Bactrim (sulfamethoxazole and trimethoprim) is a synthetic antibacterial combination product available in DS (double strength) tablets, each containing 800 mg sulfamethoxazole and 160 mg trimethoprim; in tablets, each containing 400 mg sulfamethoxazole and 80 mg trimethoprim for oral administration.

Sulfamethoxazole is N1 - (5-methyl-3-isoxazolyl) sulfanilamide; the molecular formula is C₁₀H₁₁N₃O₃S. It is almost white, odorless, tasteless compound with a molecular weight of 253.28 and the following structural formula:

Trimethoprim is 2,4-diamino-5-(3,4,5-trimethoxybenzyl) pyrimidine; the molecular formula is C₁₄H₁₈N₄O₃. It is a white to light yellow, odorless, bitter compound with a molecular weight of 290.3. It has the following structural formula:

Inactive ingredients: Docusate sodium 85%, sodium benzoate 15%, sodium starch glycolate, magnesium stearate and pregelatinized starch.

Last updated on RxList: 6/26/2007

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Bactrim (sulfamethoxazole and trimethoprim) tablets and other antibacterial drugs, Bactrim (sulfamethoxazole and trimethoprim) tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to empiric selection of therapy.

Urinary Tract Infections

For the treatment of urinary tract infections due to susceptible strains of the following organisms: Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis and Proteus vulgaris. It is recommended that initial episodes of uncomplicated urinary tract infections be treated with a single effective antibacterial agent rather than the combination.

Acute Otitis Media

For the treatment of acute otitis media in pediatric patients due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae when in the judgment of the physician sulfamethoxazole and trimethoprim offers some advantage over the use of other antimicrobial agents. To date, there are limited data on the safety of repeated use of Bactrim in pediatric patients under two years of age. Bactrim is not indicated for prophylactic or prolonged administration in otitis media at any age.

Acute Exacerbations of Chronic Bronchitis in Adults

For the treatment of acute exacerbations of chronic bronchitis due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae when in the judgment of the physician Bactrim offers some advantage over the use of a single antimicrobial agent.

Shigellosis

For the treatment of enteritis caused by susceptible strains of Shigella flexneri and Shigella sonnei when antibacterial therapy is indicated.

Pneumocystis Carinii Pneumonia

For the treatment of documented Pneumocystis carinii pneumonia and for prophylaxis against Pneumocystis carinii pneumonia in individuals who are immunosuppressed and considered to be at an increased risk of developing Pneumocystis carinii pneumonia.

Traveler's Diarrhea in Adults

For the treatment of traveler's diarrhea due to susceptible strains of enterotoxigenic E. coli.

Not recommended for use in pediatric patients less than 2 months of age.

Urinary Tract Infections and Shigellosis in Adults and Pediatric Patients, and Acute Otitis Media in Children

Adults

The usual adult dosage in the treatment of urinary tract infections is 1 Bactrim DS (double strength) tablet or 2 Bactrim tablets every 12 hours for 10 to 14 days. An identical daily dosage is used for 5 days in the treatment of shigellosis.

Children

The recommended dose for children with urinary tract infections or acute otitis media is 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim per 24 hours, given in two divided doses every 12 hours for 10 days. An identical daily dosage is used for 5 days in the treatment of shigellosis. The following table is a guideline for the attainment of this dosage:

Children 2 months of age or older:
Weight	Dose - every 12 hours
lb kg	Tablets
22 10	-
44 20	1½
66 30	VA
88 40	2 or 1 DS tablet

For Patients with Impaired Renal Function

When renal function is impaired, a reduced dosage should be employed using the following table:

Creatinine Clearance (mL/min)	Recommended Dosage Regimen
Above 30	Usual standard regimen
15-30	½ the usual regimen
Below 15	Use not recommended

Acute Exacerbations of Chronic Bronchitis in Adults

The usual adult dosage in the treatment of acute exacerbations of chronic bronchitis is 1 Bactrim DS (double strength) tablet or 2 Bactrim tablets every 12 hours for 14 days.

Pneumocystis Carinii Pneumonia

Treatment: Adults and Children

The recommended dosage for patients with documented Pneumocystis carinii pneumonia is 75 to 100 mg/kg sulfamethoxazole and 15 to 20 mg/kg trimethoprim per 24 hours given in equally divided doses every 6 hours for 14 to 21 days.¹¹ The following table is a guideline for the upper limit of this dosage.

Weight		Dose - every 6 hours
lb	kg	Tablets
18	8.	-
35	16	1
53	24	1½
70	32	2 or 1 DS tablet
88	40	2½
106	48	3 or 1½ DS tablets
141	64	4 or 2 DS tablets
176	80	5 or 2½ DS tablets

For the lower limit dose (75 mg/kg sulfamethoxazole and 15 mg/kg trimethoprim per 24 hours) administer 75% of the dose in the above table.

Prophylaxis

Adults

The recommended dosage for prophylaxis in adults is 1 Bactrim DS (double strength) tablet daily.¹²

Children

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 total daily dose should not exceed 1600 mg sulfamethoxazole and 320 mg trimethoprim.¹³ The following table is a guideline for the attainment of this dosage in children:

Body Surface Area	Dose - every 12 hours
(m2)	Tablets
0.26	-
0.53	½
1.06	1

Traveler's Diarrhea in Adults

For the treatment of traveler's diarrhea, the usual adult dosage is 1 Bactrim DS (double strength) tablet or 2 Bactrim tablets every 12 hours for 5 days.

Bactrim™ TABLETS are supplied as follows:

Bactrim™ DS (double strength) TABLETS (white, oval shaped, scored) containing 160 mg trimethoprim and 800 mg sulfamethoxazole - bottles of 100 (NDC 13310-146-01) and 500 (NDC 13310-146-05). Imprint on tablets (debossed): (front) Bactrim DS

Bactrim™ TABLETS (white, round, scored) containing 80 mg trimethoprim and 400 mg sulfamethoxazole - bottles of 100 (NDC 13310-145-01) and 500 (NDC 13310-145-05). Imprint on tablets (debossed): (front) Bactrim

Store at 20° to 25°C (68° to 77°F).

[See USP Controlled Room Temperature]

DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.

REFERENCES

11. Masur H. Prevention and treatment of Pneumocystis pneumonia. N Engl J Med. 1992; 327:1853-1880.

12. Recommendations for prophylaxis against Pneumocystis carinii pneumonia for adults and adolescents infected with human immunodeficiency virus. MMWR. 1992; 41(RR-4):1-11.

13. CDC Guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with human immunodeficiency virus. MMWR. 1991; 40(RR-2):1-13.

Manufactured for: AR SCIENTIFIC., Philadelphia, PA 19124 USA
by: MUTUAL PHARMACEUTICAL COMPANY, INC., Philadelphia, PA 19124 USA
Revised: November 2006S FDA rev date:

Last updated on RxList: 6/25/2007

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).

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, photosensitivity, conjunctival and scleral injection, 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, crystalluria and nephrotoxicity in association with cyclosporine.

Metabolic and Nutritional: Hyperkalemia (see PRECAUTIONS: Use in the Treatment of and Prophylaxis for Pneumocystis Carinii Pneumonia in Patients with Acquired Immunodeficiency Syndrome (AIDS).

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. Isolated cases of rhabdomyolysis have been reported with Bactrim, mainly in AIDS patients.

Respiratory: Cough, shortness of breath and pulmonary infiltrates (see WARNINGS).

Miscellaneous: Weakness, fatigue, insomnia.

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 and can compete with the renal transport of methotrexate, thus increasing free methotrexate concentrations. There have been reports of marked but reversible nephrotoxicity with coadministration of Bactrim and cyclosporine in renal transplant recipients.

Increased digoxin blood levels can occur with concomitant Bactrim therapy, especially in elderly patients. Serum digoxin levels should be monitored.

Increased sulfamethoxazole blood levels may occur in patients who are receiving indomethacin. Occasional reports suggest that patients receiving pyrimethamine as malaria prophylaxis in doses exceeding 25 mg weekly may develop megaloblastic anemia if Bactrim is prescribed.

The efficacy of tricyclic antidepressants can decrease when coadministered with Bactrim. Like other sulfonamide-containing drugs, Bactrim potentiates the effect of oral hypoglycemics. In the literature, a single case of toxic delirium has been reported after concomitant intake of trimethoprim/sulfamethoxazole and amantadine.

In the literature, three cases of hyperkalemia in elderly patients have been reported after concomitant intake of trimethoprim/sulfamethoxazole and an angiotensin converting enzyme inhibitor.^8,9

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 sulfamethoxazole and trimethoprim may also interfere with the Jaffé alkaline picrate reaction assay for creatinine, resulting in overestimations of about 10% in the range of normal values.

REFERENCES

7. Hardy DW, et al. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1992; 327:1842-1848.

8. Marinella Mark A. 1999. Trimethoprim-induced hyperkalemia: An analysis of reported cases. Gerontol. 45:209-212.

9. Margassery, S. and B. Bastani. 2002. Life threatening hyperkalemia and acidosis secondary to trimethoprim-sulfamethoxazole treatment. J. Nephrol. 14:410-414.

Last updated on RxList: 6/25/2007

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 SULFAMETHOXAZOLE/TRIMETHOPRIM, SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE OF SKIN RASH OR ANY SIGN OF ADVERSE REACTION. In rare instances, a skin rash may be followed by a more severe reaction, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, 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 reactions.

Cough, shortness of breath, and pulmonary infiltrates are hypersensitivity reactions of the respiratory tract that have been reported in association with sulfonamide treatment.

The sulfonamides should not be used for treatment of group A β-hemolytic streptococcal infections. In an established infection, they will not eradicate the streptococcus and, therefore, will not prevent sequelae such as rheumatic fever.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Bactrim, 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 administration of 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.

General

Prescribing Bactrim (sulfamethoxazole and trimethoprim) tablets in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Bactrim should be given with caution to patients with impaired renal or hepatic function, to those with possible folate deficiency (e.g., 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. (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Cases of hypoglycemia in non-diabetic patients treated with Bactrim are seen rarely, usually occurring after a few days of therapy. Patients with renal dysfunction, liver disease, malnutrition or those receiving high doses of Bactrim are particularly at risk.

Hematological changes indicative of folic acid deficiency may occur in elderly patients or in patients with preexisting folic acid deficiency or kidney failure. These effects are reversible by folinic acid therapy.

Trimethoprim has been noted to impair phenylalanine metabolism but this is of no significance in phenylketonuric patients on appropriate dietary restriction.

As with all drugs containing sulfonamides, caution is advisable in patients with porphyria or thyroid dysfunction.

Use in the Treatment of and Prophylaxis for 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. The incidence of hyperkalemia appears to be increased in AIDS patients receiving Bactrim. Adverse effects are generally less severe in patients receiving Bactrim for prophylaxis. A history of mild intolerance to Bactrim in AIDS patients does not appear to predict intolerance of subsequent secondary prophylaxis.⁶ However, if a patient develops skin rash or any sign of adverse reaction, therapy with Bactrim should be reevaluated (see WARNINGS).

High dosage of trimethoprim, as used in patients with Pneumocystis carinii pneumonia, induces a progressive but reversible increase of serum potassium concentrations in a substantial number of patients. Even treatment with recommended doses may cause hyperkalemia when trimethoprim is administered to patients with underlying disorders of potassium metabolism, with renal insufficiency, or if drugs known to induce hyperkalemia are given concomitantly. Close monitoring of serum potassium is warranted in these patients.

During treatment, adequate fluid intake and urinary output should be ensured to prevent crystalluria. Patients who are "slow acetylators" may be more prone to idiosyncratic reactions to sulfonamides.

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 be performed during therapy, particularly for those patients with impaired renal function.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies in animals to evaluate carcinogenic potential have not been conducted with Bactrim.

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 in vitro with sulfamethoxazole and trimethoprim alone or in combination; the concentrations used exceeded blood levels of these compounds following therapy with sulfamethoxazole and trimethoprim. Observations of leukocytes obtained from patients treated with sulfamethoxazole and trimethoprim revealed no chromosomal abnormalities.

Impairment of Fertility

No adverse effects on fertility or general reproductive performance were observed in rats given oral dosages as high as 350 mg/kg/day sulfamethoxazole plus 70 mg/kg/day trimethoprim.

Pregnancy

Teratogenic Effects

Pregnancy Category C

In rats, oral doses of 533 mg/kg or 200 mg/kg produced teratologic effects manifested mainly as cleft palates.

The highest dose which did not cause cleft palates in rats was 512 mg/kg 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 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 trimethoprim. 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 sulfamethoxazole and trimethoprim. 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 sulfamethoxazole and trimethoprim at the time of conception or shortly thereafter.

Because sulfamethoxazole and trimethoprim may interfere with folic acid metabolism, Bactrim 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 is not recommended for infants younger than 2 months of age (see INDICATIONS and CONTRAINDICATIONS sections).

Geriatric Use

Clinical studies of Bactrim did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

There may be an increased risk of severe adverse reactions in elderly patients, particularly when complicating conditions exist, e.g., impaired kidney and/or liver function, possible folate deficiency, or concomitant use of other drugs. Severe skin reactions, generalized bone marrow suppression (see WARNINGS and ADVERSE REACTIONS sections), a specific decrease in platelets (with or without purpura), and hyperkalemia 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. Increased digoxin blood levels 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 adjustments 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 ADMINISTRATION section). The trimethoprim component of Bactrim may cause hyperkalemia when administered to patients with underlying disorders of potassium metabolism, with renal insufficiency or when given concomitantly with drugs known to induce hyperkalemia, such as angiotensin converting enzyme inhibitors. Close monitoring of serum potassium is warranted in these patients. Discontinuation of Bactrim treatment is recommended to help lower potassium serum levels. 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 younger adult subjects. The mean maximum serum trimethoprim concentration was higher and mean renal clearance of trimethoprim was lower in geriatric subjects compared with younger subjects (see CLINICAL PHARMACOLOGY: Geriatric Pharmacokinetics).

REFERENCES

6. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests. Approved Standard - Sixth Edition. NCCLS Document m²-A6, Vol.17, No.1, NCCLS, Wayne, PA, January, 1997.

7. Hardy DW, et al. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1992; 327:1842-1848.

10. Brumfitt W, Pursell R. Trimethoprim/Sulfamethoxazole in the Treatment of Bacteriuria in Women. J Infect Dis. Nov 1973; 128 (Suppl):S657-S663.

Last updated on RxList: 6/25/2007

Acute

The amount of a single dose of Bactrim that is either associated with symptoms of overdosage or is likely to be life-threatening has not been reported. 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 institution of gastric lavage or emesis, forcing oral fluids, and 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 sulfamethoxazole and trimethoprim.

Chronic

Use of Bactrim 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.

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 pediatric patients less than 2 months of age. Bactrim is also contraindicated in patients with marked hepatic damage or with severe renal insufficiency when renal function status cannot be monitored.

Last updated on RxList: 6/25/2007

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 µg/mL and 46.3 ± 2.7 µg/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 µg/mL and 8.8 ± 0.9 µg/mL for trimethoprim and 70.6 ± 7.3 µg/mL and 105.6 ± 10.9 µg/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). ¹

Pharmacokinetic studies in children and adults suggest an age-dependent half-life of trimethoprim, as indicated in the following table. ²

 

Age (years)	No. of Patients	Mean TMP 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; sulfamethaxazole 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 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 N ₄ -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 µg/mL)

	TMP / SMX (1:20)
Bacteria	TMP alone	SMX 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. ^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.

 

Last updated on RxList: 6/25/2007

Patients should be counseled that antibacterial drugs including Bactrim (sulfamethoxazole and trimethoprim) tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Bactrim (sulfamethoxazole and trimethoprim) tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Bactrim (sulfamethoxazole and trimethoprim) tablets or other antibacterial drugs in the future.

Patients should be instructed to maintain an adequate fluid intake in order to prevent crystalluria and stone formation.

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 taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Last updated on RxList: 6/25/2007

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

SULFAMETHOXAZOLE/TRIMETHOPRIM- ORAL

(sull-fuh-meth-OX-uh-zole/try-METH-oh-prim)

COMMON BRAND NAME(S): Bactrim, Bethaprim, Cotrim, Septra

USES: This medication is a combination of two antibiotics used to treat a wide variety of bacterial infections (e.g., middle ear, urine, respiratory and intestinal infections). It is also used to prevent and treat a certain type of pneumonia (pneumocystis-type).

This medication should not be used in children less than 2 months of age due to the risk of serious side effects.

This medication treats only certain types of infections. It will not work for viral infections (e.g., flu). Unnecessary use or misuse of any antibiotic can lead to its decreased effectiveness.

HOW TO USE: Take this medication by mouth with a full glass of water (8 ounces or 240 milliliters), or as directed by your doctor. If stomach upset occurs, take with food or milk. Drink plenty of fluids while taking this medication to prevent unlikely kidney stones from forming, unless your doctor advises you otherwise. Dosage is based on your medical condition and response to therapy.

Antibiotics work best when the amount of medicine in your body is kept at a constant level. Therefore, take this drug at evenly spaced intervals.

Continue to take this medication until the full-prescribed amount is finished, even if symptoms disappear after a few days. Stopping it too early may allow bacteria to continue to grow, which may result in a relapse of the infection.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: Nausea, vomiting, diarrhea, loss of appetite, or headache may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: muscle weakness, mental/mood changes, new lump/growth in the neck (goiter), signs of low blood sugar (e.g., shaking, dizziness, blurred vision, unusual hunger).

Tell your doctor immediately if any of these highly unlikely but very serious side effects occur: blood in the urine, change in the amount of urine.

Seek immediate medical attention if any of these highly unlikely but very serious side effects occur: confusion, persistent headache, neck stiffness, seizures.

This medication may rarely cause serious (possibly fatal) allergic reactions and other side effects such as a severe peeling skin rash (e.g., Stevens-Johnson syndrome), blood disorders (e.g., agranulocytosis, aplastic anemia), liver damage, or lung injury. If you notice any of the following, seek immediate medical attention: skin rash/blisters, itching, swelling, persistent sore throat or fever, paleness, joint pain/aches, persistent cough, trouble breathing, easy bleeding/bruising, yellowing eyes or skin, persistent nausea/vomiting, unusual fatigue, dark urine.

This medication may rarely cause a severe intestinal condition (pseudomembranous colitis) due to a resistant bacteria. This condition may occur while receiving therapy or even weeks to months after treatment has stopped. Do not use anti-diarrhea products or narcotic pain medications if you have the following symptoms because these products may make them worse. Tell your doctor immediately if you develop: persistent diarrhea, abdominal or stomach pain/cramping, or blood/mucus in your stool.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new vaginal yeast infection (oral or vaginal fungal infection). Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge or other new symptoms.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking sulfamethoxazole with trimethoprim, tell your doctor or pharmacist if you are allergic to sulfa medications or trimethoprim; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: a certain blood disorder (anemia due to folate vitamin deficiency), a certain metabolic disorder (porphyria), severe kidney disease, severe liver disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: alcohol use, anti-seizure medication use, severe allergies, asthma, decreased bone marrow function (bone marrow suppression), diabetes, a certain other metabolic disorder (G6PD deficiency), certain intestinal conditions (e.g., malabsorption), kidney disease, liver disease.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths or sunlamps. Use a sunscreen and wear protective clothing when outdoors.

Caution is advised when using this drug in the elderly because they may be more sensitive to its side effects, especially skin reactions and blood disorders.

Patients with AIDS may be more sensitive to the side effects of the drug, especially skin reactions, fever, and blood disorders.

This medication should be used only when clearly needed during pregnancy. This medication should not be used near the expected delivery date because of possible harm to the unborn baby. Discuss the risks and benefits with your doctor.

This drug passes into breast milk. While there have been no reports of harm to healthy infants, this drug may have undesirable effects on infants who are ill or premature or have certain disorders (jaundice, high blood levels of bilirubin, G6PD deficiency). Therefore, breast-feeding is not recommended in infants with these conditions. Consult your doctor before breast-feeding any infant.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: dofetilide, methenamine.

If you are currently using any of these medications tell your doctor or pharmacist before starting sulfamethoxazole with trimethoprim.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: certain anti-diabetic medications (e.g., glipizide, glyburide, tolbutamide), "blood thinners" (e.g., warfarin), cyclosporine, digoxin, drugs which can increase potassium levels (e.g., ACE inhibitors such as captopril, lisinopril), hydantoins (e.g., phenytoin), live vaccines, methotrexate, oral PABA, procainamide, pyrimethamine, tricyclic antidepressants (e.g., amitriptyline), certain "water pills" (thiazide diuretics such as hydrochlorothiazide).

This medication may decrease the effectiveness of combination-type birth control pills. This can result in pregnancy. You may need to use an additional form of reliable birth control while using this medication. Consult your doctor or pharmacist for details.

This product can affect the results of certain lab tests. Make sure laboratory personnel and your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: severe nausea/vomiting/diarrhea, severe dizziness or drowsiness, mental/mood changes.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for another infection unless told to do so by your doctor. A different medication may be necessary in those cases.

If using this medication for an extended period, laboratory and/or medical tests (e.g., complete blood count, kidney function tests, potassium blood level, cultures) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store the US product at room temperature between 59-77 degrees F (15-25 degrees C) away from light and moisture. Do not store in the bathroom.

Store the Canadian product at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom.

Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.