Sulphamoxole
Sulphamoxole is a sulphonamide with properties similar to
those of sulphamethoxazole . It has been used in com-
bination with trimethoprim .
SULPHAMETHOXAZOLE
DESCRIPTION:
Bactrim (trimethoprim and sulfamethoxazole) IV Infusion, a sterile solution for
intravenous infusion only, is a synthetic antibacterial combination product.
Each 5 mL contains 80 mg trimethoprim (16 mg/mL) and 400 mg sulfamethoxazole (80
mg/mL) compounded with 40% propylene glycol, 10% ethyl alcohol and 0.3%
diethanolamine; 1% benzyl alcohol and 0.1% sodium metabisulfite added as
preservatives, water for injection, and pH adjusted to approximately 10 with
sodium hydroxide.
Trimethoprim is 2,4-diamino- 5-(3,4,5-trimethoxybenzyl)pyrimidine. It is a white
to light yellow, odorless, bitter compound with a molecular weight of 290.3.
Sulfamethoxazole is N1-(5-methyl- 3-isoxazolyl)sulfanilamide. It is an almost
white, odorless, tasteless compound with a molecular weight of 253.28.
ACTIONS/CLINICAL PHARMACOLOGY:
Following a 1-hour intravenous infusion of a single dose of 160 mg trimethoprim
and 800 mg sulfamethoxazole to 11 patients whose weight ranged from 105 lbs to
165 lbs (mean, 143 lbs), the peak plasma concentrations of trimethoprim and
sulfamethoxazole were 3.4 +/- 0.3 mcgm/mL and 46.3 +/- 2.7 mcgm/mL,
respectively. Following repeated intravenous administration of the same dose at
8-hour intervals, the mean plasma concentrations just prior to and immediately
after each infusion at steady state were 5.6 +/- 0.6 mcgm/mL and 8.8 +/- 0.9
mcgm/mL for trimethoprim and 70.6 +/- 7.3 mcgm/mL and 105.6 +/- 10.9 mcgm/mL for
sulfamethoxazole. The mean plasma half-life was 11.3 +/- 0.7 hours for
trimethoprim and 12.8 +/- 1.8 hours for sulfamethoxazole. All of these 11
patients had normal renal function, and their ages ranged from 17 to 78 years
(median, 60 years). (REF. 1)
Pharmacokinetic studies in children and adults suggest an age-dependent half-
life of trimethoprim, as indicated in the following table. (REF. 2)
------------------------------------------------------------------------------------------------------------------
Age No. of Mean TMP
(years) Patients Half-life (hours)
------------------------------------------------------------------------------------------------------------------
<1 2 7.67
1-10 9 5.49
10-20 5 8.19
20-63 6 12.82
------------------------------------------------------------------------------------------------------------------
Patients with severely impaired renal function exhibit an increase in the half-
lives of both components, requiring dosage regimen adjustment (See DOSAGE AND
ADMINISTRATION section).
Both trimethoprim and sulfamethoxazole exist in the blood as unbound, protein-
bound and metabolized forms; sulfamethoxazole also exists as the conjugated
form. The metabolism of sulfamethoxazole occurs predominately by N4-acetylation,
although the glucuronide conjugate has been identified. The principal
metabolites of trimethoprim are the 1- and 3-oxides and the 3'- and 4'-hydroxy
derivatives. The free forms of trimethoprim and sulfamethoxazole are considered
to be the therapeutically active forms. Approximately 44% of trimethoprim and
70% of sulfamethoxazole are bound to plasma proteins. The presence of 10 mg
percent sulfamethoxazole in plasma decreases the protein binding of trimethoprim
by an insignificant degree; trimethoprim does not influence the protein binding
of sulfamethoxazole.
Excretion of trimethoprim and sulfamethoxazole is primarily by the kidneys
through both glomerular filtration and tubular secretion. Urine concentrations
of both trimethoprim and sulfamethoxazole are considerably higher than are the
concentrations in the blood. The percent of dose excreted in urine over a 12-
hour period following the intravenous administration of the first dose of 240 mg
of trimethoprim and 1200 mg of sulfamethoxazole on day 1 ranged from 17% to
42.4% as free trimethoprim; 7% to 12.7% as free sulfamethoxazole; and 36.7% to
56% as total (free plus the N4-acetylated metabolite) sulfamethoxazole. When
administered together as Bactrim, neither trimethoprim nor sulfamethoxazole
affects the urinary excretion pattern of the other. Both trimethoprim and
sulfamethoxazole distribute to sputum and vaginal fluid; trimethoprim also
distributes to bronchial secretions, and both pass the placental barrier and are
excreted in breast milk.
MICROBIOLOGY: Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic
acid by competing with Para-aminobenzoic acid (PABA). Trimethoprim blocks the
production of tetrahydrofolic acid from dihydrofolic acid by binding to and
reversibly inhibiting the required enzyme, dihydrofolate reductase. Thus,
Bactrim blocks two consecutive steps in the biosynthesis of nucleic acids and
proteins essential to many bacteria.
In vitro studies have shown that bacterial resistance develops more slowly with
Bactrim than with either trimethoprim or sulfamethoxazole alone.
In vitro serial dilution tests have shown that the spectrum of antibacterial
activity of Bactrim includes common bacterial pathogens with the exception of
Pseudomonas Aeruginosa. The following organisms are usually susceptible:
Escherichia Coli, Klebsiella species, Enterobacter species, Morganella Morganii,
Proteus Mirabilis, indole-positive Proteus species including Proteus Vulgaris,
Haemophilus Influenzae (including ampicillin-resistant strains), Streptococcus
Pneumoniae, Shigella Flexneri and Shigella Sonnei. It should be noted, however,
that there are little clinical data on the use of Bactrim IV Infusion in serious
systemic infections due to Haemophilus Influenzae and Streptococcus Pneumoniae.
REPRESENTATIVE MINIMUM INHIBITORY CONCENTRATION VALUES
FOR BACTRIM-SUSCEPTIBLE ORGANISMS (MIC--mcgm/mL)
------------------------------------------------------------------------------------------------------------------------------------------------
TMP SMX TMP/SMX (1:20)
Bacteria alone alone TMP SMX
------------------------------------------------------------------------------------------------------------------------------------------------
Escherichia Coli 0.05-1.5 1.0-245 0.05-0.5 0.95-9.5
Proteus species
(indole positive) 0.5-5.0 7.35-300 0.05-1.5 0.95-28.5
Morganella Morganii 0.5-5.0 7.35-300 0.05-1.5 0.95-28.5
Proteus Mirabilis 0.5-1.5 7.35-30 0.05-0.15 0.95-2.85
Klebsiella species 0.15-5.0 2.45-245 0.05-1.5 0.95-28.5
Enterobacter species 0.15-5.0 2.45-245 0.05-1.5 0.95-28.5
Haemophilus
Influenzae 0.15-1.5 2.85-95 0.015-0.15 0.285-2.85
Streptococcus
Pneumoniae 0.15-1.5 7.35-24.5 0.05-0.15 0.95-2.85
Shigella Flexneri* <0.01-0.04 <0.16->320 <0.002-0.03 0.04-0.625
Shigella Sonnei* 0.02-0.08 0.625->320 0.004-0.06 0.08-1.25
-----------------------------------------------------------------------------------------------------------------------------------------------
TMP = trimethoprim SMX = sulfamethoxazole
-----------
* Rudoy RC, Nelson JD, Haltalin KC. Antimicrob Agents Chemother. May 1974;
5:439-443.
-----------
The recommended quantitative disc susceptibility method may be used for
estimating the susceptibility of bacteria to Bactrim. (REF. 3,4) With this
procedure, a report from the laboratory of "Susceptible to trimethoprim and
sulfamethoxazole" indicates that the infection is likely to respond to therapy
with Bactrim. If the infection is confined to the urine, a report of
"Intermediate susceptibility to trimethoprim and sulfamethoxazole" also
indicates that the infection is likely to respond. A report of "Resistant to
trimethoprim and sulfamethoxazole" indicates that the infection is unlikely to
respond to therapy with Bactrim.
INDICATIONS AND USAGE:
Pneumocystis Carinii Pneumonia: Bactrim IV Infusion is indicated in the
treatment of Pneumocystis Carinii pneumonia in children and adults.
Shigellosis: Bactrim IV Infusion is indicated in the treatment of enteritis
caused by susceptible strains of Shigella Flexneri and Shigella Sonnei in
children and adults.
Urinary Tract Infections: Bactrim IV Infusion is indicated in the treatment of
severe or complicated urinary tract infections due to susceptible strains of
Escherichia Coli, Klebsiella species, Enterobacter species, Morganella Morganii
and Proteus species when oral administration of Bactrim is not feasible and when
the organism is not susceptible to single- agent antibacterials effective in the
urinary tract.
Although appropriate culture and susceptibility studies should be performed,
therapy may be started while awaiting the results of these studies.
CONTRAINDICATIONS:
Bactrim is contraindicated in patients with a known hypersensitivity to
trimethoprim or sulfonamides and in patients with documented megaloblastic
anemia due to folate deficiency. Bactrim is also contraindicated in pregnant
patients and nursing mothers, because sulfonamides pass the placenta and are
excreted in the milk and may cause kernicterus. Bactrim is contraindicated in
infants less than 2 months of age.
WARNINGS:
FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE,
HAVE OCCURRED DUE TO SEVERE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC
EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC
ANEMIA AND OTHER BLOOD DYSCRASIAS.
BACTRIM SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE OF SKIN RASH OR ANY SIGN
OF ADVERSE REACTION. Clinical signs, such as rash, sore throat, fever,
arthralgia, cough, shortness of breath, pallor, purpura or jaundice may be early
indications of serious reactions. In rare instances a skin rash may be followed
by more severe reactions, such as Stevens-Johnson syndrome, toxic epidermal
necrolysis, hepatic necrosis or serious blood disorder. Complete blood counts
should be done frequently in patients receiving sulfonamides.
BACTRIM SHOULD NOT BE USED IN THE TREATMENT OF STREPTOCOCCAL PHARYNGITIS.
Clinical studies have documented that patients with group A beta- hemolytic
streptococcal tonsillopharyngitis have a greater incidence of bacteriologic
failure when treated with Bactrim than do those patients treated with
penicillin, as evidenced by failure to eradicate this organism from the
tonsillopharyngeal area.
Bactrim IV Infusion contains sodium metabisulfite, a sulfite that may cause
allergic- type reactions, including anaphylactic symptoms and life-threatening
or less severe asthmatic episodes in certain susceptible people. The overall
prevalence of sulfite sensitivity in the general population is unknown and
probably low. Sulfite sensitivity is seen more frequently in asthmatic than in
nonasthmatic people.
PRECAUTIONS:
GENERAL: Bactrim should be given with caution to patients with impaired renal
or hepatic function, to those with possible folate deficiency (eg, the elderly,
chronic alcoholics, patients receiving anticonvulsant therapy, patients with
malabsorption syndrome, and patients in malnutrition states) and to those with
severe allergies or bronchial asthma. In glucose- 6-phosphate dehydrogenase
deficient individuals, hemolysis may occur. This reaction is frequently dose-
related.
Local irritation and inflammation due to extravascular infiltration of the
infusion have been observed with Bactrim IV Infusion. If these occur the
infusion should be discontinued and restarted at another site.
USE IN THE ELDERLY: There may be an increased risk of severe adverse reactions
in elderly patients, particularly when complicating conditions exist, eg,
impaired kidney and/or liver function, or concomitant use of other drugs. Severe
skin reactions, generalized bone marrow suppression (see WARNINGS and ADVERSE
REACTIONS sections) or a specific decrease in platelets (with or without
purpura) are the most frequently reported severe adverse reactions in elderly
patients. In those concurrently receiving certain diuretics, primarily
thiazides, an increased incidence of thrombocytopenia with purpura has been
reported. Appropriate dosage adjustments should be made for patients with
impaired kidney function (see DOSAGE AND ADMINISTRATION section).
USE IN THE TREATMENT OF PNEUMOCYSTIS CARINII PNEUMONIA IN PATIENTS WITH ACQUIRED
IMMUNODEFICIENCY SYNDROME (AIDS): AIDS patients may not tolerate or respond to
Bactrim in the same manner as non-AIDS patients. The incidence of side effects,
particularly rash, fever, leukopenia, and elevated aminotransferase
(transaminase) values, with Bactrim therapy in AIDS patients who are being
treated for Pneumocystis Carinii pneumonia has been reported to be greatly
increased compared with the incidence normally associated with the use of
Bactrim in non-AIDS patients.
LABORATORY TESTS: Appropriate culture and susceptibility studies should be
performed before and throughout treatment. Complete blood counts should be done
frequently in patients receiving Bactrim; if a significant reduction in the
count of any formed blood element is noted, Bactrim should be discontinued.
Urinalyses with careful microscopic examination and renal function tests should
be performed during therapy, particularly for those patients with impaired renal
function.
DRUG INTERACTIONS: In elderly patients concurrently receiving certain
diuretics, primarily thiazides, an increased incidence of thrombocytopenia with
purpura has been reported.
It has been reported that Bactrim may prolong the prothrombin time in patients
who are receiving the anticoagulant warfarin. This interaction should be kept in
mind when Bactrim is given to patients already on anticoagulant therapy, and the
coagulation time should be reassessed.
Bactrim may inhibit the hepatic metabolism of phenytoin. Bactrim, given at a
common clinical dosage, increased the phenytoin half-life by 39% and decreased
the phenytoin metabolic clearance rate by 27%. When administering these drugs
concurrently, one should be alert for possible excessive phenytoin effect.
Sulfonamides can also displace methotrexate from plasma protein binding sites,
thus increasing free methotrexate concentrations.
DRUG/LABORATORY TEST INTERACTIONS: Bactrim, specifically the trimethoprim
component, can interfere with a serum methotrexate assay as determined by the
competitive binding protein technique (CBPA) when a bacterial dihydrofolate
reductase is used as the binding protein. No interference occurs, however, if
methotrexate is measured by a radioimmunoassay (RIA).
The presence of trimethoprim and sulfamethoxazole may also interfere with the
Jaffe alkaline picrate reaction assay for creatinine, resulting in
overestimations of about 10% in the range of normal values.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY:
Carcinogenesis: Long-term studies in animals to evaluate carcinogenic potential
have not been conducted with Bactrim IV Infusion.
Mutagenesis: Bacterial mutagenic studies have not been performed with
sulfamethoxazole and trimethoprim in combination. Trimethoprim was demonstrated
to be nonmutagenic in the Ames assay. No chromosomal damage was observed in
human leukocytes cultured in vitro with sulfamethoxazole and trimethoprim alone
or in combination; the concentrations used exceeded blood levels of these
compounds following therapy with Bactrim. Observations of leukocytes obtained
from patients treated with Bactrim revealed no chromosomal abnormalities.
Impairment Of Fertility: Bactrim IV Infusion has not been studied in animals
for evidence of impairment of fertility. However, studies in rats at oral
dosages as high as 70 mg/kg trimethoprim plus 350 mg/kg sulfamethoxazole daily
showed no adverse effects on fertility or general reproductive performance.
PREGNANCY: Teratogenic Effects: Pregnancy Category C. In rats, oral doses of
533 mg/kg sulfamethoxazole or 200 mg/kg trimethoprim produced teratological
effects manifested mainly as cleft palates.
The highest dose which did not cause cleft palates in rats was 512 mg/kg
sulfamethoxazole or 192 mg/kg trimethoprim when administered separately. In two
studies in rats, no teratology was observed when 512 mg/kg of sulfamethoxazole
was used in combination with 128 mg/kg of trimethoprim. In one study, however,
cleft palates were observed in one litter out of 9 when 355 mg/kg of
sulfamethoxazole was used in combination with 88 mg/kg of trimethoprim.
In some rabbit studies, an overall increase in fetal loss (dead and resorbed and
malformed conceptuses) was associated with doses of trimethoprim six times the
human therapeutic dose.
While there are no large, well-controlled studies on the use of trimethoprim and
sulfamethoxazole in pregnant women, Brumfitt and Pursell, (REF. 5) in a
retrospective study, reported the outcome of 186 pregnancies during which the
mother received either placebo or oral trimethoprim and sulfamethoxazole. The
incidence of congenital abnormalities was 4.5% (3 of 66) in those who received
placebo and 3.3% (4 of 120) in those receiving trimethoprim and
sulfamethoxazole. There were no abnormalities in the 10 children whose mothers
received the drug during the first trimester. In a separate survey, Brumfitt and
Pursell also found no congenital abnormalities in 35 children whose mothers had
received oral trimethoprim and sulfamethoxazole at the time of conception or
shortly thereafter.
Because trimethoprim and sulfamethoxazole may interfere with folic acid
metabolism, Bactrim IV Infusion should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects: See CONTRAINDICATIONS section.
NURSING MOTHERS: See CONTRAINDICATIONS section.
PEDIATRIC USE: Bactrim IV Infusion is not recommended for infants younger than
two months of age (see CONTRAINDICATIONS section).
DRUG INTERACTIONS:
In elderly patients concurrently receiving certain diuretics, primarily
thiazides, an increased incidence of thrombocytopenia with purpura has been
reported.
It has been reported that Bactrim may prolong the prothrombin time in patients
who are receiving the anticoagulant warfarin. This interaction should be kept in
mind when Bactrim is given to patients already on anticoagulant therapy, and the
coagulation time should be reassessed.
Bactrim may inhibit the hepatic metabolism of phenytoin. Bactrim, given at a
common clinical dosage, increased the phenytoin half-life by 39% and decreased
the phenytoin metabolic clearance rate by 27%. When administering these drugs
concurrently, one should be alert for possible excessive phenytoin effect.
Sulfonamides can also displace methotrexate from plasma protein binding sites,
thus increasing free methotrexate concentrations.
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
The most common adverse effects are gastrointestinal disturbances (nausea,
vomiting, anorexia) and allergic skin reactions (such as rash and urticaria).
FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE,
HAVE OCCURRED DUE TO SEVERE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC
EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC
ANEMIA AND OTHER BLOOD DYSCRASIAS (SEE WARNINGS SECTION). Local reaction, pain
and slight irritation on IV administration are infrequent. Thrombophlebitis has
rarely been observed.
Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia,
neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia,
methemoglobinemia, eosinophilia.
Allergic Reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis,
anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis,
angioedema, drug fever, chills, Henoch-Schoenlein purpura, serum sickness-like
syndrome, generalized allergic reactions, generalized skin eruptions,
conjunctival and scleral injection, photosensitivity, pruritus, urticaria and
rash. In addition, periarteritis nodosa and systemic lupus erythematosus have
been reported.
Gastrointestinal: Hepatitis (including cholestatic jaundice and hepatic
necrosis), elevation of serum transaminase and bilirubin, pseudomembranous
enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal
pain, diarrhea, anorexia.
Genitourinary: Renal failure, interstitial nephritis, BUN and serum creatinine
elevation, toxic nephrosis with oliguria and anuria, and crystalluria.
Neurologic: Aseptic meningitis, convulsions, peripheral neuritis, ataxia,
vertigo, tinnitus, headache.
Psychiatric: Hallucinations, depression, apathy, nervousness.
Endocrine: The sulfonamides bear certain chemical similarities to some
goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic
agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycemia
have occurred rarely in patients receiving sulfonamides.
Musculoskeletal: Arthralgia and myalgia.
Respiratory: Pulmonary infiltrates.
Miscellaneous: Weakness, fatigue, insomnia.
OVERDOSAGE:
ACUTE: Since there has been no extensive experience in humans with single doses
of Bactrim IV Infusion in excess of 25 mL (400 mg trimethoprim and 2000 mg
sulfamethoxazole), the maximum tolerated dose in humans is unknown. Signs and
symptoms of overdosage reported with sulfonamides include anorexia, colic,
nausea, vomiting, dizziness, headache, drowsiness and unconsciousness. Pyrexia,
hematuria and crystalluria may be noted. Blood dyscrasias and jaundice are
potential late manifestations of overdosage.
Signs of acute overdosage with trimethoprim include nausea, vomiting, dizziness,
headache, mental depression, confusion and bone marrow depression.
General principles of treatment include the administration of intravenous fluids
if urine output is low and renal function is normal. Acidification of the urine
will increase renal elimination of trimethoprim. The patient should be monitored
with blood counts and appropriate blood chemistries, including electrolytes. If
a significant blood dyscrasia or jaundice occurs, specific therapy should be
instituted for these complications. Peritoneal dialysis is not effective and
hemodialysis is only moderately effective in eliminating trimethoprim and
sulfamethoxazole.
CHRONIC: Use of Bactrim IV Infusion at high doses and/or for extended periods
of time may cause bone marrow depression manifested as thrombocytopenia,
leukopenia and/or megaloblastic anemia. If signs of bone marrow depression
occur, the patient should be given leucovorin 5 to 15 mg daily until normal
hematopoiesis is restored.
ANIMAL TOXICITY: The LD50 of Bactrim IV Infusion in mice is 700 mg/kg or 7.3
mL/kg; in rats and rabbits the LD50 is >500 mg/kg or >5.2 mL/kg. The vehicle
produced the same LD50 in each of these species as the active drug.
The signs and symptoms noted in mice, rats and rabbits with Bactrim IV Infusion
or its vehicle at the high IV doses used in acute toxicity studies included
ataxia, decreased motor activity, loss of righting reflex, tremors or
convulsions, and/or respiratory depression.
DOSAGE AND ADMINISTRATION:
CONTRAINDICATED IN INFANTS LESS THAN 2 MONTHS OF AGE. CAUTION--BACTRIM IV
INFUSION MUST BE DILUTED IN 5% DEXTROSE IN WATER SOLUTION PRIOR TO
ADMINISTRATION. DO NOT MIX BACTRIM IV INFUSION WITH OTHER DRUGS OR SOLUTIONS.
RAPID INFUSION OR BOLUS INJECTION MUST BE AVOIDED.
DOSAGE:
CHILDREN AND ADULTS:
Pneumocystis Carinii Pneumonia: Total daily dose is 15 to 20 mg/kg (based on
the trimethoprim component) given in 3 or 4 equally divided doses every 6 to 8
hours for up to 14 days. One investigator noted that a total daily dose of 10 to
15 mg/kg was sufficient in 10 adult patients with normal renal function. (REF.
6)
Severe Urinary Tract Infections And Shigellosis: Total daily dose is 8 to 10
mg/kg (based on the trimethoprim component) given in 2 or 4 equally divided
doses every 6, 8 or 12 hours for up to 14 days for severe urinary tract
infections and 5 days for shigellosis. The maximum recommended daily dose is 60
mL per day.
For Patients With Impaired Renal Function: When renal function is impaired, a
reduced dosage should be employed using the following table:
------------------------------------------------------------------------------
Creatinine
Clearance Recommended
(mL/min) Dosage Regimen
------------------------------------------------------------------------------
Above 30 Usual standard regimen
15-30 1/2 the usual regimen
Below 15 Use not recommended
------------------------------------------------------------------------------
Method Of Preparation: Bactrim IV Infusion must be diluted. EACH 5 ML SHOULD BE
ADDED TO 125 ML OF 5% DEXTROSE IN WATER. After diluting with 5% dextrose in
water the solution should not be refrigerated and should be used within 6 hours.
If a dilution of 5 mL per 100 mL of 5% dextrose in water is desired, it should
be used within 4 hours. If upon visual inspection there is cloudiness or
evidence of crystallization after mixing, the solution should be discarded and a
fresh solution prepared.
Multidose Vials: After initial entry into the vial, the remaining contents must
be used within 48 hours.
The following infusion systems have been tested and found satisfactory: unit-
dose glass containers; unit-dose polyvinyl chloride and polyolefin containers.
No other systems have been tested and therefore no others can be recommended.
Dilution: EACH 5 ML OF BACTRIM IV INFUSION SHOULD BE ADDED TO 125 ML OF 5%
DEXTROSE IN WATER.
Note: In Those Instances Where Fluid Restriction Is Desirable, each 5 mL may be
added to 75 mL of 5% dextrose in water. Under these circumstances the solution
should be mixed just prior to use and should be administered within 2 hours. If
upon visual inspection there is cloudiness or evidence of crystallization after
mixing, the solution should be discarded and a fresh solution prepared.
DO NOT MIX BACTRIM IV INFUSION-5% DEXTROSE IN WATER WITH DRUGS OR SOLUTIONS IN
THE SAME CONTAINER.
ADMINISTRATION: The solution should be given by intravenous infusion over a
period of 60 to 90 minutes. Rapid infusion or bolus injection must be avoided.
Bactrim IV Infusion should not be given intramuscularly.
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