Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3498
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Chloramphenicol Sodium Succinate (Injection)
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Chloramphenicol, like other potent drugs, should
be prescribed at recommended doses known to have therapeutic activity.
Administration of 50 mg/kg/day in divided doses will produce blood
levels of the magnitude to which the majority of susceptible microorganisms
will respond. As soon
as feasible an oral dosage form of another appropriate antibiotic
should be substituted for intravenous chloramphenicol sodium succinate. The following method of administration
is recommended: Intravenously as a 10% (100
mg/mL) solution to be injected over at least a one-minute interval.
This is prepared by the addition of 10 mL of an aqueous diluent such
as water for injection or 5% dextrose injection.<br/>Adults: Adults should receive 50 mg/kg/day in divided doses
at 6-hour intervals. In exceptional cases patients with infections
due to moderately resistant organisms may require increased dosage
up to 100 mg/kg/day to achieve blood levels inhibiting the pathogen,
but these high doses should be decreased as soon as possible. Adults
with impairment of hepatic or renal function or both may have reduced
ability to metabolize and excrete the drug. In instances of impaired
metabolic processes, dosages should be adjusted accordingly. (See
discussion under Neonates.) Precise
control of concentration of the drug in the blood should be carefully
followed in patients with impaired metabolic processes by the available
microtechniques (information available on request).<br/>Pediatric Patients: Dosage of 50 mg/kg/day divided into 4 doses at 6-hour
intervals yields blood levels in the range effective against most
susceptible organisms. Severe infections (eg, bacteremia or meningitis),
especially when adequate cerebrospinal fluid concentrations are desired,
may require dosage up to 100 mg/kg/day; however, it is recommended
that dosage be reduced to 50 mg/kg/day as soon as possible. Children
with impaired liver or kidney function may retain excessive amounts
of the drug.<br/>Neonates: (See section titled���Gray Syndrome���under ADVERSE REACTIONS.) A total of 25 mg/kg/day in 4 equal
doses at 6-hour intervals usually produces and maintains concentrations
in blood and tissues adequate to control most infections for which
the drug is indicated. Increased dosage in these individuals, demanded
by severe infections, should be given only to maintain the blood concentration
within a therapeutically effective range. After the first two weeks
of life, full-term neonates ordinarily may receive up to a total of
50 mg/kg/day equally divided into 4 doses at 6-hour intervals. These dosage recommendations are extremely important
because blood concentration in all premature and full-term neonates
under two weeks of age differs from that of other infants neonates. This difference is due to variations in the maturity of the metabolic
functions of the liver and the kidneys. When
these functions are immature (or seriously impaired in adults), high
concentrations of the drug are found which tend to increase with succeeding
doses.<br/>Pediatric Patients with Immature Metabolic Processes: In young infants and other pediatric patients in
whom immature metabolic functions are suspected, a dose of 25 mg/kg/day
will usually produce therapeutic concentrations of the drug in the
blood. In this group particularly, the concentration of the drug in
the blood should be carefully followed by microtechniques. (Information
available on request.)
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dailymed-instance:descripti... |
Chloramphenicol is an antibiotic that is clinically
useful for, and should be reserved for, serious infections caused by organisms susceptible to its antimicrobial
effects when less potentially hazardous therapeutic agents are ineffective
or contraindicated. Sensitivity testing is essential to determine
its indicated use, but may be performed concurrently with therapy
initiated on clinical impression that one of the indicated conditions
exists (see INDICATIONS AND USAGE section). When reconstituted as directed,
each vial contains a sterile solution equivalent to 100 mg of chloramphenicol
per mL (1g/10mL). Each gram (10 mL of a 10%
solution) of chloramphenicol sodium succinate contains approximately
52 mg (2.25 mEq) of sodium. The chemical name
for chloramphenicol sodium succinate is D-threo-(-)-2, 2-Dichloro-N-[��-
hydroxy-��-(hydroxymethyl)-p-nitrophenethyl] acetamide��-(sodium
succinate). The empirical and structural formulas
are:
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Chloramphenicol administered orally is absorbed
rapidly from the intestinal tract. In controlled studies in adult
volunteers using the recommended dosage of 50 mg/kg/day, a dosage
of 1 g every 6 hours for 8 doses was given. Using the microbiological
assay method, the average peak serum level was 11.2 mcg/mL one hour
after the first dose. A cumulative effect gave a peak rise to 18.4
mcg/mL after the fifth dose of 1 g. Mean serum levels ranged from
8 to 14 mcg/mL over the 48-hour period. Total urinary excretion of
chloramphenicol in these studies ranged from a low of 68% to a high
of 99% over a three-day period. From 8% to 12% of the antibiotic excreted
is in the form of free chloramphenicol; the remainder consists of
microbiologically inactive metabolites, principally the conjugate
with glucuronic acid. Since the glucuronide is excreted rapidly, most
chloramphenicol detected in the blood is in the microbiologically
active free form. Despite the small proportion of unchanged drug excreted
in the urine, the concentration of free chloramphenicol is relatively
high, amounting to several hundredmcg/mL in patients receiving divided
doses of 50 mg/kg/day. Small amounts of active drug are found in bile
and feces. Chloramphenicol diffuses rapidly, but its distribution
is not uniform. Highest concentrations are found in liver and kidney,
and lowest concentrations are found in brain and cerebrospinal fluid.
Chloramphenicol enters cerebrospinal fluid even in the absence of
meningeal inflammation, appearing in concentrations about half of
those found in the blood. Measurable levels are also detected in pleural
and in ascitic fluids, saliva, milk, and in the aqueous and vitreous
humors. Transport across the placental barrier occurs with somewhat
lower concentration in cord blood of neonates than in maternal blood.<br/>Microbiology: Chloramphenicol has been shown to be active against most strains
of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.<br/>Aerobic gram-negative microorganisms: Haemophilus influenzae Salmonella species, including Salmonella typhi<br/>Other microorganisms: Lymphogranuloma-psittacosis group Rickettsia Susceptibility Testing
Methods Dilution Techniques: Quantitative methods are used to
determine antimicrobial minimum inhibitory concentrations (MICs).
These MICs provide estimates of the susceptibility of bacteria to
antimicrobial compounds. The MICs should be determined using a standardized
procedure. Standardized procedures are based on a dilution method(broth or agar) or equivalent with standardized inoculum
concentrations and standardized concentrations of chloramphenicol
powder. The MIC values should be interpreted according to the following
criteria: These MIC interpretative standards
are applicable only to broth microdilution susceptibility tests with Haemophilus influenzae using Haemophilus Test Medium (HTM). A report of���Susceptible���indicates
that the pathogen is likely to be inhibited if the antimicrobial compound
in the blood reaches the concentrations usually achievable. A report
of���Intermediate���indicates that the result should be
considered equivocal, and, if the microorganism is not fully susceptible
to alternative, clinically feasible drugs, the test should be repeated.
This category implies possible clinical applicability in body sites
where the drug is physiologically concentrated or in situations where
high dosage of drug can be used. This category also provides a buffer
zone which prevents small uncontrolled technical factors from causing
major discrepancies in interpretation. A report of���Resistant���indicates that the pathogen is not likely to be inhibited if the antimicrobial
compound in the blood reaches the concentrations usually achievable;
other therapy should be selected. Standardized
susceptibility test procedures require the use of laboratory control
microorganisms to control the technical aspects of the laboratory
procedures. Standard chloramphenicol powder should provide the following
MIC values: This MIC quality control range is
applicable to only Haemophilus influenzae ATCC 49247 tested by broth microdilution procedure using Haemophilus Test Medium (HTM). Diffusion
Techniques: Quantitative methods that require measurement
of zone diameters also provide reproducible estimates of the susceptibility
of bacteria to antimicrobial compounds. One such standardized procedurerequires the use of standardized inoculum concentrations.
This procedure uses paper disks impregnated with 30��g chloramphenicol
to test the susceptibilty of microorgansims to chloramphenicol. Reports from the laboratory providing results of the standard
single-disk susceptibility test with a 30-��g chloramphenicol
disk should be interpreted according to the following criteria: These zone diameter interpretative
standards are applicable only to susceptibility tests performed by
disk diffusion with Haemophilus influenzae using Haemophilus Test
Medium (HTM). As with standardized
dilution techniques, diffusion methods require the use of laboratory
control microorganisms to control the technical aspects of the laboratory
procedures. For the diffusion technique, the 30��g chloramphenicol
disk should provide the following zone diameters in these laboratory
test quality control strains: These zone diameter quality control
limits are applicable to only Haemophilus
influenzae ATCC 49247 tested by a disk diffusion method
using Haemophilus Test Medium
(HTM).
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dailymed-instance:contraind... |
Chloramphenicol is contraindicated in individuals
with a history of previous hypersensitivity and/or toxic reaction
to it. It must not be used in the treatment
of trivial infections or where it is not indicated, as in colds, influenza,
infections of the throat; or as a prophylactic agent to prevent bacterial
infections.
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dailymed-instance:supply |
NDC 61570-405-71 (Steri-Vial No
57) Chloromycetin Sodium Succinate is freeze-dried
in the vial and supplied in Steri-Vials (rubberdiaphragm- capped vials).
When reconstituted as directed, each vial contains a sterile solution
equivalent to 100 mg of chloramphenicol per mL (1 g/10 mL). Available
in packages of 10 vials.
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WARNING Serious and fatal blood dyscrasias
(aplastic anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia)
are known to occur after the administration of chloramphenicol. In
addition, there have been reports of aplastic anemia attributed to
chloramphenicol which later terminated in leukemia. Blood dyscrasias
have occurred after both short-term and prolonged therapy with this
drug. Chloramphenicol must not be used when less potentially dangerous
agents will be effective, as described in the INDICATIONS AND USAGE
section. It must not be used in the treatment
of trivial infections or where it is not indicated, as in colds, influenza,
infections of the throat; or as a prophylactic agent to prevent bacterial
infections. Precautions: It is essential that adequate blood
studies be made during treatment with the drug. While blood studies
may detect early peripheral blood changes, such as leukopenia, reticulocytopenia,
or granulocytopenia, before they become irreversible, such studies
cannot be relied on to detect bone marrow depression prior to development
of aplastic anemia. To facilitate appropriate studies and observation
during therapy, it is desirable that patients be hospitalized.
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General: Repeated courses of chloramphenicol treatment should
be avoided if at all possible. Treatment should not be continued longer
than required to produce a cure with little or no risk or relapse
of the disease. Excessive blood levels may result
from administration of the recommended dose to patients with impaired
liver or kidney function. The dosage should be adjusted accordingly,
or preferably, the blood concentration should be determined at appropriate
intervals. The use of this antibiotic, as with
other antibiotics, may result in an overgrowth of nonsusceptible organisms,
including fungi. If infections caused by nonsusceptible organisms
appear during therapy, appropriate measures should be taken.<br/>Laboratory Tests: Baseline blood studies should be followed by periodic
blood studies approximately every two days during therapy. The drug
should be discontinued upon appearance of reticulocytopenia, leukopenia,
thrombocytopenia, anemia or any other blood study findings attributable
to chloramphenicol. However, it should be noted that such studies
do not exclude the possible later appearance of the irreversible type
of bone marrow depression.<br/>Drug Interactions: Concurrent therapy with other drugs that may cause
bone marrow depression should be avoided.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: No studies have been conducted in animals or humans
to evaluate the possibility of these effects with chloramphenicol.<br/>Pregnancy: Pregnancy Category C - Animal reproduction studies
have not been conducted with chloramphenicol. There are no adequate
and well-controlled studies to establish safety of this drug in pregnancy.
It is not known whether chloramphenicol can cause fetal harm when
administered to a pregnant woman. Orally
administered chloramphenicol has been shown to cross the
placental barrier. Because of potential toxic effects on the fetus
(See ADVERSE REACTIONS -���Gray Syndrome���), chloramphenicol
should be given to a pregnant woman only if the potential benefit
justifies the potential risk to the fetus.<br/>Nursing Mothers: Chloramphenicol is excreted in human milk following
oral administration of the drug. Because of the potential for serious
adverse reactions in nursing infants from chloramphenicol, a decision
should be made whether to discontinue nursing or to discontinue the
drug, taking into account the importance of the drug to the mother.
(See ADVERSE REACTIONS -���Gray Syndrome���).<br/>Pediatric Use: Precaution should be used in therapy of premature
and full-term neonates and infants to avoid���gray syndrome���toxicity. Due to immature metabolic processes in the neonate and infant,
excessive blood levels may result from administration of the recommended
dose. The dosage should be adjusted accordingly or, preferable, the
blood concentration should be determined at appropriate intervals.
(See ADVERSE REACTIONS -���Gray Syndrome���) See DOSAGE AND ADMINISTRATION for dosing information in the pediatric population.<br/>Geriatric Use: Clinical studies of chloramphenicol sodium succinate
did not include sufficient numbers of subjects aged 65 and over to
determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences
in responses between the elderly and younger patients. In general,
dose selection for an elderly patient should be cautious, usually
starting at the low end of the dosing range, reflecting the greater
frequency of decreased hepatic, renal, or cardiac function, and of
concomitant disease or other drug therapy. This drug is known to be
substantially execreted by the kidney, and the risk of toxic reactions
to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function,
care should be taken in dose selection, and it may be useful to monitor
renal function. Each gram (10 mL of a 10% solution)
of chloramphenicol sodium succinate contains approximately 52 mg (2.25
mEq) of sodium.<br/>Information for Patients: Patients should be counseled that diarrhea is a common
problem caused by antibiotics which usually ends when the antibiotic
is discontinued. Sometimes after starting treatment with antibiotics,
patients can develop watery and bloody stools (with or without stomach
cramps and fever) even as late as two or more months after having
takenthe last dose of the antibiotic. If this occurs, patients should
contact their physician as soon as possible.
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dailymed-instance:genericMe... |
chloramphenicol sodium succinate
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dailymed-instance:fullName |
Chloramphenicol Sodium Succinate (Injection)
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dailymed-instance:adverseRe... |
1. Blood Dyscrasias: The most serious adverse effect of chloramphenicol
is bone marrow depression. Serious and fatal blood dyscrasias (aplastic
anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia)
are known to occur after the administration of chloramphenicol. An
irreversible type of marrow depression leading to aplastic anemia
with a high rate ofmortality is characterized by the appearance weeks
or months after therapy of bone marrow aplastic or hypoplasia. Peripherally,
pancytopenia is most often observed, but in a small number of cases
only one or two of the three major cell types (erythrocytes, leukocytes,
platelets) may be depressed. A reversible type
of bone marrow depression, which is dose related, may occur. This
type of marrow depression is characterized by vacuolization of the
erythroid cells, reduction of reticulocytes and leukopenia, and responds
promptly to the withdrawal of chloramphenicol. An exact determination of the risk of serious and fatal blood dyscrasias
is not possible because of lack of accurate information regarding
1) the size of the population at risk, 2) the total number of drug-associated
dyscrasias, and 3) the total number of non-drug associated dyscrasias. In a report to the California State Assembly by the California
Medical Association and the State Department of Public Health in January
1967, the risk of fatal aplastic anemia was estimated at 1:24,200
to 1:40,500 based on two dosage levels. There
have been reports of aplastic anemia attributed to chloramphenicol
which later terminated in leukemia. Paroxysmal
nocturnal hemoglobinuria has been reported.<br/>2. Gastrointestinal Reactions: Nausea, vomiting, glossitis and stomatitis, diarrhea
and enterocolitis may occur in low incidence.<br/>3. Neurotoxic Reactions: Headache, mild depression, mental confusion, and
delirium have been described in patients receiving chloramphenicol.
Optic and peripheral neuritis have been reported, usually following
long-term therapy. If this occurs, the drug should be promptly withdrawn.<br/>4. Hypersensitivity Reactions: Fever, macular and vesicular rashes, angioedema,
urticaria, and anaphylaxis may occur. Herxheimer's reactions
have occurred during therapy for typhoid fever.<br/>5. "Gray Syndrome": Toxic reactions including fatalities have occurred
in the premature and neonate; the signs and symptoms associated with
these reactions have been referred to as the���gray syndrome.���One case of gray syndrome has been reported in a neonate born to a
mother having received chloramphenicol during labor. One case has
been reported in a 3-month-old infant. The following summarizes the
clinical and laboratory studies that have been made on these patients: a) In most cases therapy with chloramphenicol had been
instituted within the first 48 hours of life. b) Symptoms first appeared after 3 to 4 days of continued treatment
with high doses of chloramphenicol. c) The symptoms
appeared in the following order: (1) abdominal
distension with or without emesis; (2)
progressive pallid cyanosis; (3) vasomotor
collapse, frequently accompanied by irregular respiration; (4) death within a few hours of onset of these symptoms. d) The progression of symptoms from onset to exitus was
accelerated with higher dose schedules. e)Preliminary
blood serum level studies revealed unusually high concentrations of
chloramphenicol (over 90 mcg/mL after repeated doses). f) Termination of therapy upon early evidence of the associated
symptomatology frequently reversed the process with complete recovery.
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Clostridium difficile associated with diarrhea (CDAD) has been reported with use of nearly
all antibacterial agents, including Chloromycetin Sodium Succinate,
and may range in severity from mild diarrhea to fatal colitis. Treatment
with antibacterial agents alters the normal flora of the colon leading
to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD.
Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can
be refractory to antimicrobial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea
following antibiotic use. Careful medical history is necessary since
CDAD has been reported to occur over two months after the administrationof antibacterial agents. If CDAD is suspected
or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation,
antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
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dailymed-instance:indicatio... |
In accord with the concepts
in the Warning Box and this INDICATIONS AND USAGE section, chloramphenicolmust be used only in those serious infections for which less potentially
dangerous drugs are ineffective or contraindicated. However, chloramphenicol
may be chosen to initiate antibiotic therapy on the clinical impression
that one of the conditions below is believed to be present; in vitro sensitivity tests should be
performed concurrently so that the drug may be discontinued as soon
as possible if less potentially dangerous agents are indicated by
such tests. The decision to continue use of chloramphenicol rather
than another antibiotic when both are suggested by in vitro studies to be effective against
a specific pathogen should be based upon severity of the infection,
susceptibility of the pathogen to the various antimicrobial drugs,
efficacy of the various drugs in the infection, and the important
additional concepts contained in the Warning Box above. 1. Acute infections
caused by Salmonella typhi* It is not recommended for the routine
treatment of the typhoid carrier state. 2. Serious infections caused by susceptible strains
in accordance with the concepts expressed above: a) Salmonella species b) H. influenzae, specially meningeal infections c) Rickettsia d)
Lymphogranuloma-psittacosis group e) Various
gram-negative bacteria causing bacteremia, meningitis, or other serious
gram-negative infections f) Other susceptible
organisms which have been demonstrated to be resistant to all other
appropriate antimicrobial agents. 3. Cystic fibrosis regimens *In treatment of typhoid fever some authorities recommend
that chloramphenicol be administered at therapeutic levels for 8 to
10 days after the patient has become afebrile to lessen the possibility
of relapse.
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Chloramphenicol Sodium Succinate
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