APR TAXTEC

INFORMATION FOR THE USER

Piperacillin 4,000mg and Tazobactam 500mg Injection

Read all of this information carefully before you start taking this medicine because it contains important information for you.
• Keep this information. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine is prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this information.

1. COMPOSITION:
Each vial contains:
Piperacillin –4,000mg
Tazobactam – 500mg

For Intravenous use only.

2. DESCRIPTION:
Piperacillin is a broad-spectrum antibiotic that us useful against a wide variety of infections. Tazobactam is a drug that inhibits the enzyme beta lactamase which is responsible for breaking down piperacillin thereby extending its spectrum and preventing resistance.

3. PHARMACOLOGICAL 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 an inhibitor of many beta-lactamases, which commonly cause resistance to penicillins and cephalosporins. It extends the antibiotic spectrum of piperacillin to include many beta-lactamase-producing bacteria that have acquired resistance to piperacillin alone.

4. CLINICAL PHARMACOKINETICS:
The peak piperacillin & tazobactam concentrations after 4 g/0.5 g administered over 30 minutes by IV infusion are 298 μg/ml and 34 μg/ml respectively.Both piperacillin & tazobactam are approximately 30% bound to plasma proteins. The protein binding of piperacillin/tazobactam is unaffected by the presence of the other compound. It is widely distributed in tissues & body fluids, including intestinal mucosa, gallbladder, lungs, bile & bone. Mean tissue concentrations are generally 50-100% of those in plasma. Distribution into CSF is low in subjects with non-inflamed meninges.Piperacillin is metabolised to a minor microbiologically active desethyl-metabolite. Tazobactam is metabolised to a single metabolite that has been found to be microbiologically inactive.Piperacillin & Tazobactam are eliminated via the kidneys by glomerular filtration & tubular secretion. Piperacillin is excreted rapidly as unchanged substance with 68% of the administered dose appearing in the urine. Tazobactam & its metabolite are eliminated primarily by renal excretion, with 80 % of the administered dose appearing as unchanged substance & the remainder as the single metabolite. Piperacillin, tazobactam &desethylpiperacillin are also secreted in the bile. Following single or multiple doses of piperacillin/tazobactam, the plasma half-life of piperacillin & tazobactam ranged from 0.7-1.2 hours & was unaffected by dose/duration of infusion. The elimination half-lives of both piperacillin & tazobactam are increased with decreasing renal clearance.There are no significant changes in piperacillin pharmacokinetics due to tazobactam. Piperacillin appears to slightly reduce the clearance of tazobactam.
5. INDICATIONS:
Piperacillin/Tazobactam injection is indicated for:
a. Adults & adolescents:
• Severe pneumonia including hospital-acquired & ventilator-associated pneumonia
• Complicated urinary tract infections (including pyelonephritis)
• Complicated intra-abdominal infections
• Complicated skin & 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.
• May be used in the management of neutropenic patients with fever suspected to be due to a bacterial infection.
b. Children aged 2-12 years:
• Complicated intra-abdominal infections
• May be used in the management of neutropenic children with fever suspected to be due to a bacterial infection.

6. CONTRAINDICATIONS:
Piperacillin/Tazobactam is contraindicated in:
• Hypersensitivity to the active substances or any other penicillin-antibacterial agent.
• History of acute severe allergic reaction to any other beta-lactam active substances

7. WARNINGS AND PRECAUTIONS:
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 treatment careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, other beta-lactam agents (e.g cephalosporins) & other allergens. Serious& occasionally hypersensitivity (anaphylaxis) reactions have been reported in patients receiving treatment with 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& may require administration of epinephrine & other emergency measures.
Serious skin reactions, such as Stevens-Johnson syndrome have been reported in patients receiving piperacillin tazobactam. If patients develop a skin rash they should be monitored closely & Piperacillin/Tazobactam discontinued if lesions progress.
Antibiotic-induced colitis may be manifested by severe, persistent diarrhoea. The onset of colitis symptoms may occur during or after antibacterial treatment. In these cases treatment, should be discontinued.
Therapy may result in the emergence of resistant organisms, which might cause superinfections.
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 & are more likely to occur in patients with renal failure. If bleeding manifestations occur, treatment should be discontinued & appropriate therapy instituted.
Leukopenia & neutropenia may occur, especially during prolonged therapy.Periodic assessment of haematopoietic function should be performed.
Neurological complications in the form of convulsions may occur when high doses are administered, especially in patients with impaired renal function.
Each vial contains 9.39 mmol (216 mg) of sodium. This should be taken into consideration by patients on a controlled sodium diet.
Hypokalaemia may occur in patients with low potassium reserves or those receiving concomitant medicinal products that may lower potassium levels; periodic electrolyte determinations should be performed in such patients.

8. ADVERSE EFFECTS:
Common side effects include:
• Candidal superinfection
• Leukopenia, neutropenia, thrombocytopenia
• Hypersensitivity
• Headache, insomnia
• Hypotension, thrombophlebitis, phlebitis
• Diarrhea, nausea, vomiting
• Rash including maculopapular rash
• Injection site reactions
9. DRUG INTERACTIONS:
Non-depolarising muscle relaxants: Neuromuscular blockade produced by any of the non-depolarising muscle relaxants could be prolonged in the presence of piperacillin.
Oral anticoagulants: Appropriate coagulation tests should be performed more frequently and monitored regularly.
Methotrexate: May reduce the excretion of methotrexate. Serum levels should be monitored in patients to avoid toxicity.
Probenecid: Produces a longer half-life & lower renal clearance of piperacillin & tazobactam; however peak plasma concentrations of either active substance are unaffected.
10. DOSAGE:
The usual dose is 4g piperacillin/0.5g tazobactam given every 8 hours.
For nosocomial pneumonia & bacterial infections in neutropenic patients recommended dose is 4g piperacillin/0.5g tazobactam every 6 hours. Also be applicable to patients with other indicated infections when particularly severe.
11. ADMINISTRATION:
For Intravenous infusion use only.
Administration to be done by a registered medical practitioner/nurse in a proper sterile and hospital setting only.
12. PRESENTATION:
13. STORAGE:
Store below 25°C in a cool and dry pace. Protect from direct sunlight. Keep away from the reach of children.

Do not freeze.

14. MANUFACTURED BY:
15. MARKETED BY:

This information was last revised on May 2019.