Ampicillin

Name: Ampicillin

Side effects

As with other penicillins, it may be expected that untoward reactions will be essentially limited to sensitivity phenomena. They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillin and in those with a history of allergy, asthma, hay fever, or urticaria.

The following adverse reactions have been reported as associated with the use of ampicillin:

Gastrointestinal: glositis, stamatitis, nausea, vomiting, enterocolitis, pseudomembranous colitis, and diarrhea. These reactions are usually associated with oral dosage forms of the drugs.

Hypersensitivity Reactions: An erythematous, mildly pruritic, maculopapular skin rash has been reported fairly frequently. The rash, which usually does not develop within the first week of therapy, may cover the entire body including the soles, palms, and oral mucosa. The eruption usually disappears in three to seven days.

Other hypersensitivity reactions that have been reported are: skin rash, pruritus, urticaria, erythema multiforme, and an occasional case of exfoliative dermatitis. Anaphylaxis is the most serious reaction experienced and has usually been associated with the parenteral dosage form of the drug

Note: Urticaria, other skin rashes, and serum sickness-like reactions may be controlled by antihistamines, and if necessary, systemic corticosteroids. Whenever such reactions occur, ampicillin should be discontinued unless, in the opinion of the physician, the condition being treated is life-threatening, and amenable only to ampicillin therapy. Serious anaphylactoid reactions require emergency measures (see WARNINGS).

Liver: Moderate elevation in serum glutamic oxalaacetic transaminase (SGOT) has been noted, but the significance of this finding is unknown.

Hemic and Lymphatic Systems: Anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukapenia, and agranulacytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

Other: Other adverse reactions that have been reported with the use at ampicillin are laryngeal stride and high fever. An occasional patient may complain of sore mouth or tongue as with any oral penicillin preparation.

Uses of Ampicillin

Ampicillin is used in the treatment of:

  • Actinomycosis
  • Bites, Human
  • Dysentery, Bacillary
  • Escherichia coli Infections
  • Gonorrhea
  • Haemophilus Infections
  • Klebsiella Infections
  • Meningitis, Bacterial
  • Meningococcal Infections
  • Pneumococcal Infections
  • Pregnancy Complications, Infectious
  • Respiratory Tract Infections
  • Salmonella Infections
  • Skin Diseases, Bacterial
  • Soft Tissue Infections
  • Staphylococcal Infections
  • Surgical Wound Infection
  • Urinary Tract Infections
  • Listeriosis

Ampicillin is used in the prevention of:

  • Endocarditis, Bacterial

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Forms of Medication

Ampicillin is available in the following forms:

  • Injectable Solution
  • Oral Capsule
  • Oral Solution
  • Oral Suspension
  • Oral Tablet
  • Prefilled Syringe

Ampicillin 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 Clcr <10 mL/minute.9

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.

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

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

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

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

  • 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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* 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

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

Ampicillin Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

125 mg (of ampicillin)*

Ampicillin Sodium for Injection

250 mg (of ampicillin)*

Ampicillin Sodium for Injection

500 mg (of ampicillin)*

Ampicillin Sodium for Injection

1 g (of ampicillin)*

Ampicillin Sodium for Injection

2 g (of ampicillin)*

Ampicillin Sodium for Injection

10 g (of ampicillin) pharmacy bulk package*

Ampicillin Sodium for Injection

For injection, for IV infusion

1 g (of ampicillin)*

Ampicillin Sodium ADD-Vantage

2 g (of ampicillin)*

Ampicillin Sodium ADD-Vantage

What are some things I need to know or do while I take Ampicillin?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Very bad and sometimes deadly allergic side effects have rarely happened. Talk with your doctor.
  • This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take Ampicillin.
  • Have your blood work checked if you are on this medicine for a long time. Talk with your doctor.
  • If you have high blood sugar (diabetes), do not use Clinitest®. Use some other urine glucose testing like Clinistix® or Tes-Tape®.
  • Do not use longer than you have been told. A second infection may happen.
  • Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking Ampicillin.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

Ampicillin Dosage and Administration

Infections of the respiratory tract and soft tissues.

Patients weighing 40 kg (88 lbs) or more: 250 mg to 500 mg every 6 hours.

Patients weighing less than 40 kg (88 lbs): 25 to 50 mg/kg/day in equally divided doses at 6- to 8- hour intervals.

Infections of the gastrointestinal and genitourinary tracts (including those caused by Neisseria gonorrhoeae in females).

Patients weighing 40 kg (88 lbs) or more: 500 mg every 6 hours.

Patients weighing less than 40 kg (88 lbs): 50 mg/kg/day in equally divided doses at 6- to 8- hour intervals.

In the treatment of chronic urinary tract and intestinal infections, frequent bacteriological and clinical appraisal is necessary. Smaller doses than those recommended above should not be used. Higher doses should be used for stubborn or severe infections. In stubborn infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy.

Urethritis in males due to N. gonorrhoeae.

Adults – Two doses of 500 mg each at an interval of 8 to 12 hours. Treatment may be repeated if necessary or extended if required.

In the treatment of complications of gonorrheal urethritis, such as prostatitis and epididymitis, prolonged and intensive therapy is recommended. Cases of gonorrhea with a suspected primary lesion of syphilis should have darkfield examinations before receiving treatment. In all other cases where concomitant syphilis is suspected, monthly serological tests should be made for a minimum of four months.

The doses for the preceding infections may be given by either the intramuscular or intravenous route. A change to oral Ampicillin may be made when appropriate.

Bacterial Meningitis

Adults and children – 150 to 200 mg/kg/day in equally divided doses every 3 to 4 hours. (Treatment may be initiated with intravenous drip therapy and continued with intramuscular injections.) The doses for other infections may be given by either the intravenous or intramuscular route.

Neonates (less than or equal to 28 days of postnatal age) -Dosage should be based on Gestational age and Postnatal age according to Table 3.

TABLE 3: Dosage in Neonates (less than or equal to 28 days of postnatal age) for Bacterial Meningitis and Septicemia:

Gestational age (weeks)

Postnatal age (davs)

Dosage

less than or equal to 34

less than or equal to 7

100 mg/kg/day in equally divided doses every 12 hours

less than or equal to 34

greater than or equal to 8 and less than 28

150 mg/kg/day in equally divided doses every 12 hours

greater than 34

less than or equal to 28

150 mg/kg/day in equally divided doses every 8 hours

Septicemia

Adults and children – 150 to 200 mg/kg/day. Start with intravenous administration for at least three days and continue with the intramuscular route every 3 to 4 hours.

Neonates (less than or equal to 28 days of postnatal age) - Dosage should be based on Gestational age and Postnatal age according to Table 3 (above).

Treatment of all infections should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. A minimum of 10 days treatment is recommended for any infection caused by Group A beta-hemolytic streptococci to help prevent the occurrence of acute rheumatic fever or acute glomerulonephritis.

Reconstitution

IM: Dissolve contents of vial in sterile water for injection or bacteriostatic water for injection; final concentration for IM injection is 125 mg/mL or 250 mg/mL. Solutions for IM injection should be freshly prepared and used within 1 hour.

IV:

Direct IV use: Dissolve contents of 125 mg, 250 mg, or 500 mg vial in 5 mL SWFI. Alternatively, dissolve contents of 1 g or 2 g vial in 7.4 or 14.8 mL SWFI, respectively.

Intermittent infusion: Minimum volume: Concentration should not exceed 30 mg/mL due to concentration-dependent stability restrictions. Usual diluent: 500 mg/50 mL NS; 1 g/50 mL NS; 2 g/100 mL NS.

Dietary Considerations

Take on an empty stomach 30 minutes before or 2 hours after meals. Some products may contain sodium.

Drug Interactions

Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Monitor therapy

Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Chloroquine: May decrease the serum concentration of Ampicillin. Management: Chloroquine prescribing information recommends separating administration of ampicillin and chloroquine by at least 2 hours to minimize any potential negative impact of chloroquine on ampicillin bioavailability. Consider therapy modification

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Lanthanum: May decrease the serum concentration of Ampicillin. Management: Administer oral ampicillin at least two hours before or after lanthanum. Consider therapy modification

Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Monitor therapy

Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Monitor therapy

Probenecid: May increase the serum concentration of Penicillins. Management: Avoid the routine use of penicillins and probenecid, but this combination may be used advantageously in select cases with careful monitoring. Monitor for toxic effects of penicillins if probenecid is initiated or the dose is increased. Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Adverse Reactions

Frequency not defined.

Central nervous system: Brain disease (penicillin-induced), glossalgia, seizure, sore mouth

Dermatologic: Erythema multiforme, exfoliative dermatitis, skin rash, urticaria

Note: Appearance of a rash should be carefully evaluated to differentiate (if possible) nonallergic ampicillin rash from hypersensitivity reaction. Incidence is higher in patients with viral infection, Salmonella infection, lymphocytic leukemia, or patients that have hyperuricemia.

Gastrointestinal: Diarrhea, enterocolitis, glossitis, melanoglossia, nausea, oral candidiasis, pseudomembranous colitis, stomatitis, vomiting

Hematologic & oncologic: Agranulocytosis, anemia, eosinophilia, hemolytic anemia, immune thrombocytopenia, leukopenia

Hepatic: Increased serum AST

Hypersensitivity: Anaphylaxis

Immunologic: Serum sickness-like reaction

Renal: Interstitial nephritis (rare)

Respiratory: Stridor

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Dysgeusia (Syed 2016)

Pregnancy Risk Factor B Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Ampicillin crosses the placenta, providing detectable concentrations in the cord serum and amniotic fluid (Bolognese 1968; Fisher 1967; MacAulay 1966). Maternal use of ampicillin has generally not resulted in an increased risk of birth defects (Aselton 1985; Czeizel 2001b; Heinonen 1977; Jick 1981; Puhó 2007). Ampicillin is recommended for use in pregnant women for the management of preterm premature rupture of membranes (PPROM) and for the prevention of early-onset group B streptococcal (GBS) disease in newborns. Ampicillin may also be used in certain situations prior to vaginal delivery in women at high risk for endocarditis (ACOG 172, 2016; ACOG No. 120, 2011; ACOG No. 485, 2011; CDC [RR-10] 2010).

The volume of distribution of ampicillin is increased during pregnancy and the half-life is decreased. As a result, serum concentrations in pregnant patients are approximately 50% of those in nonpregnant patients receiving the same dose. Higher doses may be needed during pregnancy. Although oral absorption is not altered during pregnancy, oral ampicillin is poorly absorbed during labor (Philipson 1977; Philipson 1978; Wasz-Höckert 1970).

What happens if i miss a dose (principen)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What should i avoid while taking ampicillin (principen)?

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, stop taking ampicillin and call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

Usual Adult Dose for Bacterial Endocarditis Prophylaxis

(Not approved by FDA)

AHA recommendations: 2 g IM or IV as a single dose 30 to 60 minutes before procedure

Comments:
-Recommended for patients unable to take oral medication.
-Antibiotic prophylaxis may be used for dental procedures (involving manipulation of gingival tissues or periapical region of teeth or perforation of oral mucosa), respiratory tract procedures, or procedures on infected skin, skin structures, or musculoskeletal tissue only for patients with the highest risk of infective endocarditis.

Usual Adult Dose for Meningitis

The manufacturer recommends: 150 to 200 mg/kg/day IV in equally divided doses every 3 to 4 hours

Comments:
-Therapy may be started with IV administration and continued with IM injections.

Approved indications:
-Parenteral: Bacterial meningitis due to E coli, group B streptococci, and other gram-negative bacteria (Listeria monocytogenes, N meningitidis)
-Oral: Meningitis due to N meningitidis

Some experts recommend:
IV: 200 mg/kg/day IV in equally divided doses every 4 hours, in combination with other parenteral antibiotics
Maximum dose: 12 g/day

Intrathecal or intraventricular: 10 to 50 mg/day in addition to IV antibiotics

Usual Adult Dose for Skin or Soft Tissue Infection

The manufacturer recommends: 250 to 500 mg IM or IV every 6 hours
Some experts recommend: 250 to 500 mg orally every 6 hours or 1 to 2 g IV every 4 to 6 hours, depending on the nature and severity of the infection

Usual Adult Dose for Pharyngitis

The manufacturer recommends:
Parenteral: 250 to 500 mg IM or IV every 6 hours
Oral: 250 mg orally every 6 hours

Approved indications:
Parenteral: Respiratory tract infections due to Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Group A beta-hemolytic streptococci
Oral: Respiratory tract infections due to nonpenicillinase-producing H influenzae and staphylococci, and streptococci (including S pneumoniae)

Some experts recommend: 500 mg orally or 1 to 2 g IM or IV every 6 hours, depending on the nature and severity of the infection

Usual Adult Dose for Pneumonia

The manufacturer recommends:
Parenteral: 250 to 500 mg IM or IV every 6 hours
Oral: 250 mg orally every 6 hours

Approved indications:
Parenteral: Respiratory tract infections due to S pneumoniae, S aureus, H influenzae, and Group A beta-hemolytic streptococci
Oral: Respiratory tract infections due to nonpenicillinase-producing H influenzae and staphylococci, and streptococci (including S pneumoniae)

Some experts recommend:
Beta-lactamase negative, penicillin-susceptible: 1 to 2 g IV every 4 to 6 hours, in combination with other antibiotic(s) depending on the nature and severity of the infection

Usual Adult Dose for Typhoid Fever

The manufacturer recommends: 500 mg orally or IM or IV every 6 hours

Comments:
-Severe, chronic, or stubborn infections may require larger doses.

Approved indications: Gastrointestinal tract infections due to Salmonella species (including S typhi)

Some experts recommend:
Severe, fully susceptible: 25 mg/kg IM or IV every 6 hours for 10 to 14 days
Carrier state: 1.5 g orally or IV with probenecid 500 mg every 6 hours for 6 weeks

Comments:
-Fluoroquinolones or amoxicillin are considered the drugs of choice.

Usual Pediatric Dose for Septicemia

AAP Recommendations:
Group B streptococcal bacteremia (presumed or proven):
Neonates:
7 days or younger, 2000 g or less: 100 mg/kg IM or IV every 12 hours
7 days or younger, greater than 2000 g: 50 mg/kg IM or IV every 8 hours or 100 mg/kg IM or IV every 12 hours
8 to 28 days, 2000 g or less: 50 mg/kg IM or IV every 8 hours
8 to 28 days, greater than 2000 g: 50 mg/kg IM or IV every 6 hours

Duration of therapy: At least 10 days for treatment of bacteremia without defined focus

The Manufacturer Recommends:
Children: 150 to 200 mg/kg/day

Comments:
-Start with IV administration for at least 3 days and continue with the IM route every 3 to 4 hours

Approved indications:
-Parenteral: Septicemia due to susceptible gram-positive organisms including Streptococcus species, penicillin G-susceptible staphylococci, and enterococci; gram-negative sepsis due to E coli, P mirabilis, and Salmonella species

Usual Pediatric Dose for Surgical Prophylaxis

(Not approved by FDA)

Some experts recommend:
Liver transplant:
1 month or older: Ampicillin 50 mg/kg IV plus cefotaxime 50 mg/kg IV at induction of anesthesia and every 6 hours for 48 hours after final surgical closure

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