Tazovex Special Precautions

Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid [including shock]) reactions have been reported in patients on penicillin/cephalosporin therapy. Although anaphylaxis is more frequent following parental therapy, it has occurred in patients on oral penicillin/cephalosporin. These reactions are more likely to occur in individual with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin/cephalosporin hypersensitivity who have experienced severe reactions when treated with either a penicillin or cephalosporin. Past history of a severe allergic reaction to penicillin/cephalosporin is a contraindication to the use of piperacillin and tazobactam for injection. Before initiating therapy with any penicillin/cephalosporin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillin, cephalosporin or other allergens. If an allergic reaction occurs, piperacillin and tazobactam for injection should be discontinued and the appropriate therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids and airway management, including intubations, should also be administered as indicated.
Antibiotic-associated pseudomembranous colitis has been reported with many antibiotics including piperacillin. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases appropriate with a suitable oral antibacterial agent effective against C. difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated. Drugs that delay peristalsis eg; opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used.
Leucopenia and neutropenia may occur, especially during prolonged therapy. Therefore, periodic assessment of hematopoietic function should be performed.
Use with caution in the following circumstances: Bleeding manifestations have occurred in some patients receiving piperacillin. These reactions have something 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.
The possibility of the emergence of resistant organisms that might cause super infection should be kept in mind, particularly during prolonged treatment. If this occurs, appropriate measures should be taken.
As with other penicillins, patients may experience neuromuscular excitability or convulsion if higher than recommended doses are given intravenously.
Repeated use of lignocaine as diluent should be avoid in patients with severe liver disease or decreased hepatic blood flow due to the possibility of lignocaine toxicity (resulting from decreased metabolism and accumulation).
Combined administration of β-lactamase inhibitors and β-lactam antibiotics may be associated with a slightly increased risk of hepatic adverse reactions. The incidence of increased liver enzymes in patients treated with piperacillin alone. The potential for increased hepatic adverse reactions should be borne in mind when using piperacillin and tazobactam for injection.
Check the following before use: Periodical assessment of organ system functions including renal, hepatic and hematopoietic during prolonged therapy (≥ 21 days) is advisable.
For patients with renal impairment and/or hepatic insufficiency, measurement of serum levels of piperacillin will provide guidance for adjusting dosage.
The theoretical sodium content of each 4.5 g vial of piperacillin and tazobactam for injection is 216 mg sodium (9.39 mmol). Which may increase a patient's overall sodium intake.
Periodical electrolyte determinations should be made 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 or diuretics.
Because of its poor penetration into the CSF, piperacillin is not advised in the treatment of meningitis and brain abscess.
Antimicrobials used in high doses for short periods to treat gonorrhea may mask or delay symptoms of incubating syphilis. Therefore, prior to treatment, patients with gonorrhea should also be evaluated for syphilis. Specimens for dark field examination should be obtained from patients with any suspected primary lesion and serological tests should be made for a minimum of 4 months.
Carcinogenicity, mutagenicity and impairment of fertility: Long term carcinogenicity studies of piperacillin and tazobactam for injection in animals have not been performed. Mutagenicity studies with piperacillin and tazobactam showed no evidence of genotoxicity in assays for chromosomal and DNA damage. One assay for gene mutation (Mouse lymphoma assay) was weakly positive at tazobactam and piperacillin and concentration ≥3200 μg/mL and 2500 μg/mL, respectively. Piperacillin and tazobactam did not affect the fertility of male or female rats.
Use in pregnancy: Pregnancy Category B 1.
Adequate human studies in the use of piperacillin and tazobactam for injection during pregnancy are not available. Limited studies with piperacillin alone in rats and mice revealed no teratogenic effect or harm to the fetus. Studies with tazobactam (doses up to 3000 mg/kg IV) or tazobactam and piperacillin (doses up to 750 mg/kg and 3000 mg/kg IV) in mice showed no evidence of teratogenicity or harm to the fetus. Studies in rats at these dose levels showed no evidence of teratogenicity though maternal toxicity, in the form of decreased weight gain, was noted at the dose levels tested. Piperacillin has been found to cross the placenta in rats. Pregnant women should be treated only if the expected benefit outweighs the possible risks to the pregnant woman and fetus.
Use in lactation: Adequate clinical studies on the use of piperacillin and tazobactam for injection during pregnancy are not available. Piperacillin is excreted in low concentrations in milk. In animal studies, both piperacillin and tazobactam were excreted in the milk of lactating rats. Women who are breast-feeding should be treated only of the expected benefit outweighs the possible risks to the woman and child.
Use in children: Safety and efficacy of the use of piperacillin and tazobactam for injection in children under the age of 2 years has not yet been established.