AMPICILLIN
DESCRIPTION:
CAMPICILLIN (ampicillin) is a semisynthetic penicillin derived from the basic
penicillin nucleus, 6-amino-penicillanic acid. Ampicillin is designated
chemically as (2S,5R,6R)-6-((R)-2-Amino- 2-phenylacetamido)-3,3-dimethyl-7-oxo-
4-thia- 1-aza-bicyclo (3.2.0) heptane-2-carboxylic acid. The molecular formula
for ampicillin is C16H19N3O4S with a molecular weight of 349.40.
CAMPICILLIN capsules for oral administration contain 250 mg or 500 mg ampicillin
anhydrous. The inactive ingredients present are D&C Red 22, D&C Red 28, FD&C
Blue 1, gelatin, lactose, methylcellulose, stearic acid, and titanium dioxide.
ACTIONS/CLINICAL PHARMACOLOGY:
Ampicillin is bactericidal at low concentrations and is clinically effective not
only against the gram-positive organisms usually susceptible to penicillin G,
but also against a variety of gram- negative organisms. It is stable in the
presence of gastric acid and is well absorbed from the gastrointestinal tract.
It diffuses readily into most body tissues and fluids; however, penetration into
the cerebrospinal fluid and brain occurs only with meningeal inflammation.
Ampicillin is excreted largely unchanged in the urine; its excretion can be
delayed by concurrent administration of probenecid which inhibits the renal
tubular secretion of ampicillin. In blood serum, ampicillin is the least bound
of all the penicillins; an average of about 20% of the drug is bound to the
plasma proteins as compared to 60 to 90% for the other penicillins. Blood serum
levels of approximately 2 mcg/mL are attained within 1 to 2 hours following a
250 mg oral dose given to fasting adults. Detectable amounts persist for about 6
hours.
MICROBIOLOGY
While In Vitro studies have demonstrated the susceptibility of most strains of
the following microorganisms, clinical efficacy for infections other than those
included in the "INDICATIONS AND USAGE" section has not been documented.
Gram-Positive
Alpha- and beta-hemolytic streptococci, Streptococcus Pneumoniae, staphylococci
(non- penicillinase-producing strains), Bacillus Anthracis, Clostridium sp.,
Corynebacterium Xerose, and most strains of enterococci.
Gram-Negative
Hemophilus Influenzae, Neisseria Gonorrhoeae, Neisseria Meningitidis, Proteus
Mirabilis, and many strains of Salmonella (including S. Typhosa), Shigella, and
Escherichia Coli.
NOTE: Ampicillin is inactivated by penicillinase and therefore is ineffective
against penicillinase-producing organisms including certain strains of
staphylococci, Pseudomonas Aeruginosa, P. Vulgaris, Klebsiella Pneumoniae,
Enterobacter Aerogenes, and some strains of E. Coli. Ampicillin is not active
against Rickettsia, Mycoplasma, and "large viruses" (Miyagawanella).
Testing For Susceptibility
The invading organism should be cultured and its susceptibility demonstrated as
a guide to therapy. If the Kirby-Bauer method of disc susceptibility is used, a
10 mcg ampicillin disc should be used to determine the relative In Vitro
susceptibility.
INDICATIONS AND USAGE:
CAMPICILLIN (ampicillin) Capsules are indicated in the treatment of infections
caused by susceptible strains of the following microorganisms:
Infections Of The Genitourinary Tract Including Gonorrhea--E. Coli, P.
Mirabilis, enterococci, Shigella, S. Typhosa and other Salmonella, and non-
penicillinase-producing N. Gonorrhoeae.
Infections Of The Respiratory Tract--Non- penicillinase-producing H. Influenzae
and staphylococci, and streptococci including Streptococcus Pneumoniae.
Infections Of The Gastrointestinal Tract- -Shigella, S. Typhosa and other
Salmonella, E. Coli, P. Mirabilis, and enterococci.
Meningitis--N. Meningitidis.
Bacteriology studies to determine the causative organisms and their sensitivity
to ampicillin should be performed. Therapy may be instituted prior to the
results of susceptibility testing.
CONTRAINDICATIONS:
The use of this drug is contraindicated in individuals with a history of a
previous hypersensitivity reaction to any of the penicillins. Ampicillin is also
contraindicated in infections caused by penicillinase-producing organisms.
WARNINGS:
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have
been reported in patients on penicillin therapy. Although anaphylaxis is more
frequent following parenteral administration, it has occurred in patients on
oral penicillins. These reactions are more apt to occur in individuals with a
history of penicillin hypersensitivity and/or a history of sensitivity to
multiple allergens.
There have been well-documented reports of individuals with a history of
penicillin hypersensitivity who experienced severe hypersensitivity reactions
when treated with cephalosporins. Before initiating therapy with any penicillin,
careful inquiry should be made concerning previous hypersensitivity reactions to
penicillins, cephalosporins, or other allergens. If an allergic reaction occurs,
the drug should be discontinued and appropriate therapy instituted.
SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH
EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING
INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.
PRECAUTIONS:
GENERAL
Prolonged use of antibiotics may promote the overgrowth of nonsusceptible
organisms, including fungi. Should superinfection occur, appropriate measures
should be taken.
Patients with gonorrhea who also have syphilis should be given additional
appropriate parenteral penicillin treatment.
Treatment with ampicillin does not preclude the need for surgical procedures,
particularly in staphylococcal infections.
INFORMATION FOR THE PATIENT
1. The patient should inform the physician of any history of sensitivity to
allergens, including previous hypersensitivity reactions to penicillins and
cephalosporins (see "WARNINGS").
2. The patient should discontinue ampicillin and contact the physician
immediately if any side effect occurs (see "WARNINGS").
3. Ampicillin should be taken with a full glass (8 oz) of water, one-half hour
before or two hours after meals.
4. Diabetic patients should consult with the physician before changing diet or
dosage of diabetes medication (see "PRECAUTIONS- -DRUG/LABORATORY TEST
INTERACTION").
LABORATORY TESTS
In prolonged therapy, and particularly with high dosage regimens, periodic
evaluation of the renal, hepatic, and hematopoietic systems is recommended.
In streptococcal infections, therapy must be sufficient to eliminate the
organism (10 days minimum); otherwise, the sequelae of streptococcal disease may
occur. Cultures should be taken following completion of treatment to determine
whether streptococci have been eradicated.
Cases of gonococcal infection with a suspected lesion of syphilis should have
dark-field examinations ruling out syphilis before receiving ampicillin.
Patients who do not have suspected lesions of syphilis and are treated with
ampicillin should have a follow-up serologic test for syphilis each month for
four months to detect syphilis that may have been masked by treatment for
gonorrhea.
DRUG INTERACTIONS
When administered concurrently, the following drugs may interact with
ampicillin:
Allopurinol--Increased possibility of skin rash, particularly in hyperuricemic
patients, may occur.
Bacteriostatic Antibiotics--Chloramphenicol, erythromycins, sulfonamides, or
tetracyclines may interfere with the bactericidal effect of penicillins. This
has been demonstrated In Vitro; however, the clinical significance of this
interaction is not well-documented.
Oral Contraceptives--May be less effective and increased breakthrough bleeding
may occur.
Probenecid--May decrease renal tubular secretion of ampicillin resulting in
increased blood levels and/or ampicillin toxicity.
DRUG/LABORATORY TEST INTERACTION
After treatment with ampicillin, a false-positive reaction for glucose in the
urine may occur with copper sulfate tests (Benedict's solution, Fehling's
solution, or Clinitest(R) tablets) but not with enzyme based tests such as
Clinistix(R) and TesTape(R).
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
Long-term studies in animals have not been performed to evaluate carcinogenesis,
mutagenesis, or impairment of fertility in males or females.
PREGNANCY: TERATOGENIC EFFECTS
CATEGORY B
Reproduction studies in animals have revealed no evidence of impaired fertility
or harm to the fetus due to penicillin. There are, however, no adequate and
well-controlled studies in pregnant women. Because animal reproduction studies
are not always predictive of human response, penicillin should be used during
pregnancy only if clearly needed.
LABOR AND DELIVERY
Oral ampicillin-class antibiotics are poorly absorbed during labor. Studies in
guinea pigs showed that intravenous administration of ampicillin slightly
decreased the uterine tone and frequency of contractions, but moderately
increased the height and duration of contractions. However, it is not known
whether use of these drugs in humans during labor or delivery has immediate or
delayed adverse effects on the fetus, prolongs the duration of labor, or
increases the likelihood that forceps delivery or other obstetrical intervention
or resuscitation of the newborn will be necessary.
NURSING MOTHERS
Ampicillin-class antibiotics are excreted in milk. Ampicillin use by nursing
mothers may lead to sensitization of infants; therefore, a decision should be
made whether to discontinue nursing or to discontinue ampicillin, taking into
account the importance of the drug to the mother.
PEDIATRIC USE
Penicillins are excreted primarily unchanged by the kidney; therefore, the
incompletely developed renal function in neonates and young infants will delay
the excretion of penicillin. Administration to neonates and young infants should
be limited to the lowest dosage compatible with an effective therapeutic regimen
(see "DOSAGE AND ADMINISTRATION").
DRUG INTERACTIONS:
When administered concurrently, the following drugs may interact with
ampicillin:
Allopurinol--Increased possibility of skin rash, particularly in hyperuricemic
patients, may occur.
Bacteriostatic Antibiotics--Chloramphenicol, erythromycins, sulfonamides, or
tetracyclines may interfere with the bactericidal effect of penicillins. This
has been demonstrated In Vitro; however, the clinical significance of this
interaction is not well-documented.
Oral Contraceptives--May be less effective and increased breakthrough bleeding
may occur.
Probenecid--May decrease renal tubular secretion of ampicillin resulting in
increased blood levels and/or ampicillin toxicity.
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
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 penicillins 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: glossitis, stomatitis, nausea, vomiting, enterocolitis,
pseudomembranous colitis, and diarrhea. These reactions are usually associated
with oral dosage forms of the drug.
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 anaphylactic reactions require
emergency measures (see "WARNINGS").
Liver: A moderate elevation in serum glutamic- oxaloacetic transaminase (SGOT)
has been noted, but the significance of this finding is unknown.
Hemic And Lymphatic Systems: Anemia, thrombocytopenia, thrombocytopenic
purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during
therapy with penicillins. These reactions are usually reversible on
discontinuation of therapy and are believed to be hypersensitivity phenomena.
Other adverse reactions that have been reported with the use of ampicillin are
laryngeal stridor and high fever. An occasional patient may complain of sore
mouth or tongue as with any oral penicillin preparation.
OVERDOSAGE:
In case of overdosage, discontinue medication, treat symptomatically and
institute supportive measures as required. In patients with renal function
impairment, ampicillin-class antibiotics can be removed by hemodialysis but not
by peritoneal dialysis.
DOSAGE AND ADMINISTRATION:
Adults And Children Weighing Over 20 Kg:
FOR GENITOURINARY- OR GASTROINTESTINAL-TRACT INFECTIONS OTHER THAN GONORRHEA IN
MEN AND WOWEN- -the usual dose is 500 mg q.i.d. in equally spaced doses (i.e.,
500 mg every 6 hours); larger doses may be required for severe or chronic
infections.
FOR THE TREATMENT OF GONORRHEA IN BOTH MEN AND WOMEN--a single oral dose of 3.5
grams of ampicillin with 1 gram of probenecid administered simultaneously is
recommended. Physicians are cautioned to use no less than the above recommended
dosage for the treatment of gonorrhea. Follow-up cultures should be obtained
from the original site(s) of infection 7 to 14 days after therapy. In women, it
is also desirable to obtain culture test-of-cure from both the endocervical and
anal canals. Prolonged intensive therapy is needed for complications such as
prostatitis and epididymitis.
FOR RESPIRATORY-TRACT INFECTIONS--the usual dose is 250 mg q.i.d. in equally
spaced doses (i.e., 250 mg every 6 hours).
Children Weighing 20 Kg Or Less:
FOR GENITOURINARY- OR GASTROINTESTINAL-TRACT INFECTIONS--the usual dose is 100
mg/kg/day total, administered q.i.d. in equally divided and spaced doses (i.e.,
every 6 hours).
FOR RESPIRATORY INFECTIONS--the usual dose is 50 mg/kg/day total, administered
in equally divided and spaced doses three to four times daily (i.e., every 8 to
every 6 hours).
Doses for children should not exceed doses recommended for adults.
In All Patients, Irrespective Of Age And Weight: Larger doses may be required
for severe or chronic infections. Although ampicillin is resistant to
degradation by gastric acid, it should be administered at least one-half hour
before or two hours after meals for maximal absorption. Except for the single-
dose regimen for gonorrhea referred to above, therapy should be continued for a
minimum of 48 to 72 hours after the patient becomes asymptomatic or evidence of
bacterial eradication has been obtained. In infections caused by hemolytic
strains of streptococci, a minimum of 10 days' treatment is recommended to guard
against the risk of rheumatic fever or glomerulonephritis (see "PRECAUTIONS--
LABORATORY TESTS").
In the treatment of chronic urinary or gastrointestinal infections, frequent
bacteriologic and clinical appraisal is necessary during therapy and may be
necessary for several months afterwards. Stubborn infections may require
treatment for several weeks. Smaller doses than those indicated above should not
be used.
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