Bactrim
Co-trimoxazole
DESCRIPTION
Bactrim (trimethoprim and sulfamethoxazole) is a synthetic
antibacterial combination product available in DS (double
strength) tablets, tablets and pediatric suspension for oral
administration. Each DS tablet contains 160 mg trimethoprim
and 800 mg sulfamethoxazole plus magnesium stearate, pregelatinized
starch and sodium starch glycolate. Each tablet contains 80
mg trimethoprim and 400 mg sulfamethoxazole plus magnesium
stearate, pregelatinized starch, sodium starch glycolate,
FD&C Blue No. 1 lake, FD&C Yellow No. 6 lake and D&C
Yellow No. 10 lake. Each teaspoonful (5 mL) of the pediatric
suspension contains 40 mg trimethoprim and 200 mg sulfamethoxazole
in a vehicle containing 0.3 percent alcohol, edetate disodium,
glycerin, microcrystalline cellulose, parabens (methyl and
propyl), polysorbate 80, saccharin sodium, simethicone, sorbitol,
sucrose, FD&C Yellow No. 6, FD&C Red No. 40, flavors
and water.
Trimethoprim is 2, 4-diamino-5-(3,4,5 trimethoxybenzyl)pyrimidine;
the molecular formula is C 14 H 18 N 4 O 3 . It is a white
to light yellow, odorless, bitter compound with a molecular
weight of 290.3 and the following structural formula:
Sulfamethoxazole is N 1 -(5-methyl-3-isoxazolyl)sulfanilamide;
the molecular formula is C 10 H 11 N 3 O 3 S. It is almost
white, odorless, tasteless compound with a molecular weight
of 253.28 and the following structural formula:
CLINICAL PHARMACOLOGY
Bactrim is rapidly absorbed following oral administration.
Both sulfamethoxazole and trimethoprim 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 N 4 -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 sulfamethoxazole and trimethoprim
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.
Peak blood levels for the individual components occur 1 to
4 hours after oral administration. The mean serum half-lives
of sulfamethoxazole and trimethoprim are 10 and 8 to 10 hours,
respectively. However, 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). Detectable amounts of trimethoprim and sulfamethoxazole
are present in the blood 24 hours after drug administration.
During administration of 160 mg trimethoprim and 800 mg sulfamethoxazole
bid, the mean steady-state plasma concentration of trimethoprim
was 1.72 ?g/mL. The steady-state mean plasma levels of free
and total sulfamethoxazole were 57.4 ?g/mL and 68.0 ?g/mL,
respectively. These steady-state levels were achieved after
three days of drug administration.
1 Excretion of sulfamethoxazole and trimethoprim is primarily
by the kidneys through both glomerular filtration and tubular
secretion. Urine concentrations of both sulfamethoxazole and
trimethoprim are considerably higher than are the concentrations
in the blood. The average percentage of the dose recovered
in urine from 0 to 72 hours after a single oral dose of Bactrim
is 84.5% for total sulfonamide and 66.8% for free trimethoprim.
Thirty percent of the total sulfonamide is excreted as free
sulfamethoxazole, with the remaining as N 4 -acetylated metabolite.
2 When administered together as Bactrim, neither sulfamethoxazole
nor trimethoprim affects the urinary excretion pattern of
the other.
Both trimethoprim and sulfamethoxazole distribute to sputum,
vaginal fluid and middle ear fluid; trimethoprim also distributes
to bronchial secretion, and both pass the placental barrier
and are excreted in human milk.
Microbiology: Trimethoprim blocks the production
of tetrahydrofolic acid from dihydrofolic acid by binding
to and reversibly inhibiting the required enzyme, dihydrofolate
reductase. Sulfamethoxazole inhibits bacterial synthesis of
dihydrofolic acid by competing with para -aminobenzoic acid
(PABA). Thus, trimethoprim and sulfamethoxazole block 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 both trimethoprim and sulfamethoxazole in
combination than with either trimethoprim or sulfamethoxazole
alone.
Trimethoprim and sulfamethoxazole have 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.
Aerobic gram-positive microorganisms:
Streptococcus pneumoniae
Aerobic gram-negative microorganisms:
Escherichia coli (including susceptible enterotoxigenic strains
implicated in traveler's diarrhea)
Klebsiella species
Enterobacter species
Haemophilus influenzae
Morganella morganii
Proteus mirabilis
Proteus vulgaris
Shigella flexneri 3
Shigella sonnei 3
Other Organisms:
Pneumocystis carinii
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