Piptam

Each vial contains Piperacillin sodium equivalent to Piperacillin 4 g per vial; Tazobactam sodium equivalent to Tazobactam 0.5 g per vial.
(Ratio of Piperacillin:Tazobactam; 8:1).
Each vial of PIPTAM 4.5 G INJECTION (Piperacillin 4 g/Tazobactam 0.5 g) contains 9.82 mmol (226 mg) of sodium.

Pharmacology: Pharmacodynamics: Piperacillin sodium, a broad spectrum, semisynthetic penicillin active against many gram-positive and gram-negative aerobic and anaerobic bacteria. Piperacillin sodium is bactericidal; the drug inhibits bacterial cell wall synthesis by binding to one or more of penicillin binding proteins (PBPs); which turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls.
Tazobactam sodium inhibits many β-lactamases, including staphylococcal penicillinase. Tazobactam is a β-lactamase inhibitor and synergistically expands the spectrum of activity of Piperacillin sodium against β-lactamase-producing bacteria by irreversibly and completely inhibiting β-lactamase.
Piperacillin/Tazobactam are active in vitro against the following bacteria.
Gram-negative bacteria: Acinetobacter baumannii, Citrobacter koseri, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Morganella morganii, Moraxella catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, Salmonella enterica, Serratia marcescens.
Gram-positive bacteria: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans.
Anaerobic bacteria: Bacteroides spp, Clostridium perfringens.
Pharmacokinetics: Peak plasma concentration of Piperacillin/Tazobactam are attained immediately after completion of IV infusion.
Piperacillin plasma concentrations attained with the fixed-combination preparation of Piperacillin/Tazobactam are similar to those attained with equivalent doses of Piperacillin administered alone.
Both Piperacillin and Tazobactam are widely distributed into tissues and body fluid, including intestinal mucosa, gallbladder, lung, female reproductive tissues (uterus, ovary, fallopian tube), interstitial fluid, bile, and cross the placenta. Piperacillin is distributed into milk. Low concentrations of Piperacillin/Tazobactam are distributed into CSF. Both Piperacillin and Tazobactam are approximately 30% bound to plasma proteins in adults.
Piperacillin is metabolized to a minor microbiological active desethyl metabolite. Tazobactam is metabolized to a single metabolite that lacks pharmacologic and antibacterial activity.
In adults, 68% of a Piperacillin dose is eliminated unchanged in the urine, 10-20% in feces and 80% of a Tazobactam dose is eliminated unchanged in the urine, half-lives of Piperacillin and plasma half-lives of Tazobactam range from 0.7-1.2 hours, the half-lives of Piperacillin/Tazobactam are increased by approximately 25% and 18% respectively with cirrhosis. In the renal impairment half-lives of Piperacillin/Tazobactam increase with decreasing creatinine clearance.

PIPTAM 4.5 G INJECTION is indicated for the treatment of the following systemic and/or local bacterial infections caused by susceptible organisms have been detected or are suspected: Lower respiratory tract infections; Complicated and uncomplicated urinary tract infections; Intra-abdominal infections; Skin and skin structure infections; Gynecological infections including postpartum endometritis and pelvic inflammatory disease (PID); Bacterial septicemia.
PIPTAM 4.5 G INJECTION is indicated for polymicrobial infections including those where aerobic and anaerobic organisms are suspected (intra-abdominal, skin and skin structure, lower respiratory tract).
PIPTAM 4.5 G INJECTION, in combination with an aminoglycoside, is indicated for the management of neutropenic adults or children.
In hospitalized children 2 to 12 years of age, PIPTAM 4.5 G INJECTION is indicated for treatment of Intra-abdominal infections (including appendicitis complicated by rupture or abscess, peritonitis and biliary infections). It has not been evaluated in this indication for pediatric patients below the age of 2 years.
Infections caused by Piperacillin susceptible organisms are also amenable to PIPTAM 4.5 G INJECTION treatment due to its Piperacillin content. Therefore, the treatment of mixed infections caused by both Piperacillin-susceptible organisms and β-lactamase-producing organisms susceptible to PIPTAM 4.5 G INJECTION should not require the addition of another antibiotic.
PIPTAM 4.5 G INJECTION is particularly useful in the treatment of mixed infections and in the empiric treatment prior to the availability of the results of sensitivity tests because of its broad spectrum of activity.
PIPTAM 4.5 G INJECTION acts synergistically with aminoglycosides against certain strains of Pseudomonas aeruginosa. Combined therapy has been successful, especially in patients with impaired host defences. Both drugs should be used in full therapeutic doses. As soon as results of culture and susceptibility test become available, antimicrobial therapy should be adjusted if necessary.

Mode of administration: PIPTAM 4.5 G INJECTION given by slow intravenous infusion over 30 minutes or slow intravenous injection over 3-5 minutes.
Reconstitution direction for IV injection: Reconstituted PIPTAM 4.5 G INJECTION with one of diluents below 20 mL: 0.9% sodium chloride for injection, sterile water for injection, 5% dextrose injection.
Shake until dissolved. When swirled constantly, reconstitution generally occurs within 5 to 10 minutes.
Solution obtained clear and free from undissolved particles. Intravenous injection should be given over 3-5 minutes.
Reconstitution direction for IV infusion: Reconstituted PIPTAM 4.5 G INJECTION with 20 mL of sterile water for injection then diluted further to the desired volume (50 mL to 150 mL) with one of compatible diluents as follows: 0.9% sodium chloride for injection, sterile water for injection*, 5% dextrose injection.
Shake until dissolved, solution obtained clear and free from undissolved particles and intravenous injection should be given not less than 30 minutes.
* Maximum recommended volume of sterile water for injection per dose is 50 mL.
Avoid administered with aminoglycosides and physical incompatible drug with PIPTAM 4.5 G INJECTION.
Aseptic technique must be used to reduce the risk of contamination during reconstitution. Do not store any unused portion of the IV infusion solution for reuse.
Should be inspected visually for particulate matter or discoloration prior to administration whenever solution and container permit. Solution of Piperacillin/Tazobactam must be clear before administration.
Do not use the same equipment for injection with PIPTAM 4.5 G INJECTION and other medicine and should not be added to blood products or albumin hydrolysates.
Stability after reconstitution: Before reconstitution, store below 30°C. Use single-dose vials immediately after reconstitution.
For solution 20 mL after reconstitution, please follow these: Stable not more than 24 hours store between 20-30°C.
Stable not more than 48 hours store between 2-8°C.
Do not freeze vial after reconstitution.
For diluted solutions (50 mL or 150 mL) in the IV bags, please follow these: Stable not more than 24 hours store between 20-30°C.
Stable not more than 1 week store between 2-8°C.
Recommended dose: Adult and children receiving the adult dosage (weighing greater than 40 kg): The usual dosage of Piperacillin/Tazobactam recommended for adults is 4.5 g (4 g of Piperacillin and 0.5 g of Tazobactam) every 8 hours. For hospital-acquired pneumonia and bacterial infections in neutropenic patients, the recommended dose is 4.5 g (4 g of Piperacillin and 0.5 g of Tazobactam) every 6 hours; maximum: 18 g/day.
Recommended dosage for children patients 2-12 years of age with normal renal function: See Table 1.

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The usual duration of Piperacillin/Tazobactam therapy is 7-10 days (for hospital-acquired pneumonia; 7-14 days). Duration should be based on the severity of the infection and the patient's clinical and bacteriologic progress. For most acute infection, therapy should be continued for at least 48-72 hours after the patient becomes asymptomatic or evidence of eradication of the infection is obtained.
Elderly: Use the same dose level as adults except in cases of renal impairment.
Dosage for patient with renal impairment: Adult: Use dosage recommendation as follows: See Table 2.

Click on icon to see table/diagram/image

For patients on hemodialysis, the maximum daily dose is 8 g/1 g Piperacillin/Tazobactam. In addition, because hemodialysis removes 30%-50% of Piperacillin in 4 hours, one additional dose of 2 g/250 mg Piperacillin/Tazobactam should be administered following each dialysis period.
Children aged 2-12 years: Use dosage recommendation as follows: See Table 3.

Click on icon to see table/diagram/image

For children on hemodialysis, one additional dose of 40 mg/5 mg Piperacillin/Tazobactam /kg should be administered following each dialysis period.
Co-administration of Piperacillin/Tazobactam with aminoglycosides: Because of the in vitro inactivation of the aminoglycoside by β-lactam antibiotics, Piperacillin/Tazobactam and aminoglycoside are recommended for separated administration. Piperacillin/Tazobactam and aminoglycoside should be reconstituted, diluted, and administered separately when concomitant therapy with aminoglycosides is indicated.
Hepatitis patients: Not necessitate a change in Piperacillin/Tazobactam dosage in patients with hepatitis impairment and should monitor hepatitis enzyme.

Overdose can result in nausea, vomiting and diarrhea. The same has also been reported with the usual recommended dosages. Patients may experience neuromuscular hyperexcitability or convulsion if higher than recommended doses are given intravenously (particularly in the presence of renal failure).
No specific antidote is known. Treatment should be supportive and symptomatic according to the patient's clinical presentation. Excessive serum concentrations of either Piperacillin/Tazobactam may be reduced by hemodialysis.

Hypersensitivity to any of β-lactams (including penicillins, cephalosporins and β-lactamase inhibitors) or any component of the formulation.

Contraindicated in those who are allergic.
Drugs can cause allergic and life-threatening.
If rash irritation or swelling occurred stop using the drug and seek medical advice.

Hepatic, renal and hematologic systems should be evaluated periodically during prolonged therapy with Piperacillin/Tazobactam; monitoring hematopoietic function is especially important when the duration of therapy is 21 days or longer.
Serum electrolytes should be monitored when Piperacillin/Tazobactam is used in patients with low potassium reserves, and the possibility of hypokalemia should be considered when the drug is used in patients who have potentially low potassium reserves and who are receiving concomitant medications that may lower potassium levels.
Piperacillin/Tazobactam should be considered when the drug is administered to patients whose sodium intake is a restriction.
The diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued (CDAD, also known as antibiotic associated diarrhea and colitis or pseudomembranous colitis); however it is important to contact a clinician if watery and bloody stools occur during or as late as 2 months or longer after the last dose.
Bleeding complications could occur during therapy with Piperacillin/Tazobactam, especially when the drug is used in patients with renal impairment. If bleeding manifestations occur, the drug should be discontinued.
Piperacillin/Tazobactam should only be used to treat bacterial infections and not used to treat viral infection.
Patients also should be advised about the importance of completing the full course of therapy, skipping dose or not completing therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with Piperacillin/Tazobactam or other antibacterials in the future.
Use of anti-infective agents, with Piperacillin/Tazobactam may result in overgrowth of nonsusceptible organisms. If superinfection occurs the drug should be discontinued and appropriate therapy initiated.
Serum concentrations of Piperacillin/Tazobactam are higher and prolonged in patients with renal impairment, dose and/or frequency of administration of Piperacillin/Tazobactam should be decreased.
Prior to initiation of therapy with Piperacillin sodium and Tazobactam sodium should be a concern because there is clinical and laboratory evidence of partial cross-allergenicity among penicillin and other β-lactam antibiotic.
Leukopenia and neutropenia may occur; appears to be reversible and most frequently associated with prolonged administration, monitoring recommended.
High doses of Piperacillin/Tazobactam are administered, neurological complications in the form of convulsions may occur.
Serious skin reactions, including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalized exanthematous, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. If a skin rash develops, monitor closely. Discontinue if lesions progress.

Reproduction studies in mice and rats using various combinations of Piperacillin and Tazobactam have not revealed evidence of harm to the fetus. In addition, studies in mice and rats using Piperacillin alone or Tazobactam alone have not revealed evidence of harm to the fetus.
Piperacillin and Tazobactam both cross the placenta. There are no adequate or controlled studies using Piperacillin or Tazobactam alone or Piperacillin and Tazobactam in pregnant women so the drug should be used during pregnancy only when clearly needed.
Because Piperacillin is distributed into milk in low concentrations and because it is not known whether Tazobactam is distributed into milk, Piperacillin/Tazobactam should be used with caution in nursing women.

Gastrointestinal: diarrhea, nausea, constipation, vomiting, dyspepsia, abdominal pain, ulcerative stomatitis and pseudomembranous colitis (antibiotic associated diarrhea).
Dermatologic and sensitivity reactions: rash (maculopapular, bullous, urticaria), pruritus, hypersensitivity reaction, anaphylaxis, erythema multiforme, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms.
Hematologic: decreased hemoglobin, decreased hematocrit, thrombocytopenia, increase in platelet count, transient eosinophilia, transient leukopenia, neutropenia, agranulocytosis, prolonged prothrombin time and prolonged partial thromboplastin time.
Neurologic: headache, insomnia, dizziness, anxiety, tremor, seizures, vertigo and confusion.
Renal, Electrolyte and Genitourinary: increases serum concentration of creatinine and BUN, proteinuria, intestinal nephritis, renal failure and hypokalemia.
Hepatic: increases AST (SGOT), ALT (SGPT), alkaline phosphatase and bilirubin.
Neuromuscular and skeleton: arthralgia and myalgia.
Infection: Candidiasis.
Local reactions: phlebitis, pain, inflammation, thrombophlebitis and edema.
Other Adverse Effects: fever, hypotension, chest pain, hypoglycemia, flushing and back pain.

Non-depolarizing muscle relaxants: prolonged neuromuscular blockade has been reported when vecuronium was used concomitantly with Piperacillin. Due to their similar mechanism of action.
Probenecid: prolongs the half-life of Piperacillin/Tazobactam by 21% and 71% respectively and lower renal clearance for both piperacillin and tazobactam. However, peak plasma concentrations of either drug are unaffected.
Methotrexate: Piperacillin may decrease renal clearance of methotrexate, frequent monitoring of serum methotrexate concentrations should be performed, and patients should be monitored for signs and symptoms of methotrexate toxicity.
Aminoglycosides: the antibacterial activity of Piperacillin and aminoglycosides is synergistic in vitro against some Enterobacteriaceae and Pseudomonas aeruginosa. Concomitant use of aminoglycosides and Piperacillin in patients with end stage renal disease (ESRD) requiring hemodialysis substantially alters serum concentrations of the aminoglycoside, should be closely monitoring serum concentration of aminoglycoside.
Anticoagulants: coagulation parameters should be monitored more frequently after concomitantly with high doses of heparin, oral anticoagulants, or other drugs that affect blood coagulant or thrombocyte function.
Vancomycin: the risk of vancomycin-induced nephrotoxicity may increase due to an interaction with Piperacillin/Tazobactam. No pharmacokinetic interactions have been reported between Piperacillin/Tazobactam and vancomycin.
Laboratory test interferences: Tests for urinary glucose: the administration of Piperacillin/Tazobactam may result in a false-positive reaction for glucose in the urine using a copper-reduction method. Glucose oxidase tests for urinary glucose are recommended.
Test for Aspergillus: False-positive test results for Aspergillus were reported when the Bio-Red Laboratories Platelia Aspergillus EIA in patients receiving Piperacillin/Tazobactam injection. Positive Platelia Aspergillus EIA test results in patients receiving Piperacillin/Tazobactam should be interpreted with caution and confirmed by other diagnostic methods.

Store below 30°C prior to reconstitution. Use single-dose vials immediately after reconstitution.
The stability condition of reconstituted or diluted solutions as mentioned in Stability after reconstitution under Dosage & Administration.

Penicillins

J01CR05 - piperacillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

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