Piperacillin Sodium

(BANM, USAN, rINNM)
Synonyms: CL-227193; Natrii Piperacillinum; Piperacilin sodná sůl; Piperacilina sódica; Piperacilino natrio druska; Pipéracilline sodique; Piperacillin-nátrium; Piperacillinnatrium natricum; Piperacillinum; Piperacillinum natricum; Piperacylina sodowa; Piperasilin Sodyum; Piperasilliininatrium; T-1220.
Cyrillic synonym: Натрий Пиперациллин.

💊 Chemical information

Chemical formula: C23H26N5NaO7S = 539.5.
CAS — 59703-84-3.
ATC — J01C A12.
ATC Vet — QJ01C A12.

Pharmacopoeias.

In Chin., Eur., Jpn, and US.

Ph. Eur. 6.2

(Piperacillin Sodium). A white or almost white, hygroscopic powder. Freely soluble in water and in methyl alcohol; practically insoluble in ethyl acetate. A 10% solution in water has a pH of 5.0 to 7.0. Store in airtight containers.

USP 31

(Piperacillin Sodium). A white to off-white solid. Freely soluble in water and in alcohol. pH of a 40% solution in water is between 5.5 and 7.5. Store in airtight containers.

Incompatibility.

Piperacillin sodium has been reported to be incompatible with aminoglycosides and sodium bicarbonate.

Stability.

References. 1. Zhang Y, Trissel LA. Stability of piperacillin and ticarcillin in AutoDose Infusion System bags. Ann Pharmacother 2001; 35: 1360–3.

💊 Adverse Effects and Precautions

As for Carbenicillin Sodium. Prolongation of bleeding time has been less frequent and less severe with piperacillin than with carbenicillin.

Effects on the blood.

References.
1. Scheetz MH, et al. Systematic review of piperacillin-induced neutropenia. Drug Safety 2007; 30: 295–306.

Hypersensitivity.

In the mid 1980s there were reports of a relatively high incidence of adverse reactions to piperacillin, especially fever, in patients with cystic fibrosis.1-3 However, the manufacturers4 considered such patients to be particularly prone to allergy and cited reactions with other semisynthetic penicillins including carbenicillin and azlocillin. Similar apparent hypersensitivity reactions have been reported in patients taking high doses of piperacillin and other ureidopenicillins, over long periods for other indications,5 and with other penicillins in patients with cystic fibrosis,6 although piperacillin does appear to be most frequently implicated.6
1. Stead RJ, et al. Adverse reactions to piperacillin in cystic fibrosis. Lancet 1984; i: 857–8
2. Strandvik B. Adverse reactions to piperacillin in patients with cystic fibrosis. Lancet 1984; i: 1362
3. Stead RJ, et al. Adverse reactions to piperacillin in adults with cystic fibrosis. Thorax 1985; 40: 184–6
4. Brock PG, Roach M. Adverse reactions to piperacillin in cystic fibrosis. Lancet 1984; i: 1070–1
5. Lang R, et al. Adverse reactions to prolonged treatment with high doses of carbenicillin and ureidopenicillins. Rev Infect Dis 1991; 13: 68–72
6. Pleasants RA, et al. Allergic reactions to parenteral beta-lactam antibiotics in patients with cystic fibrosis. Chest 1994; 106: 1124–8.

Sodium content.

Each g of piperacillin sodium contains about 1.85 mmol of sodium. As piperacillin sodium has a lower sodium content than carbenicillin sodium, hypernatraemia and hypokalaemia are less likely to occur.

💊 Interactions

Neuromuscular blockers.

Piperacillin and other ureidopenicillins are reported to prolong the action of competitive muscle relaxants such as vecuronium.

💊 Antimicrobial Action

Piperacillin has a similar antimicrobial action to carbenicillin and ticarcillin, but is active against a wider range of Gram-negative organisms, including Klebsiella pneumoniae. It is also generally more active in vitro, especially against Pseudomonas aeruginosa and the Enterobacteriaceae, against Grampositive Enterococcus faecalis, and possibly against Bacteroides fragilis. There is, however, an inoculum effect, i.e. minimum inhibitory concentrations of piperacillin increase with the size of the inoculum. Combinations of piperacillin and aminoglycosides have been shown to be synergistic in vitro against Ps. aeruginosa and Enterobacteriaceae. The effect of using piperacillin with other beta lactams has been less predictable. The activity of piperacillin against some organisms, resistant because of the production of betalactamases, may be restored by tazobactam, a betalactamase inhibitor. Such organisms include betalactamase-producing strains of staphylococci, Escherichia coli, Haemophilus influenzae, and Bacteroides spp.; the activity of piperacillin against Ps. aeruginosa is not enhanced by tazobactam. Resistance has developed in Ps. aeruginosa during treatment with piperacillin, especially when used alone. There may be some cross-resistance with other antipseudomonal penicillins.
1. Higashitani F, et al. Inhibition of β-lactamases by tazobactam and in-vitro antibacterial activity of tazobactam combined with piperacillin. J Antimicrob Chemother 1990; 25: 567–74
2. Mehtar S, et al. The in-vitro activity of piperacillin/tazobactam, ciprofloxacin, ceftazidime and imipenem against multiple resistant Gram-negative bacteria. J Antimicrob Chemother 1990; 25: 915–19
3. Kempers J, MacLaren DM. Piperacillin/tazobactam and ticarcillin/clavulanic acid against resistant Enterobacteriaceae. J Antimicrob Chemother 1990; 26: 598–9.
4. Kadima TA, Weiner JH. Mechanism of suppression of piperacillin resistance in enterobacteria by tazobactam. Antimicrob Agents Chemother 1997; 41: 2177–83
5. Klepser ME, et al. Comparison of the bactericidal activities of piperacillin-tazobactam, ticarcillin-clavulanate, and ampicillinsulbactam against clinical isolates of Bacteroides fragilis, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Antimicrob Agents Chemother 1997; 41: 435–9
6. Peterson LR. Antibiotic policy and prescribing strategies for therapy of extended-spectrum beta-lactamase-producing Enterobacteriaceae: the role of piperacillin-tazobactam. Clin Microbiol Infect 2008; 14 (suppl 1): 181–4. Correction. ibid.; (suppl 5): 21–4.

💊 Pharmacokinetics

Piperacillin is not absorbed from the gastrointestinal tract. It is well absorbed after intramuscular use, with peak plasma concentrations of 30 to 40 micrograms/mL 30 to 50 minutes after a dose of 2 g. The pharmacokinetics of piperacillin are reported to be nonlinear and dose-dependent. The plasma halflife is about 1 hour, but is prolonged in neonates. In patients with severe renal impairment 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 in the circulation is bound to plasma proteins. Piperacillin is widely distributed in body tissues and fluids. It crosses the placenta into the 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 up to 20% of a dose may be excreted by this route. Plasma concentrations are enhanced by probenecid. Piperacillin is removed by haemodialysis. Piperacillin with tazobactam. The pharmacokinetics of piperacillin do not appear to be altered by tazobactam, but piperacillin reduces the renal clearance of tazobactam.
1. Heikkilä A, Erkkola R. Pharmacokinetics of piperacillin during pregnancy. J Antimicrob Chemother 1991; 28: 419–23
2. Wise R, et al. Pharmacokinetics and tissue penetration of tazobactam administered alone and with piperacillin. Antimicrob Agents Chemother 1991; 35: 1081–4
3. Johnson CA, et al. Single-dose pharmacokinetics of piperacillin and tazobactam in patients with renal disease. Clin Pharmacol Ther 1992; 51: 32–41
4. Dupon M, et al. Plasma levels of piperacillin and vancomycin used as prophylaxis in liver transplant patients. Eur J Clin Pharmacol 1993; 45: 529–34
5. Sörgel F, Kinzig M. The chemistry, pharmacokinetics and tissue distribution of piperacillin/tazobactam. J Antimicrob Chemother 1993; 31 (suppl A): 39–60
6. Reed MD, et al. Single-dose pharmacokinetics of piperacillin and tazobactam in infants and children. Antimicrob Agents Chemother 1994; 38: 2817–26
7. Bourget P, et al. Clinical pharmacokinetics of piperacillin-tazobactam combination in patients with major burns and signs of infection. Antimicrob Agents Chemother 1996; 40: 139–45
8. Occhipinti DJ, et al. Pharmacokinetics and pharmacodynamics of two multiple-dose piperacillin-tazobactam regimens. Antimicrob Agents Chemother 1997; 41: 2511–17.

💊 Uses and Administration

Piperacillin is a ureidopenicillin that is used similarly to ticarcillin for the treatment of infections caused by Pseudomonas aeruginosa, and also infections due to other susceptible bacteria. It has been used particularly in immunocompromised patients (neutropenic patients) and for biliary-tract infections, a beta-lactamase inhibitor, to widen its antibacterial spectrum to organisms usually resistant because of the production of beta-lactamases. The combination is given intravenously in a ratio of piperacillin (as the sodium salt) 8 parts to 1 part of tazobactam (as the sodium salt). Doses, calculated on piperacillin content, are similar to those of piperacillin alone.
1. Greenwood D, Finch RG, eds. Piperacillin/tazobactam: a new βlactam/β-lactamase inhibitor combination. J Antimicrob Chemother 1993; 31 (suppl A): 1–124
2. Schoonover LL, et al. Piperacillin/tazobactam: a new betalactam/beta-lactamase inhibitor combination. Ann Pharmacother 1995; 29: 501–14
3. Perry CM, Markham A. Piperacillin/tazobactam: an updated review of its use in the treatment of bacterial infections. Drugs 1999; 57: 805–43
4. Kotapati S, et al. The clinical and economic benefits of administering piperacillin-tazobactam by continuous infusion. Intensive Crit Care Nurs 2005; 21: 87–93
5. Gin A, et al. Piperacillin-tazobactam: a beta-lactam/beta-lactamase inhibitor combination. Expert Rev Anti Infect Ther 2007; 5: 365–83.

💊 Preparations

BP 2008: Piperacillin Intravenous Infusion; USP 31: Piperacillin for Injection.

Proprietary Preparations

Arg.: Algiseptico†; Piperac†; Austral.: Pipril†; Austria: Pipril; Belg.: Pipcil†; Canad.: Pipracil†; Cz.: Pipraks†; Pipril†; Denm.: Ivacin†; Ger.: Pipera†; Pipril†; Gr.: Pipril; Zobactam; Zoracilin; Hong Kong: Pipracil†; Hung.: Pipril†; India: Pipracil; Irl.: Pipril†; Israel: Picillin†; Pipracin; Pipril†; Ital.: Avocin†; Biopiper†; Cilpier; Diperil; Ecosette; Eril†; Farecillin; Peracil; Perasint; Picillin; Piperital; Pipersal; Pipertex; Reparcillin; Semipenil; Sintoplus; Viracillina†; Jpn: Pentcillin; Malaysia: Pipracil†; NZ: Pipril†; Switz.: Pipril†; Thai.: Peracin; Pipracil†; Turk.: Pipraks; USA: Pipracil†. Multi-ingredient: Arg.: Pipetexina; Tazonam; Austral.: Ta z oc in ; Austria: Ta z o n a m ; Belg.: Ta zo c i n ; Braz.: Tazoci n; Ta zoxil † ; Taz pe n †; Canad.: Ta z oc in; Chile: Ta zo nam ; Cz.: Ta z oc i n ; Denm.: Ta zo c i n; Fin.: Ta z o c i n ; Fr.: Ta z ocilline; Ger.: Tazobac; Gr.: Bactalin; Gramenox; Oliten; Tazepen; Tazidron; Tazobion; Tazocin; Tazorex; Hong Kong: Taz o ci n; Hung.: Ta zo ci n; India: Tazact; Tazofast; Tazopen; Zosyn; Indon.: Ta z o c in ; Irl.: Tazocin; Israel: Ta z o c i n ; Ital.: Tazobac; Tazocin; Malaysia: Ta z o c i n ; Mex.: Tasovak; Tazocin; Neth.: Ta z o c i n ; Norw.: Ta z o c i n ; NZ: Ta z o c i n ; Philipp.: Ta z o c in ; Pol.: Tazocin; Port.: Tazobac; S.Afr.: Tazobax; Tazocin; Singapore: Ta z oc i n; Spain: Ta z o c e l ; Swed.: Ta z o c i n ; Switz.: Ta z o b a c ; Thai.: Ta z o c i n ; Turk.: Ta z o c i n ; UK: Tazo ci n ; USA: Zosyn; Venez.: Ta zo p r i l ; Taz pe n.
Published May 08, 2019.