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Penicillins (Systemic)

This monograph includes information on the following:

1) Amoxicillin
2) Ampicillin
3) Bacampicillin
4) Carbenicillin
5) Cloxacillin
6) Dicloxacillin  
7) Flucloxacillin *
8) Methicillin  
9) Mezlocillin  
10) Nafcillin
11) Oxacillin  
12) Penicillin G
13) Penicillin V
14) Piperacillin
15) Pivampicillin *
16) Pivmecillinam *
17) Ticarcillin


INN:
Amoxicillin —Amoxicilline
Carbenicillin indanyl sodium—Carindacillin
Methicillin —Meticillin
Penicillin G benzathine— Benzathine benzylpenicillin
Penicillin V—Phenoxymethylpenicillin

BAN:
Amoxicillin—Amoxycillin
Carbenicillin indanyl sodium—Carindacillin
Penicillin G benzathine—Benzathine penicillin
Penicillin G procaine—Procaine penicillin
Penicillin V—Phenoxymethylpenicillin

VA CLASSIFICATION
Amoxicillin
Primary: AM112

Ampicillin
Primary: AM112

Bacampicillin
Primary: AM112

Carbenicillin
Primary: AM114

Cloxacillin
Primary: AM113

Dicloxacillin
Primary: AM113

Flucloxacillin
Primary: AM113

Methicillin
Primary: AM113

Mezlocillin
Primary: AM114

Nafcillin
Primary: AM113

Oxacillin
Primary: AM113

Penicillin G
Primary: AM111

Penicillin V
Primary: AM111

Piperacillin
Primary: AM114

Pivampicillin
Primary: AM112

Pivmecillinam
Primary: AM112

Ticarcillin
Primary: AM114


Commonly used brand name(s): Amoxil1; Ampicin2; Apo-Amoxi1; Apo-Ampi2; Apo-Cloxi5; Apo-Pen VK13; Ayercillin12; Bactocill11; Beepen-VK13; Betapen-VK13; Bicillin L-A12; Cloxapen5; Crysticillin 300 A.S.12; Dycill6; Dynapen6; Fluclox7; Geocillin4; Geopen4; Geopen Oral4; Ledercillin VK13; Megacillin12; Mezlin9; Nadopen-V13; Nadopen-V 20013; Nadopen-V 40013; Nafcil10; Nallpen10; Novamoxin1; Novo-Ampicillin2; Novo-Cloxin5; Novo-Pen-VK13; Nu-Amoxi1; Nu-Ampi2; Nu-Cloxi5; Nu-Pen-VK13; Omnipen2; Omnipen-N2; Orbenin5; PVF13; PVF K13; Pathocil6; Pen Vee13; Pen Vee K13; Pen-Vee13; Penbritin2; Penglobe3; Pentids12; Permapen12; Pfizerpen12; Pfizerpen-AS12; Pipracil14; Polycillin2; Polycillin-N2; Polymox1; Pondocillin15; Principen2; Prostaphlin11; Pyopen4; Selexid16; Spectrobid3; Staphcillin8; Tegopen5; Ticar17; Totacillin2; Totacillin-N2; Trimox1; Unipen10; V-Cillin K13; Veetids13; Wycillin12; Wymox1.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Not commercially available in Canada.



Category:


Antibacterial (systemic)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

General considerations
Penicillins can be classified into four broad categories, each covering a different spectrum of activity. The natural penicillins (penicillin G and penicillin V) have activity against many gram-positive organisms, gram-negative cocci, and some other gram-negative organisms. {96}0 The aminopenicillins (ampicillin, amoxicillin, bacampicillin, and pivampicillin) have activity against penicillin-sensitive gram-positive bacteria, as well as Escherichia coli , Proteus mirabilis , Salmonella sp., Shigella sp., and Haemophilus influenzae . {96}9 {96}8 The antistaphylococcal penicillins (cloxacillin, dicloxacillin, flucloxacillin, methicillin, nafcillin, and oxacillin) are also active against beta-lactamase–producing staphylococci. {96}7 {96}6 The antipseudomonal penicillins (carbenicillin, mezlocillin, piperacillin, and ticarcillin) have less activity against gram-positive organisms than the natural penicillins or aminopenicillins; however, unlike the other penicillins, these penicillins are active against some gram-negative bacilli, including Pseudomonas aeruginosa . {96}5 {96}4

Resistance to penicillins is thought to be due to 3 main mechanisms. The first is alteration of the antibiotic target sites" penicillin-binding proteins (PBPs); the second is inactivation of the penicillin by bacterially produced enzymes (beta-lactamases); and the third is decreased permeability of the cell wall to penicillins. Of these 3 mechanisms, production of beta-lactamase is the most common and the most important. {96}3 {96}2

The spectrums of activity of penicillin G and penicillin V include Staphylococcus and Streptococcus species. However, most strains of Staphylococcus aureus and Staphyloccus epidermidis produce beta-lactamases, which destroy these penicillins. {96}1 A small proportion of community-acquired strains (5 to 15%) of S. aureus remains susceptible to penicillin G. {96}0 Penicillin G also has activity against the gram-negative cocci, Neisseria meningitidis and Neisseria gonorrhoeae . However, resistance to penicillin G by beta-lactamase–producing N. gonorrhoeae has become a widespread problem in many parts of the world. {96}9 {96}8 Penicillin G is more active than penicillin V against Haemophilus and Neisseria species. Some other organisms for which penicillin G has good activity include Actinomyces israelii , Bacillus anthracis , oropharyngeal Bacteroides species, Borrelia burgdorferi , Clostridium sp., Corynebacterium diphtheriae , Erysipelothrix rhusiopathiae , Listeria monocytogenes , Spirillium minor , Streptobacillus moniliformis , and Treponema pallidum . {96}7 {96}6

The aminopenicillins have activity against H. influenzae , E. coli , P. mirabilis , and Salmonella and some Shigella species, while also retaining activity against penicillin-sensitive gram-positive bacteria. {96}5 {96}4 {96}3 However, many Enterobacteriaceae, H. influenzae , Salmonella and Shigella species are resistant to these penicillins because of beta-lactamase production by these organisms. {96}2 {96}1 {96}0 Bacampicillin and pivampicillin are esters of ampicillin that are hydrolyzed during absorption to liberate ampicillin; this results in increased bioavailability and serum concentrations of ampicillin. {134}9 {134}8 Amoxicillin has the same in vitro activity as ampicillin, although amoxicillin has slightly better activity against Enterococcus faecalis , E. coli , and Salmonella sp. {134}7

The antistaphylococcal penicillins were developed to treat beta-lactamase–producing staphylococci. These penicillins are active against both penicillin-sensitive and penicillin-resistant staphylococci, as well as Streptococcus pyogenes and Streptococcus pneumoniae . {134}6 {134}5 However, they are less potent than penicillin G against penicillin-sensitive bacteria {134}4, and they have very little activity against Enterococcus faecalis and gram-negative organisms. {134}3 {134}2 Nafcillin has more intrinsic activity than methicillin against staphylococci and streptococci. {134}1 {134}0 The mechanism of methicillin-resistant S. aureus is not due to beta-lactamase production by the organism, but results from an alteration of penicillin-binding proteins. {97}9 Methicillin-resistant staphylococci are also resistant to the other penicillins in this category.

The antipseudomonal penicillins are active against a wide variety of gram-negative bacteria, including P. aeruginosa , Enterobacter , Morganella , and Providencia species. {97}8 {97}7 These penicillins are less active than ampicillin against streptococci and enterococci; however, their activity against non-beta-lactamase–producing Haemophilus , N. meningitidis , and N. gonorrhoeae is similar to that of ampicillin. {97}6 {97}5 These agents are also destroyed by beta-lactamases produced by gram-positive and some gram-negative organisms. Ticarcillin is 2 to 4 times more active than carbenicillin against P. aeruginosa . {97}4 {97}3 Mezlocillin has a spectrum of activity similar to that of carbenicillin and ticarcillin; however, mezlocillin has better activity against non-beta-lactamase–producing strains of Klebsiella , H. influenzae , and Bacteroides fragilis . {97}2 {97}1 Piperacillin has excellent activity against streptococci, Neisseria , and Haemophilus species and is the most active penicillin against P. aeruginosa . {97}0 {97}9

Another penicillin, which does not neatly fit into any of these four categories, is pivmecillinam. Pivmecillinam is hydrolyzed during absorption to liberate the active agent, mecillinam. Mecillinam has poor activity against gram-positive organisms, Haemophilus , and Neisseria species; however, it has very good activity against many gram-negative bacteria, including E. coli , many Klebsiella , Enterobacter , and Citrobacter species. It has variable activity against Proteus sp. and does not inhibit P. aeruginosa or anaerobes, such as B. fragilis or Clostridium species. {97}8 {97}7

Accepted

Actinomycosis (treatment)—Penicillin G (parenteral) and [penicillin V]1 are indicated in the treatment of actinomycosis caused by Actinomyces sp. {97}6 {97}5 {97}4

Anthrax (treatment)—Penicillin G (parenteral) {97}3 {97}2, [penicillin V]1 {97}1 {97}0, and penicillin G procaine {97}9 {97}8 are indicated in the treatment of anthrax caused by B. anthracis .

Arthritis, gonococcal (treatment)—Penicillin G (parenteral) is indicated in the treatment of infective arthritis caused by susceptible strains of N. gonorrhoeae . {97}7 {97}6 {97}5 {97}4

Bejel (treatment)—Penicillin G benzathine {97}3 and penicillin G procaine {97}2 {97}1 are indicated in the treatment of bejel caused by Treponema pallidum endemicum . {97}0

Bone and joint infections (treatment)—Carbenicillin (parenteral) {97}9, cloxacillin (parenteral) {97}8, [methicillin]1 {97}7, [nafcillin (parenteral)]1 {97}6 {97}5, [ oxacillin (parenteral)]1 {97}4, [penicillin G (parenteral)]1 {97}3 {97}2, and piperacillin {97}1 {97}0 are indicated in the treatment of bone and joint infections caused by susceptible organisms.

Bronchitis, bacterial exacerbations (treatment)— Amoxicillin {97}9 {97}8 {97}7 {97}6, ampicillin {97}5 {97}4 {97}3 {97}2, bacampicillin {97}1 {97}0 {17}9, cloxacillin (oral) {17}8, dicloxacillin {17}7, penicillin V {17}6 {17}5 {17}4, and pivampicillin {17}3 are indicated in the treatment of bronchitis caused by susceptible organisms.

Diphtheria (prophylaxis)—Penicillin G (parenteral) {17}2 {17}1, [ penicillin G benzathine]1 {17}0, penicillin G procaine {17}9 {17}8 {17}7, and penicillin V {17}6 are indicated in the prophylaxis of diphtheria, caused by C. diphtheriae , as an adjunct to antitoxin.

Endocarditis, bacterial (prophylaxis)—[ Amoxicillin]1 {17}5 {17}4, [ampicillin]1 {17}3, penicillin G (parenteral) {17}2 {17}1, and penicillin V {17}0 {17}9 {17}8 are indicated in the prophylaxis of bacterial endocarditis caused by susceptible organisms.

Endocarditis, bacterial (treatment)—Ampicillin (parenteral) {17}7 {17}6 {17}5, carbenicillin (parenteral) {17}4, cloxacillin (parenteral) {17}3, [methicillin]1 {17}2, [nafcillin (parenteral) ]1 {17}1 {17}0, [oxacillin (parenteral)] {17}9, [penicillin G (parenteral)]1 {17}8 {17}7 and penicillin G procaine {17}6 are indicated in the treatment of bacterial endocarditis caused by susceptible organisms.

Erysipelas (treatment)—Penicillin G (parenteral) {17}5 {17}4 {17}3, penicillin V {17}2 {17}1 {17}0, and penicillin G procaine {134}9 {134}8 are indicated in the treatment of erysipelas caused by susceptible strains of group A streptococci.

Erysipeloid (treatment)—Penicillin G (parenteral), [penicillin V]1 , [penicillin G benzathine]1 , and [penicillin G procaine]1 are indicated in the treatment of erysipeloid, including endocarditis and septicemia, caused by E. rhusiopathiae . {134}7 {134}6 {134}5

Gingivitis, acute, necrotizing, ulcerative (treatment)—Penicillin G (oral and parenteral) {134}4 {134}3, penicillin V {134}2 {134}1, and penicillin G procaine {134}0 {95}9 are indicated in the treatment of acute, necrotizing, ulcerative gingivitis, also called Vincent"s angina or ``trench mouth,"" a pharyngeal and tonsillar infection caused by anaerobes and spirochetes. {95}8

Gonorrhea, endocervical and urethral, uncomplicated (treatment) —Amoxicillin, in combination with probenecid {95}7, and [penicillin G (parenteral)]1 {95}6 are indicated in the treatment of gonorrhea caused by susceptible strains of N. gonorrhoeae . However, because of resistance to penicillin, other agents, such as ceftriaxone, cefixime, or ciprofloxacin, are considered to be first-line agents. {95}5

Intra-abdominal infections (treatment)—Carbenicillin (parenteral) {95}4 {95}3, mezlocillin {95}2 {95}1, [penicillin G (parenteral)]1 {95}0, piperacillin {126}9 {126}8 {126}7, and ticarcillin {126}6 {126}5 are indicated in the treatment of intra-abdominal infections caused by susceptible organisms.

Listeriosis (treatment)—[ Ampicillin (parenteral)]1 {126}4 {126}3 and penicillin G (parenteral) {126}2 {126}1 {126}0 are indicated in the treatment of listeriosis caused by L. monocytogenes .

Meningitis, bacterial (treatment)—Ampicillin (parenteral) {126}9 {126}8 {126}7 {126}6, carbenicillin (parenteral) {126}5, [ nafcillin (parenteral)]1 {126}4, [oxacillin (parenteral)]1 {126}3, penicillin G (parenteral) {126}2 {126}1 {126}0 {17}9, [ piperacillin]1 {17}8 {17}7, and [ticarcillin]1 {17}6 are indicated in the treatment of bacterial meningitis caused by susceptible organisms.

Otitis media, acute (treatment)—Amoxicillin {17}5 {17}4 {17}3 {17}2, ampicillin {17}1 {17}0 {17}9 {17}8, bacampicillin {17}7 {17}6, penicillin G procaine {17}5 {17}4, penicillin G (oral) {17}3, penicillin V {17}2 {17}1, and pivampicillin {17}0 are indicated in the treatment of acute otitis media caused by susceptible organisms.

Pasteurella multocida infections (treatment) —[Ampicillin (parenteral)]1 {17}9, penicillin G (parenteral) {17}8 {17}7 {17}6, and [ penicillin V]1 {17}5 are indicated in the treatment of infections caused by P. multocida .

Pelvic infections, female (treatment)—[ Carbenicillin (parenteral)]1 {17}4, mezlocillin {17}3 {17}2 {17}1, piperacillin {17}0 {17}9 {17}8, and ticarcillin {17}7 {17}6 are indicated in the treatment of female pelvic infections caused by susceptible organisms.

Pericarditis, bacterial (treatment)—Penicillin G (parenteral) {17}5 {17}4, penicillin G procaine {17}3, and [nafcillin (parenteral)]1 {17}2 are indicated in the treatment of bacterial pericarditis caused by susceptible organisms.

Pharyngitis, bacterial (treatment)—Amoxicillin {17}1 {17}0, ampicillin {17}9 {17}8, bacampicillin {17}7 {17}6, cloxacillin (oral) {17}5, dicloxacillin {17}4, flucloxacillin {17}3, penicillin G benzathine {17}2 {17}1 {17}0, pencillin G (oral) {17}9, penicillin V {17}8 {17}7 {17}6 {17}5, and pivampicillin {17}4 are indicated in the treatment of bacterial pharyngitis caused by susceptible organisms.

Pinta (treatment)—Penicillin G benzathine {17}3 {17}2 {17}1 and penicillin G procaine {17}0 {17}9 are indicated in the treatment of pinta caused by Treponema carateum .

Pneumonia, bacterial (treatment)—Amoxicillin {17}8 {17}7 {17}6, ampicillin {17}5 {17}4, bacampicillin {17}3 {17}2, carbenicillin (parenteral) {17}1 {17}0, cloxacillin {95}9 {95}8, dicloxacillin {95}7, mezlocillin {95}6, penicillin G (parenteral) {95}5 {95}4 {95}3, penicillin G procaine {95}2, piperacillin {95}1 {95}0, and ticarcillin {17}9 {17}8 are indicated in the treatment of bacterial pneumonia caused by susceptible organisms.

Prostatitis (treatment)—Carbenicillin (oral) {17}7 {17}6 {17}5 is indicated in the treatment of prostatitis caused by susceptible organisms.

Rat-bite fever (treatment)—Penicillin G (parenteral) {17}4 {17}3, penicillin G procaine {17}2 {17}1 {17}0 {17}9, and [penicillin V]1 {17}8 {17}7 {17}6 are indicated in the treatment of rat-bite fever caused by S. moniliformis or S. minor .

Rheumatic fever (prophylaxis)—Penicillin V {17}5 {17}4 {17}3 {17}2, and penicillin G benzathine {17}1 {17}0 {07}9 {07}8 are indicated in the prophylaxis of rheumatic fever caused by group A streptococci.

Scarlet fever (treatment)—Penicillin V {07}7 {07}6 penicillin G procaine {07}5 {07}4, and [penicillin G (parenteral) ]1 {07}3 are indicated in the treatment of scarlet fever caused by group A streptococci.

Septicemia, bacterial (treatment)—Ampicillin (parenteral) {07}2 {07}1, carbenicillin (parenteral) {07}0 {118}9, cloxacillin (parenteral) {118}8, methicillin {118}7, mezlocillin {118}6 {118}5, nafcillin (parenteral) {118}4, oxacillin (parenteral) {118}3, penicillin G (parenteral) {118}2 {118}1 {118}0, penicillin G procaine {07}9, piperacillin {07}8 {07}7 {07}6, and ticarcillin {07}5 {07}4 {07}3 are indicated in the treatment of bacterial septicemia caused by susceptible organisms.

Sinusitis (treatment)—Amoxicillin {07}2 {07}1 {07}0 {118}9, ampicillin {118}8 {118}7 {118}6 {118}5, bacampicillin {118}4 {118}3 {118}2, cloxacillin {118}1, flucloxacillin {118}0, methicillin {17}9, nafcillin {17}8, oxacillin {17}7, and penicillin V {17}6 {17}5 are indicated in the treatment of sinusitis caused by susceptible organisms.

Skin and soft tissue infections (treatment)—Carbenicillin (parenteral) {17}4, cloxacillin {17}3 {17}2 {17}1, dicloxacillin {17}0 {103}, flucloxacillin {80}, methicillin {26}, mezlocillin {59}, nafcillin {23} {134}, oxacillin {28} {134}, penicillin G procaine {64} {85}, [penicillin G (parenteral)]1 {06} {134}, penicillin V {06} {42} {103}, piperacillin {12} {14}, pivampicillin {96}, and ticarcillin {17} {95} are indicated in the treatment of skin and soft tissue infections caused by susceptible organisms.

Syphilis (treatment)—Penicillin G benzathine is indicated in the treatment of primary, secondary, and early and late latent syphilis. {133} Penicillin G (parenteral) and penicillin G procaine, in combination with probenecid, are indicated in the treatment of tertiary syphilis. {129} Penicillin G (parenteral) is indicated in the treatment of neurosyphilis. {129} {133} Penicillin G benzathine fails to achieve adequate concentrations in the cerebrospinal fluid. {06}

Tetanus (treatment)—Penicillin G (parenteral) is indicated in the treatment of the infecting organism in tetanus, Clostridium tetani . {06} {63} {103} {134}

Ulcer, duodenal, associated with Helicobacter pylori (treatment)1—Amoxicillin is indicated as part of a triple antibiotic therapy, in combination with clarithromycin and lansoprazole, for patients who are infected with H. pylori and have duodenal ulcer disease (either active or a 1-year history of a duodenal ulcer) to eradicate the organism and thereby reduce the risk of ulcer recurrence. {151}
—Amoxicillin also is indicated as part of a dual antibiotic therapy, in combination with lansoprazole, in patients who are infected with H. pylori and have duodenal ulcer disease (either active or a 1-year history of a duodenal ulcer) when the patient is either intolerant or allergic to clarithromycin or when clarithromycin resistance is suspected or confirmed. {151}
— See Clarithromycin (Systemic) and Lansoprazole (Systemic) monographs for additional information pertaining to these medications.

Urinary tract infections, bacterial (treatment)— Amoxicillin {36} {134}, ampicillin {29} {35} {103}, bacampicillin {18} {52}, carbenicillin (oral and parenteral) {54} {78} {79} {103}, mezlocillin {59} {134}, piperacillin {12} {14} {134}, pivampicillin {96}, pivmecillinam {97}, and ticarcillin {17} {95} {103} are indicated in the treatment of bacterial urinary tract infections caused by susceptible organisms.

Yaws (treatment)—Penicillin G benzathine {62} {134}, penicillin G procaine {64} {85}, and [penicillin G (parenteral)] {06} {103} are indicated in the treatment of yaws caused by Treponema pallidum pertenue .

[Chlamydial infections in pregnant women (treatment)]1—Amoxicillin and ampicillin are used in the treatment of chlamydial infections in pregnant women who cannot tolerate erythromycin. {116} {132} {134}

[Gas gangrene infections (treatment) ]1—Penicillin G (parenteral) {103} {134} is used in the treatment of gas gangrene caused by Clostridium sp.

[Gastritis, Helicobacter pylori -associated (treatment adjunct)]1or
[Ulcer, peptic, Helicobacter pylori-associated (treatment adjunct)]1—Amoxicillin is used, in combination with metronidazole and bismuth subsalicylate, in the treatment of gastritis and peptic ulcer disease caused by H. pylori . {113} {114}

[Leptospirosis (treatment)]1—Ampicillin (parenteral) and penicillin G (parenteral) are used in the treatment of leptospirosis caused by Leptospira sp. {06} {103} {134}

[Lyme disease (treatment)]1—Amoxicillin and penicillin V are used in the treatment of early Lyme disease, caused by B. burgdorferi . {04} {05} {06} {103} Amoxicillin, in combination with probenecid, and penicillin G (parenteral) are used to treat more advanced stages of Lyme disease, including mild neurological manifestations, cardiac manifestations, and arthritis. {03} {04} {05} {103} {131}

[Typhoid fever (treatment)]1—Amoxicillin and ampicillin are used in the treatment of typhoid fever caused by Salmonella typhi . {103} {134}

Unaccepted


For carbenicillin (oral)
Since effective serum concentrations are not achieved with oral carbenicillin, it is indicated only for urinary tract infections and prostatitis. {103} {144}



For nafcillin (oral)
The oral absorption of nafcillin is erratic and the resulting serum concentrations are low; therefore, use of oral nafcillin is not recommended. {134} {144}



For penicillin G benzathine (parenteral)
Parenteral penicillin G benzathine is not indicated for the treatment of meningitis or neurosyphilis because it fails to achieve adequate concentrations in the cerebrospinal fluid (CSF). {06} {103}



For penicillin G (oral)
Because of the low serum concentrations achieved with oral penicillin G, it is not indicated for the treatment of severe infections. {82}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Table 1. Pharmacology/Pharmacokinetics



Drug
Oral
Absorption
(%)
Time to
Peak Serum
Concentration
(hr)
Peak Serum Concentration
Half-life (hr)

Creatinine
Clearance
> 50 mL/min
(0.83 mL/sec)
Creatinine
Clearance
10–30 mL/min
(0.17–0.83 mL/sec)
Creatinine
Clearance
< 10 mL/min
(0.17 mL/sec)
Dose
mcg/mL
Amoxicillin
75–90
1–2 (oral)
250 mg (oral)
3.5–5
1
4.5
12.6
Ampicillin
35–50
1.5–2 (oral)
1 (IM) *
500 mg (oral)
500 mg (IM)
500 mg (IV) *
3–6
7–14
12–29
1–1.5
3.4
19
Bacampicillin
35–50
0.5–1 (oral)
400 mg (oral)
7.9
1
4.5
12.6
Carbenicillin
30
0.5–1
(oral and IM)
500 mg (oral)
1 gram (IM)
2 grams (IV)
6.5
20
241
1–1.5
9.6
18.2
Cloxacillin
50
1–2 (oral)
500 mg (oral)
500 mg (IM)
8
16
0.5–1
  2.5
Dicloxacillin
37–50
0.5–1 (oral)
125 mg (oral)
4.7
0.5–1
  1.8
Flucloxacillin
30–50
1 (oral)
250 mg (oral)
6–10
0.7–1.3
 
 
Methicillin
  0.5–1 (IM)
1 gram (IM)
1 gram (IV)
12
60
0.3–1
  4
Mez-
locillin
  0.5–1 (IM)
1 gram (IM)
4 grams (IV)
35–45
254
0.8–1.1
2
2.6
Nafcillin
Erratic;
poor
1–2 (oral)
0.5–1 (IM)
1 gram (IM)
7.6
0.5–1.5
1.9
2.1
Oxacillin
30–35
0.5–1
(oral and IM)
500 mg (oral)
500 mg (IM)
5–7
15
0.4–0.7
  0.8
Penicillin G
(Oral)
(IV)
Benzathine (IM)
Procaine (IM)

15–30

1–2

24
4


3,200,000 units (IV)
300,000 units (IM)


2.2–17
0.03–0.05
0.5–0.7
  4.1
Penicillin V
60–73
0.5–1 (oral)
250 mg (oral)
2–3
0.5–1
  4.1
Piperacillin
  0.5 (IM)
4 grams (IV)
412
0.6–1.2
2
2.8
Pivampicillin
35–50
1 (oral)
500 mg (oral)
13
1
 
 
Pivmecillinam
Poor
0.5–1.5 (oral)
200 mg (oral)
3.3
1
 
 
Ticarcillin
  0.5–1 (IM)
3 grams (IV)
190
1–1.2
5.2
8.9
*  IV=intravenous; IM=intramuscular.
 As ampicillin.
 As mecillinam.


Table 2. Pharmacology/Pharmacokinetics



Drug
Protein
Binding
(%)
Hepatic
Biotransformation
(%)
Renal
Elimination
(% unchanged)
Vol D
(L/kg)
Removal by
Hemodialysis
Amoxicillin
Low (20)
10
60–75
0.36
Yes
Ampicillin
Low (20)
10
75–90
0.29
Yes
Bacampicillin
Low (18–20) *
10 *
70–75 *
0.29 *
Yes
Carbenicillin
Moderate (50)
0–2
36 (oral)
75–95 (intravenous)
0.12
Yes
Cloxacillin
Very high (95)
20
30–60
0.11
No
Dicloxacillin
Very high (95–98)
10
50–70
0.08
No
Flucloxacillin
Very high (94)

 
50–65

 
No
Methicillin
Low to moderate
(40)
10
60–80
0.36
No
Mezlocillin
Low to moderate
(16–42)
20–30
55–60
0.23
Yes
Nafcillin
High (90)
60–70
11–30
1.1
No
Oxacillin
High (90–94)
45
55–60
0.4
No
Penicillin G
(Oral)
(Parenteral)
Benzathine (IM)
Procaine
Moderate (60)
20

20
60–90
0.5–0.7
Yes
Penicillin V
High (80)
55
20–40
0.5
Yes
Piperacillin
Low (16)
20–30
60–80
0.23
Yes
Pivampicillin
Low (20) *
10 *
25–30 *

 

 
Pivmecillinam
Low (5–10)

 
60–80

 
Yes §
Ticarcillin
Moderate
(45–60)
15
60–80
0.16
Yes
*  As ampicillin.
 Hemodialysis removes 30–50% of piperacillin in 4 hours.
 As mecillinam.
§ Hemodialysis removes 50–70% of pivmecillinam in 4 hours.


Physicochemical characteristics:

Chemical group—
    Amoxicillin: Aminopenicillin {06}
    Ampicillin: Aminopenicillin {06}
    Bacampicillin: Aminopenicillin {06}
    Carbenicillin: Carboxypenicillin {07}
    Cloxacillin: Isoxazolyl penicillin {06}
    Dicloxacillin: Isoxazolyl penicillin {06}
    Flucloxacillin: Isoxazolyl penicillin {06}
    Mezlocillin: Acylureidopenicillin {07}
    Oxacillin: Isoxazolyl penicillin {06}
    Piperacillin: Acylureidopenicillin {07}
    Pivampicillin: Aminopenicillin {06}
    Ticarcillin: Carboxypenicillin {07}
Molecular weight—
{02}    Amoxicillin: 419.45
    Ampicillin: 349.40
    Ampicillin sodium: 371.39
    Bacampicillin hydrochloride: 501.98
    Carbenicillin disodium: 422.36
    Carbenicillin indanyl sodium: 516.54
    Cloxacillin sodium: 475.88
    Dicloxacillin sodium: 510.32
    Flucloxacillin: 453.87
    Methicillin sodium: 420.41
    Mezlocillin sodium: 561.56
    Nafcillin sodium: 454.47
    Oxacillin sodium: 441.43
    Penicillin G benzathine: 981.19
    Penicillin G potassium: 372.48
    Penicillin G procaine: 588.72
    Penicillin G sodium: 356.37
    Penicillin V potassium: 388.48
    Piperacillin sodium: 539.54
    Pivampicillin hydrochloride: 500.01
    Pivmecillinam: 439.57
    Ticarcillin disodium: 428.38

Mechanism of action/Effect:

Bactericidal; inhibit bacterial cell wall synthesis. Action is dependent on the ability of penicillins to reach and bind penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs (which include transpeptidases, carboxypeptidases, and endopeptidases) are enzymes that are involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. {07} Penicillins bind to, and inactivate, PBPs, resulting in the weakening of the bacterial cell wall and lysis. {06} {07}

Distribution:

Penicillins are widely distributed to most tissues and body fluids, including peritoneal fluid, blister fluid, urine (high concentrations), pleural fluid, middle ear fluid, intestinal mucosa, bone, gallbladder, lung, female reproductive tissues, and bile. Distribution into the cerebrospinal fluid (CSF) is low in subjects with noninflamed meninges, as is penetration into purulent bronchial secretions. {22} {25} {30} {37} {59} {82}

Penicillins also cross the placenta and are distributed into breast milk. {30} {37}

Biotransformation:

Hepatic metabolism accounts for less than 30% of the biotransformation of most penicillins, with the exception of nafcillin and oxacillin. {06} {07}

Bacampicillin—A prodrug of ampicillin; bacampicillin is hydrolyzed by esterases in the intestinal wall during absorption to produce ampicillin. {18} Bacampicillin provides earlier and higher peak concentrations of ampicillin than administration of ampicillin does. {06}

Carbenicillin indanyl sodium—After absorption, carbenicillin indanyl sodium is rapidly converted to carbenicillin by hydrolysis of the ester linkage. {78}

Penicillin G benzathine (intramuscular)—Slowly released from the intramuscular injection site and hydrolyzed to penicillin G, resulting in serum concentrations that are much lower but much more prolonged than other parenteral penicillins. {62}

Penicillin G procaine—Dissolves slowly at the site of injection, giving a plateau-type blood level at 4 hours, which falls slowly over the next 15 to 20 hours. {64}

Pivampicillin—A prodrug of ampicillin, which is converted during absorption to ampicillin, formaldehyde, and pivalic acid, by non-specific esterases in most body tissues. {96} Pivampicillin provides earlier and higher peak concentrations of ampicillin than administration of ampicillin does. {06}

Pivmecillinam—A prodrug of mecillinam, which is converted during absorption to mecillinam, formaldehyde, and pivalic acid, by nonspecific esterases in most body tissues. {97}

Elimination:
    Primarily renal (glomerular filtration and tubular secretion). {06} {07}
    Hepatic metabolism accounts for less than 30% of the elimination of most penicillins, with the exception of nafcillin and oxacillin. {06} {07}
    Biliary—Some penicillins, such as ampicillin {06} {30}, mezlocillin {06} {59}, nafcillin {06} {25}, penicillin G {06}, piperacillin {06} {14}, and pivmecillinam {06} {97}, may be excreted in the bile in high concentrations. Approximately 10% of cloxacillin, dicloxacillin, flucloxacillin, and oxacillin is recovered in the bile. {06}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients allergic to one penicillin may be allergic to other penicillins also. {17} {22} {30} {37} {101}

Patients allergic to cephalosporins or cephamycins may be allergic to penicillins also. {30} {37} Patients allergic to procaine or other ester-type local anesthetics may also be allergic to sterile penicillin G procaine suspension, which is an equimolar compound of procaine and penicillin G. {64}

Carcinogenicity

Amoxicillin, ampicillin, bacampicillin, cloxacillin, dicloxacillin, methicillin, nafcillin, oxacillin, penicillin G, penicillin V—Long-term studies have not been performed in animals. {19} {22} {24} {26} {27} {30} {37} {43} {52} {62}

Carbenicillin—Long-term studies have not been performed in animals. Rats given 25 to 100 mg per kg of body weight (mg/kg) per day of carbenicillin for 18 months developed mild liver pathology (bile duct hyperplasia) at all dose levels, but there was no evidence of drug-related neoplasia. {54}

Mutagenicity

Amoxicillin, ampicillin, bacampicillin, cloxacillin, dicloxacillin, methicillin, nafcillin, oxacillin, penicillin G, penicillin V—Long-term studies have not been performed in animals. {19} {22} {24} {26} {27} {30} {37} {43} {52} {62}

Pregnancy/Reproduction
Fertility—
Amoxicillin: Studies in mice and rats at doses up to 10 times the human dose of amoxicillin revealed no evidence of impaired fertility. {37}

Bacampicillin: Studies in mice and rats given doses of up to 750 mg/kg (more than 25 times the usual human dose) showed no evidence of impaired fertility. Also, bacampicillin had no effect on the reproductive organs of rats or dogs receiving daily oral doses of up to 800 and 650 mg, respectively, for 6 months. {52}

Carbenicillin: Administration of carbenicillin at doses of up to 1000 mg/kg had no apparent effect on the fertility or reproductive performance of rats. {54}

Cloxacillin, dicloxacillin, methicillin, nafcillin, oxacillin, penicillin G, penicillin V: Reproductive studies performed in the mouse, rat, and rabbit given these penicillins have revealed no evidence of impaired fertility. {20} {22} {24} {26} {27} {43} {62}

Mezlocillin: Studies in mice and rats given doses up to twice the usual human dose have not shown that mezlocillin impairs fertility. {59}

Piperacillin: Studies in mice and rats given doses up to 4 times the human dose of piperacillin have shown no evidence of impaired fertility. {12}

Ticarcillin: Reproductive studies done in mice and rats given ticarcillin have revealed no evidence of impaired fertility. {17}

Pregnancy—
Penicillins cross the placenta. Adequate and well-controlled studies in humans have not been done to determine whether penicillins are teratogenic; however, penicillins are widely used in pregnant women and problems have not been documented. {30} {37} {52} {54}

Amoxicillin: Studies in mice and rats at doses up to 10 times the human dose of amoxicillin revealed no evidence of harm to the fetus. {37}

FDA Pregnancy Category B.

Ampicillin: Studies in animals given doses several times the human dose have revealed no evidence of adverse effects in the fetus. {30}

FDA Pregnancy Category B.

Bacampicillin: Studies in mice and rats given doses of up to 750 mg/kg (more than 25 times the usual human dose) have not shown that bacampicillin causes adverse effects in the fetus. {52}

FDA Pregnancy Category B.

Carbenicillin: Reproductive studies using doses of 500 or 1000 mg/kg in rats, 200 mg/kg in mice, and 500 mg/kg in monkeys showed no harm to the fetus. {54}

FDA Pregnancy Category B.

Cloxacillin, dicloxacillin, methicillin, nafcillin, oxacillin, penicillin G, penicillin V: Reproductive studies performed in the mouse, rat, and rabbit given these penicillins have revealed no evidence of impaired fertility or harm to the fetus. {20} {22} {24} {26} {27} {43} {62}

FDA Pregnancy Category B.

Flucloxacillin, pivampicillin, pivmecillinam: Safety during pregnancy has not been established. {80} {96} {97}

Mezlocillin: Studies in mice and rats given doses up to twice the usual human dose have not shown that mezlocillin causes adverse effects in the fetus. {59}

FDA Pregnancy Category B.

Piperacillin: Studies in mice and rats given doses up to 4 times the usual human dose have not shown that piperacillin causes adverse effects in the fetus. {12}

FDA Pregnancy Category B.

Ticarcillin: Reproductive studies done in mice and rats given ticarcillin have not shown that ticarcillin causes adverse effects in the fetus. {17}

FDA Pregnancy Category B.

Breast-feeding

Penicillins are distributed into breast milk, some in low concentrations. {12} {18} {30} {37} {54} {59} {80} {101} Although significant problems in humans have not been documented, the use of penicillins by nursing mothers may lead to sensitization, diarrhea, candidiasis, and skin rash in the infant. {08}

Pediatrics

Many penicillins have been used in pediatric patients and no pediatrics-specific problems have been documented to date. However, the incompletely developed renal function of neonates and young infants may delay the excretion of renally eliminated penicillins. {09} {22} {25} {26} {62} {80}

Because pivampicillin and pivmecillinam have been associated with a decrease in serum carnitine, it is recommended that these penicillins be avoided in children less than 3 months of age. {96} {97}

The 200-mg and the 400-mg chewable tablets of amoxicillin contain 1.8 mg and 3.6 mg phenylalanine, respectively, produced through the metabolism of aspartame. These dosage forms should be used with caution, if at all, in patients with phenylketonuria. The other strengths and dosage forms of amoxicillin do not contain phenylalanine. {152}


Geriatrics


Penicillins have been used in geriatric patients and no geriatrics-specific problems have been documented to date. However, elderly patients are more likely to have age-related renal function impairment, which may require an adjustment in dosage in patients receiving penicillins.


Dental

Prolonged use of penicillins may lead to the development of oral candidiasis. {30} {37} {79} {101}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Allopurinol{10}{18}{30}    (concurrent use with ampicillin or bacampicillin may significantly increase the possibility of skin rash, especially in hyperuricemic patients; however, it has not been established that allopurinol, rather than the presence of hyperuricemia, is responsible for this effect)


» Aminoglycosides{07}{14}{59}    (mixing penicillins with aminoglycosides in vitro has resulted in substantial mutual inactivation; if these groups of antibacterials are to be administered concurrently, they should be administered at separate sites at least 1 hour apart)


» Angiotensin-converting enzyme (ACE) inhibitors or
» Diuretics, potassium-sparing or
» Potassium-containing medications, other or
» Potassium supplements{63}    (concurrent administration of these medications with parenteral penicillin G potassium may promote serum potassium accumulation with possible resultant hyperkalemia, especially in patients with renal insufficiency; concurrent administration with ACE inhibitors may result in hyperkalemia since reduction of aldosterone production induced by ACE inhibitors may lead to elevation of serum potassium)


» Anticoagulants, coumarin- or indandione-derivative or
» Heparin or
» Thrombolytic agents{07}{12}{17}{79}    (concurrent use of these medications with high-dose parenteral carbenicillin, piperacillin, or ticarcillin may increase the risk of hemorrhage because these penicillins inhibit platelet aggregation; patients should be monitored carefully for signs of bleeding; concurrent use of these penicillins with thrombolytic agents may increase the risk of severe hemorrhage and is not recommended)


» Anti-inflammatory drugs, nonsteroidal (NSAIDs), especially aspirin or
Diflunisal, very high doses or
Other salicylates or
» Platelet aggregation inhibitors, other (see Appendix II ) or
» Sulfinpyrazone{07}{12}{17}{79}    (concurrent use of these medications with high-dose parenteral carbenicillin, piperacillin, or ticarcillin may increase the risk of hemorrhage because of additive inhibition of platelet function; in addition, hypoprothrombinemia induced by large doses of salicylates and the gastrointestinal ulcerative or hemorrhagic potential of NSAIDs, salicylates, or sulfinpyrazone may also increase the risk of hemorrhage when these medications are used concurrently with these penicillins)


Chloramphenicol or
Erythromycins or
Sulfonamides or
Tetracyclines{11}{63}    (since bacteriostatic drugs may interfere with the bactericidal effect of penicillins in the treatment of meningitis or in other situations in which a rapid bactericidal effect is necessary, it is best to avoid concurrent therapy; however, chloramphenicol and ampicillin are sometimes administered concurrently to pediatric patients)


» Cholestyramine or{122}
» Colestipol{123}    (may impair absorption of oral penicillin G when used concurrently; patients should be advised to take oral penicillin G and these medications several hours apart)


» Contraceptives, estrogen-containing, oral{120}{121}    (there have been case reports of reduced oral contraceptive effectiveness in women taking ampicillin, amoxicillin, and penicillin V, resulting in unplanned pregnancy. This is thought to be due to a reduction in enterohepatic circulation of estrogens. Although the association is weak, patients should be advised of this information and given the option to use an alternate or additional method of contraception while taking any of these penicillins)


Disulfiram{18}{52}    (metabolism of the ester moiety of bacampicillin yields acetaldehyde and ethanol, which are later converted to acetaldehyde; furthermore, since disulfiram blocks the hepatic conversion of acetaldehyde to nontoxic compounds, concurrent use with bacampicillin may result in nausea, vomiting, confusion, and cardiovascular abnormalities)


Hepatotoxic medications, other (see Appendix II ){12}{20}{24}{27}{59}{80}    (concurrent use of other hepatotoxic medications with cloxacillin, dicloxacillin, flucloxacillin, mezlocillin, nafcillin, oxacillin, or piperacillin may increase the potential for hepatotoxicity)


» Methotrexate{138}{139}{140}{141}    (concurrent use with penicillins has resulted in decreased clearance of methotrexate and in methotrexate toxicity; this is thought to be due to competition for renal tubular secretion; patients should be closely monitored; leucovorin doses may need to be increased and administered for longer periods of time)


» Probenecid{18}{30}{54}{59}{97}{101}    (probenecid decreases renal tubular secretion of penicillins when used concurrently; this effect results in increased and prolonged serum concentrations, prolonged elimination half-life, and increased risk of toxicity. Penicillins and probenecid are often used concurrently to treat sexually transmitted diseases [STDs] or other infections in which high and/or prolonged antibiotic serum and tissue concentrations are required)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
» Glucose, urine{13}{30}{52}    (high urinary concentrations of a penicillin may produce false-positive or falsely elevated test results with copper sulfate tests [Benedict's, Clinitest, or Fehling's]; glucose enzymatic tests [ Clinistix or Testape] are not affected)


Direct antiglobulin (Coombs') tests{14}{59}{63}{105}    (false-positive result may occur during therapy with any penicillin)


Protein, urine{59}{107}    (high urinary concentrations of mezlocillin or ticarcillin may produce false-positive protein reactions [pseudoproteinuria] with the sulfosalicylic acid and boiling test, the acetic acid test, the biuret reaction, and the nitric acid test; bromophenol blue reagent test strips [ Multi-stix] are reportedly unaffected)

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) and
Alkaline phosphatase and
Aspartate aminotransferase (AST [SGOT]) and
Lactate dehydrogenase (LDH), serum    (values may be increased {12} {18} {20} {22} {59} {79} {80})


Bilirubin, serum{14}{17}{59}    (an increase has been associated with mezlocillin, piperacillin, and ticarcillin)


Blood urea nitrogen (BUN) and
Creatinine, serum{14}{59}{80}    (an increase has been associated with flucloxacillin, mezlocillin, and piperacillin)


Estradiol or
Estriol, total conjugated or
Estriol-glucuronide or
Estrone, conjugated{35}{52}    (concentrations may be transiently decreased in pregnant women following administration of ampicillin and bacampicillin)


» Partial thromboplastin time (PTT) and
» Prothrombin time (PT){14}{17}{105}    (an increase has been associated with intravenous carbenicillin, piperacillin, and ticarcillin)


Potassium, serum{14}{17}{59}{63}{79}    (hyperkalemia may occur following administration of large doses of parenteral penicillin G potassium because of high potassium content; hypokalemia may occur following administration of parenteral carbenicillin, mezlocillin, piperacillin, or ticarcillin, which may act as a nonreabsorbable anion in the distal renal tubules; this may cause an increase in pH and result in increased urinary potassium loss; the risk of hypokalemia increases with use of larger doses)


Sodium, serum{14}{17}{59}{79}{84}    (hypernatremia may occur following administration of large doses of parenteral carbenicillin, mezlocillin, penicillin G sodium, or ticarcillin because of the high sodium content of these medications)


Uric acid, serum{80}    (flucloxacillin may transiently decrease the serum uric acid concentration in some patients)


White blood cell count{14}{37}{124}    (leukopenia or neutropenia is associated with the use of all penicillins; the effect is more likely to occur with prolonged therapy and severe hepatic function impairment)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Allergy to penicillins{18}{30}{37}{54}
Risk-benefit should be considered when the following medical problems exist
Allergy, general, history of sensitivity to multiple allergens{18}{37}{54}
» Bleeding disorders, history of{14}{17}{79}    (some penicillins, especially carbenicillin, piperacillin, and ticarcillin, may cause platelet dysfunction and hemorrhage)


Carnitine deficiency{96}{97}    (pivampicillin and pivmecillinam may reduce serum carnitine concentrations by increasing the urinary excretion of carnitine; use of these penicillins is not recommended in patients with carnitine deficiency or in infants up to 3 months of age)


» Congestive heart failure (CHF) or
Hypertension{17}{79}    (the sodium content of high doses of parenteral carbenicillin and ticarcillin should be considered in patients who require sodium restriction)


» Cystic fibrosis{14}    (patients with cystic fibrosis may be at increased risk of fever and skin rash when given piperacillin)


» Gastrointestinal disease, history of, especially antibiotic-associated colitis{14}{18}{30}    (penicillins may cause pseudomembranous colitis)


» Mononucleosis, infectious{18}{30}    (a morbilliform skin rash may occur in a high percentage [43 to 100%] of patients taking ampicillin, bacampicillin, or pivampicillin)


» Phenylketonuria{152}    (the 200-mg and the 400-mg chewable tablets of amoxicillin and clavulanate contain aspartame, which is metabolized to phenylalanine, and may be hazardous to patients with phenylketonuria)


» Renal function impairment{17}{18}{63}{79}    (because most penicillins are excreted through the kidneys, a reduction in dosage, or increase in dosing interval, is recommended in patients with renal function impairment; also, the sodium content of high doses of parenteral carbenicillin and ticarcillin, and the potassium content of high doses of penicillin G potassium, should be considered in patients with severe renal function impairment)



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):


For carbenicillin (parenteral), piperacillin, ticarcillin
» Partial thromboplastin time (PTT) and
» Prothrombin time (PT){12}{17}{79}    (may be required prior to and during prolonged therapy in patients with renal function impairment who are receiving high doses since hemorrhagic manifestations may occur, although this effect is rare)


» Potassium, serum or
» Sodium, serum{12}{17}{79}    (determinations may be required periodically in patients with low potassium reserves and in patients receiving cytotoxic medications or diuretics who are also receiving high doses since hypokalemia may occur; also, because of the high sodium content of these medications, hypernatremia may occur)


For methicillin
» Renal function determinations{26}{112}    (may be required during prolonged therapy since methicillin may cause interstitial nephritis in up to 33% of patients treated with methicillin for more than 10 days)


For mezlocillin
Potassium, serum{59}    (may be required periodically during prolonged therapy in patients receiving high doses since hypokalemia may occur)


For penicillin G (parenteral)
Potassium, serum or
» Sodium, serum{63}    (may be required periodically during therapy in patients receiving high doses of penicillin G potassium or penicillin G sodium since hyperkalemia or hypernatremia may occur; very high doses of penicillin G potassium may cause severe or fatal hyperkalemia; very high doses of penicillin G sodium may cause congestive heart failure)


For all penicillins (if Clostridium difficile colitis occurs)
» Stool cytotoxin assays{15}{16}{117}    (enzyme immunoassay of stool samples for the presence of C. difficile toxins may be required prior to treatment of patients with antibiotic-associated colitis to document the presence of C. difficile toxins; however, C. difficile and its toxins may persist following treatment with oral vancomycin, metronidazole, or cholestyramine, despite clinical improvement; follow-up cultures and toxin assays are not recommended if clinical improvement is complete)




Side/Adverse Effects

Note: In clinical trials using combination therapy with amoxicillin plus clarithromycin and lansoprazole, or amoxicillin plus lansoprazole, no adverse reactions specific to these drug combinations were observed. {151} Adverse reactions that have occurred have been limited to those previously reported with amoxicillin, clarithromycin, or lansoprazole. {151} The side effects most commonly reported with the amoxicillin and lansoprazole combination were diarrhea and headache; the side effects most commonly reported with amoxicillin, clarithromycin, and lansoprazole combination were diarrhea, headache, and taste perversion. {151} See Clarithromycin (Systemic) and Lansoprazole (Systemic) monographs for additional information pertaining to these medications.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent {18} {30} {37} {79} {80} {101}
    
Allergic reactions, specifically anaphylaxis (fast or irregular breathing; puffiness or swelling around face; shortness of breath; sudden, severe decrease in blood pressure), exfoliative dermatitis (red, scaly skin), serum sickness–like reactions (skin rash; joint pain; fever), skin rash, hives, or itching

Incidence rare
    
Clostridium difficile colitis (severe abdominal or stomach cramps and pain; abdominal tenderness; watery and severe diarrhea, which may also be bloody; fever){14}{17}{18}{30}
    
hepatotoxicity (fever; nausea and vomiting; yellow eyes or skin){14}{20}{24}{27}{80}{109}{110}
    
interstitial nephritis (fever; possibly decreased urine output; skin rash){14}{24}{26}{27}{35}{79}
    
leukopenia or neutropenia (sore throat and fever){14}{17}{18}{25}{26}{30}{37}
    
mental disturbances (anxiety; confusion; agitation or combativeness; depression; seizures; hallucinations; expressed fear of impending death){64}
    
pain at site of injection{25}{59}{79}{101}
    
platelet dysfunction or thrombocytopenia (unusual bleeding or bruising){14}{17}{25}{84}{108}
    
seizures{14}{18}{22}{59}

Note: Hepatotoxicity has been associated with several penicillins, especially cloxacillin, dicloxacillin, flucloxacillin, and oxacillin; however, flucloxacillin appears to have a very high association with cholestatic jaundice, especially in older patients and those receiving flucloxacillin for more than 14 days. {109} {110} Also, one small study found HIV-infected patients to be more susceptible to oxacillin-hepatotoxicity (81%) than HIV-negative patients (4.5%). {127}
Interstitial nephritis is seen primarily with methicillin, and to a lesser degree with nafcillin and oxacillin, but may occur with any penicillin. {22} {24} {27} {111} {112}
Mental disturbances are toxic reactions to the procaine content of penicillin G procaine; this reaction may be seen in patients who receive a large single dose of the medication, as in the treatment of gonorrhea. {64}
Platelet dysfunction is primarily associated with carbenicillin, piperacillin, and ticarcillin; it may be more pronounced in patients with renal insufficiency due to the prolongation of the penicillin's half-life and uremic platelet dysfunction. {07} {14} {17} {79} {118}
Clostridium difficile colitis may occur up to several weeks after discontinuation of these medications. {15} {16} {117}
Seizures are more likely to occur in patients receiving high doses of a penicillin and/or patients with severe renal function impairment. {22} {63} {118}




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Gastrointestinal reactions (mild diarrhea; nausea or vomiting){18}{30}{54}
    
headache{14}{80}
    
oral candidiasis (sore mouth or tongue; white patches in mouth and/or on tongue){22}{30}{37}{79}{80}
    
vaginal candidiasis (vaginal itching and discharge){22}{30}{37}{79}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose
Specific treatment—Hemodialysis may aid in the removal of penicillins from the blood.

Supportive care—Since there is no specific antidote, treatment of penicillin overdose should be symptomatic and supportive. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Penicillins (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Allergy to penicillins, cephalosporins, or cephamycins

Pregnancy—Penicillins cross the placenta





Breast-feeding—Penicillins are distributed into breast milk





Use in children—Neonates and young infants may have reduced elimination of renally eliminated penicillins due to incompletely developed renal function; aspartame-containing amoxicillin products should be used with caution, if at all, in patients with phenylketonuria

Other medications, especially aminoglycosides; angiotensin-converting enzyme inhibitors; cholestyramine; colestipol; coumarin- or indandione-derivative anticoagulants; estrogen-containing oral contraceptives; heparin; methotrexate; nonsteroidal anti-inflammatory drugs (NSAIDs), especially aspirin; other platelet aggregation inhibitors; other potassium-containing medications; potassium-sparing diuretics; potassium supplements; probenecid; sulfinpyrazone; or thrombolytic agents
Other medical problems, especially a history of bleeding disorders; congestive heart failure; cystic fibrosis; active or history of gastrointestinal disease, especially antibiotic-associated colitis; infectious mononucleosis; phenylketonuria; or renal function impairment

Proper use of this medication
Taking on an empty stomach (for ampicillin, bacampicillin oral suspension, carbenicillin, cloxacillin, dicloxacillin, flucloxacillin, nafcillin, oxacillin, penicillin G) {22} {27} {35} {78} {80} {82} {101} {104}

Taking on a full or empty stomach (for amoxicillin, bacampicillin tablets, penicillin V, pivampicillin, pivmecillinam) {18} {37} {42} {96} {97}

Taking amoxicillin suspension straight or mixed with formulas, milk, fruit juice, water, ginger ale, or other cold drinks; taking immediately after mixing; drinking full dose {36}

Not drinking acidic fruit juices or other acidic beverages within 1 hour of taking oral penicillin G

Proper administration technique for oral liquids and/or pediatric drops

Not using after expiration date

» Compliance with full course of therapy, especially in streptococcal infections

» Importance of not missing doses and taking at evenly spaced times

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Checking with physician if no improvement within a few days

» For severe diarrhea, checking with physician before taking any antidiarrheals; for mild diarrhea, kaolin- or attapulgite-containing antidiarrheals may be used, but antiperistaltic antidiarrheals should be avoided; checking with physician or pharmacist if mild diarrhea continues or worsens

» Possibly using an alternate or additional method of contraception if taking estrogen-containing oral contraceptives concurrently, especially with ampicillin, amoxicillin, or penicillin V

» Diabetic patients: False-positive reactions with copper sulfate urine glucose tests may occur {13} {30} {52}

Possible interference with diagnostic tests


Side/adverse effects
Signs of potential side effects, especially allergic reactions, Clostridium difficile colitis, hepatotoxicity, interstitial nephritis, leukopenia or neutropenia, mental disturbances, pain at site of injection, platelet dysfunction or thrombocytopenia, and seizures


General Dosing Information
Therapy should be continued for at least 10 days in Group A beta-hemolytic streptococcal infections to help prevent the occurrence of acute rheumatic fever. {18} {30} {42} {80}

For oral dosage forms only
Penicillins, except amoxicillin, bacampicillin hydrochloride tablets, penicillin V, pivampicillin, and pivmecillinam, should preferably be taken with a full glass (240 mL) of water on an empty stomach (either 1 hour before or 2 hours after meals) to obtain optimum serum and/or urine concentrations. Amoxicillin, bacampicillin hydrochloride tablets, penicillin V, pivampicillin, and pivmecillinam may be taken on a full or empty stomach. {18} {37} {42} {96} {97}

For treatment of adverse effects
Serious anaphylactoid reactions require immediate emergency treatment, which consists of the following: {17} {18} {30} {37} {101}

   • Parenteral epinephrine.
   • Oxygen.
   • Intravenous corticosteroids.
   • Airway management (including intubation).
For Clostridium difficile colitis—

   • Some patients may develop Clostridium difficile colitis during or following administration of penicillins. {117}
   • C. difficile colitis may result in severe watery diarrhea, which may occur during therapy or up to several weeks after therapy is discontinued. If diarrhea occurs, administration of antiperistaltic antidiarrheals (e.g., opioids, diphenoxylate and atropine combination, loperamide, paregoric) is not recommended since they may delay the removal of toxins from the colon, thereby prolonging and/or worsening the condition. {15}
   • Mild cases may respond to discontinuation of the medication alone. Moderate to severe cases may require fluid, electrolyte, and protein replacement. {17}
   • In cases not responding to the above measures or in more severe cases, oral doses of vancomycin, metronidazole, or cholestyramine may be used. Oral vancomycin is effective in doses of 125 mg every 6 hours for 5 to 10 days. The dose of metronidazole is 250 to 500 mg every 8 hours and the dose of cholestyramine is 4 grams four times a day. Recurrences, which occur in approximately 25% of patients treated with vancomycin or metronidazole, may be treated with a second course of these medications. {15} {16} {117}
   • Cholestyramine resin has been shown to bind C. difficile toxin in vitro . If cholestyramine resin is administered in conjunction with oral vancomycin, the medications should be administered several hours apart since the resin has been shown to bind oral vancomycin also. {16}


AMOXICILLIN

Summary of Differences


Category:
Aminopenicillin.



Pharmacology/pharmacokinetics:
High oral absorption (75 to 90%).



Precautions:
Pediatrics—Patients with phenylketonuria should be aware that the 200-mg and the 400-mg chewable tablets contain 1.8 mg and 3.6 mg phenylalanine, respectively, as a component of aspartame. Other dosage forms and strengths do not contain aspartame.

Drug interactions and/or related problems—May also interact with oral contraceptives.

Medical considerations/Contraindications—Caution also needed in infectious mononucleosis. The amoxicillin products containing aspartame (200-mg and 400-mg chewable tablets) are hazardous to patients with phenylketonuria.



Additional Dosing Information
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. {134} Patients whose renal function impairment is severe (glomerular filtration rate of < 30 mL per minute) should not receive the 875-mg tablet. {152}

The 200-mg and the 400-mg chewable tablets contain phenylalanine. {152}

For oral dosage forms only {36} {37}
Amoxicillin may be taken on a full or empty stomach.

Amoxicillin may be taken with formulas, milk, fruit juice, water, ginger ale, or other cold drinks.


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

AMOXICILLIN CAPSULES USP

Usual adult dose
Antibacterial


• Ear, nose, and throat infections:


Mild or moderate—Oral, 500 mg every twelve hours or 250 mg every eight hours. {151}


Severe—Oral, 875 mg every twelve hours or 500 mg every eight hours. {151}


• Lower respiratory tract infections:


Mild, moderate, or severe—Oral, 875 mg every twelve hours or 500 mg every eight hours. {151}


• Skin or skin structure infections:


Mild or moderate—Oral, 500 mg every twelve hours or 250 mg every eight hours. {151}


Severe—Oral, 875 mg every twelve hours or 500 mg every eight hours. {151}


• Genitourinary tract infections:


Mild or moderate—Oral, 500 mg every twelve hours or 250 mg every eight hours. {151}


Severe—Oral, 875 mg every twelve hours or 500 mg every eight hours. {151}


• Gonorrhea, acute uncomplicated (anogenital and urethral infections): Oral, 3 grams as a single dose. {151}


• Endocarditis, bacterial (prophylaxis): Oral, 3 grams one hour before the procedure, then 1.5 grams six hours after the initial dose. {115} {130}


• Duodenal ulcer, Helicobacter pylori –associated1:


Triple antibiotic therapy: Oral, 1000 mg amoxicillin with 500 mg clarithromycin and 30 mg lansoprazole two times a day at twelve-hour intervals for fourteen days. {151}


Dual antibiotic therapy: Oral, 1000 mg amoxicillin with 30 mg lansoprazole three times a day at eight-hour intervals for fourteen days. {151}


[Chlamydia, treatment in pregnant women]1: Oral, 500 mg every eight hours for seven to ten days. {116} {132} {133}

[Gastritis, Helicobacter pylori ]1 or

[Ulcer, peptic, Helicobacter pylori ]1: Oral, 500 mg four times a day; or 750 mg three times a day. {113} {114}

[Lyme disease]1: Oral, 250 to 500 mg three or four times a day for three to four weeks. Duration of therapy is based on clinical response. Treatment failures have occurred and retreatment may be necessary. {03} {04} {05} {131}

Patients with severe renal function impairment require an adjustment in dosage as follows {152}:

• Patients with a glomerular filtration rate of 10-30 mL per minute—Oral, 500 mg or 250 mg every twelve hours, depending on the severity of the infection.


• Patients with a glomerular filtration rate of < 10 mL per minute—Oral, 500 mg or 250 mg every twenty-four hours, depending on the severity of the infection.


• Patients on hemodialysis—Oral, 500 mg or 250 mg every twenty-four hours, depending on the severity of the infection. An additional dose should be administered both during and at the end of the dialysis session.
Note: Patients with severe renal function impairment (glomerular filtration rate of < 30 mL per minute) should not receive the 875-mg tablet. {152}





Usual adult prescribing limits
4.5 grams a day. {130}

Usual pediatric dose
Antibacterial
Gonorrhea, endocervical and urethral, uncomplicated: Oral, 50 mg per kg of body weight and 25 mg of probenecid per kg of body weight simultaneously as a single dose in prepubertal children. However, probenecid is not recommended in children under 2 years of age. {38} {132}

Duodenal ulcer, Helicobactor pylori –associated1: Safety and efficacy have not been established for pediatric or adolescent patients. {151}

[Lyme disease]1: Oral, 6.7 to 13.3 mg per kg of body weight every eight hours for ten to thirty days. Duration of therapy is based on clinical response. Treatment failures have occurred and retreatment may be necessary. {03} {04} {05}

For all other indications: Infants and children up to 40 kg of body weight, see Amoxicillin for Oral Suspension USP .

Children 40 kg of body weight and over—See Usual adult dose. {151}


Strength(s) usually available
U.S.—


250 mg (Rx) [Amoxil] [Trimox] [Wymox][Generic]


500 mg (Rx) [Amoxil] [Trimox] [Wymox][Generic]

Canada—


250 mg (Rx) [Amoxil] [Apo-Amoxi] [Novamoxin] [Nu-Amoxi]


500 mg (Rx) [Amoxil] [Apo-Amoxi] [Novamoxin] [Nu-Amoxi]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.


AMOXICILLIN FOR ORAL SUSPENSION USP

Usual adult dose
See Amoxicillin Capsules USP .

Usual adult prescribing limits
See Amoxicillin Capsules USP .

Usual pediatric dose
Antibacterial


• Neonates and infants up to 3 months of age: Oral, not more than 30 mg per kg of body weight per day in divided doses every twelve hours. {152}


• Infants 3 months of age and older and children weighing less than 40 kg: {151}

• Ear, nose, and throat infections—


Mild or moderate: Oral, 20 mg per kg of body weight per day in divided doses every eight hours or 25 mg per kg of body weight per day in divided doses every twelve hours. {152}


Severe: Oral, 40 mg per kg of body weight per day in divided doses every eight hours or 45 mg per kg of body weight per day in divided doses every twelve hours. {152}


• Lower respiratory tract infections—


Mild, moderate, or severe: Oral, 40 mg per kg of body weight per day in divided doses every eight hours or 45 mg per kg of body weight per day in divided doses every twelve hours. {152}


• Skin or skin structure infections—


Mild or moderate: Oral, 20 mg per kg of body weight per day in divided doses every eight hours or 25 mg per kg of body weight per day in divided doses every twelve hours. {152}


Severe: Oral, 40 mg per kg of body weight per day in divided doses every eight hours or 45 mg per kg of body weight per day in divided doses every twelve hours. {152}


• Genitourinary tract infections—


Mild or moderate: Oral, 20 mg per kg of body weight per day in divided doses every eight hours or 25 mg per kg of body weight per day in divided doses every twelve hours. {152}


Severe: Oral, 40 mg per kg of body weight per day in divided doses every eight hours or 45 mg per kg of body weight per day in divided doses every twelve hours. {152}


• Gonorrhea, acute uncomplicated (anogenital or urethral) infections—


Oral, 50 mg per kg of body weight and 25 mg of probenecid per kg of body weight simultaneously as a single dose in prepubertal children. However, probenecid is not recommended in children under 2 years of age. {151}


• Duodenal ulcer, Helicobactor pylori –associated1


Safety and efficacy have not been established for pediatric or adolescent patients. {151}



• Children 40 kg of body weight and over—See Usual adult dose. {151}


Strength(s) usually available
U.S.—


50 mg per mL (when reconstituted according to manufacturer"s instructions) (Rx) [Amoxil] [Trimox] [Polymox]


125 mg per 5 mL (when reconstituted according to manufacturer"s instructions) (Rx) [Amoxil] [Polymox] [Trimox] [Wymox][Generic]


200 mg per 5 mL (when reconstituted according to manufacturer"s instructions) (Rx) [Amoxil{152}]


250 mg per 5 mL (when reconstituted according to manufacturer"s instructions) (Rx) [Amoxil] [Polymox] [Trimox] [Wymox][Generic]


400 mg per 5 mL (when reconstituted according to manufacturer"s instructions) (Rx) [Amoxil{152}]

Canada—


50 mg per mL (when reconstituted according to manufacturer"s instructions) (Rx) [Amoxil]


125 mg per 5 mL (when reconstituted according to manufacturer"s instructions) (Rx) [Amoxil] [Apo-Amoxi] [Novamoxin] [Nu-Amoxi]


250 mg per 5 mL (when reconstituted according to manufacturer"s instructions) (Rx) [Amoxil] [Apo-Amoxi] [Novamoxin] [Nu-Amoxi]

Packaging and storage:
Prior to reconstitution, store between 15 and 30 °C (59 and 86 °F). Store in a tight container.

Stability:
After reconstitution, suspensions retain their potency for up to 14 days at room temperature or for up to 14 days if refrigerated, depending on the manufacturer. {36} {37} {38}

Note: Some manufacturers prefer refrigerated storage. {38} {39} {40}


Auxiliary labeling:
   • Refrigerate.
   • Shake well.
   • Continue medication for full time of treatment.
   • Beyond-use date.
   • Take by mouth only (pediatric drops).

Note: Explain administration technique for pediatric drops (50 mg per mL).
When dispensing, include a calibrated liquid-measuring device.



AMOXICILLIN TABLETS

Usual adult dose
See Amoxicillin Capsules USP .

Usual adult prescribing limits
See Amoxicillin Capsules USP .

Usual pediatric dose
See Amoxicillin Capsules USP .

Strength(s) usually available
U.S.—


500 mg (Rx) [Amoxil{151}]


875 mg (Rx) [Amoxil{151}]

Canada—
Not commercially available.

Packaging and storage:
Store at or below 25 °C (77 °F). {151}

Auxiliary labeling:
   • Continue medication for full time of treatment.


AMOXICILLIN TABLETS (CHEWABLE) USP

Usual adult dose
See Amoxicillin Capsules USP .

Usual adult prescribing limits
See Amoxicillin Capsules USP .

Usual pediatric dose
See Amoxicillin Capsules USP .

Strength(s) usually available
U.S.—


125 mg (Rx) [Amoxil]


200 mg (Rx) [Amoxil{152} (aspartame [containing 1.8 mg phenylalanine])]


250 mg (Rx) [Amoxil][Generic]


400 mg (Rx) [Amoxil{152} (aspartame [containing 3.6 mg phenylalanine])]

Canada—


125 mg (Rx) [Amoxil]


250 mg (Rx) [Amoxil]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). Store in a tight container.

Auxiliary labeling:
   • Should be chewed or crushed.
   • Continue medication for full time of treatment.


AMPICILLIN

Summary of Differences


Category:
Aminopenicillin.



Precautions:
Drug interactions and/or related problems—Also interacts with allopurinol and oral contraceptives.

Medical considerations/contraindications—Caution also needed in infectious mononucleosis.



Additional Dosing Information
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. {134}


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

AMPICILLIN CAPSULES USP

Usual adult and adolescent dose
Antibacterial
Oral, 250 to 500 mg every six hours. {30}

[ Typhoid fever]1: Oral, 25 mg per kg of body weight every six hours. {134}


Usual adult prescribing limits
4 grams a day. {35}

Usual pediatric dose
Antibacterial
Infants and children up to 20 kg of body weight: A product of suitable strength is not available for infants and children up to 20 kg of body weight. See Ampicillin for Oral Suspension USP . {30}

Children 20 kg of body weight and over: See Usual adult and adolescent dose. {30}


Strength(s) usually available
U.S.—


250 mg (Rx) [Omnipen] [Principen] [Totacillin][Generic]


500 mg (Rx) [Omnipen] [Principen] [Totacillin][Generic]

Canada—


250 mg (Rx) [Apo-Ampi] [Novo-Ampicillin] [Nu-Ampi] [Penbritin]


500 mg (Rx) [Apo-Ampi] [Novo-Ampicillin] [Nu-Ampi] [Penbritin]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.
   • Take on empty stomach.


AMPICILLIN FOR ORAL SUSPENSION USP

Usual adult and adolescent dose
See Ampicillin Capsules USP .

Usual adult prescribing limits
See Ampicillin Capsules USP .

Usual pediatric dose
Antibacterial
Infants and children up to 20 kg of body weight: Oral, 12.5 to 25 mg per kg of body weight every six hours; or 16.7 to 33.3 mg per kg of body weight every eight hours {32}

Children 20 kg of body weight and over: See Usual adult and adolescent dose. {32}


Strength(s) usually available
U.S.—


100 mg per mL (Rx) [Polycillin]


125 mg per 5 mL (Rx) [Omnipen] [Polycillin] [Principen] [Totacillin][Generic]


250 mg per 5 mL (Rx) [Omnipen] [Polycillin] [Principen] [Totacillin][Generic]


500 mg per 5 mL (Rx) [Polycillin]

Canada—


125 mg per 5 mL (Rx) [Apo-Ampi] [Novo-Ampicillin] [Nu-Ampi]


250 mg per 5 mL (Rx) [Apo-Ampi] [Novo-Ampicillin] [Nu-Ampi] [Penbritin]

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Stability:
After reconstitution, suspensions retain their potency for 7 days at room temperature or for 14 days if refrigerated, depending on manufacturer. {30} {31} {32} {35}

Auxiliary labeling:
   • Refrigerate.
   • Shake well.
   • Continue medication for full time of treatment.
   • Beyond-use date.
   • Take by mouth only (pediatric drops).
   • Take on empty stomach.

Note: Explain administration technique for pediatric drops (100 mg per mL).
When dispensing, include a calibrated liquid-measuring device.




Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

Note: The dosing and strengths of the dosage forms available are expressed in terms of ampicillin base (not the sodium salt).


AMPICILLIN SODIUM STERILE USP

Usual adult and adolescent dose
Antibacterial
Intramuscular or intravenous, 250 to 500 mg (base) every six hours. {29}

Endocarditis, bacterial

Meningitis, bacterial or

Septicemia, bacterial: Intramuscular or intravenous, 1 to 2 grams (base) every three to four hours. {29} {103} {134}

Listeriosis: Intramuscular or intravenous, 50 mg per kg of body weight every six hours. {134}

[Leptospirosis]1: Intramuscular or intravenous, 500 mg to 1 gram every six hours. {134}

[Typhoid fever]1: Intramuscular or intravenous, 25 mg per kg of body weight every six hours. {134}


Usual adult prescribing limits
14 grams a day. {29}

Usual pediatric dose
Antibacterial {29}


Meningitis, bacterial:
Neonates up to 2 kg of body weight—Intramuscular or intravenous, 25 to 50 mg per kg of body weight every twelve hours during the first week of life {125} {126}, then 50 mg per kg of body weight every eight hours thereafter. {126} {142}

Neonates 2 kg of body weight and over—Intramuscular or intravenous, 50 mg per kg of body weight every eight hours during the first week of life {126} {142}, then 50 mg per kg of body weight every six hours thereafter. {142}



For all other indications:
Infants up to 20 kg of body weight—Intramuscular or intravenous, 12.5 mg (base) per kg of body weight every six hours.

Infants and children 20 kg of body weight and over—See Usual adult and adolescent dose.



Strength(s) usually available
U.S.—


125 mg (base) (Rx) [Omnipen-N] [Polycillin-N][Generic]


250 mg (base) (Rx) [Omnipen-N] [Polycillin-N] [Totacillin-N][Generic]


500 mg (base) (Rx) [Omnipen-N] [Polycillin-N] [Totacillin-N][Generic]


1 gram (base) (Rx) [Omnipen-N] [Polycillin-N] [Totacillin-N][Generic]


2 grams (base) (Rx) [Omnipen-N] [Polycillin-N] [Totacillin-N][Generic]


10 grams (base) (Rx) [Omnipen-N] [Polycillin-N][Generic]

Canada—


125 mg (base) (Rx) [Ampicin] [Penbritin]


250 mg (base) (Rx) [Ampicin] [Penbritin]


500 mg (base) (Rx) [Ampicin] [Penbritin]


1 gram (base) (Rx) [Ampicin] [Penbritin]


2 grams (base) (Rx) [Ampicin] [Penbritin]

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect the reconstituted solution from freezing.

Preparation of dosage form:
To prepare initial dilution for intramuscular use, depending on the manufacturer, add 0.9 to 1.2 mL of sterile water for injection or bacteriostatic water for injection to each 125-mg vial, 0.9 to 1.9 mL of diluent to each 250-mg vial, 1.2 to 1.8 mL of diluent to each 500-mg vial, 2.4 to 7.4 mL of diluent to each 1-gram vial, and 6.8 mL of diluent to each 2-gram vial. {29}

To prepare initial dilution for direct intermittent intravenous use, add 5 mL of sterile water for injection or bacteriostatic water for injection to each 125-, 250-, or 500-mg vial or at least 7.4 to 10 mL of diluent to each 1- or 2-gram vial. The resulting solution should be administered slowly over a 3- to 5-minute period for each 125- to 500-mg dose or over a 10- to 15-minute period for each 1- to 2-gram dose. More rapid administration may result in convulsive seizures. {29}

Intravenous infusions of sterile ampicillin sodium should be administered in a suitable diluent in a concentration not exceeding 30 mg per mL (see manufacturer"s package insert). {29}

For reconstitution of pharmacy bulk vials or piggyback infusion bottles, see manufacturer"s labeling for instructions.

Stability:
After reconstitution for intramuscular or direct intravenous use, solutions retain their potency for 1 hour. {29}

After reconstitution for intravenous infusion, solutions in concentrations up to 30 mg per mL retain at least 90% of their potency for 2 to 8 hours at room temperature or for up to 72 hours if refrigerated in suitable diluents (see manufacturer"s package insert). {29}

Concentrated solutions (100 mg per mL) prepared from pharmacy bulk vials retain their potency for 2 hours at room temperature or for 4 hours if refrigerated. {29}

Diluted solutions (20 mg per mL or less) in 5% dextrose injection retain their potency for 2 hours at room temperature or for 3 hours if refrigerated. {29}

Incompatibilities:
Extemporaneous admixtures of beta-lactam antibacterials (penicillins and cephalosporins) and aminoglycosides may result in substantial mutual inactivation. If these groups of antibacterials are administered concurrently, they should be administered in separate sites at least 1 hour apart. Do not mix them in the same intravenous bag, bottle, or tubing. {07} {118}

When aminoglycosides and penicillins are administered separately by different routes, a reduction in aminoglycoside serum concentration may occur. Usually this is clinically significant only in patients with severely impaired renal function when the excretion of both medications is delayed. {07} {118}

Additional information:
The sodium content is approximately 3.4 mEq (3.4 mmol) per gram of ampicillin, depending on the manufacturer. {76} {77} This must be considered in patients on a restricted sodium intake when calculating total daily sodium intake.


BACAMPICILLIN

Summary of Differences


Category:
Aminopenicillin.



Pharmacology/pharmacokinetics:
Hydrolyzed to ampicillin during absorption.



Precautions:
Drug interactions and/or related problems—Also interacts with allopurinol and disulfiram.

Medical considerations/contraindications—Caution also needed in infectious mononucleosis.



Additional Dosing Information
Bacampicillin is stable in the presence of gastric acid. Also, food does not delay or reduce absorption of bacampicillin hydrochloride tablets. Therefore, the tablets may be taken on a full or empty stomach. However, bacampicillin hydrochloride oral suspension should preferably be taken with a full glass (240 mL) of water on an empty stomach (either 1 hour before or 2 hours after meals) to obtain optimum serum and/or urine concentrations. {104}

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. {134} The serum half-life increases when the creatinine clearance is below 30 mL per minute (0.50 mL per second). {18}


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of bacampicillin hydrochloride (not the base).


BACAMPICILLIN HYDROCHLORIDE FOR ORAL SUSPENSION USP

Usual adult and adolescent dose
Antibacterial
Oral, 400 to 800 mg every twelve hours. {18}


Usual adult prescribing limits
3.2 grams a day. {18}

Usual pediatric dose
Antibacterial
Oral, 12.5 to 25 mg per kg of body weight every twelve hours. {52} {104}


Strength(s) usually available
U.S.—


125 mg per 5 mL (Rx) [Spectrobid]

Note: 125 mg of bacampicillin hydrochloride are equivalent to 87.5 mg of ampicillin.


Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Stability:
After reconstitution, suspensions retain their potency for 10 days if refrigerated. {104}

Auxiliary labeling:
   • Refrigerate.
   • Shake well.
   • Continue medication for full time of treatment.
   • Beyond-use date.
   • Take on empty stomach.

Note: When dispensing, include a calibrated liquid-measuring device.



BACAMPICILLIN HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
See Bacampicillin Hydrochloride for Oral Suspension USP .

Usual adult prescribing limits
See Bacampicillin Hydrochloride for Oral Suspension USP .

Usual pediatric dose
Infants and children up to 25 kg of body weight—Use of the tablets is not recommended. See Bacampicillin Hydrochloride for Oral Suspension USP . {18}

Children 25 kg of body weight and over—See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


400 mg (Rx) [Spectrobid]

Canada—


400 mg (Rx) [Penglobe (scored)]


800 mg (Rx) [Penglobe (scored)]

Note: 400 mg of bacampicillin hydrochloride are equivalent to 280 mg of ampicillin. {52}


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.


CARBENICILLIN

Summary of Differences


Category:
Antipseudomonal penicillin.



Pharmacology/pharmacokinetics:
Renal elimination of oral carbenicillin is approximately 36%, and 75 to 95% for intravenous carbenicillin.



Precautions:
Drug interactions and/or related problems—Parenteral carbenicillin also interacts with anticoagulants and other medications that affect blood clotting.

Laboratory value alterations—May increase bleeding time; may also cause hypernatremia.

Medical considerations/contraindications—Caution in patients with a history of bleeding disorders, congestive heart failure, or hypertension.

Patient monitoring—Bleeding time and serum potassium and sodium determinations may be required (parenteral only).



Additional Dosing Information

For oral dosage forms only
Patients with severely impaired renal function (creatinine clearance less than 10 mL per minute) will not achieve therapeutic urine concentrations of carbenicillin. {54}

For parenteral dosage forms only
Intramuscular injections should not exceed 2 grams in each site. {105}

Intermittent infusions may be administered over a 30- to 40-minute period. {78}

Patients with impaired renal function may require a reduction in dose and should be observed for hemorrhagic complications. {78}


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of carbenicillin indanyl sodium (not the base).


CARBENICILLIN INDANYL SODIUM TABLETS USP

Usual adult and adolescent dose
Antibacterial
Oral, 500 mg to 1 gram every six hours. {54}


Usual pediatric dose
Dosage has not been established. {54}

Strength(s) usually available
U.S.—


500 mg (Rx) [Geocillin]

Canada—


500 mg (Rx) [Geopen Oral]

Note: 500 mg of carbenicillin indanyl sodium are equivalent to 382 mg of carbenicillin and 118 mg of indanyl sodium. {54}


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.



Parenteral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of carbenicillin disodium (not the base).


CARBENICILLIN DISODIUM STERILE USP

Usual adult and adolescent dose
Antibacterial
Intramuscular or intravenous, 50 to 83.3 mg per kg of body weight every four hours. {105}

Urinary tract infections: Intramuscular or intravenous, 1 to 2 grams every six hours; or up to 50 mg per kg of body weight every six hours. {105}


Usual adult prescribing limits
Up to 40 grams a day. {105}

Usual pediatric dose
Antibacterial
Neonates up to 2 kg of body weight: Intramuscular or intravenous, 75 mg per kg of body weight every twelve hours during the first week of life; followed by 75 mg per kg of body weight every eight hours thereafter. {126}

Neonates 2 kg of body weight and over: Intramuscular or intravenous, 75 mg per kg of body weight every eight hours during the first week of life; followed by 75 mg per kg of body weight every six hours thereafter. {126}

Older infants and children: Intramuscular or intravenous, 25 to 75 mg per kg of body weight every six hours; or 16.7 to 50 mg per kg of body weight every four hours. {79}


Size(s) usually available:
U.S.—


1 gram (Rx) [Geopen]


2 grams (Rx) [Geopen]


5 grams (Rx) [Geopen]


10 grams (Rx) [Geopen]


30 grams (Rx) [Geopen]

Canada—


1 gram (Rx) [Pyopen]


5 grams (Rx) [Pyopen]

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
To prepare initial dilution for intramuscular use, depending on the manufacturer, add 2 to 3.6 mL of sterile water for injection or bacteriostatic water for injection (preserved with 0.9% benzyl alcohol) to each 1-gram vial, 4 to 7.2 mL of diluent to each 2-gram vial, and 7 to 17 mL of diluent to each 5-gram vial. Lidocaine hydrochloride injection 0.5% (without epinephrine) may also be used as a diluent for intramuscular use. {105}

To prepare initial dilution for direct intravenous use, reconstitute as directed above for intramuscular use. Each gram of carbenicillin should be further diluted with the addition of not less than 5 mL of diluent. The resulting solution should be administered as slowly as possible to avoid vein irritation. {105}

For reconstitution of pharmacy bulk vials or piggyback infusion bottles, see manufacturer"s labeling for instructions.

Caution—Use of diluents containing benzyl alcohol is not recommended for preparation of medications for use in neonates. A fatal toxic syndrome consisting of metabolic acidosis, CNS depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with this use.

Stability:
After reconstitution for intramuscular or direct intravenous use, solutions retain their potency for 24 hours at room temperature or for 72 hours if refrigerated. {105}

Intravenous infusions in suitable diluents (see manufacturer"s package insert), concentrated solutions (200 mg per mL), or diluted solutions (10 to 100 mg per mL) prepared from pharmacy bulk vials retain their potency for 24 hours at room temperature or for 72 hours if refrigerated. {105}

Incompatibilities:
Extemporaneous admixtures of beta-lactam antibacterials (penicillins and cephalosporins) and aminoglycosides may result in substantial mutual inactivation. If these groups of antibacterials are administered concurrently, they should be administered in separate sites at least 1 hour apart. Do not mix them in the same intravenous bag, bottle, or tubing. {07} {118}

When aminoglycosides and penicillins are administered separately by different routes, a reduction in aminoglycoside serum concentration may occur. Usually this is clinically significant only in patients with severely impaired renal function when the excretion of both medications is delayed. {07} {118}

Additional information:
The sodium content is approximately 4.7 to 5.3 mEq (4.7 to 5.3 mmol) {105}, but may be as high as 6.5 mEq (6.5 mmol) {79}, per gram of carbenicillin. This must be considered in patients on a restricted sodium intake when calculating total daily sodium intake.


CLOXACILLIN

Summary of Differences
Category: Penicillinase-resistant penicillin.

Pharmacology/pharmacokinetics: Very high plasma protein binding (95%).

Precautions: Drug interactions and/or related problems—May interact with other hepatotoxic medications.

Side/adverse effects: May be an increased risk of hepatotoxicity.


Additional Dosing Information
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. {134}

Cloxacillin should be taken on an empty stomach, preferably 1 hour before meals. {101}


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of cloxacillin base (not the sodium salt).


CLOXACILLIN SODIUM CAPSULES USP

Usual adult and adolescent dose
Antibacterial
Oral, 250 to 500 mg (base) every six hours. {19} {101}


Usual adult prescribing limits
6 grams (base) a day. {101}

Usual pediatric dose
Antibacterial {19} {101}
Infants and children up to 20 kg of body weight: Oral, 6.25 to 12.5 mg (base) per kg of body weight every six hours.

Children 20 kg of body weight and over: See Usual adult and adolescent dose.


Strength(s) usually available
U.S.—


250 mg (base) (Rx) [Cloxapen][Generic]


500 mg (base) (Rx) [Cloxapen][Generic]

Canada—


250 mg (base) (Rx) [Apo-Cloxi] [Novo-Cloxin] [Nu-Cloxi] [Orbenin]


500 mg (base) (Rx) [Apo-Cloxi] [Novo-Cloxin] [Nu-Cloxi] [Orbenin]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.
   • Take on empty stomach.


CLOXACILLIN SODIUM FOR ORAL SOLUTION USP

Usual adult and adolescent dose
See Cloxacillin Sodium Capsules USP .

Usual adult prescribing limits
See Cloxacillin Sodium Capsules USP .

Usual pediatric dose
See Cloxacillin Sodium Capsules USP .

Strength(s) usually available
U.S.—


125 mg per 5 mL (base) (Rx) [Tegopen][Generic]

Canada—


125 mg per 5 mL (base) (Rx) [Apo-Cloxi] [Novo-Cloxin] [Nu-Cloxi] [Orbenin]

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Stability:
After reconstitution, solutions retain their potency for 14 days if refrigerated. {20}

Auxiliary labeling:
   • Refrigerate.
   • Continue medication for full time of treatment.
   • Beyond-use date.
   • Take on empty stomach.

Note: When dispensing, include a calibrated liquid-measuring device.




Parenteral Dosage Forms

Note: The dosing and dosage forms available are expressed in terms of cloxacillin base (not the sodium salt).


CLOXACILLIN SODIUM INJECTION

Usual adult and adolescent dose
Antibacterial
Intravenous, 250 to 500 mg (base) every six hours. {101}


Usual adult prescribing limits
6 grams (base) a day. {101}

Usual pediatric dose
Antibacterial {101}
Infants and children up to 20 kg of body weight: Intravenous, 6.25 to 12.5 mg (base) per kg of body weight every six hours.

Children 20 kg of body weight and over: See Usual adult and adolescent dose.


Note: Cystic fibrosis patients: Intravenous, 25 mg (base) per kg of body weight every six hours. {119}


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


250 mg (base) (Rx) [Orbenin] [Tegopen]


500 mg (base) (Rx) [Orbenin] [Tegopen]


2 grams (base) (Rx) [Orbenin] [Tegopen]

Packaging and storage:
Prior to reconstitution, store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
To prepare for intramuscular injection, add 1.9 mL or 1.7 mL of sterile water for injection to each 250 mg or 500 mg vial, respectively, and shake to dissolve. {101}

To prepare for intravenous injection, add 4.9 mL, 4.8 mL, or 6.8 mL of sterile water for injection to each 250 mg, 500 mg, or 2 gram vial, respectively, and shake to dissolve. {101}

For direct intravenous use, the resulting solution should be administered slowly over a 2- to 4-minute period. {101}

For intermittent intravenous use, the resulting solution should be further diluted with a suitable diluent (see manufacturer"s package insert). It may be administered over a 30- to 40-minute period. {101}

Stability:
After reconstitution with suitable diluents (see manufacturer"s package insert), solutions retain their potency for 24 hours at controlled room temperature (25 °C [77 °F]), or 72 hours if refrigerated. {101}

Incompatibilities:
Extemporaneous admixtures of beta-lactam antibacterials (penicillins and cephalosporins) and aminoglycosides may result in substantial mutual inactivation. If these groups of antibacterials are administered concurrently, they should be administered in separate sites at least 1 hour apart. Do not mix them in the same intravenous bag, bottle, or tubing. {07} {118}

When aminoglycosides and penicillins are administered separately by different routes, a reduction in aminoglycoside serum concentration may occur. Usually this is clinically significant only in patients with severely impaired renal function when the excretion of both medications is delayed. {07} {118}


DICLOXACILLIN

Summary of Differences
Category: Penicillinase-resistant penicillin.

Pharmacology/pharmacokinetics: Very high plasma protein binding (95 to 98%).

Precautions: Drug interactions and/or related problems—May react with other hepatotoxic medications.

Side/adverse effects: May be an increased risk of hepatotoxicity.


Additional Dosing Information
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. {134}

Dicloxacillin should be taken on an empty stomach, preferably 1 hour before meals. {22}


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of dicloxacillin base (not the sodium salt).


DICLOXACILLIN SODIUM CAPSULES USP

Usual adult and adolescent dose
Antibacterial
Oral, 125 to 250 mg (base) every six hours. {22}


Usual adult prescribing limits
6 grams (base) a day.

Usual pediatric dose
Antibacterial
Infants and children up to 40 kg of body weight: Oral, 3.125 to 6.25 mg (base) per kg of body weight every six hours. {22}

Children 40 kg of body weight and over: See Usual adult and adolescent dose. {22}


Note: Cystic fibrosis patients: Oral, 12.5 to 25 mg (base) per kg of body weight every six hours. {119}


Strength(s) usually available
U.S.—


125 mg (base) (Rx) [Dynapen]


250 mg (base) (Rx) [Dycill] [Dynapen] [Pathocil][Generic]


500 mg (base) (Rx) [Dycill] [Dynapen] [Pathocil][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.
   • Take on empty stomach.


DICLOXACILLIN SODIUM FOR ORAL SUSPENSION USP

Usual adult and adolescent dose
See Dicloxacillin Sodium Capsules USP .

Usual adult prescribing limits
See Dicloxacillin Sodium Capsules USP .

Usual pediatric dose
See Dicloxacillin Sodium Capsules USP .

Strength(s) usually available
U.S.—


62.5 mg per 5 mL (base) (Rx) [Dynapen] [Pathocil]

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Stability:
After reconstitution, suspensions retain their potency for 7 days at room temperature or for 14 days if refrigerated. {22}

Auxiliary labeling:
   • Refrigerate.
   • Shake well.
   • Continue medication for full time of treatment.
   • Beyond-use date.
   • Take on empty stomach.

Note: When dispensing, include a calibrated liquid-measuring device.



FLUCLOXACILLIN

Summary of Differences


Category:
Penicillinase-resistant penicillin.



Pharmacology/pharmacokinetics:
Very high plasma protein binding (94%).



Precautions:
Drug interactions and/or related problems—May react with other hepatotoxic medications.

Laboratory value alterations—May transiently decrease the serum uric acid concentration in some patients.



Side/adverse effects:
May be an increased risk of cholestatic jaundice.



Additional Dosing Information
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. {134}

Flucloxacillin should be taken on an empty stomach, preferably 1 hour before meals. {80}


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of flucloxacillin sodium (not the base).


FLUCLOXACILLIN SODIUM CAPSULES

Usual adult and adolescent dose
Antibacterial
Oral, 250 to 500 mg every six hours. {80}


Usual pediatric dose
Antibacterial
Children less than 12 years of age and up to 40 kg of body weight: Oral, 125 to 250 mg every six hours; or 6.25 to 12.5 mg per kg of body weight every six hours {80}

Infants up to 6 months of age: Oral, 6.25 mg per kg of body weight every six hours. {80}


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


250 mg (Rx) [Fluclox]


500 mg (Rx) [Fluclox]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.
   • Take on empty stomach.


FLUCLOXACILLIN FOR ORAL SUSPENSION USP

Usual adult and adolescent dose
See Flucloxacillin Sodium Capsules .

Usual pediatric dose
See Flucloxacillin Sodium Capsules .

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


125 mg per 5 mL (Rx) [Fluclox]


250 mg per 5 mL (Rx) [Fluclox]

Packaging and storage:
Prior to reconstitution, store between 15 and 30 °C (59 and 86 °F). Store in a tight container.

Stability:
After reconstitution, the suspension retains its potency for 7 days when refrigerated. {80}

Auxiliary labeling:
   • Refrigerate.
   • Shake well.
   • Continue medication for full time of treatment.
   • Beyond-use date.
   • Take on empty stomach.

Note: When dispensing, include a calibrated liquid-measuring device.



METHICILLIN

Summary of Differences
Category: Penicillinase-resistant penicillin.

Precautions: Patient monitoring—Renal function determinations may be required because of interstitial nephritis.

Side/adverse effects—May be increased risk of interstitial nephritis.


Additional Dosing Information
Methicillin sodium for injection should be administered by deep intragluteal injection or by intravenous injection only. {26}

Patients with impaired renal function require a reduction in dose. {26}


Parenteral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of methicillin sodium (not the base).


METHICILLIN SODIUM FOR INJECTION USP

Usual adult and adolescent dose
Antibacterial
Intramuscular, 1 gram every four to six hours.

Intravenous, 1 gram every six hours. {26}


Usual adult prescribing limits
24 grams a day.

Usual pediatric dose
Antibacterial


Meningitis, bacterial:
Neonates up to 2 kg of body weight—Intramuscular or intravenous, 25 to 50 mg per kg of body weight every twelve hours during the first week of life {125} {126}, then 50 mg per kg of body weight every eight hours thereafter. {126}

Neonates 2 kg of body weight and over—Intramuscular or intravenous, 50 mg per kg of body weight every eight hours during the first week of life {126}, then 50 mg per kg of body weight every six hours thereafter. {126}



For all other indications:
Infants and children up to 40 kg of body weight—Intramuscular or intravenous, 25 mg per kg of body weight every six hours. {26}

Children 40 kg of body weight and over—See Usual adult and adolescent dose. {26}



Note: Cystic fibrosis patients—Intramuscular or intravenous, 50 mg per kg of body weight every six hours. {119}


Size(s) usually available:
U.S.—


1 gram (Rx) [Staphcillin]


4 grams (Rx) [Staphcillin]


6 grams (Rx) [Staphcillin]


10 grams (Rx) [Staphcillin]

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store between 15 and 30 °C (59 and 86 °F).

Preparation of dosage form:
To prepare initial dilution for intramuscular use, add 1.5 mL of sterile water for injection or 0.9% sodium chloride injection to each 1-gram vial, 5.7 mL of diluent to each 4-gram vial, and 8.6 mL of diluent to each 6-gram vial to provide a concentration of 500 mg per mL. {26}

To prepare initial dilution for direct intravenous use, reconstitute as directed above for intramuscular use. Each mL (500 mg) of the resulting solution should be further diluted in 25 mL of 0.9% sodium chloride injection and administered at the rate of 10 mL per minute. {26}

For reconstitution of pharmacy bulk vials or piggyback infusion bottles, see manufacturer"s labeling for instructions.

Stability:
After reconstitution for intramuscular use, solutions retain their potency for 24 hours at room temperature or for 4 days if refrigerated. {26}

After reconstitution for intravenous use, solutions in concentrations of 2 to 20 mg per mL retain at least 90% of their potency for 8 hours at room temperature in suitable diluents (see manufacturer"s package insert). {26}

Incompatibilities:
Extemporaneous admixtures of beta-lactam antibacterials (penicillins and cephalosporins) and aminoglycosides may result in substantial mutual inactivation. If these groups of antibacterials are administered concurrently, they should be administered in separate sites at least 1 hour apart. Do not mix them in the same intravenous bag, bottle, or tubing. {07} {118}

When aminoglycosides and penicillins are administered separately by different routes, a reduction in aminoglycoside serum concentration may occur. Usually this is clinically significant only in patients with severely impaired renal function when the excretion of both medications is delayed. {07} {118}

Extemporaneous admixtures of other drugs with methicillin sodium for injection are not recommended. {26}

Additional information:
The total sodium content is approximately 2.24 mEq (2.24 mmol) per gram of methicillin sodium. {106} This must be considered in patients on a restricted sodium intake when calculating total daily sodium intake.


MEZLOCILLIN

Summary of Differences


Category:
Antipseudomonal penicillin.



Precautions:
Drug interactions and/or related problems—May also interact with other hepatotoxic medications.

Laboratory value alterations—May produce false-positive protein reactions with various urine protein tests.

Patient monitoring—Serum potassium determinations may be required.



Additional Dosing Information
Intramuscular injections should not exceed 2 grams in each site. {59}

Adults with impaired renal function may require a reduction in dose as follows: {59}

Creatinine Clearance
(mL/min)/(mL/sec)

Dose
> 30/0.50
See Usual adult and adolescent dose
10–30/0.17–0.50
1.5 to 3 grams every 6 to 8 hours
< 10/0.17
1.5 to 2 grams every 8 hours
Hemodialysis patients
3 to 4 grams after each dialysis,
then every 12 hours
Peritoneal dialysis
patients
3 grams every 12 hours



Parenteral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of mezlocillin sodium (not the base).


MEZLOCILLIN SODIUM STERILE USP

Usual adult and adolescent dose
Antibacterial
Intramuscular or intravenous, 33.3 to 58.3 mg per kg of body weight every four hours; 50 to 87.5 mg per kg of body weight every six hours; or 3 to 4 grams every four to six hours. {59}

Urinary tract infections, complicated: Intravenous, 37.5 to 50 mg per kg of body weight every six hours; or 3 grams every six hours. {59}

Urinary tract infections, uncomplicated: Intramuscular or intravenous, 25 to 3l.25 mg per kg of body weight every six hours; or l.5 to 2 grams every six hours. {59}


Usual adult prescribing limits
24 grams a day. {59}

Usual pediatric dose
Antibacterial
Neonates up to 2 kg of body weight: Intramuscular or intravenous, 50 to 75 mg per kg of body weight every twelve hours during the first week of life {125} {126}, then 50 mg per kg of body weight every eight hours thereafter. {126}

Neonates 2 kg of body weight and over: Intramuscular or intravenous, 50 mg per kg of body weight every eight hours during the first week of life {126}, then 50 mg per kg of body weight every six hours thereafter. {126}

Infants over 1 month of age and children up to 12 years of age: Intramuscular or intravenous, 50 mg per kg of body weight every four hours. {59}


Size(s) usually available:
U.S.—


1 gram (Rx) [Mezlin]


2 grams (Rx) [Mezlin]


3 grams (Rx) [Mezlin]


4 grams (Rx) [Mezlin]


20 grams (Rx) [Mezlin]

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store below 30 °C (86 °F). After reconstitution, if precipitation occurs during refrigeration, the solution may be warmed to 37 °C (98.6 °F) for 20 minutes in a water bath, and shaken well.

Preparation of dosage form:
To prepare initial dilution for intramuscular use, add 3 to 4 mL of sterile water for injection or 0.5 or 1% lidocaine hydrochloride injection (without epinephrine) to each 1-gram vial and shake vigorously. {59}

The resulting solution should be administered slowly over a 12- to 15-second period to minimize discomfort. {59}

To prepare initial dilution for intravenous use, add at least 10 mL of sterile water for injection, 5% dextrose injection, or 0.9% sodium chloride injection to each 1-gram vial and shake vigorously. For direct intravenous use, the resulting solution should be administered slowly over a 3- to 5-minute period to minimize vein irritation. The concentration should not exceed 10% (100 mg per mL). {59}

For intermittent intravenous use, the resulting solution should be further diluted in 50 to 100 mL of a suitable diluent (see manufacturer"s package insert). It may be administered over a 30-minute period by direct infusion or by a Y-type hook-up. {59}

For reconstitution of piggyback infusion bottles, see manufacturer"s labeling for instructions. If the Y-type or piggyback method of administration is used, the primary infusion should be temporarily discontinued during infusion of mezlocillin. {59}

Stability:
After reconstitution with suitable diluents (see manufacturer"s package insert), solutions at concentrations of 10 and 100 mg per mL retain at least 90% of their potency for 24 to 72 hours at controlled room temperature (15 to 30 °C [59 to 86 °F]) or for 1 to 7 days if refrigerated. {59}

After reconstitution with sterile water for injection, 0.9% sodium chloride injection, or 5% dextrose injection, solutions at concentrations of up to 100 mg per mL retain their potency for 4 weeks when frozen at -12 °C (10 °F). {59}

After reconstitution with sterile water for injection, 0.9% sodium chloride injection, or 0.5 or 1% lidocaine hydrochloride injection (without epinephrine), solutions at concentrations of up to 250 mg per mL retain their potency for 24 hours at room temperature. {59}

Solutions range from clear and colorless to pale yellow in color. However, the powder and reconstituted solution may darken slightly during storage; this darkening does not affect their potency. {59}

Incompatibilities:
Extemporaneous admixtures of beta-lactam antibacterials (penicillins and cephalosporins) and aminoglycosides may result in substantial mutual inactivation. If these groups of antibacterials are administered concurrently, they should be administered in separate sites at least 1 hour apart. Do not mix them in the same intravenous bag, bottle, or tubing. {07} {118}

When aminoglycosides and penicillins are administered separately by different routes, a reduction in aminoglycoside serum concentration may occur. Usually this is clinically significant only in patients with severely impaired renal function when the excretion of both medications is delayed. {07} {118}

Additional information:
The sodium content is approximately 1.9 mEq (43 mg) per gram of mezlocillin. {59} This must be considered in patients on a restricted sodium intake when calculating total daily sodium intake.


NAFCILLIN

Summary of Differences


Category:
Penicillinase-resistant penicillin.



Pharmacology/pharmacokinetics:
Oral absorption—Erratic and poor.

Protein binding—High (90%).

Hepatic biotransformation—High (60–70%).



Precautions:


Drug interactions and/or related problems—
May also interact with other hepatotoxic medications.




Side/adverse effects:
May be an increased risk of interstitial nephritis.



Additional Dosing Information
Nafcillin sodium for injection should be administered by deep intragluteal injection or by intravenous injection only. {24}


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of nafcillin base (not the sodium salt).


NAFCILLIN SODIUM CAPSULES USP

Usual adult and adolescent dose
Antibacterial
Oral, 250 mg to 1 gram (base) every four to six hours. {25}


Usual adult prescribing limits
6 grams (base) daily.

Usual pediatric dose
Antibacterial


Pharyngitis, bacterial:
Oral, 250 mg (base) every eight hours. {25}



For all other indications:
Neonates—Oral, 10 mg (base) per kg of body weight every six to eight hours.

Older infants and children—Oral, 6.25 to 12.5 mg (base) per kg of body weight every six hours. {25}



Strength(s) usually available
U.S.—


250 mg (base) (Rx) [Unipen]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.
   • Take on empty stomach.


NAFCILLIN SODIUM TABLETS USP

Usual adult and adolescent dose
See Nafcillin Sodium Capsules USP .

Usual adult prescribing limits
See Nafcillin Sodium Capsules USP .

Usual pediatric dose
See Nafcillin Sodium Capsules USP .

Strength(s) usually available
U.S.—


500 mg (base) (Rx) [Unipen]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Continue medication for full time of treatment.
   • Take on empty stomach.



Parenteral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of nafcillin base (not the sodium salt).


NAFCILLIN SODIUM FOR INJECTION USP

Usual adult and adolescent dose
Antibacterial {25}
Bone and joint infections

Endocarditis, bacterial

Meningitis, bacterial or

Pericarditis, bacterial:


Intravenous, 1.5 to 2 grams every four to six hours. {103}
For all other indications:


Intramuscular, 500 mg (base) every four to six hours.


Intravenous, 500 mg to 1.5 grams (base) every four hours.


Usual adult prescribing limits
Intramuscular—Up to 12 grams (base) a day.

Intravenous—Up to 20 grams (base) a day.

Usual pediatric dose
Antibacterial


Meningitis, bacterial:


Neonates up to 2 kg of body weight—
Intramuscular or intravenous, 25 to 50 mg per kg of body weight every twelve hours during the first week of life {125} {126}, then 50 mg per kg of body weight every eight hours thereafter. {126}



Neonates 2 kg of body weight and over—
Intramuscular or intravenous, 50 mg per kg of body weight every eight hours during the first week of life {126}, then 50 mg per kg of body weight every six hours thereafter. {126}




For all other indications:


Neonates—
Intramuscular, 10 mg (base) per kg of body weight every twelve hours. {25}

Intravenous, 10 to 20 mg (base) per kg of body weight every four hours; or 20 to 40 mg per kg of body weight every eight hours.



Older infants and children—
Intramuscular, 25 mg (base) per kg of body weight every twelve hours. {25}

Intravenous, 10 to 20 mg (base) per kg of body weight every four hours; or 20 to 40 mg per kg of body weight every eight hours.




Size(s) usually available:
U.S.—


500 mg (base) (Rx) [Nafcil] [Nallpen][Generic]


1 gram (base) (Rx) [Nafcil] [Nallpen] [Unipen][Generic]


2 grams (base) (Rx) [Nafcil] [Nallpen] [Unipen][Generic]


10 grams (base) (Rx) [Nafcil] [Nallpen] [Unipen][Generic]

Canada—


500 mg (base) (Rx) [Unipen]

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
To prepare initial dilution for intramuscular use, depending on the manufacturer, add 1.7 to 1.8 mL of sterile water for injection or bacteriostatic water for injection to each 500-mg vial, 3.4 mL of diluent to each 1-gram vial, or 6.6 to 6.8 mL of diluent to each 2-gram vial to provide 250 mg (base) per mL. {24}

To prepare initial dilution for direct intravenous use, reconstitute as directed above for intramuscular use. The resulting solution should be further diluted in 15 to 30 mL of sterile water for injection or 0.9% sodium chloride injection and administered over a 5- to 10-minute period. {25}

For reconstitution of pharmacy bulk vials or piggyback infusion bottles, see manufacturer"s labeling for instructions.

Intravenous infusions of nafcillin sodium for injection should be administered in suitable diluents (see manufacturer"s package insert) in a concentration of 2 to 40 mg per mL. Infusions should be administered over at least a 30- to 60-minute period to avoid vein irritation. {25}

Stability:
After reconstitution for intramuscular use, solutions retain their potency for 3 days at room temperature or for 7 days if refrigerated, depending on the manufacturer. {24} {25}

After reconstitution for intravenous use, solutions in concentrations of 2 to 40 mg per mL retain at least 90% of their potency for 24 hours at room temperature or for 96 hours if refrigerated (depending on the manufacturer) in suitable diluents (see manufacturer"s package insert). {25}

Concentrated solutions (100 mg per mL) prepared from pharmacy bulk vials retain their potency for 8 hours at room temperature or for 48 hours if refrigerated. {25}

Concentrated solutions (250 mg per mL) retain their potency for 3 days at room temperature or for 7 days if refrigerated or frozen.

Incompatibilities:
Extemporaneous admixtures of beta-lactam antibacterials (penicillins and cephalosporins) and aminoglycosides may result in substantial mutual inactivation. If these groups of antibacterials are administered concurrently, they should be administered in separate sites at least 1 hour apart. Do not mix them in the same intravenous bag, bottle, or tubing. {07} {118}

When aminoglycosides and penicillins are administered separately by different routes, a reduction in aminoglycoside serum concentration may occur. Usually this is clinically significant only in patients with severely impaired renal function when the excretion of both medications is delayed. {07} {118}

Additional information:
The total sodium content is approximately 2.9 mEq (2.9 mmol) per gram of nafcillin. {25} This must be considered in patients on a restricted sodium intake when calculating total daily sodium intake.


OXACILLIN

Summary of Differences
Category: Penicillinase-resistant penicillin.

Pharmacology/pharmacokinetics: High plasma protein binding (90%).

Precautions: Drug interactions and/or related problems—May also interact with other hepatotoxic medications.

Side/adverse effects: May be an increased risk of hepatotoxicity and interstitial nephritis.


Additional Dosing Information
Patients with impaired renal function do not generally require a reduction in dose. {134}


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of oxacillin base (not the sodium salt).


OXACILLIN SODIUM CAPSULES USP

Usual adult and adolescent dose
Antibacterial
Oral, 500 mg to 1 gram (base) every four to six hours. {27}


Usual adult prescribing limits
6 grams (base) a day.

Usual pediatric dose
Antibacterial
Children up to 40 kg of body weight: Oral, 12.5 to 25 mg (base) per kg of body weight every six hours. {27}

Children 40 kg of body weight and over: See Usual adult and adolescent dose. {27}


Strength(s) usually available
U.S.—


250 mg (base) (Rx) [Bactocill] [Prostaphlin][Generic]


500 mg (base) (Rx) [Bactocill] [Prostaphlin][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.
   • Take on empty stomach.


OXACILLIN SODIUM FOR ORAL SOLUTION USP

Usual adult and adolescent dose
See Oxacillin Sodium Capsules USP .

Usual adult prescribing limits
See Oxacillin Sodium Capsules USP .

Usual pediatric dose
See Oxacillin Sodium Capsules USP .

Strength(s) usually available
U.S.—


250 mg per 5 mL (base) (Rx) [Prostaphlin][Generic]

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store between 15 and 30 °C (59 and 86 °F). Store in a tight container.

Stability:
After reconstitution, solutions retain their potency for 7 days at room temperature or for 14 days if refrigerated. {27}

Auxiliary labeling:
   • Refrigerate.
   • Continue medication for full time of treatment.
   • Beyond-use date.
   • Take on empty stomach.

Note: When dispensing, include a calibrated liquid-measuring device.




Parenteral Dosage Forms

OXACILLIN SODIUM FOR INJECTION USP

Usual adult and adolescent dose
Antibacterial
Intramuscular or intravenous, 250 mg to 1 gram (base) every four to six hours. {28}

Meningitis, bacterial: Intravenous, 1.5 to 2 grams every four hours. {103}


Usual pediatric dose
Antibacterial


Meningitis, bacterial:
Neonates up to 2 kg of body weight—Intramuscular or intravenous, 25 to 50 mg per kg of body weight every twelve hours during the first week of life {125} {126}, then 50 mg per kg of body weight every eight hours thereafter. {126}

Neonates 2 kg of body weight and over—Intramuscular or intravenous, 50 mg per kg of body weight every eight hours during the first week of life {126}, then 50 mg per kg of body weight every six hours thereafter. {126}



For all other indications:
Premature infants and neonates—Intramuscular or intravenous, 6.25 mg (base) every six hours. {28}

Children up to 40 kg of body weight—Intramuscular or intravenous, 12.5 to 25 mg (base) per kg of body weight every six hours; or 16.7 mg per kg of body weight every four hours.

Children 40 kg of body weight and over—See Usual adult and adolescent dose. {28}



Size(s) usually available:
U.S.—


250 mg (base) (Rx) [Prostaphlin]


500 mg (base) (Rx) [Bactocill] [Prostaphlin][Generic]


1 gram (base) (Rx) [Bactocill] [Prostaphlin][Generic]


2 grams (base) (Rx) [Bactocill] [Prostaphlin][Generic]


4 grams (base) (Rx) [Bactocill] [Prostaphlin]


10 grams (base) (Rx) [Bactocill] [Prostaphlin][Generic]

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store between 15 and 30 °C (59 and 86 °F).

Preparation of dosage form:
To prepare initial dilution for intramuscular use, depending on the manufacturer, add 1.4 mL of sterile water for injection to each 250-mg vial, 2.7 to 2.8 mL of diluent to each 500-mg vial, 5.7 mL of diluent to each 1-gram vial, 11.4 to 11.5 mL of diluent to each 2-gram vial, and 21.8 to 23 mL of diluent to each 4-gram vial to provide a concentration of 250 mg per 1.5 mL. {28}

To prepare initial dilution for direct intravenous use, add 5 mL of sterile water for injection or 0.9% sodium chloride injection to each 250- or 500-mg vial, 10 mL of diluent to each 1-gram vial, 20 mL of diluent to each 2-gram vial, and 40 mL of diluent to each 4-gram vial. The resulting solution should be administered slowly over a 10-minute period. {28}

Intravenous infusions of oxacillin sodium for injection should be administered in a suitable diluent in a concentration of up to 40 mg per mL (see manufacturer"s package insert). {28}

For reconstitution of pharmacy bulk vials, piggyback infusion bottles, and dual-compartment vials, see manufacturer"s labeling for instructions.

Stability:
After reconstitution for intramuscular use, solutions retain their potency for 4 days at room temperature or for 7 days if refrigerated. {28}

Concentrated solutions (100 mg per mL) prepared from pharmacy bulk vials retain their potency for 48 hours at room temperature or for 7 days if refrigerated. {28}

Diluted solutions (up to 40 mg per mL) retain their potency for 72 hours at room temperature, for 7 days if refrigerated, or for 30 days if frozen. {28}

Solutions (10 to 50 mg per mL) prepared from piggyback infusion bottles retain their potency for 24 hours at room temperature. {28}

Incompatibilities:
Extemporaneous admixtures of beta-lactam antibacterials (penicillins and cephalosporins) and aminoglycosides may result in substantial mutual inactivation. If these groups of antibacterials are administered concurrently, they should be administered in separate sites at least 1 hour apart. Do not mix them in the same intravenous bag, bottle, or tubing. {07} {118}

When aminoglycosides and penicillins are administered separately by different routes, a reduction in aminoglycoside serum concentration may occur. Usually this is clinically significant only in patients with severely impaired renal function when the excretion of both medications is delayed. {07} {118}

Additional information:
The total sodium content (derived from dibasic sodium phosphate buffer and oxacillin sodium) is approximately 2.8 to 3.1 mEq (64 to 71 mg) per gram of oxacillin. {28} This must be considered in patients on a restricted sodium intake when calculating total daily sodium intake.


PENICILLIN G

Summary of Differences


Category:
Natural penicillin.



Pharmacology/pharmacokinetics:
Oral absorption low (15 to 30%).


Time to peak serum concentration—
Benzathine salt: 24 hours.

Procaine salt: 4 hours.




Precautions:


Cross-sensitivity and/or related problems—
Cross-sensitivity with other ester-type local anesthetics may also occur with administration of penicillin G procaine.



Drug interactions and/or related problems—
Use of angiotensin-converting enzyme (ACE) inhibitors, potassium-sparing diuretics, other potassium-containing medications, or potassium supplements with parenteral penicillin G potassium may promote hyperkalemia; also oral penicillin G may interact with cholestyramine and colestipol.



Patient monitoring—
Serum potassium or sodium determinations may be required (parenteral only).




Side/adverse effects:
May be an increased risk of mental disturbances with administration of penicillin G procaine.



Additional Dosing Information
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. {134}

For oral dosage forms only
Oral administration of penicillin G commonly results in low serum concentrations. Therefore, severe infections should not be treated with oral penicillin during the acute stage. {82}

Penicillin G is an acid-labile penicillin; therefore, concurrent administration with acidic fruit juices and other acidic beverages should be avoided. {143}


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of penicillin G benzathine (not the base).


PENICILLIN G BENZATHINE SUSPENSION

Usual adult and adolescent dose
Antibacterial
Oral, 200,000 to 500,000 Units (125 to 312 mg) every four to six hours. {82}

Continuous prophylaxis of streptococcal infections in patients with a history of rheumatic heart disease: Oral, 200,000 to 250,000 Units (125 to 156 mg) every twelve hours. {82}


Usual adult prescribing limits
2,000,000 Units a day. {82}

Usual pediatric dose
Antibacterial
Infants and children up to 12 years of age: Oral, 4167 to 15,000 Units per kg of body weight every four hours; 6250 to 22,500 Units per kg of body weight every six hours; or 8333 to 30,000 Units per kg of body weight every eight hours. {82}

Children 12 years of age and older: See Usual adult and adolescent dose.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


250,000 Units (156 mg) per 5 mL (Rx) [Megacillin]


500,000 Units (312 mg) per 5 mL (Rx) [Megacillin]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Stability:
The reconstituted suspension may be stored at room temperature until the labeled expiration date. {82}

Auxiliary labeling:
   • Continue medication for full time of treatment.
   • Take on empty stomach.
   • Beyond-use date.


PENICILLIN G POTASSIUM FOR ORAL SOLUTION USP

Usual adult and adolescent dose
See Penicillin G Benzathine Suspension .

Usual adult prescribing limits
See Penicillin G Benzathine Suspension .

Usual pediatric dose
See Penicillin G Benzathine Suspension .

Strength(s) usually available
U.S.—


400,000 Units (250 mg) per 5 mL (Rx)[Generic]

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Stability:
After reconstitution, solutions retain their potency for 14 days if refrigerated. {143}

Auxiliary labeling:
   • Refrigerate.
   • Continue medication for full time of treatment.
   • Beyond-use date.
   • Take on empty stomach.

Note: When dispensing, include a calibrated liquid-measuring device.



PENICILLIN G POTASSIUM TABLETS USP

Usual adult and adolescent dose
See Penicillin G Benzathine Suspension .

Usual adult prescribing limits
See Penicillin G Benzathine Suspension .

Usual pediatric dose
See Penicillin G Benzathine Suspension .

Strength(s) usually available
U.S.—


200,000 Units (125 mg) (Rx)[Generic]


250,000 Units (156 mg) (Rx)[Generic]


400,000 Units (250 mg) (Rx) [Pentids][Generic]


800,000 Units (500 mg) (Rx)[Generic]

Canada—


500,000 Units (312 mg) (Rx) [Megacillin (scored)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.
   • Take on empty stomach.



Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

Note: The dosing and strengths of the dosage forms available are expressed in terms of penicillin G salt (not the base).


STERILE PENICILLIN G BENZATHINE SUSPENSION USP

Usual adult and adolescent dose
Antibacterial
Bejel

Pinta or

Yaws: Intramuscular, 1,200,000 Units as a single dose. {103} {134}

Continuous prophylaxis of streptococcal infections in patients with a history of rheumatic heart disease: Intramuscular, 1,200,000 Units every three to four weeks. {134}

Pharyngitis, streptococcal: Intramuscular, 1,200,000 Units as a single dose. {62} {103} {134}

Syphilis (primary, secondary, and early latent): Intramuscular, 2,400,000 Units as a single dose. {129} {133}

Syphilis (tertiary and late latent, excluding neurosyphilis): Intramuscular, 2,400,000 Units once a week for three weeks. {129} {133}


Usual adult prescribing limits
2,400,000 Units a day. {62}

Usual pediatric dose
Antibacterial


Pharyngitis, group A streptococcal:
Infants and children up to 27.3 kg of body weight—Intramuscular, 300,000 to 600,000 Units as a single dose. {62}

Children 27.3 kg of body weight and over—Intramuscular, 900,000 Units as a single dose. {62}



Rheumatic fever (prophylaxis):
Intramuscular, 1,200,000 Units every two or three weeks. {128}



Syphilis (primary, secondary, and early latent):
Intramuscular, 50,000 Units per kg of body weight, up to 2,400,000 Units, as a single dose. {133}



Syphilis (late latent or latent of unknown duration):
Intramuscular, 50,000 Units per kg of body weight once a week for three weeks. {133}



Strength(s) usually available
U.S.—


600,000 Units in 1 mL (Rx) [Bicillin L-A] [Permapen]


1,200,000 Units in 2 mL (Rx) [Bicillin L-A]


2,400,000 Units in 4 mL (Rx) [Bicillin L-A]


3,000,000 Units in 10 mL (Rx) [Bicillin L-A]

Canada—


1,200,000 Units in 2 mL (Rx) [Bicillin L-A]

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F).

Additional information:
For deep intramuscular use only. Do not administer intravenously, intra-arterially, subcutaneously, by fat-layer injection, or into or near a nerve. Intravenous injection may cause embolic or toxic reactions. Intra-arterial injection may cause extensive necrosis of the extremity or organ, especially in children. Subcutaneous and fat-layer injection may cause pain and induration. Injection into or near a nerve may result in permanent neurological damage. {62}

Injection of penicillin G benzathine should be made at a slow, steady rate to prevent blockage of the needle because of the high concentration of suspended material. {62}

Intramuscular administration of penicillin G benzathine results in much lower and more prolonged serum concentrations than those attained with other parenteral penicillins. {62}


PENICILLIN G POTASSIUM FOR INJECTION USP

Usual adult and adolescent dose
Antibacterial
Intramuscular or intravenous, 1,000,000 to 5,000,000 Units every four to six hours. {84}

Actinomycosis: Intramuscular or intravenous, 10,000,000 to 20,000,000 Units a day for two to six weeks. {63} {103} {134}

Anthrax: Intramuscular or intravenous, 2,000,000 Units every six hours. {103} {134}

Clostridial infections: Intramuscular or intravenous, 20,000,000 Units a day. {63}

Erysipelas: Intramuscular or intravenous, 600,000 to 2,000,000 Units every six hours. {134}

Erysipeloid endocarditis: Intramuscular or intravenous, 12,000,000 to 20,000,000 Units a day. {103} {134}

Listeriosis: Intramuscular or intravenous, 300,000 Units per kg of body weight a day. {134}

Meningitis, bacterial: Intramuscular or intravenous, 50,000 Units per kg of body weight every four hours {134}; or 24,000,000 Units daily divided every two to four hours. {103}

Neurosyphilis: Intravenous, 2,000,000 to 4,000,000 Units every four hours for ten to fourteen days. {129} {133}

Pasteurella multocida septicemia and meningitis: Intramuscular or intravenous, 4,000,000 to 6,000,000 Units a day. {63}

Pericarditis, bacterial: Intramuscular or intravenous, 20,000,000 to 30,000,000 Units a day for four to six weeks. {103}

Rat-bite fever: Intramuscular or intravenous, 20,000,000 Units a day. {134}

[Leptospirosis]1: Intramuscular or intravenous, 1,500,000 Units every six hours. {103} {134}

[Lyme disease]1: Intravenous, 20,000,000 to 24,000,000 Units a day for two to three weeks. Duration of therapy is based on clinical response. Treatment failures have occurred and retreatment may be necessary. {03} {04} {05} {131}


Usual adult prescribing limits
80,000,000 Units a day. {63}

Usual pediatric dose
Antibacterial


Listeriosis in neonates:
500,000 to 1,000,000 Units daily. {63}



Meningitis, bacterial:
Neonates up to 2 kg of body weight—Intramuscular or intravenous, 25,000 to 50,000 Units per kg of body weight every twelve hours during the first week of life {125} {126}, then 50,000 Units per kg of body weight every eight hours thereafter. {126}

Neonates 2 kg of body weight and over—Intramuscular or intravenous, 50,000 Units per kg of body weight every eight hours during the first week of life, then 50,000 Units per kg of body weight every six hours thereafter. {126}



Syphilis, congenital:
Intramuscular or intravenous, 50,000 Units per kg of body weight every twelve hours for the first week of life, then 50,000 Units per kg of body weight every eight hours for the next ten to fourteen days. {133}



[Lyme disease]1:
Intravenous, 250,000 to 400,000 Units per kg of body weight daily for two to three weeks. Duration of therapy is based on clinical response. Treatment failures have occurred and retreatment may be necessary. {03} {04} {05} {131}



For all other indications:
Premature and full-term neonates—Intramuscular or intravenous, 30,000 Units per kg of body weight every twelve hours. {84}

Older infants and children—Intramuscular or intravenous, 8333 to 16,667 Units per kg of body weight every four hours; or 12,500 to 25,000 Units per kg of body weight every six hours. {84}



Size(s) usually available:
U.S.—


1,000,000 Units (Rx)[Generic]


5,000,000 Units (Rx) [Pfizerpen][Generic]


10,000,000 Units (Rx)[Generic]


20,000,000 Units (Rx) [Pfizerpen][Generic]

Canada—


1,000,000 Units (Rx)[Generic]


5,000,000 Units (Rx)[Generic]


10,000,000 Units (Rx)[Generic]

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
To prepare initial dilution for intramuscular or intravenous use, see manufacturer"s labeling for instructions.

To prepare for further dilution for intravenous use, see manufacturer"s labeling for instructions.

Stability:
After reconstitution, solutions retain their potency for 24 hours at room temperature or for 7 days if refrigerated. {63} {84}

Incompatibilities:
Penicillin G potassium is rapidly inactivated by oxidizing and reducing agents, such as alcohols and glycols. {84}

Extemporaneous admixtures of beta-lactam antibacterials (penicillins and cephalosporins) and aminoglycosides may result in substantial mutual inactivation. If these groups of antibacterials are administered concurrently, they should be administered in separate sites at least 1 hour apart. Do not mix them in the same intravenous bag, bottle, or tubing. {07} {118}

When aminoglycosides and penicillins are administered separately by different routes, a reduction in aminoglycoside serum concentration may occur. Usually this is clinically significant only in patients with severely impaired renal function when the excretion of both medications is delayed. {07} {118}

Additional information:
Daily doses of 10,000,000 Units or more should be administered by slow intravenous infusion or by intermittent piggyback infusion because of possible electrolyte imbalance. {84}

The potassium content and sodium content (derived from sodium citrate buffer) of penicillin G potassium for injection are approximately 1.7 mEq (66.3 mg) and 0.3 mEq (6.9 mg) per 1,000,000 Units of penicillin G, respectively. {63} The sodium content must be considered in patients on a restricted sodium intake when calculating total daily sodium intake.


STERILE PENICILLIN G PROCAINE SUSPENSION USP

Usual adult and adolescent dose
Antibacterial
Intramuscular, 600,000 to 1,200,000 Units a day. {64}

Diphtheria: Intramuscular, 300,000 to 600,000 Units a day as adjunctive therapy to diphtheria antitoxin. {64} {134}

Neurosyphilis: Intramuscular, 2,400,000 Units a day, and 500 mg of probenecid orally four times a day, for ten to fourteen days. {129} {133}

Rat-bite fever: Intramuscular, 600,000 Units every twelve hours for ten to fourteen days. {103} {134}


Usual pediatric dose
Antibacterial
Syphilis, congenital: Intramuscular, 50,000 Units per kg of body weight a day for ten to fourteen days. {133}


Strength(s) usually available
U.S.—


600,000 Units in 1 mL (Rx) [Wycillin]


1,200,000 Units in 2 mL (Rx) [Wycillin]


2,400,000 Units in 4 mL (Rx) [Wycillin]


3,000,000 Units in 10 mL (Rx) [Crysticillin 300 A.S.] [Pfizerpen-AS]

Canada—


3,000,000 Units per 10 mL (Rx) [Ayercillin (propylparaben 0.013%)]


5,000,000 Units per 10 mL (base) (Rx) [Wycillin]

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F).

Additional information:
For deep intramuscular use only. Do not administer intravenously, intra-arterially, or into or near a nerve. Intravenous injection may cause embolic or toxic reactions. Intra-arterial injection may cause extensive necrosis of the extremity or organ, especially in children. {64}

Some patients may experience immediate toxic reactions to procaine, especially when administered in large single doses. These reactions, usually transient, may be characterized by anxiety, confusion, agitation or combativeness, depression, seizures, hallucinations, or expressed fear of impending death. {64}


PENICILLIN G SODIUM FOR INJECTION USP

Usual adult and adolescent dose
See Penicillin G Potassium for Injection USP .

Usual adult prescribing limits
See Penicillin G Potassium for Injection USP .

Usual pediatric dose
See Penicillin G Potassium for Injection USP .

Size(s) usually available:
U.S.—


5,000,000 Units (Rx)[Generic]

Canada—


1,000,000 Units (Rx)[Generic]


5,000,000 Units (Rx)[Generic]


10,000,000 Units (Rx)[Generic]

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
To prepare initial dilution for intramuscular or intravenous use, see manufacturer"s labeling for instructions.

Stability:
After reconstitution, solutions retain their potency for 24 hours at room temperature or for 7 days if refrigerated. {84}

Incompatibilities:
Penicillin G sodium is rapidly inactivated by acids, alkalies, and oxidizing agents and in carbohydrate solutions at alkaline pH.

Extemporaneous admixtures of beta-lactam antibacterials (penicillins and cephalosporins) and aminoglycosides may result in substantial mutual inactivation. If these groups of antibacterials are administered concurrently, they should be administered in separate sites at least 1 hour apart. Do not mix them in the same intravenous bag, bottle, or tubing. {07} {118}

When aminoglycosides and penicillins are administered separately by different routes, a reduction in aminoglycoside serum concentration may occur. Usually this is clinically significant only in patients with severely impaired renal function when the excretion of both medications is delayed. {07} {118}

Additional information:
Daily doses of 10,000,000 Units or more should be administered by slow intravenous infusion to avoid causing possible electrolyte imbalance. {84}

The sodium content is approximately 2 mEq (2 mmol) per million Units of penicillin G. This must be considered in patients on a restricted sodium intake when calculating total daily sodium intake. {84}


PENICILLIN V

Summary of Differences
Category: Penicillin G–related natural penicillin.

Precautions: Drug interactions and/or related problems—Also interacts with oral contraceptives.


Additional Dosing Information
Penicillin V may be taken on a full or empty stomach. {42}

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. {134}


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

Note: The dosing and strengths of the dosage forms available are expressed in terms of penicillin V salt (not the base).


PENICILLIN V BENZATHINE SUSPENSION

Usual adult and adolescent dose
Antibacterial
Oral, 200,000 to 500,000 Units every six to eight hours. {88}

Continuous prophylaxis of streptococcal infections in patients with a history of rheumatic heart disease: Oral, 200,000 Units every twelve hours. {88}


Usual pediatric dose
Antibacterial
Infants and children up 60 kg of body weight: Oral, 100,000 to 250,000 Units every six to eight hours. {88}

Children 60 kg of body weight and over: See Usual adult and adolescent dose. {88}


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


250,000 Units (156 mg) per 5 mL (Rx) [PVF]


300,000 Units (180 mg) per 5 mL (Rx) [Pen-Vee]


500,000 Units (300 mg) per 5 mL (Rx) [Pen-Vee] [PVF]

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Stability:
Store at room temperature. {88}

Auxiliary labeling:
   • Continue medication for full time of treatment.
   • Beyond-use date.

Note: When dispensing, include a calibrated liquid-measuring device.



PENICILLIN V POTASSIUM FOR ORAL SOLUTION USP

Usual adult and adolescent dose
Antibacterial
Oral, 125 to 500 mg (200,000 to 800,000 Units) every six to eight hours. {42}

Continuous prophylaxis of streptococcal infections in patients with a history of rheumatic heart disease: Oral, 125 to 250 mg (200,000 to 400,000 Units) every twelve hours. {134}

Erysipelas: Oral, 500 mg every six hours. {134}

Erysipeloid, uncomplicated: Oral, 250 mg every six hours for five to ten days. {103}

Gingivitis, acute, necrotizing, ulcerative: Oral, 500 mg every six hours. {103}

Pasteurellainfections: Oral, 500 mg every six hours for ten to fourteen days. {134}

Rat-bite fever: Oral, 500 mg every six hours for fourteen days. {103} {134}

[Lyme disease]1: Oral, 250 to 500 mg three or four times a day for three to four weeks. Duration of therapy is based on clinical response. Treatment failures have occurred and retreatment may be necessary. {04} {05}


Usual adult prescribing limits
7.2 grams (11,520,000 Units) a day.

Usual pediatric dose
Antibacterial


[Lyme disease]1:
Oral, 5 to 12.5 mg per kg of body weight four times a day for three to four weeks. Duration of therapy is based on clinical response. Treatment failures have occurred and retreatment may be necessary. {04} {05} {131}



For all other indications:
Infants and children up to 12 years of age—Oral, 2.5 to 8.3 mg (4167 to 13,280 Units) per kg of body weight every four hours; 3.75 to 12.5 mg (6250 to 20,000 Units) per kg of body weight every six hours; or 5 to 16.7 mg (8333 to 26,720 Units) per kg of body weight every eight hours. {42}

Children 12 years of age and older—See Usual adult and adolescent dose. {42}



Strength(s) usually available
U.S.—


125 mg (200,000 Units) per 5 mL (Rx) [Beepen-VK] [Betapen-VK] [Ledercillin VK] [Pen Vee K] [Veetids][Generic]


250 mg (400,000 Units) per 5 mL (Rx) [Beepen-VK] [Betapen-VK] [Ledercillin VK] [Pen Vee K] [V-Cillin K] [Veetids][Generic]

Canada—


125 mg (200,000 Units) per 5 mL (Rx) [Apo-Pen VK] [Nadopen-V 200] [V-Cillin K]


250 mg (400,000 Units) per 5 mL (Rx) [Nadopen-V 400] [V-Cillin K]


300 mg (500,000 Units) per 5 mL (Rx) [Apo-Pen VK] [Novo-Pen-VK]

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Stability:
After reconstitution, solutions retain their potency for 14 days if refrigerated. {42}

Auxiliary labeling:
   • Refrigerate.
   • Continue medication for full time of treatment.
   • Beyond-use date.
   • Shake well.

Note: When dispensing, include a calibrated liquid-measuring device.



PENICILLIN V POTASSIUM TABLETS USP

Usual adult and adolescent dose
See Penicillin V Potassium for Oral Solution USP .

Usual adult prescribing limits
See Penicillin V Potassium for Oral Solution USP .

Usual pediatric dose
See Penicillin V Potassium for Oral Solution USP .

Strength(s) usually available
U.S.—


250 mg (400,000 Units) (Rx) [Beepen-VK] [Ledercillin VK] [Pen Vee K] [V-Cillin K] [Veetids][Generic]


500 mg (800,000 Units) (Rx) [Beepen-VK] [Ledercillin VK] [Pen Vee K] [V-Cillin K] [Veetids][Generic]

Canada—


250 mg (400,000 Units) (Rx) [Ledercillin VK (scored)] [V-Cillin K]


300 mg (500,000 Units) (Rx) [Apo-Pen VK] [Nadopen-V (scored)] [Novo-Pen-VK] [Nu-Pen-VK] [Pen Vee (scored)] [PVF K (scored)]


500 mg (800,000 Units) (Rx) [Ledercillin VK]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.


PIPERACILLIN

Summary of Differences


Category:
Antipseudomonal penicillin.



Precautions:
Drug interactions and/or related problems—Also interacts with anticoagulants and other medications that affect blood clotting, and other hepatotoxic medications.

Laboratory value alterations—May increase bleeding time.

Medical considerations/contraindications—Caution in patients with a history of bleeding disorders and cystic fibrosis.

Patient monitoring—Serum potassium and sodium determinations may be required.



Additional Dosing Information
Intramuscular injections should not exceed 2 grams in each site. {14}

Adults with impaired renal function may require a reduction in dose as follows {14}:

Creatinine Clearance
(mL/min)/(mL/sec)
Dose
(base)
> 40/0.67
See Usual adult and
adolescent dose

20–40/0.33–0.67
3 to 4 grams every 8 hours
<20/0.33
3 to 4 grams every 12 hours
Hemodialysis patients
1 gram after each dialysis, then
2 grams every 8 hours



Parenteral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of piperacillin base (not the sodium salt).


PIPERACILLIN SODIUM STERILE USP

Usual adult and adolescent dose
Antibacterial
Intramuscular or intravenous, 3 to 4 grams (base) every four to six hours. {12} {14}

Meningitis, bacterial: Intravenous, 4 grams every four hours {103}; or 75 mg per kg of body weight every six hours. {134}

Urinary tract infections, complicated: Intravenous, 3 to 4 grams (base) every six to eight hours. {14}

Urinary tract infections, uncomplicated: Intramuscular or intravenous, 1.5 to 2 grams (base) every six hours or 3 to 4 grams every twelve hours. {14}


Usual adult prescribing limits
24 grams (base) a day. {14}

Usual pediatric dose
Antibacterial


Meningitis, bacterial {126}:
Neonates up to 2 kg of body weight—Intramuscular or intravenous, 50 mg per kg of body weight every twelve hours during the first week of life, then 50 mg per kg of body weight every eight hours thereafter.

Neonates 2 kg of body weight and over—Intramuscular or intravenous, 50 mg per kg of body weight every eight hours during the first week of life, then 50 mg per kg of body weight every six hours thereafter.



For all other indications:
Infants and children under 12 years of age—Dosage has not been established. {12} {14}

Children 12 years of age and older—See Usual adult and adolescent dose.



Note: Cystic fibrosis patients—Intravenous, 350 to 450 mg per kg of body weight daily. {119}


Size(s) usually available:
U.S.—


2 grams (base) (Rx) [Pipracil]


3 grams (base) (Rx) [Pipracil]


4 grams (base) (Rx) [Pipracil]


40 grams (base) (Rx) [Pipracil]

Canada—


2 grams (base) (Rx) [Pipracil]


3 grams (base) (Rx) [Pipracil]


4 grams (base) (Rx) [Pipracil]

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
To prepare initial dilution for intramuscular use, add 4 mL of sterile water for injection or 0.5 or 1% lidocaine hydrochloride injection (without epinephrine) to each 2-gram vial, 6 mL of diluent to each 3-gram vial, and 7.8 mL of diluent to each 4-gram vial to provide a concentration of 1 gram (base) per 2.5 mL. {14}

To prepare initial dilution for intravenous use, add at least 5 mL of a suitable diluent (see manufacturer"s package insert) for each gram of piperacillin and shake well until dissolved. For direct intravenous use, the resulting solution should be administered slowly over a 3- to 5-minute period. For intermittent intravenous use, the resulting solution should be further diluted with a suitable diluent (see manufacturer"s package insert) to at least 50 mL. It should be administered over approximately a 20- to 30-minute period. {12}

For reconstitution of pharmacy bulk vials or piggyback infusion bottles, see manufacturer"s labeling for instructions.

Stability:
After reconstitution with suitable diluents (see manufacturer"s package insert), solutions retain their potency for 24 hours at controlled room temperature, 7 days if refrigerated, or 1 month if frozen at -15 °C (5 °F). {12}

Incompatibilities:
Because of chemical instability, piperacillin should not be used for intravenous admixtures with solutions containing only sodium bicarbonate. {14}

Extemporaneous admixtures of beta-lactam antibacterials (penicillins and cephalosporins) and aminoglycosides may result in substantial mutual inactivation. If these groups of antibacterials are administered concurrently, they should be administered in separate sites at least 1 hour apart. Do not mix them in the same intravenous bag, bottle, or tubing. {07} {118}

When aminoglycosides and penicillins are administered separately by different routes, a reduction in aminoglycoside serum concentration may occur. Usually this is clinically significant only in patients with severely impaired renal function when the excretion of both medications is delayed. {07} {118}

Additional information:
The sodium content is approximately 1.98 mEq (45.5 mg) per gram of piperacillin. {14} This must be considered in patients on a restricted sodium intake when calculating total daily sodium intake.


PIVAMPICILLIN

Summary of Differences
Category: Aminopenicillin.

Pharmacology/pharmacokinetics: Converted to ampicillin during absorption.

Pediatrics: Should be avoided in children up to 3 months of age since pivampicillin decreases serum carnitine concentrations.

Precautions: Medical considerations/contraindications—Caution in patients with carnitine deficiency.


Additional Dosing Information
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. {134}

Pivampicillin may be taken on a full or empty stomach. {96}


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of pivampicillin (not the ampicillin base).


PIVAMPICILLIN FOR ORAL SUSPENSION USP

Usual adult and adolescent dose
Antibacterial
Oral, 525 to 1050 mg two times a day. {96}


Usual pediatric dose
Antibacterial
Infants 3 to 12 months of age: Oral, 20 to 30 mg per kg of body weight two times a day.

Children 1 to 3 years of age: Oral, 175 mg two times a day. {96}

Children 4 to 6 years of age: Oral, 262.5 mg two times a day. {96}

Children 7 to 10 years of age: Oral, 350 mg two times a day {96}

Children 10 years of age and older: See Usual adult and adolescent dose .


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


35 mg per mL (Rx) [Pondocillin]

Note: 35 mg of pivampicillin are equivalent to 26.4 mg of ampicillin. {96}


Packaging and storage:
Prior to reconstitution, store between 15 and 30 °C (59 and 86 °F). Store in a tight container.

Auxiliary labeling:
   • Shake well.
   • Continue medication for full time of treatment.
   • Beyond-use date.

Note: When dispensing, include a calibrated liquid-measuring device.



PIVAMPICILLIN TABLETS

Usual adult and adolescent dose
Antibacterial
Oral, 500 mg to 1 gram two times a day. {96}


Usual pediatric dose
Antibacterial
Children 10 years of age and over: See Usual adult and adolescent dose. {96}

Children up to 10 years of age: A product of suitable strength is not available for infants and children up to 10 years of age. See Pivampicillin for Oral Suspension USP .


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


500 mg (Rx) [Pondocillin]

Note: 500 mg of pivampicillin are equivalent to 377 mg of ampicillin. {96}


Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.


PIVMECILLINAM

Summary of Differences
Category: Aminopenicillin.

Pharmacology/pharmacokinetics: Converted to mecillinam during absorption.

Pediatrics: Should be avoided in children up to 3 months of age since pivmecillinam decreases serum carnitine concentrations.

Precautions: Medical considerations/contraindications—Caution in patients with carnitine deficiency.


Additional Dosing Information
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. {134}

Pivmecillinam may be taken on a full or empty stomach. {97}


Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of pivmecillinam hydrochloride (not the mecillinam base).


PIVMECILLINAM HYDROCHLORIDE TABLETS

Usual adult and adolescent dose
Antibacterial
Oral, 200 mg two to four times a day for three days. {97}


Usual pediatric dose
Antibacterial
Children up to 40 kg of body weight: Dosage has not been established. {97}

Children 40 kg of body weight and over: See Usual adult and adolescent dose . {97}


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


200 mg (Rx) [Selexid]

Note: 200 mg of pivmecillinam hydrochloride is equivalent to 137 mg of mecillinam. {97}


Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). Store in a tight container.

Auxiliary labeling:
   • Continue medication for full time of treatment.


TICARCILLIN

Summary of Differences


Category:
Antipseudomonal penicillin.



Precautions:
Drug interactions and/or related problems—Also interacts with anticoagulants and other medications that affect blood clotting.

Laboratory value alterations—May increase bleeding time and may cause false-positive protein reaction for various urine protein tests.

Medical considerations/contraindications—Caution in patients with a history of bleeding disorders, and congestive heart failure or hypertension.

Patient monitoring—Bleeding time and serum potassium and sodium determinations may be required.



Additional Dosing Information
Intramuscular injections should not exceed 2 grams in each site. {17}

Patients with impaired renal function should be observed for hemorrhagic complications. {17}

Note: After an initial intravenous loading dose of 3 grams (base), adults with impaired renal function may require a reduction in dose as follows: {17}

Creatinine Clearance
(mL/min)/(mL/sec)
Dose
(base)
> 60/1
3 grams every 4 hours
30–60/0.5–1
2 grams every 4 hours
10–30/0.17–0.5
2 grams every 8 hours
<10/0.17
2 grams every 12 hours
<10 with impaired
hepatic function
2 grams every 24 hours
Hemodialysis
2 grams every 12 hours
plus 3 grams after dialysis
Peritoneal
dialysis
3 grams every 12 hours




Parenteral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of ticarcillin base (not the sodium salt).


TICARCILLIN DISODIUM STERILE USP

Usual adult and adolescent dose
Antibacterial
Intravenous infusion, 3 grams (base) every four hours; or 4 grams every six hours. {17}

Meningitis, bacterial: Intravenous infusion, 75 mg per kg of body weight every six hours. {134}

Urinary tract infections, complicated: Intravenous infusion, 3 grams (base) every six hours.

Urinary tract infections, uncomplicated: Intramuscular or intravenous, 1 gram (base) every six hours.


Usual adult prescribing limits
24 grams a day. {95}

Usual pediatric dose
Antibacterial


Neonates up to 2 kg of body weight:
Intramuscular or intravenous, 75 mg per kg of body weight every twelve hours during the first week of life; followed by 75 mg per kg of body weight every eight hours thereafter. {126}



Neonates 2 kg of body weight and over:
Intramuscular or intravenous, 75 mg per kg of body weight every eight hours during the first week of life; followed by 75 mg per kg of body weight every six hours thereafter. {126}



Children up to 40 kg of body weight:
Intravenous infusion, 33.3 to 50 mg (base) per kg of body weight every four hours; or 50 to 75 mg per kg of body weight every six hours. {17}

Urinary tract infections, bacterial (complicated)—Intravenous infusion, 25 to 33.3 mg (base) per kg of body weight every four hours; or 37.5 to 50 mg per kg of body weight every six hours. {17}

Urinary tract infections, bacterial (uncomplicated)—Intramuscular or intravenous, 12.5 to 25 mg (base) per kg of body weight every six hours; or 16.7 to 33.3 mg per kg of body weight every eight hours. {17}



Children 40 kg of body weight and over:
See Usual adult and adolescent dose. {17}



Size(s) usually available:
U.S.—


1 gram (base) (Rx) [Ticar]


3 grams (base) (Rx) [Ticar]


6 grams (base) (Rx) [Ticar]


20 grams (base) (Rx) [Ticar]


30 grams (base) (Rx) [Ticar]

Canada—


1 gram (base) (Rx) [Ticar]


3 grams (base) (Rx) [Ticar]


6 grams (base) (Rx) [Ticar]


20 grams (base) (Rx) [Ticar]

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
To prepare initial dilution for intramuscular use, add 2 mL of sterile water for injection, 1% lidocaine hydrochloride injection (without epinephrine), or sodium chloride injection to each 1-gram vial to provide a concentration of 1 gram per 2.6 mL. {17}

To prepare initial dilution for direct intravenous use, add at least 4 mL of 5% dextrose, 0.9% sodium chloride, or lactated Ringer"s injection to each 1-gram vial. Each gram of ticarcillin may be further diluted if desired. The resulting solution should be administered as slowly as possible to avoid vein irritation. {17}

Intermittent infusions may be administered over a 30-minute to 2-hour period in adults. In neonates, intermittent infusions may be administered over a 10- to 20-minute period. {17}

For reconstitution of pharmacy bulk vials or piggyback infusion bottles, see manufacturer"s labeling for instructions.

Stability:
After reconstitution for intramuscular use, solutions retain their potency for 12 hours at room temperature or for 24 hours if refrigerated. {95}

After reconstitution for intravenous use, solutions in concentrations of 10 to 50 mg per mL retain at least 90% of their potency for 48 to 72 hours at room temperature or for 14 days if refrigerated in suitable diluents (see manufacturer"s package insert). {17}

If frozen after reconstitution with sterile water for injection, 0.9% sodium chloride injection, 5% dextrose injection, Ringer"s injection, or lactated Ringer"s injection, solutions in concentrations up to 100 mg per mL retain their potency up to 30 days at -18 °C (0 °F). Once thawed, solutions must be used within 24 hours. {17}

Incompatibilities:
Extemporaneous admixtures of beta-lactam antibacterials (penicillins and cephalosporins) and aminoglycosides may result in substantial mutual inactivation. If these groups of antibacterials are administered concurrently, they should be administered in separate sites at least 1 hour apart. Do not mix them in the same intravenous bag, bottle, or tubing. {07} {118}

When aminoglycosides and penicillins are administered separately by different routes, a reduction in aminoglycoside serum concentration may occur. Usually this is clinically significant only in patients with severely impaired renal function when the excretion of both medications is delayed. {07} {118}

Additional information:
The sodium content is approximately 5.2 mEq (5.2 mmol), but may be as high as 6.5 mEq (6.5 mmol), per gram of ticarcillin. {17} This must be considered in patients on a restricted sodium intake when calculating total daily sodium intake.



Revised: 06/11/1999



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  1. Ampicillin (Marsam). Red book 1994. Montvale, NJ: Medical Economics Data; 1994. p. 103.
  1. Amoxil (SmithKline Beecham—US), Issued 7/98, Rec 10/98.
  1. Amoxil (SmithKline Beecham—US), Issued 4/99, Rec 5/99.
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