Drug Monograph
Student Name : Rawan Sajdi Almutairi ID: 439480304
Date: subject : PHP 511
Generic Name: Ampicillin
Trade Name : APO-Ampi [DSC]; NOVO-Ampicillin
Drug Class: Antibiotic, Penicillin
Indications:
FDA-Labeled Indications
Gonorrhea
Infectious disease of digestive tract
Infectious disease of genitourinary system
Respiratory tract infection
Non-FDA Labeled Indications
Postoperative wound infection, Topical use
Premature rupture of membranes
Mechanism Of Action:
Ampicillin is a semisynthetic penicillin (beta-lactam antibiotic) that shares the same
mechanism of action as the other penicillins.
It works by inhibiting bacterial cell-wall synthesis through binding to one or more
penicillin bind proteins of actively dividing cells.
Ampicillin may be bactericidal or bacteriostatic depending on drug concentration and
the microorganism involved. Ampicillin is inactivated by penicillinase and therefore is
ineffective against penicillinase-producing organisms.
Pharmacokinetics
Absorption
Tmax, oral: 1 to 2 hours following 500 mg dose
Bioavailability, Oral: 50% (fasting state)
Effects of food: delays or reduces oral absorption
Distribution
Vd: 19.5 to 27 L
Protein binding: 20%
Excretion
Renal: 40% to 92% unchanged
Renal clearance: 280 mL/min
Dialyzable: Yes (hemodialysis), 62%; Yes (hemofiltration) (Golper et al, 1985)
Elimination Half Life
1 to 1.9 hours (normal patients); (Gorden et al, 1972); 4 to 5 hours (renal
failure); 15 to 20 hours (oliguria); 2 to 4 hours (newborn); up to 6 hours
(premature infant); 1.6 hours (pregnancy)
Dosing
Adult Dosing
Infectious disease of digestive tract
500 mg ORALLY every 6 hours
Infectious disease of genitourinary system
500 mg ORALLY every 6 hours
Premature rupture of membranes
2 g IV every 6 hours, with erythromycin 250 mg every 6 hours for 48 hours
followed by amoxicillin 250 mg ORALLY every 8 hours and erythromycin
base 333 mg every 8 hours for 5 days (study dose) OR 1 g IV every 6 hours
for 24 hours followed by 500 mg ORALLY every 6 hours until the patient
returns for delivery, then ampicillin 1 g IV every 6 hours until delivery
(study dose)
Respiratory tract infection
250 mg ORALLY every 6 hours
Pediatric Dosing
Infectious disease of digestive tract
(20 kg or less) 100 mg/kg/day ORALLY in divided doses every 6 hours
(greater than 20 kg) 500 mg ORALLY every 6 hours
Infectious disease of genitourinary system
(20 kg or less) 100 mg/kg/day ORALLY in divided doses every 6 hours
(greater than 20 kg) 500 mg ORALLY every 6 hours
Respiratory tract infection
50 mg/kg/day ORALLY divided every 6 to 8 hours; MAX 1000 mg/day
Dose Adjustments
renal impairment: CrCl 10 to 50 mL/min, change interval to every 6 to 12 hours;
CrCl less than 10 mL/min, change interval to every 12 to 16 hours
geriatric: no adjustments recommended
hemodialysis: maintenance dose following hemodialysis
peritoneal dialysis (adults): 250 mg every 12 hours
continuous hemofiltration: 250 mg to 2 g every 6 to 12 hours
Adverse effects:
Common
Dermatologic:Rash, Urticaria
Gastrointestinal:Diarrhea
Serious
Dermatologic:Erythema multiforme, Erythroderma, Stevens-Johnson syndrome,
Toxic epidermal necrolysis
Gastrointestinal:Clostridium difficile colitis
Hematologic:Agranulocytosis, Thrombocytopenia
Immunologic:Anaphylaxis, Hypersensitivity reaction
Administration & Storage issues:
Enteral route
enteral feedings should be interrupted or discontinued for an hour before and
2 hours after administration
interrupt enteral feeding for 30 minutes before and after dosing if the tube is
placed in the stomach
Oral
take one-half hour before or 2 hours after meals
(suspension) shake well before measuring the dose
Preparation for Administration: Adult
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 or
bacteriostatic water for injection. Alternatively, dissolve contents of 1 g or 2 g vial in
7.4 or 14.8 mL SWFI or bacteriostatic water for injection, 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.
Preparation for Administration: Pediatric
Oral: Reconstitute powder for oral suspension with appropriate amount of water as
specified on the bottle. Shake vigorously until suspended.
Parenteral:
IM: Reconstitute vial with SWFI to a final concentration of 125 to 250 mg/mL (see
manufacturer's labeling for specific details).
IV:
IV push: Reconstitute vial with SWFI (see manufacturer's labeling for specific details).
Intermittent IV infusion: Concentration should not exceed 30 mg/mL due to
concentration-dependent stability restrictions.
storage/stability
Oral:
Capsules: Store at 20°C to 25°C (68°F to 77°F).
Oral suspension: Store dry powder at 20°C to 25°C (68°F to 77°F). Once
reconstituted, oral suspension is stable for 14 days under refrigeration.
IV:
Store intact vials at 20°C to 25°C (68°F to 77°F).
Solutions for IM or direct IV should be used within 1 hour.
Stability of parenteral admixture in NS at 25°C (77°F) is 8 hours (concentrations up
to 30 mg/mL) and at 4°C (39°F) is 24 hours (concentration of 30 mg/mL) or 48
hours (concentrations up to 20 mg/mL). Protect from freezing.
compatibility:
Ampicillin plus ceftriaxone combined therapy has been widely recommended for the
treatment of Enterococcus faecalis infective endocarditis (7, 8). Enterococcal
endocarditis treatment routinely enforces 4 to 6 weeks of therapy.
Medication Safety Issues
Contraindications
Hypersensitivity (eg, anaphylaxis) to ampicillin, any component of the formulation,
or other penicillins; infections caused by penicillinase-producing organisms
Warnings/Precautions
Concerns related to adverse effects:
• Hypersensitivity/anaphylactoid reactions: Serious and occasionally severe or fatal
hypersensitivity (anaphylactoid) reactions have been reported in patients on
penicillin therapy, especially with a history of beta-lactam hypersensitivity or a
history of sensitivity to multiple allergens. Serious anaphylactoid reactions require
emergency treatment and airway management. Appropriate treatments must be
readily available.
• Rash: Appearance of a rash should be carefully evaluated to differentiate a
nonallergic ampicillin rash from a hypersensitivity reaction; rash occurs in 5% to
10% of children and is a generalized dull red, maculopapular rash, generally
appearing 3 to 14 days after the start of therapy. It normally begins on the trunk
and spreads over most of the body. It may be most intense at pressure areas,
elbows, and knees.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection,
including Clostridioides difficile–associated diarrhea (CDAD) and
pseudomembranous colitis; CDAD has been observed >2 months postantibiotic
treatment.
Disease-related concerns:
• Infectious mononucleosis: A high percentage of patients with infectious
mononucleosis have developed rash during therapy; ampicillin-class antibiotics not
recommended in these patients. Rash (generalized maculopapular and pruritic)
usually appears 7 to 10 days after initiation and usually resolves within a week of
discontinuation. It is not known whether these patients are truly allergic to ampicillin
• Renal impairment: Use with caution in patients with renal impairment; dosage
adjustment recommended.
Pregnancy Considerations
Ampicillin crosses the placenta.
Drug Interactions
Acemetacin: May increase the serum concentration of Penicillins. Risk C:
Monitor therapy
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions
to Ampicillin. Risk C: Monitor therapy
Aminoglycosides: Penicillins may decrease the serum concentration of
Aminoglycosides. Primarily associated with extended spectrum penicillins, and
patients with renal dysfunction. Risk C: Monitor therapy
Atenolol: Ampicillin may decrease the bioavailability of Atenolol. Risk C: Monitor
therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus
clausii. Management: Bacillus clausii should be taken in between antibiotic
doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG
(Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of
BCG Vaccine (Immunization). Risk C: Monitor therapy
Chloroquine: May decrease the serum concentration of Ampicillin. Management:
Separate the administration of ampicillin and chloroquine by at least 2 hours to
minimize any potential negative impact of chloroquine on ampicillin
bioavailability. Risk D: Consider therapy modification
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera
Vaccine. Management: Avoid cholera vaccine in patients receiving systemic
antibiotics, and within 14 days following the use of oral or parenteral antibiotics.
Risk X: Avoid combination
Dichlorphenamide: Penicillins may enhance the hypokalemic effect of
Dichlorphenamide. Risk C: Monitor therapy
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect
of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Food Interactions
Food decreases ampicillin absorption rate; may decrease ampicillin serum
concentration. Management: Take at equal intervals around-the-clock, preferably on
an empty stomach (30 minutes before or 2 hours after meals). Maintain adequate
hydration, unless instructed to restrict fluid intake.
Test Interactions
May interfere with urinary glucose tests using cupric sulfate (Benedict's solution,
Clinitest®)
Some penicillin derivatives may accelerate the degradation of aminoglycosides in
vitro, leading to a potential underestimation of aminoglycoside serum concentration.
Patient counseling:
Instruct patient to report diarrhea, which may range in severity from mild to
life-threatening pseudomembranous colitis.
Drug may decrease effectiveness of oral contraceptives with concurrent use.
Recommend additional form of birth control.
This drug may cause glossitis, stomatitis, nausea, vomiting, laryngeal stridor, or
high fever.
Advise patient to report the development of a late skin rash, which may cover
the entire body and be erythematous, mildly pruritic, and maculopapular.
Instruct patient to take the drug with a full 8 ounce glass of water one-half
hour before or 2 hours after meals.
PRECEPTOR NAME:RAWAB SAJDI. Sig:……………
