical trial data are lacking.
Treatment duration.
The usual duration of treatment for most indications is 5–14 days. However, the duration of therapy should be determined based on the patient's condition, severity of infection, and results of clinical and bacteriological examinations.
Instructions for preparation of solution for intravenous administration.
The solution for intravenous administration must be prepared under aseptic conditions. Before administration, the prepared solution should be visually inspected for the absence of mechanical particles and discoloration. Only clear solutions free of particulate matter should be used.
The contents of the vial should be reconstituted with the diluent in the volume specified in the table below. Shake the vial until the powder is completely dissolved. Reconstitution of the solution occurs within 5–10 minutes with continuous shaking.
| Contents of the vial |
Volume of solvent* to be added to the vial |
| Piperacillin/tazobactam 2 g/0.25 g |
10 ml |
| Piperacillin/tazobactam 4 g/0.5 g |
20 ml |
* Compatible solvents for reconstitution:
- 0.9% sodium chloride solution
- sterile water for injection1
- 5% glucose solution
1 The maximum recommended volume of sterile water for injection per 50 ml dose is 50 ml.
Reconstituted solutions should be withdrawn from the vial using a syringe. If reconstitution is performed according to the recommendations, withdrawal of the vial contents using a syringe will ensure availability of the declared amount of piperacillin/tazobactam. Reconstituted solutions may be further diluted to the required volume (from 50 ml to 150 ml) with one of the following compatible diluents:
- 0.9% sodium chloride solution
- 5% glucose solution.
Concomitant administration with aminoglycosides
Due to in vitro inactivation of aminoglycosides by beta-lactam antibiotics, TAZPEN 2.25 and TAZPEN 4.5 and aminoglycosides are recommended to be administered separately. If concomitant therapy with aminoglycosides is indicated, TAZPEN 2.25 or TAZPEN 4.5 and aminoglycosides should be reconstituted, diluted, and administered separately. A Y-type catheter should be used for administration. When administering concomitantly via a Y-type catheter, the following requirements must be observed:
| Aminoglycoside |
Piperacillin/tazobactam dose |
Volume of Tazpen diluent (ml) |
Aminoglycoside concentration range* (mg/ml) |
Compatible solutions |
| Amikacin |
2 g/0.25 g 4 g/0.5 g |
50, 100, 150 |
1.75–7.5 |
0.9% sodium chloride solution or 5% glucose solution |
| Gentamicin |
2 g/0.25 g 4 g/0.5 g |
50, 100, 150 |
0.7–3.32 |
0.9% sodium chloride solution or 5% glucose solution |
*Aminoglycoside dosage depends on body weight, the nature of the infection (serious or life-threatening), and renal function (creatinine clearance).
Compatibility of TAZOCIN 2.25 or TAZOCIN 4.5 with other aminoglycosides has not been established. Only the concentrations and diluents for amikacin and gentamicin listed in the table above have been demonstrated as compatible for co-administration via a Y-type catheter. Simultaneous co-administration via a Y-type catheter by any method other than that specified above may result in inactivation of the aminoglycoside by TAZOCIN 2.25 or TAZOCIN 4.5.
Children.
The drug may be administered to children aged 2 years and older.
Overdose.
Symptoms. There have been reports of overdose with the drug. Most of these cases, including nausea, vomiting, and diarrhea, occurred following administration of the usual recommended doses. Neurological and muscular excitability or seizures may occur in patients who exceed the recommended intravenous doses (especially in patients with renal impairment).
Treatment. In case of overdose, further administration of piperacillin/tazobactam should be discontinued. No specific antidote is known.
Treatment is supportive and symptomatic, depending on the patient's condition.
Excess serum concentrations of piperacillin or tazobactam may be reduced by hemodialysis.
Adverse reactions.
The most commonly reported adverse drug reaction was diarrhea (observed in 1 out of 10 patients). The most severe adverse reactions are pseudomembranous colitis and toxic epidermal necrolysis, occurring in 1 to 10 out of 10,000 patients.
The frequency of pancytopenia, anaphylactic shock, and Stevens-Johnson syndrome cannot be estimated based on available data.
The adverse reactions listed below are classified by organ systems and frequency of occurrence. The following classification of adverse event frequencies is used: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); and frequency not known (cannot be estimated based on available data).
| Body system classes |
Adverse reactions and their frequency |
| Infections and infestations |
Common: candidiasis superinfection* Uncommon: pseudomembranous colitis |
| Blood and lymphatic system disorders |
Common: thrombocytopenia, anemia* Uncommon: leukopenia Rare: agranulocytosis Frequency unknown: pancytopenia*, neutropenia, hemolytic anemia*, thrombocytosis*, eosinophilia* |
| Immune system disorders |
Frequency unknown: anaphylactoid shock*, anaphylactic shock*, anaphylactoid reaction*, anaphylactic reaction*, hypersensitivity reactions* |
| Metabolism and nutrition disorders |
Uncommon: hypokalemia |
| Psychiatric disorders |
Common: insomnia Frequency unknown: delirium* |
| Nervous system disorders |
Common: headache Uncommon: seizure* |
| Vascular disorders |
Uncommon: arterial hypotension, phlebitis, thrombophlebitis, hot flush |
| Respiratory, thoracic and mediastinal disorders |
Rare: epistaxis Frequency unknown: eosinophilic pneumonia |
| Gastrointestinal disorders |
Very common: diarrhea Common: abdominal pain, vomiting, constipation, nausea, dyspepsia Rare: stomatitis |
| Hepatobiliary disorders |
Frequency unknown: hepatitis*, jaundice |
| Skin and subcutaneous tissue disorders |
Common: rash, pruritus Uncommon: erythema multiforme*, urticaria, maculopapular rash* Rare: toxic epidermal necrolysis* Frequency unknown: Stevens-Johnson syndrome*, exfoliative dermatitis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)*, acute generalized exanthematous pustulosis*, bullous dermatitis, purpura |
| Musculoskeletal, connective tissue and bone disorders |
Uncommon: arthralgia, myalgia |
| Renal and urinary disorders |
Frequency unknown: renal failure, tubulointerstitial nephritis* |
| General disorders and administration site conditions |
Common: pyrexia, infusion site reactions Uncommon: chills |
| Investigations |
Common: increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), decreased total blood protein and albumin levels, positive direct Coombs test, increased creatinine, alkaline phosphatase and blood urea levels, prolonged activated partial thromboplastin time Uncommon: decreased blood glucose, increased blood bilirubin, prolonged prothrombin time Frequency unknown: prolonged bleeding time, increased blood gamma-glutamyltransferase levels |
* Adverse reactions identified during the post-marketing period.
Piperacillin therapy has been associated with an increased incidence of fever and rash in patients with cystic fibrosis.
Effects of the class of beta-lactam antibiotics
Beta-lactam antibiotics, including piperacillin/tazobactam, may cause manifestations of encephalopathy and seizures.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.
Shelf life.
3 years.
Storage conditions.
Store in the original packaging, protected from light, at a temperature not exceeding 25 °C. Keep out of the reach and sight of children.
The shelf life of the reconstituted solution is no more than 12 hours when stored refrigerated at 2 to 8 °C.
From a microbiological standpoint, the reconstituted solution should be used immediately. If the reconstituted medicinal product is not used immediately, the storage period for use is no more than 12 hours when stored refrigerated at 2 to 8 °C.
Incompatibilities.
TAZPEN 2.25 or TAZPEN 4.5 must not be mixed with other medicinal products except those mentioned in the section "Method of administration and dosage."
If concomitant administration with another antibiotic (e.g., aminoglycosides) is required, the products should be administered separately. Mixing beta-lactam antibiotics with aminoglycosides in vitro may result in significant inactivation of the aminoglycoside.
The product must not be mixed with other substances in a syringe or infusion bottle, as compatibility has not been established.
Due to chemical instability, the medicinal product should not be used in solutions containing only sodium bicarbonate.
TAZPEN 2.25 or TAZPEN 4.5 must not be added to blood products or albumin hydrolysates.
Packaging.
2 g/0.25 g or 4 g/0.5 g in vials; 1 vial of powder in a cardboard box.
Prescription status.
Prescription only.
Manufacturer.
Cooper Pharmaceuticals S.A.
Cooper Pharmaceuticals S.A.
Manufacturer's address and place of business.
64 Aristovoulou Str. 11853 Athens, Greece
64 Aristovoulou Str. 11853 Athens, Greece
Marketing Authorization Holder.
M.BIOTECH LIMITED
M.BIOTECH LIMITED
Address of the Marketing Authorization Holder.
Gladstone House, 77-79 High Street, Egham TW20 9HY, Surrey, United Kingdom
Gladstone House, 77-79 High Street, Egham TW20 9HY, Surrey, United Kingdom