Professional Information
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. {06} 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 . {06} {103} The antistaphylococcal penicillins (cloxacillin, dicloxacillin, flucloxacillin, methicillin, nafcillin, and oxacillin) are also active against beta-lactamase–producing staphylococci. {134} {144} 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 . {103} {134}
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. {06} {07}
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. {144} A small proportion of community-acquired strains (5 to 15%) of S. aureus remains susceptible to penicillin G. {145} 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. {06} {144} 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 . {06} {144}
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. {06} {103} {144} However, many Enterobacteriaceae, H. influenzae , Salmonella and Shigella species are resistant to these penicillins because of beta-lactamase production by these organisms. {06} {134} {144} 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. {18} {96} Amoxicillin has the same in vitro activity as ampicillin, although amoxicillin has slightly better activity against Enterococcus faecalis , E. coli , and Salmonella sp. {06}
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} {144} However, they are less potent than penicillin G against penicillin-sensitive bacteria {06}, and they have very little activity against Enterococcus faecalis and gram-negative organisms. {134} {144} Nafcillin has more intrinsic activity than methicillin against staphylococci and streptococci. {134} {144} 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. {134} 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. {06} {07} 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. {134} {144} 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 . {07} {134} 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 . {134} {144} Piperacillin has excellent activity against streptococci, Neisseria , and Haemophilus species and is the most active penicillin against P. aeruginosa . {134} {144}
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. {134} {144}
Accepted
Actinomycosis (treatment)—Penicillin G (parenteral) and [penicillin V]1 are indicated in the treatment of actinomycosis caused by Actinomyces sp. {63} {103} {134}
Anthrax (treatment)—Penicillin G (parenteral) {06} {63}, [penicillin V]1 {103} {134}, and penicillin G procaine {64} {85} 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 . {06} {63} {103} {134}
Bejel (treatment)—Penicillin G benzathine {62} and penicillin G procaine {64} {85} are indicated in the treatment of bejel caused by Treponema pallidum endemicum . {134}
Bone and joint infections (treatment)—Carbenicillin (parenteral) {79}, cloxacillin (parenteral) {101}, [methicillin]1 {103}, [nafcillin (parenteral)]1 {103} {134}, [ oxacillin (parenteral)]1 {134}, [penicillin G (parenteral)]1 {06} {103}, and piperacillin {12} {14} are indicated in the treatment of bone and joint infections caused by susceptible organisms.
Bronchitis, bacterial exacerbations (treatment)— Amoxicillin {36} {41} {103} {134}, ampicillin {29} {35} {103} {134}, bacampicillin {18} {52} {103}, cloxacillin (oral) {19}, dicloxacillin {21}, penicillin V {42} {88} {103}, and pivampicillin {96} are indicated in the treatment of bronchitis caused by susceptible organisms.
Diphtheria (prophylaxis)—Penicillin G (parenteral) {06} {63}, [ penicillin G benzathine]1 {134}, penicillin G procaine {64} {85} {134}, and penicillin V {134} are indicated in the prophylaxis of diphtheria, caused by C. diphtheriae , as an adjunct to antitoxin.
Endocarditis, bacterial (prophylaxis)—[ Amoxicillin]1 {103} {115}, [ampicillin]1 {103}, penicillin G (parenteral) {63} {103}, and penicillin V {42} {88} {103} are indicated in the prophylaxis of bacterial endocarditis caused by susceptible organisms.
Endocarditis, bacterial (treatment)—Ampicillin (parenteral) {30} {103} {134}, carbenicillin (parenteral) {79}, cloxacillin (parenteral) {101}, [methicillin]1 {134}, [nafcillin (parenteral) ]1 {103} {134}, [oxacillin (parenteral)] {134}, [penicillin G (parenteral)]1 {103} {134} and penicillin G procaine {64} are indicated in the treatment of bacterial endocarditis caused by susceptible organisms.
Erysipelas (treatment)—Penicillin G (parenteral) {06} {63} {134}, penicillin V {42} {88} {134}, and penicillin G procaine {64} {134} 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 . {63} {103} {134}
Gingivitis, acute, necrotizing, ulcerative (treatment)—Penicillin G (oral and parenteral) {63} {82}, penicillin V {42} {88}, and penicillin G procaine {64} {85} 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. {103}
Gonorrhea, endocervical and urethral, uncomplicated (treatment) —Amoxicillin, in combination with probenecid {132}, and [penicillin G (parenteral)]1 {132} 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. {133}
Intra-abdominal infections (treatment)—Carbenicillin (parenteral) {79} {134}, mezlocillin {59} {134}, [penicillin G (parenteral)]1 {134}, piperacillin {12} {14} {134}, and ticarcillin {17} {134} are indicated in the treatment of intra-abdominal infections caused by susceptible organisms.
Listeriosis (treatment)—[ Ampicillin (parenteral)]1 {103} {134} and penicillin G (parenteral) {63} {103} {134} are indicated in the treatment of listeriosis caused by L. monocytogenes .
Meningitis, bacterial (treatment)—Ampicillin (parenteral) {29} {35} {103} {134}, carbenicillin (parenteral) {79}, [ nafcillin (parenteral)]1 {103}, [oxacillin (parenteral)]1 {103}, penicillin G (parenteral) {06} {63} {103} {134}, [ piperacillin]1 {103} {134}, and [ticarcillin]1 {134} are indicated in the treatment of bacterial meningitis caused by susceptible organisms.
Otitis media, acute (treatment)—Amoxicillin {36} {41} {103} {134}, ampicillin {29} {35} {103} {134}, bacampicillin {18} {52}, penicillin G procaine {64} {85}, penicillin G (oral) {82}, penicillin V {42} {88}, and pivampicillin {96} are indicated in the treatment of acute otitis media caused by susceptible organisms.
Pasteurella multocida infections (treatment) —[Ampicillin (parenteral)]1 {134}, penicillin G (parenteral) {06} {103} {134}, and [ penicillin V]1 {134} are indicated in the treatment of infections caused by P. multocida .
Pelvic infections, female (treatment)—[ Carbenicillin (parenteral)]1 {134}, mezlocillin {59} {103} {134}, piperacillin {12} {14} {134}, and ticarcillin {17} {134} are indicated in the treatment of female pelvic infections caused by susceptible organisms.
Pericarditis, bacterial (treatment)—Penicillin G (parenteral) {63} {103}, penicillin G procaine {85}, and [nafcillin (parenteral)]1 {103} are indicated in the treatment of bacterial pericarditis caused by susceptible organisms.
Pharyngitis, bacterial (treatment)—Amoxicillin {36} {41}, ampicillin {29} {35}, bacampicillin {18} {52}, cloxacillin (oral) {19}, dicloxacillin {21}, flucloxacillin {80}, penicillin G benzathine {62} {103} {134}, pencillin G (oral) {82}, penicillin V {42} {88} {103} {134}, and pivampicillin {96} are indicated in the treatment of bacterial pharyngitis caused by susceptible organisms.
Pinta (treatment)—Penicillin G benzathine {62} {103} {134} and penicillin G procaine {64} {85} are indicated in the treatment of pinta caused by Treponema carateum .
Pneumonia, bacterial (treatment)—Amoxicillin {36} {41} {103}, ampicillin {29} {35}, bacampicillin {18} {52}, carbenicillin (parenteral) {78} {79}, cloxacillin {19} {101}, dicloxacillin {21}, mezlocillin {59}, penicillin G (parenteral) {06} {63} {134}, penicillin G procaine {85}, piperacillin {12} {14}, and ticarcillin {17} {95} are indicated in the treatment of bacterial pneumonia caused by susceptible organisms.
Prostatitis (treatment)—Carbenicillin (oral) {54} {103} {134} is indicated in the treatment of prostatitis caused by susceptible organisms.
Rat-bite fever (treatment)—Penicillin G (parenteral) {63} {134}, penicillin G procaine {64} {85} {103} {134}, and [penicillin V]1 {06} {103} {134} are indicated in the treatment of rat-bite fever caused by S. moniliformis or S. minor .
Rheumatic fever (prophylaxis)—Penicillin V {06} {42} {88} {134}, and penicillin G benzathine {06} {62} {82} {134} are indicated in the prophylaxis of rheumatic fever caused by group A streptococci.
Scarlet fever (treatment)—Penicillin V {42} {88} penicillin G procaine {64} {85}, and [penicillin G (parenteral) ]1 {06} are indicated in the treatment of scarlet fever caused by group A streptococci.
Septicemia, bacterial (treatment)—Ampicillin (parenteral) {29} {35}, carbenicillin (parenteral) {79} {134}, cloxacillin (parenteral) {101}, methicillin {26}, mezlocillin {59} {134}, nafcillin (parenteral) {23}, oxacillin (parenteral) {28}, penicillin G (parenteral) {06} {63} {134}, penicillin G procaine {85}, piperacillin {12} {14} {134}, and ticarcillin {17} {95} {134} are indicated in the treatment of bacterial septicemia caused by susceptible organisms.
Sinusitis (treatment)—Amoxicillin {36} {41} {103} {134}, ampicillin {29} {35} {103} {134}, bacampicillin {18} {52} {134}, cloxacillin {19}, flucloxacillin {80}, methicillin {26}, nafcillin {23}, oxacillin {28}, and penicillin V {42} {88} are indicated in the treatment of sinusitis caused by susceptible organisms.
Skin and soft tissue infections (treatment)—Carbenicillin (parenteral) {79}, cloxacillin {19} {103} {134}, dicloxacillin {21} {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 |
|
† 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 |
† 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}
Summary of Differences
Category:
Aminopenicillin.
Pharmacology/pharmacokinetics:
High oral absorption