Tazopen

Piperacillin sodium, tazobactam sodium.

Each vial contains: Piperacillin (as sodium) USP 2 g, Tazobactam (as sodium) 250 mg.
Each vial contains: Piperacillin (as sodium) USP 4 g, Tazobactam (as sodium) 500 mg.
Piperacillin and Tazobactam Sodium is a white to off-white, odorless, bitter in taste, very hygroscopic. An injectable antibacterial combination product consisting of the semisynthetic antibiotic piperacillin sodium and the (beta)-lactamase inhibitor tazobactam sodium for intravenous administration.

Pharmacology: Pharmacokinetics: Piperacillin and Tazobactam is not absorbed from the gastrointestinal tract. It is well absorbed after intramuscular administration, peak plasma concentrations of 30 to 50 μg per mL being observed 30 to 50 minutes after a dose of 2 g. The pharmacokinetics of Piperacillin and Tazobactam Sodium are reported to be nonlinear and dose-dependent. The plasma half-life is about one hour, but is prolonged in neonates. In patients with severe renal insufficiency there may be a threefold increase in half-life; in those with end stage renal failure half-lives of 4 to 6 hours have been reported, and in those with both renal and hepatic impairment much longer half-lives may result. About 20% of Piperacillin and Tazobactam Sodium in the circulation is bound to plasma proteins.
Piperacillin is widely distributed in body tissues and fluids. It crosses the placenta into fetal circulation and small amounts are distributed into breast milk. There is little diffusion into the CSF except when the meninges are inflamed.
About 60 to 80% of a dose is excreted unchanged in the urine by glomerular filtration and tubular secretion within 24 hours, achieving high concentrations. High concentrations are also found in the bile and about 20% of a dose may be excreted by this route.
Plasma concentration are enhanced if probenecid is administered concomitantly.
Piperacillin with tazobactam: The pharmacokinetics of piperacillin do not appear to be altered by the co-administration of tazobactam, but piperacillin reduces the renal clearance of tazobactam.

Piperacillin and Tazobactam Sodium is indicated for the treatment of patients with moderate to severe infections caused by penicillin-resistant, piperacillin/tazobactam-susceptible, (beta)-lactamase producing strains of the designated microorganisms in the specified conditions listed as follows: Appendicitis (complicated by rupture or abscess) and peritonitis caused by piperacillin-resistant, (beta)-lactamase producing strains of Escherichia coli or the following members of Bacteroides fragilis group: B. fragilis, B. ovatus, B. thetaiotamicron, or B. vulgatus.
Uncomplicated and complicated skin and skin structure infections, including cellulitis, cutaneous abscesses and ischemic/diabetic foot infections caused by piperacillin-resistant, (beta)-lactamase producing strains of Staphylococcus aureus.
Postpartum endometritis or pelvic inflammatory disease caused by piperacillin-resistant, (beta)-lactamase producing strains of Escherichia coli.
Community-acquired pneumonia (moderate severity only) caused by piperacillin-resistant, (beta)-lactamase producing strains (Haemophilus influenzae).
Nosocomial pneumonia (moderate to severe) caused by piperacillin-resistant, (beta) lactamase producing strains of Staphylococcus aureus.

Piperacillin and Tazobactam sodium should be administered by intravenous route over 30 minutes.
Renal Insufficiency: In patients with renal insufficiency (Creatinine Clearance < 90 mL/min), the intravenous dose of Piperacillin and Tazobactam Sodium should be adjusted to the degree of actual renal function impairment.
In patients with nosocomial pneumonia receiving concomitant aminoglycoside therapy, the aminoglycoside dosage should be adjusted according to the recommendations of the manufacturer.
Dosage Recommendation: For All Indication Including Nosocomial Pneumonia: See table.

Click on icon to see table/diagram/image

Hemodialysis: The maximum dose is 2 g/250 mg Piperacillin and Tazobactam Sodium every eight hours. In addition, because hemodialysis removes 30% to 40% of a Piperacillin and Tazobactam Sodium in four hours, one additional dose of 750 mg Piperacillin and Tazobactam Sodium should be administered following each dialysis period.
Duration of Therapy: The usual duration of Piperacillin and Tazobactam Sodium treatment is from seven to ten days. However, the recommended duration of Piperacillin and Tazobactam Sodium treatment of nosocomial pneumonia is seven to fourteen days. In all conditions, the duration of therapy should be guided by the severity of the infection and the patient's clinical and bacteriologist progress.
Intravenous Administration: 4 g/500 mg vial should be reconstituted with 20 mL of Water for Injection.
2 g/250 mg vial should be reconstituted with 10 mL of Water for Injection.
Reconstituted Solution can be further diluted in a compatible intravenous diluent, Bacteriostatic Water for Injection or Bacteriostatic Sodium Chloride Injection (with parabens or benzyl alcohol) (recommended volume per dose 50-150 mL). Single dose vial should be used immediately after reconstitution. Discard any unused portion.

Information on overdosage of Piperacillin and Tazobactam Sodium in humans is not available.
Excessive serum levels of either piperacillin or tazobactam may be reduced by hemodialysis. No specific antidote is known.

Piperacillin and Tazobactam Sodium is contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins, or (beta)-lactamase inhibitors.

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity. If an allergic reactions occur, piperacillin and tazobactam sodium should be discontinued and appropriate therapy instituted. Serious anaphylactic reactions required immediate emergency treatment with epinephrine, oxygen, intravenous steroids and airway management, including intubation, should also be administered as indicated.

General: Bleeding manifestation have occurred in some patients receiving (beta)-lactam antibiotics, including piperacillin. These reactions have sometimes 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 occurs Piperacillin and Tazobactam Sodium should be discontinued and appropriate therapy instituted.
As with other penicillins, patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given intravenously.
This should be considered when treating patients requiring restricted salt intake. Periodic electrolyte determinations should be performed in patients with low potassium reserves, and the possibility of hypokalemia should be kept in mind with patients who have potentially low potassium reserves, and who are receiving cytotoxic therapy diuretics.
Use in Pregnancy: Reproduction studies have been performed in rats and have revealed no evidence of impaired fertility due to piperacillin/tazobactam administered up to a dose which is similar to the maximum recommended human daily dose based on body-surface area (mg/m²).
Use in Lactation: Piperacillin is excreted in low concentrations in human milk; tazobactam concentrations in human milk have not been studied. Caution should be exercised when Piperacillin and Tazobactam Sodium is administered to a nursing woman.
Use in Children: Safety and efficacy in pediatric patients have not been established.
Use in the Elderly: Patients over 65 years are not at increased risk of developing adverse effects solely because of age. However, dosage should be adjusted in the presence of renal insufficiency.

Use in Pregnancy: Reproduction studies have been performed in rats and have revealed no evidence of impaired fertility due to piperacillin/tazobactam administered up to a dose which is similar to the maximum recommended human daily dose based on body-surface area (mg/m²).
Use in Lactation: Piperacillin is excreted in low concentrations in human milk; tazobactam concentrations in human milk have not been studied. Caution should be exercised when Piperacillin and Tazobactam Sodium is administered to a nursing woman.

Autonomic nervous system: hypotension, ileus, syncope.
Body as a whole: rigors, back pain, malaise, [asthenia, chest pain].
Cardiovascular: tachycardia, including supraventricular and ventricular; bradycardia; arrhythmia, including atrial fibrillation, ventricular fibrillation, cardiac failure, circulatory failure, myocardial infarction, [angina].
Central nervous system: tremor, convulsions, vertigo.
Gastrointestinal: melena, flatulence, hemorrhage, gastritis, hiccough, ulcerative stomatitis, [fecal incontinence, gastric ulcer, pancreatitis].
Pseudomembranous colitis was reported in one patient during the clinical trials. The onset pseudomembranous colitis symptoms may occur during or after antibacterial treatment.
Hearing and Vestibular System: tinnitus, [deafness, earache].
Hypersensitivity: anaphylaxis.
Metabolic and Nutritional: symptomatic hypoglycemia, thirst, [gout, vitamin B₁₂ deficiency anemia].
Musculoskeletal: myalgia, arthralgia.
Platelet, Bleeding, Clotting: mesenteric embolism, purpura, epistaxis, pulmonary embolism, [ecchymosis, hemoptysis]
Psychiatric: confusion, hallucination, depression.
Reproductive, Female: leucorrhea, vaginitis, [perineal irritation/pain].
Reproductive, Male: [balanoposthitis].
Respiratory: pharyngitis, pulmonary edema, bronchospasm, coughing, [atelectasis, dyspnea, hypoxia].
Skin and Appendages: genital pruritus, diaphoresis, [conjunctivitis, xerosis].
Special senses: taste perversion.
Urinary: retention, dysuria, oliguria, hematuria, incontinence, [urinary tract infection with trichomonas, yeast in urine].
Vision: photophobia.
Vascular (extracardiac): flushing, [cerebrovascular accident].
Gastrointestinal: hepatitis, cholestatic jaundice.
Hematologic: hemolytic anemia.
Renal: rarely, interstitial nephritis.

Aminoglycosides: The mixing of Piperacillin and Tazobactam Sodium with an aminoglycosides in vitro can result in substantial inactivation of the aminoglycoside should be reconstituted and administered separately.
Probenecid: Probenecid administered concomitantly with Piperacillin and Tazobactam Sodium prolongs the half-life of piperacillin by 21% and that of tazobactam by 71%.
Vancomycin: No pharmacokinetic interactions have been noted between Piperacillin and Tazobactam Sodium and vancomycin.
Heparin: Coagulation parameters should be tested more frequently and monitored regularly during simultaneous administration of high doses of heparin, oral anticoagulants, or other drugs that may affect the blood coagulation system or the thrombocyte function.
Vecuronium: Piperacillin when used concomitantly with vecuronium has been implicated in the prolongation of the neuromuscular blockade of vecuronium.

Store at temperatures not exceeding 30°C.

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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