Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
Piperacillin belongs to the group of medicines known as "broad-spectrum penicillin antibiotics". It can kill many kinds of bacteria. Tazobactam can prevent some resistant bacteria from surviving the effects of piperacillin. This means that when piperacillin and tazobactam are given together, more types of bacteria are killed. Piperacillin/Tazobactam is used in adults and adolescents to treat bacterial infections, such as those affecting the lower respiratory tract (lungs), urinary tract (kidneys and bladder), abdomen, skin or blood. Piperacillin/Tazobactam may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections). Piperacillin/Tazobactam is used in children aged 2-12 years to treat infections of the abdomen such as appendicitis, peritonitis (infection of the fluid and lining of the abdominal organs), and gallbladder (biliary) infections. Piperacillin/Tazobactam may be used to treat bacterial infections in patients with low white blood cell counts (reduced resistance to infections). In certain serious infections, your doctor may consider using Piperacillin/Tazobactam in combination with other antibiotics.
Warnings and precautions Talk to your doctor, pharmacist or nurse before using Piperacillin/Tazobactam - if you have allergies. If you have several allergies, make sure you tell your doctor or other healthcare professional before receiving this product. - if you are suffering from diarrhoea before, or if you develop diarrhoea during or after your treatment. In this case, make sure you tell your doctor or other healthcare professional immediately. Do not take any medicine for the diarrhoea without first checking with your doctor. - if you have low levels of potassium in your blood. Your doctor may want to check your kidneys before you take this medicine and may perform regular blood tests during treatment. - if you have kidney or liver problems, or are receiving haemodialysis. Your doctor may want to check your kidneys before you take this medicine, and may perform regular blood tests during treatment. - if you are taking another antibiotic called vancomycin at the same time as Piperacillin/Tazobactam, this may increase the risk of kidney injury (see also Other medicines and Piperacillin/Tazobactam in this leaflet). - if you are taking certain medicines (called anticoagulants) to avoid an excess of blood clotting (see also Other medicines and Piperacillin/Tazobactam in this leaflet) or any unexpected bleeding occurs during the treatment. In this case, you should inform your doctor or other healthcare professional immediately. - if you develop convulsions (fits) during the treatment. In this case, you should inform your doctor or other healthcare professional. - if you think you developed a new or worsening infection. In this case, you should inform your doctor or other healthcare professional. - if you have serious skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP). Stop using Piperacillin/Tazobactam and seek medical attention immediately if you notice any of the symptoms described in section 4. Haemophagocytic lymphohistiocytosis There have been reports about a disease in which the immune system makes too many of otherwise normal white blood cells called histiocytes and lymphocytes, resulting in inflammation (haemophagocytic lymphohistiocytosis). This condition may be life-threatening if not diagnosed and treated early. If you experience multiple symptoms such as fever, swollen glands, feeling weak, feeling lightheaded, shortness of breath, bruising, or skin rash, contact your doctor immediately. Children Piperacillin/Tazobactam is not recommended for use in children below the age of 2 years due to insufficient data on safety and effectiveness. Other medicines and Piperacillin/Tazobactam Tell your doctor or other healthcare professional if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. Some medicines may interact with piperacillin and tazobactam. These include: - medicine for gout (probenecid). This can increase the time it takes for piperacillin and tazobactam to leave your body. - medicines to thin your blood or to treat blood clots (e.g., heparin, warfarin or acetylsalicylic acid). - medicines used to relax your muscles during surgery. Tell your doctor if you are going to have a general anaesthetic. - methotrexate (medicine used to treat cancer, arthritis or psoriasis). Piperacillin and tazobactam can increase the time it takes for methotrexate to leave your body. - medicines that reduce the level of potassium in your blood (e.g., tablets enhancing urination or some medicines for cancer).
- medicines containing the other antibiotics tobramycin, gentamicin or vancomycin. Tell your doctor if you have kidney problems. Taking Piperacillin/Tazobactam and vancomycin at the same time may increase the risk of kidney injury even if you have no kidney problems. Effect on laboratory tests Tell the doctor or laboratory staff that you are taking Piperacillin/Tazobactam if you have to provide a blood or urine sample. Pregnancy and breast-feeding If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or other healthcare professional for advice before receiving this medicine. Your doctor will decide if Piperacillin/Tazobactam is right for you. Piperacillin and tazobactam can pass to a baby in the womb or through breast milk. If you are breastfeeding, your doctor will decide if Piperacillin/Tazobactam is right for you. Driving and using machines The use of Piperacillin/Tazobactam is not expected to affect the ability to drive or use machines. Piperacillin/Tazobactam contains sodium Piperacillin/Tazobactam 2 g/0.25 g This medicine contains 108 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 5.4% of the recommended maximum daily dietary intake of sodium for an adult. Piperacillin/Tazobactam 4 g/0.5 g This medicine contains 216 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 10.8% of the recommended maximum daily dietary intake of sodium for an adult. This should be taken into consideration if you are on a controlled-sodium diet.
Common side effects (may affect up to 1 in 10 people): - yeast infection
You will be given Piperacillin/Tazobactam until the sign of infection has gone completely (5 to 14 days). Patients with kidney problems Your doctor may need to reduce the dose of Piperacillin/Tazobactam or how often you are given it. Your doctor may also want to test your blood to make sure that your treatment is at the right dose, especially if you have to take this medicine for a long time. If you receive more Piperacillin/Tazobactam than you should As you will receive Piperacillin/Tazobactam from a doctor or other healthcare professional, you are unlikely to be given the wrong dose. However, if you experience side effects, such as convulsions (fits), or think you have been given too much, tell your doctor immediately. If you miss a dose of Piperacillin/Tazobactam If you think you have not been given a dose of Piperacillin/Tazobactam, tell your doctor or other healthcare professional immediately. If you have any further questions on the use of this medicine, ask your doctor or nurse.
Like all medicines, this medicine can cause side effects, although not everybody gets them. See a doctor immediately if you experience any of these potentially serious side effects of Piperacillin/Tazobactam: The serious side effects (with frequency in brackets) of piperacillin/tazobactam are: - serious skin rashes [Stevens-Johnson syndrome, dermatitis bullous (Not known), dermatitis exfoliative (Not known), toxic epidermal necrolysis (Rare)] appearing initially as reddish target-like spots or circular patches often with central blisters on the trunk. Additional signs include ulcers in the mouth, throat, nose, extremities, genitals and conjunctivitis (red and swollen eyes). The rash may progress to widespread blistering or peeling of the skin and potentially may be life threatening -severe potentially fatal allergic condition (drug reaction with eosinophilia and systemic symptoms) that can involve the skin and most importantly other organs under the skin such as the kidney and the liver -a skin condition (acute generalised exanthematous pustulosis) accompanied by fever, which consists of numerous tiny fluid filled blisters contained within large areas of swollen and reddened skin - swelling of the face, lips, tongue or other parts of the body (Not known) - shortness of breath, wheezing or trouble breathing (Not known) - severe rash or hives (Uncommon), itching or rash on the skin (Common) - yellowing of the eyes or skin (Not known) - damage to blood cells [the signs include: being breathless when you do not expect it, red or brown urine (Not known), nosebleeds (Rare) and small spot bruising (Not known), severe decrease in white blood cells (Rare)] - severe or persistent diarrhoea accompanied by a fever or weakness (Rare) If any of the following side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or other healthcare professional. Very common side effects (may affect more than 1 in 10 people): - diarrhoea
- decrease in platelets, decrease of red blood cells or blood pigment/haemoglobin, abnormal lab test (positive direct Coombs), prolonged blood clotting time (activated partial thromboplastin time prolonged) - decrease in blood protein - headache, sleeplessness - abdominal pain, vomiting, nausea, constipation, upset stomach - increase in blood liver enzymes - skin rash, itching - abnormal kidney blood tests - fever, injection site reaction Uncommon side effects (may affect up to 1 in 100 people): - decrease in white blood cells (leukopenia), prolonged blood clotting time (prothrombin time prolonged) - decreased blood potassium, decreased blood sugar - fits (convulsions), seen in patients on high doses or with kidney problems - low blood pressure, inflammation of the veins (felt as tenderness or redness in the affected area), reddening of skin - increase of a blood pigment breakdown product (bilirubin) - skin reactions with redness, formation of skin lesions, nettle rash - joint and muscle pain - chills Rare side effects (may affect up to 1 in 1,000 people): -severe decrease in white blood cells (agranulocytosis), bleeding of the nose -serious infection of the colon, inflammation of the mucous lining of the mouth -detachment of the top layer of the skin all over the body (toxic epidermal necrolysis)
Not known side effects (frequency cannot be estimated from the available data): -severe decrease of red blood cells, white blood cells and platelets (pancytopenia), decrease in white blood cells (neutropenia), decrease of red blood cells due to premature breakdown or degradation, small spot bruising, bleeding time prolonged, increase of platelets, increase of a specific type of white blood cells (eosinophilia) -allergic reaction and severe allergic reaction -inflammation of the liver, yellow staining of the skin or whites of the eyes -serious body wide allergic reaction with skin and mucous lining rashes, blistering and various skin eruption (Stevens-Johnson Syndrome), severe allergic condition involving skin and other organs such as the kidney and the liver (drug reaction with eosinophilia and systemic symptoms), numerous tiny fluid filled blisters contained within large areas of swollen and reddened skin accompanied by fever (acute generalised exanthematous pustulosis), skin reactions with blistering (dermatitis bullous) -poor kidney function and kidney problems -a form of lung disease where eosinophils (a form of white blood cell) appear in the lung in increased numbers -acute disorientation and confusion (delirium). Piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients. Beta‑lactam antibiotics, including piperacillin/tazobactam, may lead to manifestations of encephalopathy (damage or disease that affects the brain) and convulsions (fits). Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects, you can help provide more information on the safety of this medicine.
Do not use this medicine after the expiry date which is stated on the pack after EXP. The expiry date refers to the last day of that month.
Unopened vials: Store below 25°C. Store in the original package in order to protect from light. After reconstitution: Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and for 48 hours at 2-8°C, after reconstitution with one of the compatible solvents. After dilution: Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and for 48 hours at 2-8°C, after dilution with one of the compatible solvents. From a microbiological point of view, the product 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 and dilution have taken place in controlled and validated aseptic conditions. For single use only. Discard any unused solution. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
Content of vial Volume of solvent* to be
added to vial
This leaflet was last revised in August 2024 Other sources of information The following information is intended for healthcare professionals only: Instructions for use Piperacillin/Tazobactam will be given by intravenous infusion (a drip for 30 minutes). The reconstitution and dilution is to be made under aseptic conditions. The solution is to be inspected visually for particulate matter and discolouration prior 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. When swirled constantly, reconstitution generally occurs within 5 to 10 minutes (for details on handling, please see below).
Displacement
Approximate concentration per ml 2 g/0.25 g (2 g piperacillin and 0.25 g tazobactam) 10 ml 1.6 ml Piperacillin: 172.4 mg/ml
Volume
Tazobactam: 21.5 mg/ml 4 g/0.5 g (4 g piperacillin and 0.5 g tazobactam) 20 ml 3 ml Piperacillin: 173.9 mg/ml
Tazobactam: 21.7 mg/ml * Compatible solvents for reconstitution: - 0.9% (9 mg/ml) sodium chloride solution for injection - Sterile water for injections(1) - Glucose 5% (1) Maximum recommended volume of sterile water for injection per dose is 50 ml. The reconstituted solutions should be withdrawn from the vial by syringe. When reconstituted as directed, the vial contents withdrawn by syringe will provide the labelled amount of piperacillin and tazobactam. The reconstituted solutions may be further diluted to the desired volume (e.g. 50 ml to 150 ml) with one of the following compatible solvents: - 0.9% (9 mg/ml) sodium chloride solution for injection - Glucose 5% - Dextran 6% in 0.9% (9 mg/ml) sodium chloride After reconstitution: Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and for 48 hours at 2-8°C, after reconstitution with one of the compatible solvents. After dilution: Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and for 48 hours at 2-8°C, after dilution with one of the compatible solvents. From a microbiological point of view, the product 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 and dilution have taken place in controlled and validated aseptic conditions.
Incompatibilities This medicinal product must not be mixed with other medicinal products except those mentioned above. Whenever piperacillin/tazobactam is used concurrently with another antibiotic (e.g., aminoglycosides), the substances must be administered separately. The mixing of beta-lactam antibiotics with aminoglycosides, in vitro can result in substantial inactivation of the aminoglycoside. Piperacillin/tazobactam should not be mixed with other substances in a syringe or infusion bottle since compatibility has not been established. Piperacillin/tazobactam should be administered through an infusion set separately from any other drugs unless compatibility is proven. Because of chemical instability, piperacillin/tazobactam should not be used in solutions containing only sodium bicarbonate. Piperacillin/Tazobactm is not compatible with lactated Ringer's solution (Hartmann's solution) and for co-administration via a Y-site. Piperacillin/tazobactam should not be added to blood products or albumin hydrolysates.
Piperacillin/Tazobactam 4 g/0.5 g powder for solution for infusion comes as infusion containing 4g / 0.5g. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
The active substance in Piperacillin/Tazobactam 4 g/0.5 g powder for solution for infusion is piperacillin sodium, tazobactam sodium.
Medicines with the same active substance, strength and form include: Piperacillin/Tazobactam 4 g / 0.5 g powder for solution for infusion, Piperacillin/Tazobactam 4 g/0.5 g powder and solvent for solution for infusion, Piperacillin/Tazobactam 4 g/0.5 g powder for solution for infusion. In total there are 6 equivalent products. They are interchangeable only if your prescriber or pharmacist says so.
This leaflet reproduces the patient information leaflet approved for Piperacillin/Tazobactam 4 g/0.5 g powder for solution for infusion, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
Piperacillin/Tazobactam 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
- 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 diabetic foot infections)
Treatment of patients with bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above.
Piperacillin/Tazobactam may be used in the management of neutropenic patients with fever suspected to be due to a bacterial infection.
Note: Use for bacteraemia due to extended-beta-lactamase (ESBL) producing E. coli and K. pneumoniae (ceftriaxone non-susceptible), is not recommended in adult patients, see section 5.1.
Children 2 to 12 years of age
- Complicated intra-abdominal infections
Piperacillin/Tazobactam may be used in the management of neutropenic children with fever suspected to be due to a bacterial infection.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Posology
The dose and frequency of Piperacillin/Tazobactam 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 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 (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 patients on haemodialysis, one additional dose of piperacillin/tazobactam 2 g/0.25 g should be administered following each dialysis period, because haemodialysis removes 30%-50% of piperacillin in 4 hours.
Hepatic impairment
No dose adjustment is necessary (see section 5.2).
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 (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 (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 in children 0- 2 years of age has not been established.
No data from controlled clinical studies are available.
Treatment duration
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.
Method of administration
Piperacillin/Tazobactam 4 g/0.5 g is administered by intravenous infusion (over 30 minutes).
For instructions on reconstitution of the medicinal product before administration, see section 6.6.
Hypersensitivity to the active substances, 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).
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, 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.
Piperacillin/Tazobactam may cause severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalised exanthematous pustulosis (see section 4.8). If patients develop a skin rash they should be monitored closely and piperacillin/tazobactam discontinued if lesions progress.
Haemophagocytic lymphohistiocytosis (HLH): Cases of HLH have been reported in patients treated with piperacillin/tazobactam, often following treatment longer than 10 days. HLH is a life-threatening syndrome of pathologic immune activation characterised by clinical signs and symptoms of an excessive systemic inflammation (e.g., fever, hepatosplenomegaly, hypertriglyceridaemia, hypofibrinogenaemia, high serum ferritin, cytopenias and haemophagocytosis). Patients who develop early manifestations of pathologic immune activation should be evaluated immediately. If diagnosis of HLH is established piperacillin/tazobactam treatment should be discontinued.
Antibiotic-induced pseudomembranous colitis may be manifested by severe, persistent diarrhoea which may be life-threatening. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment. In these cases Piperacillin/Tazobactam, should be discontinued.
Therapy with piperacillin/tazobactam 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 (seizures) may occur when high doses are administered, especially in patients with impaired renal function (see section 4.8).
Hypokalaemia may occur in patients with low potassium reserves or those receiving concomitant medicinal products that may lower potassium levels; periodic electrolyte determinations may be advisable in such patients.
Renal Impairment
Due to its potential nephrotoxicity (see section 4.8), piperacillin/tazobactam should be used with care in patients with renal impairment or in haemodialysis patients.
Intravenous dosages and administration intervals should be adjusted to the degree of renal function impairment (see section 4.2).
In a secondary analysis using data from a large multicenter, randomized-controlled trial when glomerular filtration rate (GFR) was examined after administration of frequently used antibiotics in critically ill patients, the use of piperacillin/tazobactam was associated with a lower rate of reversible GFR improvement compared with the other antibiotics. This secondary analysis concluded that piperacillin/tazobactam was a cause of delayed renal recovery in these patients.
Combined use of piperacillin/tazobactam and vancomycin may be associated with an increased incidence of acute kidney injury (see section 4.5).
Sodium
Piperacillin/Tazobactam 4 g/0.5 g contains approximately 216 mg of sodium per vial, equivalent to 10.8% of the WHO recommended daily intake of 2 g for an adult.
This should be taken into consideration for patients who are on a controlled sodium diet.
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 mechanisms of 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.
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, serum levels of methotrexate should be monitored in patients to avoid substance toxicity.
Probenecid
As with other penicillins, concurrent administration 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
Studies have detected an increased incidence of acute kidney injury in patients concomitantly administered piperacillin/tazobactam and vancomycin as compared to vancomycin alone (see section 4.4). Some of these studies have reported that the interaction is vancomycin dose-dependent. 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 therapy.
A number of chemical urine 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 Aspergillus EIA tests may lead to false-positive results for patients receiving piperacillin/tazobactam.
Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported.
Positive test results for the assays listed above in patients receiving piperacillin/tazobactam should be confirmed by other diagnostic methods.
Pregnancy
There are no or a limited amount of data from the use of piperacillin/tazobactam in pregnant women.
Studies in animals have shown developmental toxicity, 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 human milk; tazobactam concentrations 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).
No studies on the effect on the ability to drive and use machines have been performed.
The most commonly reported adverse reaction is diarrhoea (occurring in 1 patient out of 10).
Among the most serious adverse reactions pseudo-membranous colitis and toxic epidermal necrolysis occur in 1 to 10 patients in 10,000. The frequencies for pancytopenia, anaphylactic shock and Stevens-Johnson syndrome cannot be estimated from the currently available data.
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
Very common
(≥ 1/10)
Common
(≥ 1/100 to < 1/10)
Uncommon
(≥ 1/1,000 to < 1/100)
Rare
(≥ 1/10,000 to < 1/1,000)
Frequency not known (cannot be estimated from available data)
Infections and infestations
candida infection*
pseudo-membranous colitis
Blood and lymphatic system disorders
thrombocytopenia, anaemia*
leukopenia
agranulocytosis
pancytopenia*, neutropenia, haemolytic anaemia*, thrombocytosis*eosinophilia*,
Immune system disorders
anaphylactoid shock*, anaphylactic shock*, anaphylactoid reaction*, anaphylactic reaction*, hypersensitivity*
Metabolism and nutrition disorders
hypokalaemia
Psychiatric disorders
insomnia
delirium*
Nervous system disorders
headache
seizure*
Vascular disorders
hypotension, phlebitis, thrombophlebitis, flushing
Respiratory, thoracic and mediastinal disorders
epistaxis
eosinophilic pneumonia
Gastrointestinal disorders
diarrhoea
abdominal pain, vomiting, constipation, nausea, dyspepsia
stomatitis
Hepatobiliary disorders
hepatitis*, jaundice
Skin and subcutaneous tissue disorders
rash, pruritus
erythema multiforme*, urticaria, rash maculo-papular*
toxic epidermal necrolysis*
Stevens-Johnson syndrome*, dermatitis exfoliative, drug reaction with eosinophilia and systemic symptoms (DRESS)*, acute generalised exanthematous pustulosis (AGEP)*, dermatitis bullous, purpura
Musculoskeletal and connective tissue disorders
arthralgia, myalgia
Renal and urinary disorders
renal failure, tubulointerstitial nephritis*
General disorders and administration site conditions
pyrexia, injection site reaction
chills
Investigations
alanine aminotransferase increased, aspartate aminotransferase increased, protein total decreased, blood albumin decreased, Coombs direct test positive, blood creatinine increased, blood alkaline phosphatase increased, blood urea increased, activated partial thromboplastin time prolonged
blood glucose decreased, blood bilirubin increased, prothrombin time prolonged
Investigations
* ADR identified post marketing
Piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.
Beta-lactam antibiotic class effects
Beta-lactam antibiotics, including piperacillin/tazobactam, may lead to manifestations of encephalopathy and convulsions (see section 4.4).
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
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's clinical presentation.
Excessive serum concentrations of either piperacillin or tazobactam may be reduced by haemodialysis (see section 4.4).
Ask anything about Piperacillin/Tazobactam 4 g/0.5 g powder for solution for infusion. The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
Answers come from the patient leaflet published on the electronic medicines compendium (emc). They are not medical advice. Ask a pharmacist or your GP if you are unsure. For urgent help call NHS 111, or 999 in an emergency.
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