Bactrim

Acute Otitis Media: For the treatment of acute otitis media in pediatric patients due to suscep- tible strains of Streptococcus pneumoniae or Haemophilus influenzae when in the judgment ofthe physician sulfamethoxazole and trimethoprim offers some advantage over the use of other Susceptibility Testing Methods:
antimicrobial agents. To date, there are limited data on the safety of repeated use of BACTRIM sulfamethoxazole and trimethoprim DS in pediatric patients under two years of age. BACTRIM is not indicated for prophylactic or pro- Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs).
(double strength) tablets and tablets USP longed administration in otitis media at any age.
These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The Acute Exacerbations of Chronic Bronchitis in Adults: For the treatment of acute exacerbations of chronic MICs should be determined using a standardized procedure. Standardized procedures are based To reduce the development of drug-resistant bacteria and maintain the effectiveness of Bactrim bronchitis due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae when in the (sulfamethoxazole and trimethoprim) tablets and other antibacterial drugs, Bactrim (sulfamethox- on a dilution method4 (broth or agar) or equivalent with standardized inoculum concentrations judgment of the physician BACTRIM offers some advantage over the use of a single antimicrobial agent.
azole and trimethoprim) tablets should be used only to treat or prevent infections that are proven and standardized concentrations of sulfamethoxazole/trimethoprim powder. The MIC values should Shigellosis: For the treatment of enteritis caused by susceptible strains of Shigella flexneri and or strongly suspected to be caused by bacteria.
be interpreted according to the following criteria: Shigella sonnei when antibacterial therapy is indicated.
Pneumocystis Carinii Pneumonia: For the treatment of documented Pneumocystis carinii pneu- For testing Enterobacteriaceae: monia and for prophylaxis against Pneumocystis carinii pneumonia in individuals who are immuno- BACTRIM (sulfamethoxazole and trimethoprim) is a synthetic antibacterial combination product suppressed and considered to be at an increased risk of developing Pneumocystis carinii pneumonia.
available in DS (double strength) tablets, each containing 800 mg sulfamethoxazole and 160 mg Traveler's Diarrhea in Adults: For the treatment of traveler's diarrhea due to susceptible strains trimethoprim; in tablets, each containing 400 mg sulfamethoxazole and 80 mg trimethoprim for of enterotoxigenic E. coli.
When testing either Haemophilus influenzaea or Streptococcus pneumoniaeb: Sulfamethoxazole is N1 - (5-methyl-3-isoxazolyl) sulfanilamide; the molecular formula is C10H11N3O3S.
BACTRIM is contraindicated in patients with a known hypersensitivity to trimethoprim or sulfon- It is almost white, odorless, tasteless compound with a molecular weight of 253.28 and the fol- amides and in patients with documented megaloblastic anemia due to folate deficiency. BACTRIM lowing structural formula: 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 a. These interpretative standards are applicable only to broth microdilution susceptibility tests pediatric patients less than 2 months of age. BACTRIM is also contraindicated in patients with with Haemophilus influenzae using Haemophilus Test Medium (HTM)4.
marked hepatic damage or with severe renal insufficiency when renal function status cannot be b. These interpretative standards are applicable only to broth microdilution susceptibility tests using cation-adjusted Mueller-Hinton broth with 2% to 5% lysed horse blood4.
Trimethoprim is 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine; the molecular formula is C14H18N4O3.
FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE,
A report of "Susceptible" indicated that the pathogen is likely to be inhibited if the antimicrobial It is a white to light yellow, odorless, bitter compound with a molecular weight of 290.3. It has HAVE OCCURRED DUE TO SEVERE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME,
compound in the blood reaches the concentrations usually achievable. A report of "Intermediate" the following structural formula: TOXIC EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS,
indicates that the result should be considered equivocal, and, if the microorganism is not fully sus- APLASTIC ANEMIA AND OTHER BLOOD DYSCRASIAS.
ceptible 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 sit- SULFONAMIDES, INCLUDING SULFONAMIDE-CONTAINING PRODUCTS SUCH AS SUL-
uations where high dosage of drug can be used. This category also provides a buffer zone which FAMETHOXAZOLE/TRIMETHOPRIM, SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE
prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A OF SKIN RASH OR ANY SIGN OF ADVERSE REACTION.
In rare instances, a skin rash may be report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial followed by a more severe reaction, such as Stevens-Johnson syndrome, toxic epidermal necrol- compound in the blood reaches the concentrations usually achievable; other therapy should be ysis, hepatic necrosis, and serious blood disorders (see PRECAUTIONS). Clinical signs, such as
rash, sore throat, fever, arthralgia, pallor, purpura or jaundice may be early indications of serious Cough, shortness of breath, and pulmonary infiltrates are hypersensitivity reactions of the res-
Standardized susceptibility test procedures require the use of laboratory control microorganisms piratory tract that have been reported in association with sulfonamide treatment.
to control the technical aspects of the laboratory procedures. Standard sulfamethoxazole/trimetho-prim powder should provide the following range of values: The sulfonamides should not be used for treatment of group A
-hemolytic streptococcal infec- Inactive ingredients: Docusate sodium 85%, sodium benzoate 15%, sodium starch glycolate,
tions. In an established infection, they will not eradicate the streptococcus and, therefore, will magnesium stearate and pregelatinized starch.
not prevent sequelae such as rheumatic fever.
Escherichia coli Pseudomembranous colitis has been reported with nearly all antibacterial agents, including
0.03/0.59 - 0.25/4.75 BACTRIM is rapidly absorbed following oral administration. Both sulfamethoxazole and trimetho- sulfamethoxazole/trimethoprim, and may range in severity from mild to life-threatening. There-
0.12/2.4 — 1/19 prim exist in the blood as unbound, protein-bound and metabolized forms; sulfamethoxazole also fore, it is important to consider this diagnosis in patients who present with diarrhea sub-
exists as the conjugated form. The metabolism of sulfamethoxazole occurs predominately by N c. This quality control range is applicable only to Haemophilus influenzae ATCC 49247 tested by broth sequent to the administration of antibacterial agents.
microdilution procedure using Haemophilus Test Medium (HTM)4.
acetylation, although the glucuronide conjugate has been identified. The principal metabolites of Treatment with antibacterial agents alters the normal flora of the colon and may permit over- trimethoprim are the 1- and 3-oxides and the 3'- and 4'-hydroxy derivatives. The free forms of d. This quality control range is applicable to tests performed by the broth microdilution method growth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one pri- sulfamethoxazole and trimethoprim are considered to be the therapeutically active forms. Approx- only using cation-adjusted Mueller-Hinton broth with 2% to 5% lysed horse blood4.
mary cause of "antibiotic-associated colitis." imately 70% of sulfamethoxazole and 44% of trimethoprim are bound to plasma proteins. The After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should presence of 10 mg percent sulfamethoxazole in plasma decreases the protein binding of trimetho- be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone.
Quantitative methods that require measurement of zone diameters also provide reproducible estimates prim by an insignificant degree; trimethoprim does not influence the protein binding of sul- In moderate to severe cases, consideration should be given to management with fluids and elec- of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure5 requires trolytes, protein supplementation, and treatment with an anti-bacterial drug effective against C. diffi- the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with Peak blood levels for the individual components occur 1 to 4 hours after oral administration. The 1.25/23.75 µg of sulfamethoxazole/trimethoprim to test the susceptibility of microorganisms to sul- mean serum half-lives of sulfamethoxazole and trimethoprim are 10 and 8 to 10 hours, respec- tively. However, patients with severely impaired renal function exhibit an increase in the half- Reports from the laboratory providing results of the standard single-disk susceptibility test with General: Prescribing Bactrim (sulfamethoxazole and trimethoprim) tablets in the absence of a proven lives of both components, requiring dosage regimen adjustment (see DOSAGE AND
a 1.25/23.75 µg of sulfamethoxazole/trimethoprim disk should be interpreted according to the fol- or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit ADMINISTRATION section). Detectable amounts of sulfamethoxazole and trimethoprim are pre-
to the patient and increases the risk of the development of drug-resistant bacteria.
sent in the blood 24 hours after drug administration. During administration of 800 mg sul- BACTRIM should be given with caution to patients with impaired renal or hepatic function, to those famethoxazole and 160 mg trimethoprim b.i.d., the mean steady-state plasma concentration of For testing either Enterobacteriaceae or Haemophilus influenzaee : with possible folate deficiency (e.g., the elderly, chronic alcoholics, patients receiving anticonvulsant trimethoprim was 1.72 µg/mL. The steady-state mean plasma levels of free and total sul- Zone Diameter (mm) therapy, patients with malabsorption syndrome, and patients in malnutrition states) and to those famethoxazole were 57.4 µg/mL and 68.0 µg/mL, respectively. These steady-state levels were with severe allergies or bronchial asthma. In glucose-6-phosphate dehydrogenase deficient individ- achieved after three days of drug administration.1 Excretion of sulfamethoxazole and trimetho- uals, hemolysis may occur. This reaction is frequently dose-related. (see CLINICAL PHARMA-
prim is primarily by the kidneys through both glomerular filtration and tubular secretion. Urine COLOGY and DOSAGE AND ADMINISTRATION).
concentrations of both sulfamethoxazole and trimethoprim are considerably higher than are the e. These zone diameter standards are applicable only for disk diffusion testing with Haemophilus Cases of hypoglycemia in non-diabetic patients treated with BACTRIM are seen rarely, usually concentrations in the blood. The average percentage of the dose recovered in urine from 0 to influenzae and Haemophilus Test Medium (HTM)5.
occurring after a few days of therapy. Patients with renal dysfunction, liver disease, malnutri- 72 hours after a single oral dose of sulfamethoxazole and trimethoprim is 84.5% for total sul- tion or those receiving high doses of BACTRIM are particularly at risk.
fonamide and 66.8% for free trimethoprim. Thirty percent of the total sulfonamide is excreted as When testing Streptococcus pneumoniaef: free sulfamethoxazole, with the remaining as N Zone Diameter (mm) Hematological changes indicative of folic acid deficiency may occur in elderly patients or in patients 4-acetylated metabolite.2 When administered together with preexisting folic acid deficiency or kidney failure. These effects are reversible by folinic acid as sulfamethoxazole and trimethoprim, neither sulfamethoxazole nor trimethoprim affects the uri- nary excretion pattern of the other.
Trimethoprim has been noted to impair phenylalanine metabolism but this is of no significance Both sulfamethoxazole and trimethoprim distribute to sputum, vaginal fluid and middle ear fluid; in phenylketonuric patients on appropriate dietary restriction.
trimethoprim also distributes to bronchial secretion, and both pass the placental barrier and are f. These zone diameter interpretative standards are applicable only to tests performed using excreted in human milk.
Mueller-Hinton agar supplemented with 5% defibrinated sheep blood when incubated in 5% CO 5 As with all drugs containing sulfonamides, caution is advisable in patients with porphyria or thy- roid dysfunction.
Geriatric Pharmacokinetics: The pharmacokinetics of sulfamethoxazole 800 mg and trimethoprim Interpretation should be as stated above for results using dilution techniques. Interpretation involves Use in the Treatment of and Prophylaxis for Pneumocystis Carinii Pneumonia in Patients
160 mg were studied in 6 geriatric subjects (mean age: 78.6 years) and 6 young healthy sub- correlation of the diameter obtained in the disk test with the MIC for sulfamethoxazole/trimethoprim.
with Acquired Immunodeficiency Syndrome (AIDS): AIDS patients may not tolerate or respond
jects (mean age: 29.3 years) using a non-US approved formulation. Pharmacokinetic values for to BACTRIM in the same manner as non-AIDS patients. The incidence of side effects, particu- sulfamethoxazole in geriatric subjects were similar to those observed in young adult subjects.
As with standardized dilution techniques, diffusion methods require the use of laboratory control larly rash, fever, leukopenia and elevated aminotransferase (transaminase) values, with BACTRIM The mean renal clearance of trimethoprim was significantly lower in geriatric subjects compared microorganisms that are used to control the technical aspects of the laboratory procedures. For therapy in AIDS patients who are being treated for Pneumocystis carinii pneumonia has been with young adult subjects (19 mL/h/kg vs. 55 mL/h/kg). However, after normalizing by body the diffusion technique, the 1.25/23.75 µg sulfamethoxazole/trimethoprim disk* should provide the reported to be greatly increased compared with the incidence normally associated with the use weight, the apparent total body clearance of trimethoprim was on average 19% lower in geri- following zone diameters in these laboratory test quality control strains: of BACTRIM in non-AIDS patients. The incidence of hyperkalemia appears to be increased in atric subjects compared with young adult subjects.3 Zone Diameter Ranges (mm) AIDS patients receiving BACTRIM. Adverse effects are generally less severe in patients receiving Escherichia coli BACTRIM for prophylaxis. A history of mild intolerance to BACTRIM in AIDS patients does not Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid appear to predict intolerance of subsequent secondary prophylaxis.6 However, if a patient develops (PABA). Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to skin rash or any sign of adverse reaction, therapy with BACTRIM should be reevaluated (see and reversibly inhibiting the required enzyme, dihydrofolate reductase. Thus, sulfamethoxazole and trimetho- WARNINGS).
*Mueller-Hinton agar should be checked for excessive levels of thymidine or thymine. To deter- prim blocks two consecutive steps in the biosynthesis of nucleic acids and proteins essential to many mine whether Mueller-Hinton medium has sufficiently low levels of thymidine and thymine, an High dosage of trimethoprim, as used in patients with Pneumocystis carinii pneumonia, induces Enterococcus faecalis (ATCC 29212 or ATCC 33186) may be tested with sulfamethoxazole/trimetho- a progressive but reversible increase of serum potassium concentrations in a substantial number In vitro studies have shown that bacterial resistance develops more slowly with both sul- prim disks. A zone of inhibition ≥20 mm that is essentially free of fine colonies indicates a suffi- of patients. Even treatment with recommended doses may cause hyperkalemia when trimetho- famethoxazole and trimethoprim in combination than with either sulfamethoxazole or trimethoprim ciently low level of thymidine and thymine.
prim is administered to patients with underlying disorders of potassium metabolism, with renal insufficiency, or if drugs known to induce hyperkalemia are given concomitantly. Close moni- g. This quality control range is applicable only to Haemophilus influenzae ATCC 49247 tested by Sulfamethoxazole and trimethoprim have been shown to be active against most strains of the toring of serum potassium is warranted in these patients.
a disk diffusion procedure using Haemophilus Test Medium (HTM)5.
following microorganisms, both in vitro and in clinical infections as described in the INDICA-
During treatment, adequate fluid intake and urinary output should be ensured to prevent crystal- h. This quality control range is applicable only to tests performed by disk diffusion using Mueller- TIONS AND USAGE section.
luria. Patients who are "slow acetylators" may be more prone to idiosyncratic reactions to sulfon- Hinton agar supplemented with 5% defibrinated sheep blood when incubated in 5% CO 5.
Aerobic gram-positive microorganisms:
INDICATIONS AND USAGE
Information for Patients: Patients should be counseled that antibacterial drugs including Bactrim
(sulfamethoxazole and trimethoprim) tablets should only be used to treat bacterial infections.
Aerobic gram-negative microorganisms:
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Bactrim (sul-famethoxazole and trimethoprim) tablets and other antibacterial drugs, Bactrim (sulfamethoxazole and They do not treat viral infections (e.g., the common cold). When Bactrim (sulfamethoxazole and Escherichia coli (including susceptible enterotoxigenic strains implicated in traveler's diarrhea) trimethoprim) tablets should be used only to treat or prevent infections that are proven or strongly trimethoprim) tablets are prescribed to treat a bacterial infection, patients should be told that suspected to be caused by susceptible bacteria. When culture and susceptibility information are although it is common to feel better early in the course of therapy, the medication should be available, they should be considered in selecting or modifying antibacterial therapy. In the absence taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) of such data, local epidemiology and susceptibility patterns may contribute to empiric selection of decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bac- teria will develop resistance and will not be treatable by Bactrim (sulfamethoxazole and trimetho- Proteus mirabilis prim) tablets or other antibacterial drugs in the future.
Proteus vulgaris Urinary Tract Infections: For the treatment of urinary tract infections due to susceptible strains of the Patients should be instructed to maintain an adequate fluid intake in order to prevent crystal- Shigella flexneri following organisms: Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, luria and stone formation.
Shigella sonnei Proteus mirabilis and Proteus vulgaris. It is recommended that initial episodes of uncomplicated uri-nary tract infections be treated with a single effective antibacterial agent rather than the combina- Laboratory Tests: 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 Schoenlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin Traveler's Diarrhea in Adults:
be performed during therapy, particularly for those patients with impaired renal function.
eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria and rash. In addi- For the treatment of traveler's diarrhea, the usual adult dosage is 1 BACTRIM DS (double Drug Interactions: In elderly patients concurrently receiving certain diuretics, primarily thiazides,
tion, periarteritis nodosa and systemic lupus erythematosus have been reported.
strength) tablet; 2 BACTRIM tablets every 12 hours for 5 days.
an increased incidence of thrombocytopenia with purpura has been reported.
Gastrointestinal: Hepatitis (including cholestatic jaundice and hepatic necrosis), elevation of serum HOW SUPPLIED
It has been reported that BACTRIM may prolong the prothrombin time in patients who are receiving transaminase and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, the anticoagulant warfarin. This interaction should be kept in mind when BACTRIM is given to nausea, emesis, abdominal pain, diarrhea, anorexia.
BACTRIM™ TABLETS are supplied as follows: patients already on anticoagulant therapy, and the coagulation time should be reassessed.
Genitourinary: Renal failure, interstitial nephritis, BUN and serum creatinine elevation, toxic nephrosis BACTRIM™ DS (double strength) TABLETS (white, oval shaped, scored) containing 160 mgtrimethoprim and 800 mg sulfamethoxazole – bottles of 100 (NDC 13310-146-01) and 500 (NDC BACTRIM may inhibit the hepatic metabolism of phenytoin. BACTRIM, given at a common clinical with oliguria and anuria, crystalluria and nephrotoxicity in association with cyclosporine. 13310-146-05). Imprint on tablets (debossed): (front) BACTRIM DS dosage, increased the phenytoin half-life by 39% and decreased the phenytoin metabolic clearance rate Metabolic and Nutritional: Hyperkalemia (see PRECAUTIONS: Use in the Treatment of and
by 27%. When administering these drugs concurrently, one should be alert for possible excessive pheny- Prophylaxis for Pneumocystis Carinii Pneumonia in Patients with Acquired Immunodeficiency
BACTRIM™ TABLETS (white, round, scored) containing 80 mg trimethoprim and 400 mg sul- toin effect.
famethoxazole – bottles of 100 (NDC 13310-145-01) and 500 (NDC 13310-145-05). Imprint ontablets (debossed): (front) BACTRIM Sulfonamides can also displace methotrexate from plasma protein binding sites and can com- Neurologic: Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache.
pete with the renal transport of methotrexate, thus increasing free methotrexate concentrations.
Psychiatric: Hallucinations, depression, apathy, nervousness.
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature] There have been reports of marked but reversible nephrotoxicity with coadministration of BACTRIM Endocrine: The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (aceta- and cyclosporine in renal transplant recipients.
zolamide and the thiazides) and oral hypoglycemic agents. Cross-sensitivity may exist with these DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.
Increased digoxin blood levels can occur with concomitant BACTRIM therapy, especially in elderly agents. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides.
patients. Serum digoxin levels should be monitored.
Musculoskeletal: Arthralgia and myalgia. Isolated cases of rhabdomyolysis have been reported 1. Kremers P, Duvivier J, Heusghem C. Pharmacokinetic Studies of Co-Trimoxazole in Man after Increased sulfamethoxazole blood levels may occur in patients who are receiving indomethacin.
with BACTRIM, mainly in AIDS patients.
Single and Repeated Doses. J Clin Pharmacol. Feb-Mar 1974; 14:112-117.
Occasional reports suggest that patients receiving pyrimethamine as malaria prophylaxis in doses Respiratory: Cough, shortness of breath and pulmonary infiltrates (see WARNINGS).
2. Kaplan SA, et al. Pharmacokinetic Profile of Trimethoprim-Sulfamethoxazole in Man. J Infect exceeding 25 mg weekly may develop megaloblastic anemia if BACTRIM is prescribed.
Miscellaneous: Weakness, fatigue, insomnia.
Dis. Nov 1973; 128 (Suppl): S547-S555.
3. Varoquaux O, et al Pharmacokinetics of the trimethoprim-sulfamethoxazole combination in The efficacy of tricyclic antidepressants can decrease when coadministered with BACTRIM.
the elderly. Br J Clin Pharmacol 1985;20;575-581 Like other sulfonamide-containing drugs, BACTRIM potentiates the effect of oral hypoglycemics.
Acute: The amount of a single dose of BACTRIM that is either associated with symptoms of over-dosage or is likely to be life-threatening has not been reported. Signs and symptoms of overdosage 4. Rudoy RC, Nelson JD, Haltalin KC. Antimicrobial Agents Chemother. May 1974;5:439-443.
In the literature, a single case of toxic delirium has been reported after concomitant intake of reported with sulfonamides include anorexia, colic, nausea, vomiting, dizziness, headache, drowsi- 5. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Sus- ness and unconsciousness. Pyrexia, hematuria and crystalluria may be noted. Blood dyscrasias and ceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Fourth Edition. NCCLS In the literature, three cases of hyperkalemia in elderly patients have been reported after con- jaundice are potential late manifestations of overdosage.
document M7-A4, Vol.17 No. 2 NCCLS, Wayne, PA, January, 1997.
comitant intake of trimethoprim/sulfamethoxazole and an angiotensin converting enzyme inhibitor.8,9 6. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicro- Signs of acute overdosage with trimethoprim include nausea, vomiting, dizziness, headache, mental bial Disk Susceptibility Tests. Approved Standard – Sixth Edition. NCCLS Document M2-A6, Drug/Laboratory Test Interactions: BACTRIM, specifically the trimethoprim component, can inter-
depression, confusion and bone marrow depression.
Vol.17, No.1, NCCLS, Wayne, PA, January, 1997.
fere with a serum methotrexate assay as determined by the competitive binding protein technique General principles of treatment include the institution of gastric lavage or emesis, forcing oral fluids, 7. Hardy DW, et al. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentami- (CBPA) when a bacterial dihydrofolate reductase is used as the binding protein. No interference and the administration of intravenous fluids if urine output is low and renal function is normal. Acid- dine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired occurs, however, if methotrexate is measured by a radioimmunoassay (RIA).
ification of the urine will increase renal elimination of trimethoprim. The patient should be moni- immunodeficiency syndrome. N Engl J Med. 1992; 327:1842-1848.
The presence of sulfamethoxazole and trimethoprim may also interfere with the Jaffé alkaline picrate tored with blood counts and appropriate blood chemistries, including electrolytes. If a significant 8. Marinella Mark A. 1999. Trimethoprim-induced hyperkalemia: An analysis of reported cases.
reaction assay for creatinine, resulting in overestimations of about 10% in the range of normal 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 9. Margassery, S. and B. Bastani. 2002. Life threatening hyperkalemia and acidosis secondary to Carcinogenesis, Mutagenesis, Impairment of Fertility:
sulfamethoxazole and trimethoprim.
trimethoprim-sulfamethoxazole treatment. J. Nephrol. 14:410-414.
Carcinogenesis: Long-term studies in animals to evaluate carcinogenic potential have not been Chronic: Use of BACTRIM at high doses and/or for extended periods of time may cause bone 10. Brumfitt W, Pursell R. Trimethoprim/Sulfamethoxazole in the Treatment of Bacteriuria in conducted with BACTRIM.
marrow depression manifested as thrombocytopenia, leukopenia and/or megaloblastic anemia. If Women. J Infect Dis. Nov 1973; 128 (Suppl):S657-S663.
signs of bone marrow depression occur, the patient should be given leucovorin 5 to 15 mg daily 11. Masur H. Prevention and treatment of Pneumocystis pneumonia. N Engl J Med. 1992; Mutagenesis: Bacterial mutagenic studies have not been performed with sulfamethoxazole and trimetho- until normal hematopoiesis is restored.
prim in combination. Trimethoprim was demonstrated to be nonmutagenic in the Ames assay. No 12. Recommendations for prophylaxis against Pneumocystis carinii pneumonia for adults and chromosomal damage was observed in human leukocytes in vitro with sulfamethoxazole and trimetho- DOSAGE AND ADMINISTRATION
adolescents infected with human immunodeficiency virus. MMWR. 1992; 41(RR-4):1-11.
prim alone or in combination; the concentrations used exceeded blood levels of these compounds Not recommended for use in pediatric patients less than 2 months of age.
13. CDC Guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected following therapy with sulfamethoxazole and trimethoprim. Observations of leukocytes obtained from Urinary Tract Infections and Shigellosis in Adults and Pediatric Patients, and Acute Otitis Media
with human immunodeficiency virus. MMWR. 1991; 40(RR-2):1-13.
patients treated with sulfamethoxazole and trimethoprim revealed no chromosomal abnormalities.
Impairment of Fertility: No adverse effects on fertility or general reproductive performance were observed Adults: The usual adult dosage in the treatment of urinary tract infections is 1 BACTRIM DS in rats given oral dosages as high as 350 mg/kg/day sulfamethoxazole plus 70 mg/kg/day trimethoprim.
(double strength) tablet, 2 BACTRIM tablets every 12 hours for 10 to 14 days. An identical daily Pregnancy: Teratogenic Effects: Pregnancy Category C. In rats, oral doses of 533 mg/kg or 200 dosage is used for 5 days in the treatment of shigellosis.
mg/kg produced teratologic effects manifested mainly as cleft palates.
Children: The recommended dose for children with urinary tract infections or acute otitis media Manufactured for: The highest dose which did not cause cleft palates in rats was 512 mg/kg or 192 mg/kg trimetho- is 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim per 24 hours, given in two divided doses prim when administered separately. In two studies in rats, no teratology was observed when 512 every 12 hours for 10 days. An identical daily dosage is used for 5 days in the treatment of Philadelphia, PA 19124 USA mg/kg of sulfamethoxazole was used in combination with 128 mg/kg of trimethoprim. In one study, shigellosis. The following table is a guideline for the attainment of this dosage: however, cleft palates were observed in one litter out of 9 when 355 mg/kg of sulfamethoxazole Children 2 months of age or older: MUTUAL PHARMACEUTICAL COMPANY, INC.
was used in combination with 88 mg/kg of trimethoprim.
Dose--every 12 hours Philadelphia, PA 19124 USA In some rabbit studies, an overall increase in fetal loss (dead and resorbed and malformed con- ceptuses) was associated with doses of trimethoprim 6 times the human therapeutic dose.
While there are no large, well-controlled studies on the use of sulfamethoxazole and trimethoprim in pregnant women, Brumfitt and Pursell,10 in a retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or sulfamethoxazole and trimetho- prim. The incidence of congenital abnormalities was 4.5% (3 of 66) in those who received placeboand 3.3% (4 of 120) in those receiving sulfamethoxazole and trimethoprim. There were no abnor- For Patients with Impaired Renal Function: When renal function is impaired, a reduced dosage
Revised: March 2005Ch malities in the 10 children whose mothers received the drug during the first trimester. In a sep- should be employed using the following table: arate survey, Brumfitt and Pursell also found no congenital abnormalities in 35 children whose Creatinine Recommended mothers had received oral sulfamethoxazole and trimethoprim at the time of conception or shortlythereafter.
Clearance (mL/min) Because sulfamethoxazole and trimethoprim may interfere with folic acid metabolism, BACTRIM Usual standard regimen should be used during pregnancy only if the potential benefit justifies the potential risk to the 1/2 the usual regimen Use not recommended Nonteratogenic Effects: See CONTRAINDICATIONS section.
Acute Exacerbations of Chronic Bronchitis in Adults:
Nursing Mothers: See CONTRAINDICATIONS section.
The usual adult dosage in the treatment of acute exacerbations of chronic bronchitis is 1 BACTRIM Pediatric Use: BACTRIM is not recommended for infants younger than 2 months of age (see
DS (double strength) tablet, 2 BACTRIM tablets every 12 hours for 14 days.
INDICATIONS and CONTRAINDICATIONS sections).
Geriatric Use: Clinical studies of BACTRIM did not include sufficient numbers of subjects aged
Treatment: Adults and Children: 65 and over to determine whether they respond differently from younger subjects.
The recommended dosage for patients with documented Pneumocystis carinii pneumonia is 75 to There may be an increased risk of severe adverse reactions in elderly patients, particularly when 100 mg/kg sulfamethoxazole and 15 to 20 mg/kg trimethoprim per 24 hours given in equally divided complicating conditions exist, e.g., impaired kidney and/or liver function, possible folate defi-ciency, or concomitant use of other drugs. Severe skin reactions, generalized bone marrow sup- doses every 6 hours for 14 to 21 days.11 The following table is a guideline for the upper limit of pression (see WARNINGS and ADVERSE REACTIONS sections), a specific decrease in platelets
this dosage.
(with or without purpura), and hyperkalemia are the most frequently reported severe adverse reac- Dose--every 6 hours tions in elderly patients. In those concurrently receiving certain diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported. Increased digoxin bloodlevels can occur with concomitant BACTRIM therapy, especially in elderly patients. Serum digoxin levels should be monitored. Hematological changes indicative of folic acid deficiency may occur in elderly patients. These effects are reversible by folinic acid therapy. Appropriate dosage adjust- ments should be made for patients with impaired kidney function and duration of use should be as short as possible to minimize risks of undesired reactions (see DOSAGE AND ADMINISTRA-
TION section). The trimethoprim component of BACTRIM may cause hyperkalemia when admin-
3 or 1 1/2 DS tablets 4 or 2 DS tablets istered to patients with underlying disorders of potassium metabolism, with renal insufficiency or 5 or 2 1/2 DS tablets when given concomitantly with drugs known to induce hyperkalemia, such as angiotensin con-verting enzyme inhibitors. Close monitoring of serum potassium is warranted in these patients.
For the lower limit dose (75 mg/kg sulfamethoxazole and 15 mg/kg trimethoprim per 24 hours) Discontinuation of BACTRIM treatment is recommended to help lower potassium serum levels.
administer 75% of the dose in the above table.
Bactrim Tablets contain 1.8 mg sodium (0.08 mEq) of sodium per tablet. Bactrim DS Tablets contain 3.6 mg (0.16 mEq) of sodium per tablet.
Pharmacokinetics parameters for sulfamethoxazole were similar for geriatric subjects and youngeradult subjects. The mean maximum serum trimethoprim concentration was higher and mean renal The recommended dosage for prophylaxis in adults is 1 BACTRIM DS (double strength) tablet daily.12 clearance of trimethoprim was lower in geriatric subjects compared with younger subjects (see CLINICAL PHARMACOLOGY: Geriatric Pharmacokinetics).
For children, the recommended dose is 750 mg/m2 /day sulfamethoxazole with 150 mg/m2/day trimethoprim given orally in equally divided doses twice a day, on 3 consecutive days per week.
The most common adverse effects are gastrointestinal disturbances (nausea, vomiting, anorexia) The total daily dose should not exceed 1600 mg sulfamethoxazole and 320 mg trimethoprim.13 and allergic skin reactions (such as rash and urticaria). FATALITIES ASSOCIATED WITH THE
The following table is a guideline for the attainment of this dosage in children: ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE, HAVE OCCURRED DUE TO SEVERE
Body Surface Area Dose--every 12 hours REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS,
FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC ANEMIA AND OTHER BLOOD
DYSCRASIAS (SEE WARNINGS SECTION).
Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia.
Allergic Reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergicmyocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-

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