Ampicillin Trihydrate

Class: Aminopenicillins
Note: This monograph also contains information on Ampicillin, Ampicillin Sodium, Ampicillin Trihydrate
Chemical Name: [2S - [2α,5α,6β(S*)]] - 6 - [(Aminophenylacetyl)amino] - 3,3 - dimethyl - 7 - oxo - 4 - thia - 1 - azabicyclo[3.2.0]heptane - 2 - carboxylic acid
Molecular Formula: C₁₆H₁₉N₃O₄SC₁₆H₁₉N₃O₄S^•NaC₁₆H₁₉N₃O₄S^•3H₂O
CAS Number: 69-53-4
Brands: Principen

Introduction

Antibacterial; β-lactam antibiotic; aminopenicillin.^{1 2 8 9}

Uses for Ampicillin Trihydrate

Endocarditis

Treatment of enterococcal endocarditis;^{2 4 6 7} used in conjunction with an aminoglycoside.^{4 6 7}

Treatment of endocarditis caused by slow-growing fastidious gram-negative bacilli termed the HACEK group† (i.e., Haemophilus parainfluenzae, H. aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae).^{6 7} Used in conjunction with gentamicin; consider that these infections may involve β-lacatamase-producing bacteria resistant to ampicillin alone.^{6 7}

Treatment of endocarditis caused by susceptible staphylococci, streptococci, E. coli, P. mirabilis, or Salmonella.²

Prevention of bacterial endocarditis in patients undergoing certain dental, oral, respiratory tract, or esophageal procedures† who have cardiac conditions that put them at moderate or high risk.¹⁰ AHA recommends ampicillin as a drug of choice.¹⁰

Prevention of bacterial endocarditis in patients undergoing certain GU and GI (except esophageal) procedures† who have cardiac conditions that put them at moderate or high risk.¹⁰ AHA recommends ampicillin as a drug of choice.¹⁰ Used alone in those at moderate risk or in conjunction with gentamicin in those at high risk.¹⁰

Consult most recent AHA recommendations for specific information on which cardiac conditions are associated with high or moderate risk of endocarditis and which procedures require prophylaxis.¹⁰

Meningitis and Other CNS Infections

Treatment of meningitis caused by susceptible Neisseria meningitidis,^{2 5} Streptococcus agalactiae (group B streptococci),^{2 5} Listeria monocytogenes,^{2 4 5} E. coli,^{2 5} H. influenzae†,⁵ or S. pneumoniae†.

Drug of choice for empiric treatment of neonatal S. agalactiae meningitis.⁵ An aminoglycoside (IV gentamicin) used concomitantly until in vitro susceptibility testing is complete and a clinical response obtained;⁵ treatment can then be changed to penicillin G.⁵

Drug of choice for L. monocytogenes meningitis;^{4 5 9} used alone or in conjunction with an aminoglycoside (e.g., gentamicin).^{4 5 9}

Penicillin G usually preferred for N. meningitidis meningitis and penicillin-susceptible S. pneumoniae meningitis.⁵ For H. influenzae meningitis, cefotaxime, ceftriaxone, or, alternatively, ampicillin in conjunction with chloramphenicol is recommended; ampicillin should not be used alone (see Ampicillin-resistant Haemophilus influenzae under Cautions).⁵

Respiratory Tract Infections

Treatment of respiratory tract infections caused by susceptible Staphylococcus aureus (including penicillinase-producing strains), Streptococcus (including S. pneumoniae), S. pyogenes (group A β-hemolytic streptococci), or H. influenzae (nonpenicillinase-producing strains only).^{1 2 9}

Generally should not be used for the treatment of streptococcal or staphylococcal infections when a natural penicillin would be effective.^{4 5 8 9} Should not be used alone for empiric treatment of respiratory tract infections when ampicillin-resistant H. influenzae may be involved.^{5 9}

Septicemia

Treatment of septicemia caused by susceptible staphylococci, streptococci, enterococci, E. coli, P. mirabilis, or Salmonella.^{2 9}

Urinary Tract Infections (UTIs)

Treatment of UTIs caused by susceptible enterococci, E. coli, or Proteus mirabilis.^{1 2 9}

A drug of choice for enterococcal UTIs.^{4 9} Because of high urinary concentrations, may be effective when used alone,⁹ but consider that enterococci resistant to ampicillin have been reported.⁴

Eikenella Infections

Treatment of infections caused by Eikenella corrodens†; drug of choice.⁴

Gonorrhea and Associated Infections

Previously used for treatment of acute uncomplicated gonorrhea (anogenital and urethral) caused by susceptible Neisseria gonorrhoeae.¹ Has been used for gonococcal urethritis.² No longer recommended for gonorrhea or gonococcal urethritis by CDC or other experts (high incidence of penicillin-resistant strains).¹¹

Listeria Infections

Treatment of infections caused by Listeria monocytogenes; used alone or in conjunction with an aminoglycoside.^{5 9}

A drug of choice for Listeria infections occurring during pregnancy, granulomatosis infantiseptica, sepsis, endocarditis, meningitis, and foodborne infections.^{4 5 9 9} (See Meningitis and Other CNS Infections under Uses.)

Pertussis

Has been used to treat and prevent secondary pulmonary infections in patients with pertussis†.⁹ Erythromycin generally considered drug of choice for treatment of catarrhal stage of pertussis and to shorten the period of communicability of the disease.^{5 9} Ampicillin, like most other anti-infectives, does not shorten clinical course of pertussis.⁹

Typhoid Fever and Other Salmonella Infections

Alternative for treatment of typhoid fever (enteric fever) caused by susceptible Salmonella typhi.^{2 4 5 9} Drugs of choice are third generation cephalosporins (e.g., ceftriaxone, cefotaxime) or fluoroquinolones (e.g., ciprofloxacin, ofloxacin);⁴ consider that multidrug-resistant strains of S. typhi (strains resistant to ampicillin, amoxicillin, chloramphenicol, and/or co-trimoxazole) reported with increasing frequency.⁵

Treatment of chronic carriers of S. typhi†; drugs of choice are fluoroquinolones (e.g., ciprofloxacin), ampicillin, or amoxicillin (with probenecid).^{5 8 9}

Treatment of gastroenteritis caused by susceptible Salmonella.^{2 4 5}

Long-term suppressive or maintenance therapy (secondary prophylaxis) in HIV-infected patients to prevent recurrence of nontyphi Salmonella septicemia†.

Shigella Infections

Treatment of GI infections caused by susceptible Shigella.^{1 2 5 9}

Anti-infectives generally indicated in addition to fluid and electrolyte replacement for severe shigellosis.^{5 9} Previously considered a drug of choice for shigellosis (especially in children),⁹ but strains of S. flexneri and S. sonnei resistant to ampicillin reported with increasing frequency.⁹ Fluoroquinolones, ceftriaxone, or co-trimoxazole now considered drugs of choice for empiric treatment,^{4 5 9} especially in areas where ampicillin-resistant strains of Shigella have been reported.^{5 9}

Prevention of Perinatal Group B Streptococcal Disease

Prevention of early-onset neonatal group B streptococcal (GBS) disease†.⁵

Intrapartum anti-infective prophylaxis to prevent early-onset neonatal GBS disease is administered to women identified as GBS carriers during routine prenatal GBS screening performed at 35–37 weeks during the current pregnancy and to women who have GBS bacteriuria during the current pregnancy, a previous infant with invasive GBS disease, unknown GBS status with delivery at <37 weeks gestation, amniotic membrane rupture for ≥18 hours, or intrapartum temperature of ≥38°C.

When intrapartum GBS prophylaxis is indicated, IV penicillin G is the drug of choice. Although IV ampicillin can be used, CDC and AAP state that penicillin G is preferred since it has a narrower spectrum of activity and is less likely to select for antibiotic-resistant organisms.

Perioperative Prophylaxis

Has been used for perioperative prophylaxis† in patients undergoing vaginal hysterectomy or cesarean section. Cephalosporins (cefazolin, cefotetan, cefoxitin) usually drugs of choice for perioperative prophylaxis in patients undergoing obstetric and gynecologic surgery.

Perioperative prophylaxis in patients undergoing biliary tract or intestinal surgery including appendectomy†. Cephalosporins (cefazolin, cefoxitin) usually drugs of choice.

Ampicillin Trihydrate Dosage and Administration

Administration

Administer orally,¹ by slow IV injection or infusion,² or by IM injection.²

Parenteral route used for treatment of moderately severe or severe infections.² Oral route should not be used for initial treatment of severe, life-threatening infections, but may be used as follow-up after parenteral ampicillin.

Oral Administration

Administer orally with a full glass of water 1 hour before or 2 hours after meals.¹

IV Administration

Reconstitution

Reconstitute vials containing 125, 250, or 500 mg with 5 mL of sterile or bacteriostatic water for injection.² Alternatively, reconstitute vials containing 1 or 2 g with 7.4 or 14.8 mL, respectively, of sterile or bacteriostatic water for injection.²

Rate of Administration

Solutions reconstituted from 125-, 250-, or 500-mg vials may be given by IV injection over a period of 3–5 minutes.² Solutions reconstituted from 1- or 2-g vials should be given IV over a period of ≥10–15 minutes.²

For IV infusion, concentration and rate of administration should be adjusted so that the total dose is administered before the drug is inactivated in the IV solution.²

IM Administration

Reconstitution

Reconstitute with sterile or bacteriostatic water for injection according to manufacturer's directions to provide solutions containing 125 or 250 mg/mL.²

Dosage

Available as ampicillin trihydrate¹ and ampicillin sodium² ; dosage expressed in terms of ampicillin.^{1 2}

Duration of therapy depends on type and severity of infection and should be determined by clinical and bacteriologic response of the patient.^{1 2} For most infections, therapy should be continued for ≥48–72 hours after patient becomes asymptomatic or evidence of eradication of the infection has been obtained.^{1 2} More prolonged therapy may be necessary for some infections.^{1 2}

Pediatric Patients

General Pediatric Dosage

Oral

Children ≥1 month of age: AAP recommends 50–100 mg/kg daily given in 4 divided doses for mild to moderate infections.⁵

AAP states oral route is inappropriate for severe infections.⁵

IV or IM

Neonates <1 week of age: AAP recommends 25–50 mg/kg every 12 hours in those weighing ≤2 kg or 25–50 mg/kg every 8 hours in those weighing >2 kg.⁵

Neonates 1–4 weeks of age: AAP recommends 25–50 mg/kg every 12 hours for those weighing <1.2 kg, 25–50 mg/kg every 8 hours for those weighing 1.2–2 kg, or 25–50 mg/kg every 6 hours for those weighing >2 kg.⁵

Children ≥1 month of age: AAP recommends 100–150 mg/kg daily given in 4 divided doses for mild to moderate infections or 200–400 mg/kg daily given in 4 divided doses for severe infections.⁵

Endocarditis

Treatment of Endocarditis Caused by Viridans Streptococci or S. bovis

IV

300 mg/kg daily given in 4–6 divided doses for 4 weeks.⁷ Used in conjunction with IM or IV gentamicin (3 mg daily given during the first 2 weeks).⁷

Treatment of Enterococcal Endocarditis

IV

300 mg/kg daily given in 4–6 divided doses for 4–6 weeks.⁷ Used in conjunction with IM or IV gentamicin (3 mg daily given for 4–6 weeks).⁷

Prevention of Bacterial Endocarditis in Patients Undergoing Certain Dental, Oral, Respiratory Tract, or Esophageal Procedures†

IV or IM

50 mg/kg given 30 minutes prior to the procedure.¹⁰

Prevention of Enterococcal Endocarditis in Patients Undergoing Certain Genitourinary or GI (except Esophageal) Procedures†

IV or IM

For moderate-risk patients, 50 mg/kg given 30 minutes prior to the procedure.¹⁰

For high-risk patients, 50 mg/kg (up to 2 g) as a single dose in conjunction with a single dose of gentamicin (1.5 mg/kg) given 30 minutes prior to the procedure followed a dose of IM or IV ampicillin (25 mg/kg) given 6 hours later or, alternatively, oral amoxicillin (25 mg/kg) given 6 hours later.¹⁰

GI Infections

Oral

Children weighing ≤20 kg: 100 mg/kg daily in 4 divided doses.¹

Children weighing >20 kg: 500 mg 4 times daily.¹ Severe or chronic infections may require higher dosage.¹

IV or IM

Children weighing <40 kg: 50 mg/kg daily in divided doses every 6–8 hours.²

Children weighing ≥40 kg: 500 mg every 6 hours.² Severe or chronic infections may require higher dosage.¹

Meningitis and Other CNS Infections

Empiric Treatment of Meningitis

IV

Neonates and children <2 months of age: 100–300 mg/kg daily given in divided doses; used in conjunction with IM gentamicin pending results of in vitro susceptibility tests.

Children 2 months to 12 years of age: 200–400 mg/kg daily given in divided doses every 4–6 hours; used in conjunction with IV chloramphenicol.

Treatment of Meningitis Caused by S. agalactiae

IV

AAP recommends 200–300 mg/kg daily given in 3 divided for neonates ≤7 days of age or 300 mg/kg daily given in 4–6 divided doses for neonates >7 days of age.⁵

Respiratory Tract Infections

Oral

Children weighing ≤20 kg: 50 mg/kg daily in 3 or 4 divided doses.¹

Children weighing >20 kg: 250 mg 4 times daily.¹

IV or IM

Children weighing <40 kg: 25–50 mg/kg daily in divided doses every 6–8 hours.²

Children weighing ≥40 kg: 250–500 mg every 6 hours.²

Septicemia

IV or IM

150–200 mg/kg daily.²

Skin and Skin Structure Infections

IV or IM

Children weighing <40 kg: 25–50 mg/kg daily in divided doses every 6–8 hours.²

Children weighing ≥40 kg: 250–500 mg every 6 hours.²

Urinary Tract Infections (UTIs)

Oral

Children weighing ≤20 kg: 100 mg/kg daily in 4 divided doses.¹

Children weighing >20 kg: 500 mg 4 times daily.¹ Severe or chronic infections may require higher dosage.¹

IV or IM

Children weighing <40 kg: 50 mg/kg daily in divided doses every 6–8 hours.²

Children weighing ≥40 kg: 500 mg every 6 hours.² Severe or chronic infections may require higher dosage.¹

Adults

Endocarditis

Treatment of Enterococcal Endocarditis

IV

12 g daily (by continuous IV infusion or in 6 equally divided IV doses) in conjunction with IM or IV gentamicin (1 mg/kg every 8 hours).⁶ Treatment with both drugs generally should be continued for 4–6 weeks, but patients who had symptoms of infection for >3 months before treatment was initiated and patients with prosthetic heart valves require ≥6 weeks of therapy with both drugs.⁶

Treatment of Endocarditis Caused by HACEK group (i.e., H. parainfluenzae, H. aphrophilus, A. actinomycetemcomitans, C. hominis, E. corrodens, K. kingae)†

IV

12 g daily (by continuous IV infusion or in 6 equally divided IV doses) in conjunction with IM or IV gentamicin (1 mg/kg every 8 hours).⁶ Treatment with both drugs generally should be continued for 4 weeks.⁶

Prevention of Bacterial Endocarditis in Patients Undergoing Certain Dental, Oral, Respiratory Tract, or Esophageal Procedures†

IV or IM

2 g as a single dose given 30 minutes prior to the procedure.¹⁰

Prevention of Enterococcal Endocarditis in Patients Undergoing Certain GU or GI (except Esophageal) Procedures†

IV or IM

For moderate-risk patients, 2 g given 30 minutes prior to the procedure.¹⁰

For high-risk patients, 2 g as a single dose in conjunction with a single dose of gentamicin (1.5 mg/kg) given 30 minutes prior to the procedure followed by a dose of IM or IV ampicillin (1 g) given 6 hours later or, alternatively, a dose of oral amoxicillin (1 g) given 6 hours later.¹⁰

GI Infections

Oral

500 mg 4 times daily.¹

IV or IM

Adults weighing <40 kg: 50 mg/kg daily in divided doses every 6–8 hours.²

Adults weighing ≥40 kg: 500 mg every 6 hours.²

Meningitis and Other CNS Infections

IV, then IM

150–200 mg/kg daily in divided doses every 3–4 hours.² Use IV initially, may switch to IM after 3 days.²

Respiratory Tract Infections

Oral

250 mg 4 times daily.¹

IV or IM

Adults weighing <40 kg: 25–50 mg/kg daily in divided doses every 6–8 hours.²

Adults weighing ≥40 kg: 250–500 mg every 6 hours.²

Septicemia

IV or IM

150–200 mg/kg daily.²

Skin and Skin Structure Infections

IV or IM

Adults weighing <40 kg: 25–50 mg/kg daily in divided doses every 6–8 hours.²

Adults weighing ≥40 kg: 250–500 mg every 6 hours.²

Urinary Tract Infections (UTIs)

Oral

500 mg 4 times daily.¹

IV or IM

Adults weighing <40 kg: 50 mg/kg daily in divided doses every 6–8 hours.²

Adults weighing ≥40 kg: 500 mg every 6 hours.²

Gonorrhea and Associated Infections

Uncomplicated Gonorrhea

Oral

3.5 g as a single dose (with 1 g of oral probenecid).¹ No longer recommended for gonorrhea by CDC or other experts.¹¹

Gonococcal Urethritis

IV or IM

500 mg initially followed by 500 mg 8–12 hours later.² No longer recommended by CDC or other experts.¹¹

Prevention of Perinatal Group B Streptococcal (GBS) Disease†

IV

An initial 2-g dose (at time of labor or rupture of membranes) followed by 1 g every 4 hours until delivery.

Prescribing Limits

Pediatric Patients

Pediatric dosage should not exceed adult dosage.¹

Special Populations

Renal Impairment

Dosage adjustments necessary in patients with renal impairment.⁹

Some clinicians suggest that adults with GFR 10–50 mL/minute receive the usual dose every 6–12 hours and that adults with GFR <10 mL/minute receive the usual dose every 12–16 hours. Alternatively, some clinicians suggest that modification of usual dosage is unnecessary in adults with Cl_cr ≥ 30 mL/minute, but that adults with Cl_cr ≤10 mL/minute should receive the usual dose every 8 hours.

Patients undergoing hemodialysis should receive a supplemental dose after each dialysis period.

Geriatric Patients

No dosage adjustments except those related to renal impairment. (See Renal Impairment under Dosage and Administration.)

Cautions for Ampicillin Trihydrate

Contraindications

• 
  

  Known hypersensitivity to any penicillin.^{1 2}

  
  

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.^{1 2} Discontinue and institute appropriate therapy if superinfection occurs.^{1 2}

Treatment with anti-infectives may permit overgrowth of clostridia.¹ Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.¹

Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone.¹ Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.¹

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with penicillins.^{1 2 9}

Prior to initiation of therapy, make careful inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.^{1 2} Partial cross-allergenicity occurs among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.^{1 2}

If a severe hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).^{1 2}

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of ampicillin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.^{1 2} In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.^{1 2}

Mononucleosis

Possible increased risk of rash in patients with mononucleosis; use in these patients not recommended.

Ampicillin-resistant Haemophilus influenzae

Because of increasing prevalence of ampicillin-resistant H. influenzae,⁵ the drug should not be used alone for empiric treatment of serious infections (e.g., meningitis, pneumonia) when H. influenzae may be involved.^{5 9}

Laboratory Monitoring

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.^{1 2}

Sodium Content

Powder for injection contains 2.9 mEq of sodium per g of ampicillin.²

Specific Populations

Pregnancy

Category B.^{1 2}

Lactation

Distributed into milk.^{1 2 9} Use with caution.^{1 2}

Pediatric Use

Renal clearance of ampicillin may be delayed in neonates and young infants because of incompletely developed renal function.^{1 9} Use lowest effective dosage.¹

Renal Impairment

Dosage adjustments necessary in renal impairment.⁹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea, nausea), rash.

Interactions for Ampicillin Trihydrate

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Allopurinol	Possible increased incidence of rash	Unclear whether potentiation of rash is caused by allopurinol or hyperuricemia present in these patients Clinical importance has not been determined; some clinicians suggest that concomitant use of the drugs should be avoided if possible
Aminoglycosides	In vitro evidence of synergistic antibacterial effects against enterococci; used to therapeutic advantage in treatment of endocarditis and other severe enterococcal infections Potential in vitro and in vivo inactivation of aminoglycosidesHID
Chloramphenicol	In vitro evidence of antagonism	Clinical importance unclear
Hormonal contraceptives	Possible decreased efficacy of estrogen-containing oral contraceptives and increased incidence of breakthrough bleeding	Some clinicians suggest that a supplemental method of contraception be used in patients receiving oral contraceptives and ampicillin concomitantly, other clinicians state that most women taking oral contraceptives probably do not need to use alternative contraceptive precautions while receiving ampicillin
Methotrexate	Possible decreased renal clearance of methotrexate with penicillins; possible increased methotrexate concentrations and hematologic and GI toxicity	Monitor closely if used concomitantly
Probenecid	Decreased renal tubular secretion of ampicillin; increased and prolonged ampicillin concentrations may occur9
Sulbactam	Synergistic bactericidal effect against many strains of β-lactamase-producing bacteria
Sulfonamides	In vitro evidence of antagonism1	Clinical importance unclear1
Tests for glucose	Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution1 2	Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)1 2
Tests for uric acid	Possible falsely increased serum uric acid concentrations when copper-chelate method is used; phosphotungstate and uricase methods appear to be unaffected by the ampicillin

Ampicillin Trihydrate Pharmacokinetics

Absorption

Bioavailability

30–55% of an oral dose absorbed from the GI tract in fasting adults; peak serum concentrations attained within 1–2 hours.⁹

Following IM administration, peak serum concentrations generally attained more quickly and are higher than following equivalent oral doses.⁹

Rapid IV administration results in peak serum concentrations immediately after completion of the infusion; serum concentrations may still be detectable 6 hours later.

Food

Food generally decreases rate and extent of absorption.⁹

Distribution

Extent

Distributed into ascitic, synovial, and pleural fluids. Also distributed into liver, bile,⁹ lungs, gallbladder, prostate, muscle, middle ear effusions, bronchial secretions, sputum, maxillary sinus secretions, tonsils, saliva, sweat, and tears.

Distributed into CSF in concentrations 11–65% of simultaneous serum concentrations; highest CSF concentrations occur 3–7 hours after an IV dose.

Readily crosses the placenta.⁹ Distributed into milk in low concentrations.

Plasma Protein Binding

15–25%.^{1 2 9}

Protein binding is lower in neonates than in children or adults; ampicillin reportedly 8–12% bound to serum proteins in neonates.

Elimination

Metabolism

Partially metabolized by hydrolysis of the β-lactam ring to penicilloic acid which is microbiologically inactive.⁹

Elimination Route

Eliminated in urine by renal tubular secretion and to a lesser extent by glomerular filtration.⁹ Small amounts also excreted in feces and bile.⁹

In adults with normal renal function, approximately 20–64% of a single oral dose⁹ excreted unchanged in urine within 6–8 hours. Approximately 60–70% of a single IM dose or 73–90% of a single IV dose excreted unchanged in urine.

Half-life

0.7–1.5 hours in adults with normal renal function.⁹

Half-life is 4 hours in neonates 2–7 days of age, 2.8 hours in neonates 8–14 days of age, and 1.7 hours in neonates 15–30 days of age.⁹

Special Populations

Serum concentrations higher and more prolonged in premature or full-term neonates <6 days of age than in full-term neonates ≥6 days of age.

Renal clearance decreased in geriatric patients because of diminished tubular secretory ability; serum concentrations may be higher and half-life prolonged. In those 67–76 years of age, half-life ranges from 1.4–6.2 hours.

Serum concentrations are higher and half-life prolonged in patients with impaired renal function. Half-life may range from 7.4–21 hours in patients with Cl_cr <10 mL/minute⁹

Stability

Storage

Oral

Capsules

Tight container at 15–30°C; avoid excessive heat.¹

For Suspension

Tight container at 15–30°C.¹ After reconstitution, discard after 7 days if stored at room temperature or after 14 days if refrigerated.¹

Parenteral

Powder for Injection or Infusion

Solutions for IM injection or IV injection or infusion should be used within 1 hour after reconstitution and should not be frozen.²

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Isolyte M or P with dextrose 5%
Incompatible
Amino acids 4.25%, dextrose 25%
Dextran 40 10% in sodium chloride 0.9%
Dextran 40 10% in dextrose 5% in water
Dextran 70 6% in sodium chloride 0.9%
Dextran 70 6% in dextrose 5% in water
Dextrose 5% in sodium chloride 0.9%
Dextrose 5 or 10% in water
Fat emulsion 10%, IV
Fructose 5.25%
Hetastarch 6%
Invert sugar 7.5% with electrolytes
Invert sugar 10% in water
Ringer’s injection, lactated
Sodium bicarbonate 1.4%
Sodium lactate (1/6) M
Variable
Ringer’s injection
Sodium chloride 0.9%

Drug Compatibility

Admixture CompatibilityHID

Compatible
Cefotiam HCl
Clindamycin phosphate
Erythromycin lactobionate
Floxacillin sodium
Furosemide
Incompatible
Amikacin sulfate
Chlorpromazine HCl
Dopamine HCl
Gentamicin sulfate
Hydralazine HCl
Prochlorperazine mesylate
Variable
Aztreonam
Cefepime HCl
Cimetidine HCl
Heparin sodium
Hydrocortisone sodium succinate
Metronidazole
Metronidazole HCl with sodium bicarbonate
Ranitidine HCl
Sodium bicarbonate
Verapamil HCl

Y-Site CompatibilityHID

Compatible
Acyclovir sodium
Amifostine
Anidulafungin
Aztreonam
Bivalirudin
Cyclophosphamide
Dexmedetomidine HCl
Docetaxel
Doxapram HCl
Doxorubicin HCl liposome injection
Enalaprilat
Esmolol HCl
Etoposide phosphate
Famotidine
Filgrastim
Fludarabine phosphate
Foscarnet sodium
Gemcitabine HCl
Granisetron HCl
Heparin sodium
Heparin sodium with hydrocortisone sodium succinate
Hetastarch in lactated electrolyte injection (Hextend)
Labetalol HCl
Levofloxacin
Linezolid
Magnesium sulfate
Melphalan HCl
Meperidine HCl
Milrinone acetate
Morphine sulfate
Multivitamins
Ofloxacin
Pantoprazole sodium
Pemetrexed disodium
Perphenazine
Phytonadione
Potassium chloride
Propofol
Remifentanil HCl
Tacrolimus
Teniposide
Theophylline
Thiotepa
Vitamin B complex with C
Incompatible
Amphotericin B cholesteryl sulfate complex
Epinephrine HCl
Fenoldopam mesylate
Fluconazole
Hydralazine HCl
Lansoprazole
Midazolam HCl
Nicardipine HCl
Ondansetron HCl
Sargramostim
Verapamil HCl
Vinorelbine tartrate
Variable
Calcium gluconate
Diltiazem HCl
Hetastarch in sodium chloride 0.9%
Hydromorphone HCl
Vancomycin HCl

Actions and SpectrumActions

• 
  

  Based on spectrum of activity, classified as an aminopenicillin.^{8 9} Aminopenicillins have enhanced activity against gram-negative bacteria compared with natural and penicillinase-resistant penicillins.^{8 9}

  
  


• 
  

  Usually bactericidal.^{1 2}

  
  


• 
  

  Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.^{1 2}

  
  


• 
  

  Spectrum of activity includes many gram-positive and -negative aerobes and some anaerobes.^{1 9 12}

  
  


• 
  

  Gram-positive aerobes: active in vitro and in clinical infections against Staphylococcus (β-lactamase-negative strains only), Streptococcus pneumoniae, other Streptococcus (α- and β-hemolytic strains only), and Enterococcus faecalis.^{1 9 12} Also active against Corynebacteriun and Listeria monocytogenes.^{1 9 12}

  
  


• 
  

  Gram-negative aerobes: active in vitro and in clinical infections against H. influenzae, N. gonorrhoeae, E. coli, Proteus mirabilis, Salmonella, and Shigella.^{1 9 12} Also active in vitro against Bordetella pertussis, Eikenella corrodens, and Neisseria meningitidis.⁹ Inactive against Citrobacter, Enterobacter, Klebsiella, Providencia, and Serratia.^{9 12}

  
  


• 
  

  Gram-positive and gram-negative bacteria that produce β-lactamases, including β-lactamase-producing S. aureus and E. faecalis, are resistant.^{9 12}

  
  


• 
  

  Complete cross-resistance generally occurs between ampicillin and amoxicillin.

  
  

Advice to Patients

• 
  

  Advise patients that antibacterials (including ampicillin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).

  
  


• 
  

  Importance of completing the entire prescribed course of treatment, even if feeling better after a few days.

  
  


• 
  

  Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with ampicillin or other antibacterials in the future.

  
  


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  Importance of taking oral ampicillin with a full glass of water 1 hour before or 2 hours after a meal.¹

  
  


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  Importance of discontinuing therapy and informing clinician if an allergic reaction occurs.¹

  
  


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  Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

  
  


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  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


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  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ampicillin (Trihydrate)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	250 mg (of ampicillin)*	Principen	Sandoz
		500 mg (of ampicillin)*	Principen	Sandoz
	For suspension	125 mg (of ampicillin) per 5 mL*	Principen	Sandoz
		250 mg (of ampicillin) per 5 mL*	Principen	Sandoz

Ampicillin Sodium

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection	125 mg (of ampicillin)	Ampicillin Sodium for Injection	Sandoz
		250 mg (of ampicillin)	Ampicillin Sodium for Injection	Sandoz
		500 mg (of ampicillin)	Ampicillin Sodium for Injection	Sandoz
		1 g (of ampicillin)	Ampicillin Sodium for Injection	Sandoz
		2 g (of ampicillin)	Ampicillin Sodium for Injection	Sandoz
		10 g (of ampicillin) pharmacy bulk package	Ampicillin Sodium for Injection	Sandoz
	For injection, for IV infusion	1 g (of ampicillin)	Ampicillin Sodium ADD-Vantage	Sandoz
		2 g (of ampicillin)	Ampicillin Sodium ADD-Vantage	Sandoz