PIPERACILLIN
DESCRIPTION:
PIPRACIL(R) piperacillin sodium is a semisynthetic broad-spectrum penicillin for
parenteral use derived from D(-)alpha- aminobenzylpenicillin. The chemical name
of piperacillin sodium is 4-Thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid,
6[[[[(4-ethyl- 2,3-dioxo- 1-piperazinyl)carbonyl]amino]phenylacetyl]amino]- 3,3-
dimethyl-7-oxo-, monosodium salt, [2S- [2alpha, 5alpha,6beta(S*)]].
PIPRACIL is a white to off-white solid having the characteristic appearance of
products prepared by freeze-drying. Freely soluble in water and in alcohol. The
pH of the aqueous solution is 5.5 to 7.5. One g contains 1.85 mEq (42.5 mg) of
sodium (Na+).
ACTIONS/CLINICAL PHARMACOLOGY:
Intravenous Administration. In healthy adult volunteers, mean serum levels
immediately after a two to three minute intravenous injection of 2, 4, or 6 g
were 305, 412, and 775 mcg/mL. Serum levels lack dose proportionality.
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PIPERACILLIN SERUM LEVELS IN ADULTS
(MCG/ML) AFTER A TWO- TO THREE-MINUTE IV INJECTION
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DOSE 0 10 MIN 20 MIN 30 MIN 1 H 1.5 H
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2 305 202 156 67 40 24
(159-615) (164-225) (52-165) (41-88) (25-57) (18-31)
4 412 344 295 117 93 60
(389-484) (315-379) (269-330) (98-138) (78-110) (50-67)
6 775 609 563 325 208 138
(695-849) (530-670) (492-630) (292-363) (180-239) (115-175)
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PIPERACILLIN SERUM LEVELS IN ADULTS
(MCG/ML) AFTER A TWO- TO THREE-MINUTE IV INJECTION
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DOSE 2 H 3 H 4 H 6 H 8 H
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2 20 8 3 2 --
(14-24) (3-11) (2-4) (<0.6-3)
4 36 20 8 4 0.9
(26-51) (17-24) (7-11) (3.7-4.1) (0.7-1)
6 90 38 33 8 3.2
(71-113) (29-53) (25-44) (3-19) (<2-6)
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PIPERACILLIN SERUM LEVELS IN ADULTS
(MCG/ML) AFTER A 30-MINUTE IV INFUSION
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DOSE 0 5 MIN 10 MIN 15 MIN 30 MIN 45 MIN
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4 244 215 186 177 141 146
(155-298) (169-247) (140-209) (142-213) (122-156) (110-265)
6 353 298 298 272 229 180
(324-371) (242-339) (232-331) (219-314) (185-249) (144-209)
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PIPERACILLIN SERUM LEVELS IN ADULTS
(MCG/ML) AFTER A 30-MINUTE IV INFUSION
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DOSE 1 H 1.5 H 2 H 4 H 6 H 7.5 H
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4 105 72 53 15 4 2
(85-133) (53-105) (36-69) (6-24) (1-9) (0.5-3)
6 149 104 73 22 16 --
(117-171) (89-113) (66-94) (12-39) (5-49) --
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A 30-minute infusion of 6 g every 6 h gave, on the fourth day, a mean peak
serum concentration of 420 mcg/mL.
Intramuscular Administration. PIPRACIL is rapidly absorbed after intramuscular
injection. In healthy volunteers, the mean peak serum concentration occurs
approximately 30 minutes after a single dose of 2 g and is about 36 mcg/mL. The
oral administration of 1 g probenecid before injection produces an increase in
piperacillin peak serum level of about 30%. The area under the curve (AUC) is
increased by approximately 60%.
GENERAL: PIPRACIL is not absorbed when given orally. Peak serum concentrations
are attained approximately 30 minutes after intramuscular injections and
immediately after completion of intravenous injection or infusion. The serum
half-life in healthy volunteers ranges from 36 minutes to one hour and 12
minutes. The mean elimination half-life of PIPRACIL in healthy adult volunteers
is 54 minutes following administration of 2 g and 63 minutes following 6 g. As
with other penicillins, PIPRACIL is eliminated primarily by glomerular
filtration and tubular secretion; it is excreted rapidly as unchanged drug in
high concentrations in the urine. Approximately 60% to 80% of the administered
dose is excreted in the urine in the first 24 hours. Piperacillin urine
concentrations, determined by microbioassay, were as high as 14,100 mcg/mL
following a 6 g intravenous dose and 8,500 mcg/mL following a 4 g intravenous
dose. These urine drug concentrations remained well above 1,000 mcg/mL
throughout the dosing interval. The elimination half-life is increased twofold
in mild to moderate renal impairment and fivefold to sixfold in severe
impairment.
PIPRACIL binding to human serum proteins is 16%. The drug is widely distributed
in human tissues and body fluids, including bone, prostate, and heart and
reaches high concentrations in bile. After a 4 g bolus, maximum biliary
concentrations averaged 3,205 mcg/mL. It penetrates into the cerebrospinal fluid
in the presence of inflamed meninges. Because PIPRACIL is excreted by the
biliary route as well as by the renal route, it can be used safely in
appropriate dosage (see DOSAGE AND ADMINISTRATION) in patients with severely
restricted kidney function, and can be used effectively in treatment of
hepatobiliary infections.
MICROBIOLOGY: PIPRACIL 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. In
Vitro, piperacillin is active against most strains of clinical isolates of the
following microorganisms:
Aerobic And Faculatively Anaerobic Organisms
Gram-Negative Bacteria:
Escherichia Coli
Proteus Mirabilis
Proteus Vulgaris
Morganella Morganii (formerly Proteus Morganii)
Providencia Rettgeri (formerly Proteus Rettgeri)
Serratia species including S Marcescens and S Liquefaciens
Klebsiella Pneumoniae
Klebsiella species
Enterobacter species including E Aerogenes and E Cloacae
Citrobacter species including C Freundii and C Diversus
Salmonella species*
Shigella species*
Pseudomonas Aeruginosa
Pseudomonas species including P Cepacia,* P Maltophilia,* and P Fluorescens
Acinetobacter species (formerly Mima-Herellea)
Haemophilus Influenzae (non-beta-lactamase- producing strains)
Neisseria Gonorrhoeae
Neisseria Meningitidis*
Moraxella species*
Yersinia species* (formerly Pasteurella)
Gram-Positive Bacteria:
Group D streptococci including
Enterococci (Streptococcus Faecalis, S Faecium)
Non-enterococci*
Beta-hemolytic streptococci including
Group A Streptococcus (S Pyogenes)
Group B Streptococcus (S Agalactiae)
Streptococcus Pneumoniae
Streptococcus Viridans
Staphylococcus Aureus (non-penicillinase- producing)*
Staphylococcus Epidermidis (non-penicillinase- producing)*
Anaerobic Bacteria:
Actinomyces species*
Bacteroides species including
B Fragilis group (B Fragilis, B Vulgatus)
Non-B Fragilis group (B Melaninogenicus)
B Asaccharolyticus*
Clostridium species including
C Perfringens and C Difficile*
Eubacterium species
Fusobacterium species including
F Nucleatum and F Necrophorum
Peptococcus species
Peptostreptococcus species
Veillonella species
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*Piperacillin has been shown to be active In Vitro against these organisms;
however, clinical efficacy has not yet been established.
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In Vitro, PIPRACIL is inactivated by staphylococcal beta-lactamases, and beta-
lactamases produced by gram-negative bacteria. However, it is active against
beta-lactamase- producing gonococci.
Many strains of gram-negative organisms resistant to certain antibiotics have
been found to be susceptible to PIPRACIL.
PIPRACIL has excellent activity against gram- positive organisms, including
enterococci (S Faecalis). It is active against obligate anaerobes such as
Bacteroides species and also against C Difficile (which has been associated with
pseudomembranous colitis).
Piperacillin is active against many gram-negative bacteria including
Enterobacteriaceae, Klebsiella, Serratia, Pseudomonas, E Coli, Proteus, and
Citrobacter, and, in addition, it is active against anaerobes and enterococci.
In Vitro tests show piperacillin to act synergistically with aminoglycoside
antibiotics against most isolates of P Aeruginosa.
SUSCEPTIBILITY TESTING: The use of a 100 mcg piperacillin antibiotic disk with
susceptibility test methods which measure zone diameter gives an accurate
estimation of susceptibility of organisms to PIPRACIL. The following standard
procedure* has been recommended for use with disks for testing antimicrobials.
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*NCCLS Approved Standard; M2-A2 (Formerly ASM-2) Performance Standards for
Antimicrobic Disk Susceptibility Tests, Second Edition, available from the
National Committee of Clinical Laboratory Standards.
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With this type of procedure, a report of "susceptible" from the laboratory
indicates that the infecting organism is likely to respond to therapy. A report
of "intermediate susceptibility" suggests that the organism would be susceptible
if high dosage is used or if the infection is confined to tissue and fluids (eg,
urine) in which high antibiotic levels are obtained. A report of "resistant"
indicates that the infecting organism is not likely to respond to therapy. With
the piperacillin disk, a zone of 18 mm or greater indicates susceptibility, zone
sizes of 14 mm or less indicate resistance, and zone sizes of 15 to 17 mm
indicate intermediate susceptibility.
Haemophilus and Neisseria species which give zones of >/= 29 mm are susceptible;
resistant strains give zones of = 28 mm. The above interpretive criteria are
based on the use of the standardized procedure. Antibiotic susceptibility
testing requires carefully prescribed procedures. Susceptibility tests are
biased to a considerable degree when different methods are used.
The standardized procedure requires the use of control organisms. The 100 mcg
piperacillin disk should give zone diameters between 24 and 30 mm for E Coli
ATCC No. 25922 and between 25 and 33 mm for Pseudomonas Aeruginosa ATCC No.
27853.
Dilution methods such as those described in the International Collaborative
Study** have been used to determine susceptibility of organisms to PIPRACIL.
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**Acta Pathol Microbiol Scand (B) 1971;suppl 217.
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Enterobacteriaceae, Pseudomonas species and Acinetobacter sp are considered
susceptible if the minimal inhibitory concentration (MIC) of piperacillin is no
greater than 64 mcg/mL and are considered resistant if the MIC is greater than
128 mcg/mL.
Haemophilus and Neisseria species are considered susceptible if the MIC of
piperacillin is = to 1 mcg/mL.
When anaerobic organisms are isolated from infection sites, it is recommended
that other tests such as the modified Broth-Disk Method**/* be used to determine
the antibiotic susceptibility of these slowly growing organisms.
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**/*Wilkins TD and Thiel T. Antimicrob Agents Chemother 1973;3:350-356.
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INDICATIONS AND USAGE:
Therapeutic. PIPRACIL is indicated for the treatment of serious infections
caused by susceptible strains of the designated organisms in the conditions as
listed below.
Intra-Abdominal Infections including hepatobiliary and surgical infections
caused by E Coli, P Aeruginosa, enterococci, Clostridium sp, anaerobic cocci,
and Bacteroides sp, including B Fragilis.
Urinary Tract Infections caused by E Coli, Klebsiella sp, P Aeruginosa, Proteus
sp, including P Mirabilis, and enterococci.
Gynecologic Infections including endometritis, pelvic inflammatory disease,
pelvic cellulitis caused by Bacteroides sp including B Fragilis, anaerobic
cocci, Neisseria Gonorrhoeae, and enterococci (S Faecalis).
Septicemia including bacteremia caused by E Coli, Klebsiella sp, Enterobacter
sp, Serratia sp, P Mirabilis, S Pneumoniae, enterococci, P Aeruginosa,
Bacteroides sp, and anaerobic cocci.
Lower Respiratory Tract Infections caused by E Coli, Klebsiella sp, Enterobacter
sp, Pseudomonas Aeruginosa, Serratia sp, H Influenzae, Bacteroides sp, and
anaerobic cocci. Although improvement has been noted in patients with cystic
fibrosis, lasting bacterial eradication may not necessarily be achieved.
Skin And Skin Structure Infections caused by E Coli, Klebsiella sp, Serratia sp,
Acinetobacter sp, Enterobacter sp, Pseudomonas Aeruginosa, indole-positive
Proteus sp, Proteus Mirabilis, Bacteroides sp, including B Fragilis, anaerobic
cocci, and enterococci.
Bone And Joint Infections caused by P Aeruginosa, enterococci, Bacteroides sp,
and anaerobic cocci.
Gonococcal Infections. PIPRACIL has been effective in the treatment of
uncomplicated gonococcal urethritis.
PIPRACIL has also been shown to be clinically effective for the treatment of
infections at various sites caused by Streptococcus species including Group A
beta-hemolytic Streptococcus and S Pneumoniae; 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 is particularly
useful for the treatment of mixed infections and presumptive therapy prior to
the identification of the causative organisms.
Also, PIPRACIL 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.
Prophylaxis. PIPRACIL is indicated for prophylactic use in surgery including
intra- abdominal (gastrointestinal and biliary) procedures, vaginal
hysterectomy, abdominal hysterectomy, and cesarean section. Effective
prophylactic use depends on the time of administration, and PIPRACIL
Piperacillin Sodium should be given one-half to one hour before the operation so
that effective levels can be achieved in the site prior to the procedure.
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 should be obtained for identification of the causative organism so
that appropriate therapy can be instituted.
CONTRAINDICATIONS:
A history of allergic reactions to any of the penicillins and/or cephalosporins.
WARNINGS:
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have
been reported in patients receiving therapy with penicillins. These reactions
are more apt to occur in persons with a history of sensitivity to multiple
allergens.
There have been reports of patients with a history of penicillin
hypersensitivity who have experienced severe hypersensitivity reactions when
treated with a cephalosporin. Before initiating therapy with PIPRACIL, careful
inquiry should be made concerning previous hypersensitivity reactions to
penicillins, cephalosporins, and other allergens. If an allergic reaction occurs
during therapy with PIPRACIL, the antibiotic should be discontinued. The usual
agents (antihistamines, pressor amines, and corticosteroids) should be readily
available. SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT
WITH EPINEPHRINE. OXYGEN AND INTRAVENOUS CORTICOSTEROIDS AND AIRWAY MANAGEMENT
INCLUDING INTUBATION SHOULD ALSO BE ADMINISTERED AS NECESSARY.
PRECAUTIONS:
GENERAL
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.
Bleeding manifestations 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 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 is a monosodium salt containing 1.85 mEq 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.
Antimicrobials used in high doses for short periods to treat gonorrhea may mask
or delay the symptoms of incubating syphilis. Therefore, prior to treatment,
patients with gonorrhea should also be evaluated for syphilis. Specimens for
darkfield examination should be obtained from patients with any suspected
primary lesion, and serologic tests should be performed. In all cases where
concomitant syphilis is suspected, monthly serological tests should be made for
a minimum of 4 months.
As with other semisynthetic penicillins, PIPRACIL therapy has been associated
with an increased incidence of fever and rash in cystic fibrosis patients.
DRUG INTERACTIONS
The mixing of piperacillin with an aminoglycoside In Vitro can result in
substantial inactivation of the aminoglycoside.
Piperacillin when used concomitantly with vecuronium has been implicated in the
prolongation of the neuromuscular blockage of vecuronium. Due to their similar
mechanism of action, it is expected that the neuromuscular blockade produced by
any of the non-depolarizing muscle relaxants could be prolonged in the presence
of piperacillin. (See package insert for vecuronium bromide.)
PREGNANCY--PREGNANCY CATEGORY B
Although reproduction studies in mice and rats performed at doses up to 4 times
the human dose have shown no evidence of impaired fertility or harm to the
fetus, safety of PIPRACIL use in pregnant women has not been determined by
adequate and well-controlled studies. Because animal reproduction studies are
not always predictive of human response, this drug should be used during
pregnancy only if clearly needed. It has been found to cross the placenta in
rats.
NURSING MOTHERS
Caution should be exercised when PIPRACIL is administered to nursing mothers. It
is excreted in low concentrations in milk.
PEDIATRIC USE
Dosages for children under the age of 12 have not been established. The safety
of PIPRACIL in neonates is not known. In dog neonates, dilated renal tubules and
peritubular hyalinization occurred following administration of PIPRACIL.
DRUG INTERACTIONS:
The mixing of piperacillin with an aminoglycoside In Vitro can result in
substantial inactivation of the aminoglycoside.
Piperacillin when used concomitantly with vecuronium has been implicated in the
prolongation of the neuromuscular blockage of vecuronium. Due to their similar
mechanism of action, it is expected that the neuromuscular blockade produced by
any of the non-depolarizing muscle relaxants could be prolonged in the presence
of piperacillin. (See package insert for vecuronium bromide.)
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
ADVERSE EFFECTS
PIPRACIL 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.
Local Reactions. In clinical trials thrombophlebitis was noted in 4% of
patients. Pain, erythema, and/or induration at the injection site occurred in 2%
of patients. Less frequent reactions including ecchymosis, deep vein thrombosis
and hematomas have also occurred.
Gastrointestinal. Diarrhea and loose stools were noted in 2% of patients. Other
less frequent reactions included vomiting, nausea, increases in liver enzymes
(LDH, SGOT, SGPT), hyperbilirubinemia, cholestatic hepatitis, bloody diarrhea
and, rarely, pseudomembranous colitis.
Hypersensitivity Reactions. Anaphylactoid Reactions, see WARNINGS.
Rash was noted in 1% of patients. Other less frequent findings included
pruritus, vesicular eruptions, positive Coombs tests.
Other dermatologic manifestations such as erythema multiforme and Stevens-
Johnson syndrome have been reported rarely.
Renal. Elevations of creatinine or BUN, and, rarely, interstitial nephritis.
Central Nervous System. Headache, dizziness, fatigue.
Hemic And Lymphatic. Reversible leukopenia, neutropenia, thrombocytopenia
and/or eosinophilia have been reported. As with other beta-lactam antibiotics,
reversible leukopenia (neutropenia) is more apt to occur in patients receiving
prolonged therapy at high dosages or in association with drugs known to cause
this reaction.
Serum Electrolytes. Individuals with liver disease or individuals receiving
cytotoxic therapy or diuretics were reported rarely to demonstrate a decrease in
serum potassium concentrations with high doses of piperacillin.
Skeletal. Rarely, prolonged muscle relaxation.
Other. Superinfection, including candidiasis. Hemorrhagic manifestations.
DOSAGE AND ADMINISTRATION:
PIPRACIL may be administered by the intramuscular route (see Note) or
intravenously or given in a three- to five-minute intravenous injection. The
usual dosage of PIPRACIL 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 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.
NOTE: THE ADD-VANTAGE VIAL IS NOT FOR IM USE.
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DOSAGE RECOMMENDATIONS
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TYPE OF INFECTION USUAL TOTAL DAILY DOSE
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Serious infections such as septicemia, nosocomial 12-18 g/d IV
pneumonia, intra-abdominal infections, aerobic (200-300 mg/kg/d)
and anaerobic gynecologic infections, and anaerobic in divided doses
gynecologic skin and soft tissue infections every 4 to 6 h
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Complicated urinary tract infections 8-16 g/d IV (125-200
mg/kg/d) in divided
doses every 6 to 8 h
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Uncomplicated urinary tract 6-8 g/d IM or IV (100-125
infections and most community- mg/kg/d) in divided
acquired pneumonia doses every 6 to 12 h
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Uncomplicated gonorrhea infections 2 g IM* as a one-time
dose
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*One g of probenecid given orally one-half hour prior to injection.
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The average duration of PIPRACIL treatment is from seven to 10 days, except in
the treatment of gynecologic infections, in which it is from 3 to 10 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
Group A beta-hemolytic streptococcal infections should be maintained for at
least ten days to reduce the risk of rheumatic fever or glomerulonephritis.
When PIPRACIL is given concurrently with aminoglycosides, both drugs should be
used in full therapeutic doses.
Renal Impairment
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DOSAGE IN RENAL IMPAIRMENT
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Creatinine Urinary Tract Urinary Tract Serious Systemic
Clearance Infection Infection Infection
ml/min (uncomplicated) (complicated)
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>40 No dosage adjustment necessary
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20-40 No dosage 9 g/day 12 g/day
adjustment 3 g every 4 g every
necessary 8 h 8 h
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<20 6 g/day 6 g/day 8 g/day
3 g every 3 g every 4 g every
12 h 12 h 12 h
For patients on hemodialysis the maximum daily dose is 6 g/day (2 g every 8
hours). In addition, because hemodialysis removes 30%-50% of piperacillin in 4
hours, 1 g additional dose should be administered following each dialysis
period.
For patients with renal failure and hepatic insufficiency, measurement of serum
levels of PIPRACIL will provide additional guidance for adjusting dosage.
Prophylaxis
When possible, PIPRACIL should be administered as a 20- to 30-minute infusion
just prior to anesthesia. Administration while the patient is awake will
facilitate identification of possible adverse reactions during drug infusion.
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INDICATION 1st Dose 2nd Dose 3rd Dose
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Intra-abdominal 2 g IV just prior 2 g during 2 g every 6 h Post-Op
Surgery to surgery surgery for no more than 24 h
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Vaginal 2 g IV just prior 2 g 6 h after 2 g 12 h after
Hysterectomy to surgery 1st dose 1st dose
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Cesarean 2 g IV after 2 g 4 h after 2 g 8 h after
Section cord is clamped 1st dose 1st dose
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Abdominal 2 g IV just prior 2 g on return to 2 g after 6 h
Hysterectomy to surgery recovery room
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Infants and Children: Dosages in infants and children under 12 years of age have
not been established.
PRODUCT RECONSTITUTION/DOSAGE PREPARATION
CONVENTIONAL VIALS:
DILUENTS FOR RECONSTITUTION
Sterile Water for Injection
Bacteriostatic* Water for Injection
Sodium Chloride Injection
Bacteriostatic* Sodium Chloride Injection
Dextrose 5% in Water
Dextrose 5% and 0.9% Sodium Chloride
Lidocaine HCl 0.5% to 1% (without epinephrine)**
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* Either Parabens or Benzyl Alcohol
** For Intramuscular Use Only. Lidocaine is contraindicated in patients with a
known history of hypersensitivity to local anesthetics of the amide type.
----------
CONVENTIONAL VIALS:
INTRAVENOUS SOLUTIONS
Dextrose 5% in Water
0.9% Sodium Chloride
Dextrose 5% and 0.9% Sodium Chloride
Lactated Ringer's Injection*/*
Dextran 6% in 0.9% Sodium Chloride
INTRAVENOUS ADMIXTURES
Normal Saline (+ KCl 40 mEq)
5% Dextrose in Water (+ KCl 40 mEq)
5% Dextrose/Normal Saline (+ KCl 40 mEq)
Ringer's Injection (+ KCl 40 mEq)
Lactated Ringer's Injection (+ KCl 40 mEq)*/*
----------
*/* When PIPRACIL(R) is further diluted with Lactated Ringer's Injection, the
diluted solution must be administered within 2 hours.
----------
ADD-VANTAGE**/* VIALS:
ADD-VANTAGE SYSTEM ADMIXTURES
Dextrose 5% in Water (50 or 100 mL)
0.9% Sodium Chloride (50 or 100 mL)
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**/* (ADD-Vantage is the registered trademark of Abbott Laboratories.)
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INTRAVENOUS ADMINISTRATION
Reconstitution Directions For Conventional Vials: Reconstitute each gram of
PIPRACIL Sterile Piperacillin Sodium with at least 5 mL of a suitable diluent
(except Lidocaine HCl 0.5% to 1% without epinephrine) listed above. Shake well
until dissolved. Reconstituted solution may be further diluted to the desired
volume (eg, 50 or 100 mL) in the above listed intravenous solutions and
admixtures.
Reconstitution Directions For Add-Vantage Vials: See Instruction Sheet provided
in box.
Reconstitution Directions For Pharmacy Bulk Vial: Reconstitute the 40 g vial
with 172 mL of a suitable diluent (except Lidocaine HCl 0.5% to 1% without
epinephrine) listed above to achieve a concentration of 1 g per 5 mL.
DIRECTIONS FOR ADMINISTRATION
INTERMITTENT IV INFUSION: Infuse diluted solution over a period of about 30
minutes. During infusion it is desirable to discontinue the primary intravenous
solution.
INTRAVENOUS INJECTION (BOLUS)
Reconstituted solution should be injected slowly over a 3- to 5-minute period to
help avoid vein irritation.
INTRAMUSCULAR ADMINISTRATION (CONVENTIONAL VIALS ONLY)
Reconstitution Directions: Reconstitute each gram of PIPRACIL with 2 mL of a
suitable diluent listed above to achieve a concentration of 1 g per 2.5 mL.
Shake well until dissolved.
DIRECTIONS FOR ADMINISTRATION
When indicated by clinical and bacteriological findings, intramuscular
administration of 6 to 8 g daily of PIPRACIL, in divided doses, may be utilized
for initiation of therapy. In addition, intramuscular administration of the drug
may be considered for maintenance therapy after clinical and bacteriologic
improvement has been obtained with intravenous piperacillin sodium treatment.
Intramuscular administration should not exceed 2 g per injection at any one
site.
The preferred site is the upper outer quadrant of the buttock (ie, gluteus
maximus).
The deltoid area should be used only if well- developed, and then only with
caution to avoid radial nerve injury. Intramuscular injections should not be
made into the lower or mid-third of the upper arm.
STABILITY OF PIPRACIL FOLLOWING RECONSTITUTION
PIPRACIL is stable in both glass and plastic containers when reconstituted with
recommended diluents and when diluted with the intravenous solutions and
intravenous admixtures indicated above.
Extensive stability studies have demonstrated chemical stability (potency, pH,
and clarity) through 24 hours at room temperature, up to one week refrigerated,
and up to one month frozen (-10 deg to -20 deg C). (Note: The 40 g Pharmacy Bulk
Vial should not be frozen after reconstitution.) Appropriate consideration of
aseptic technique and individual hospital policy, however, may recommend
discarding unused portions after storage for 48 hours under refrigeration and
discarding after 24 hours' storage at room temperature.
ADD-VANTAGE SYSTEM
Stability studies with the ad-mixed ADD-Vantage system have demonstrated
chemical stability (potency, pH, and clarity) through 24 hours at room
temperature. (Note: The admixed ADD-Vantage should not be refrigerated or frozen
after reconstitution.)
Additional stability data available upon request.
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