Pipracil Information
Pipracil (Piperacillin sodium)
Pipracil (Piperacillin sodium) Description
Pipracil (Piperacillin sodium) , sterile piperacillin sodium, is a semisynthetic broad-spectrum penicillin for parenteral use derived from D(-)-α-aminobenzylpenicillin. The chemical name of piperacillin sodium is sodium (2,5,6)-6-[()-2-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-2-phenylacetamido]-3,-3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate. The chemical formula is CHNNaOS, and the molecular weight is 539.54. Its structural formula is:
Piperacillin sodium powder is a white to off-white solid having the characteristic appearance of products prepared by freeze-drying. It is freely soluble in water and in alcohol. The pH of an aqueous solution containing 400 milligrams per milliliter ranges from 5.5 to 7.5. One g contains 1.85 mEq (42.5 mg) of sodium (Na).
Pipracil (Piperacillin sodium) Clinical Pharmacology
In healthy adult volunteers, mean serum piperacillin concentrations immediately after a two‑to three‑minute intravenous injection of 2, 4, or 6 g were 305, 412, and 775 μg/mL, respectively. Serum concentrations lack dose proportionality.
A 30-minute infusion of 6 g every 6 h gave, on the fourth day, a mean peak serum concentration of 420 μg/mL.
Pipracil (Piperacillin sodium) Microbiology
Piperacillin is an antibiotic which exerts its bactericidal activity by inhibiting both septum and cell wall synthesis. It is active against a variety of gram-positive and gram-negative aerobic and anaerobic bacteria. Piperacillin has been shown to be active against most strains of the following microorganisms, both and in clinical infections as described in the section.
The following data are available,
At least 90% of the following microorganisms exhibit anminimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for piperacillin. However, the safety and effectiveness of piperacillin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Pipracil (Piperacillin sodium) Indications And Usage
Uncomplicated Gonococcal Urethritis caused by
Pipracil (Piperacillin sodium) has also been shown to be clinically effective for the treatment of infections at various sites caused by species including and ; however, infections caused by these organisms are ordinarily treated with more narrow spectrum penicillins. Because of its broad spectrum of bactericidal activity against gram-positive and gram-negative aerobic and anaerobic bacteria, Pipracil (Piperacillin sodium) is particularly useful for the treatment of mixed infections and presumptive therapy prior to the identification of the causative organisms.
Also, Pipracil (Piperacillin sodium) may be administered as single drug therapy in some situations where normally two antibiotics might be employed.
Piperacillin has been successfully used with aminoglycosides, especially in patients with impaired host defenses. Both drugs should be used in full therapeutic doses.
Appropriate cultures should be made for susceptibility testing before initiating therapy and therapy adjusted, if appropriate, once the results are known.
The prophylactic use of piperacillin should be stopped within 24 hours, since continuing administration of any antibiotic increases the possibility of adverse reactions, but in the majority of surgical procedures, does not reduce the incidence of subsequent infections. If there are signs of infection, specimens for culture and susceptibility testing should be obtained for identification of the causative microorganism so that appropriate therapy can be instituted.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Pipracil (Piperacillin sodium) and other antibacterial drugs, Pipracil (Piperacillin sodium) should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Pipracil (Piperacillin sodium) Contraindications
Pipracil (Piperacillin sodium) is contraindicated in patients with a history of allergic reactions to any of the betalactams, including penicillins and/or cephalosporins.
Pipracil (Piperacillin sodium) Warnings
SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC/ANAPHYLACTOID) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS 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 HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH Pipracil (Piperacillin sodium) , CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, Pipracil (Piperacillin sodium) SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of , and surgical evaluation should be instituted as clinically indicated.
Pipracil (Piperacillin sodium) Precautions
Bleeding manifestations have occurred in some patients receiving β-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 occur, the antibiotic should be discontinued and appropriate therapy instituted.
The possibility of the emergence of resistant organisms which might cause superinfections 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 convulsions if higher than recommended doses are given intravenously.
Pipracil (Piperacillin sodium) is a monosodium salt containing 1.85 mEq of Na per g (42.5 mg of Na per g). This should be considered when treating patients requiring restricted salt intake. Periodic 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.
Leukopenia and neutropenia may occur during prolonged therapy.
As with other semisynthetic penicillins, Pipracil (Piperacillin sodium) therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.
Prescribing Pipracil (Piperacillin sodium) in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Patients should be counseled that antibacterial drugs including Pipracil (Piperacillin sodium) should only be used to treat bacterial infections. They do not treat viral infections (eg, the common cold). When Pipracil (Piperacillin sodium) is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Pipracil (Piperacillin sodium) or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of antibiotic. If this occurs, patients should contact their physician as soon as possible.
While piperacillin possesses the characteristic low toxicity of the penicillin group of antibiotics, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy is advisable.
All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with piperacillin should have a follow-up serologic test for syphilis after 3 months.
As with other penicillins, the administration of Pipracil (Piperacillin sodium) may result in a false-positive reaction for glucose in the urine using a copper-reduction method. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.
There have been reports of positive test results using the Bio-Rad Laboratories Platelia EIA test in patients receiving piperacillin/tazobactam injection who were subsequently found to be free of infection. Cross-reactions with non- polysaccharides and polyfuranoses with the Bio-Rad Laboratories Platelia EIA test have been reported.
Therefore, positive test results in patients receiving piperacillin should be interpreted cautiously and confirmed by other diagnostic methods.
Safety and effectiveness in pediatric patients have not been established.
Data from published pharmacokinetics studies indicate that the elimination half-life of piperacillin in neonates is twofold to fourfold longer than that seen in pediatric patients 1 month of age and above as well as in adults. In infants, children, and adolescents, the elimination half-life of piperacillin is shorter than that observed in adults. As in adults, the elimination of piperacillin is decreased in pediatric patients with renal impairment. (See .)
Clinical studies of Pipracil (Piperacillin sodium) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Pipracil (Piperacillin sodium) contains 42.5 mg (1.85 mEq) of sodium per gram. At the usual recommended doses, patients would receive between 255 and 765 mg/day (11.1 and 33.3 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. The total sodium content from dietary and non-dietary sources may be clinically important with regard to such diseases as congestive heart failure.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Pipracil (Piperacillin sodium) Adverse Reactions
Pipracil (Piperacillin sodium) is generally well tolerated. The most common adverse reactions have been local in nature, following intravenous or intramuscular injection. The following adverse reactions may occur:
Rash was noted in 1% of patients. Other less frequent findings included pruritus, vesicular eruptions, and positive Coombs tests.
Other dermatologic manifestations, such as erythema multiforme, urticaria, toxic epidermal necrolysis and Stevens-Johnson syndrome, have been reported.
Piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.
Pipracil (Piperacillin sodium) Overdosage
There is no specific information on overdose with Pipracil (Piperacillin sodium) . Other penicillin-class drugs in overdosage, however, have the potential to cause neuromuscular hyperirritability or convulsive seizures. In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required. Piperacillin can be removed by hemodialysis but not peritoneal dialysis.
Pipracil (Piperacillin sodium) Dosage And Administration
Pipracil (Piperacillin sodium) may be administered by the intramuscular route (see NOTE) or intravenously as a three- to five-minute intravenous injection or as a 20- to 30-minute infusion. The usual dosage of Pipracil (Piperacillin sodium) for serious infections is 3 to 4 g given every four to six hours as a 20- to 30-minute infusion. For serious infections, the intravenous route should be used.
Pipracil (Piperacillin sodium) should not be mixed with an aminoglycoside in a syringe or infusion bottle since this can result in inactivation of the aminoglycoside.
The maximum daily dose for adults is usually 24 g/day, although higher doses have been used.
Intramuscular injections (see NOTE) should be limited to 2 g per injection site. This route of administration has been used primarily in the treatment of patients with uncomplicated gonorrhea and urinary tract infections.
The average duration of Pipracil (Piperacillin sodium) treatment is from seven to ten days, except in the treatment of gynecologic infections, which is from three to ten days; the duration should be guided by the patient's clinical and bacteriological progress. For most acute infections, treatment should be continued for at least 48 to 72 hours after the patient becomes asymptomatic. Antibiotic therapy for infections should be maintained for at least ten days to reduce the risk of rheumatic fever.
When Pipracil (Piperacillin sodium) is given concurrently with aminoglycosides, both drugs should be used in full therapeutic doses.
Pipracil (Piperacillin sodium) How Supplied
Pipracil (Piperacillin sodium) (piperacillin for injection) is available in vials containing freeze-dried piperacillin sodium powder equivalent to two, three, and four g of piperacillin. One g of piperacillin (as a monosodium salt) contains 1.85 mEq (42.5 mg) of sodium.
Pipracil (Piperacillin sodium) References
Wyeth Pharmaceuticals Inc.Philadelphia, PA 19101
W10440C007ET01Rev 03/07
