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It should be noted, however, that there are little clinical data on the use of sulfamethoxazole and trimethoprim injection in serious systemic infections due to Haemophilus influenzae and Streptococcus pneumoniae.Pneumocystis Carinii Pneumonia Sulfamethoxazole and trimethoprim injection is indicated in the treatment of Pneumocystis carinii pneumonia in children and adults.
Both sulfamethoxazole and trimethoprim distribute to sputum and vaginal fluid; trimethoprim also distributes to bronchial secretions, and both pass the placental barrier and are excreted in breast milk.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.SULFONAMIDES, INCLUDING SULFONAMIDE-CONTAINING PRODUCTS SUCH AS SMX AND TMP INJECTION, SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE SKIN RASH OR ANY SIGN OF ADVERSE REACTION.Thus, this combination 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 this combination than with either sulfamethoxazole or trimethoprim alone.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.
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.
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 sulfamethoxazole and trimethoprim is primarily by the kidneys through both glomerular filtration and tubular secretion.
PCP: 15-20mg/kg/day (based on TMP component) divided q6h.