Bactrim DS 800 MG/ 160 MG Oral Tablet
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.
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.
Thrombocytopenia Thrombocytopenia has been reported with both sulfamethoxazole and trimethoprim usage.
A case control study found a 124-fold increased risk of severe thrombocytopenia (platelets <30,000 µL, requiring hospitalization) with sulfamethoxazole and trimethoprim in combination with an incidence of 2 cases per 1000 patient-years of exposure.
6 The incidence of less severe thrombocytopenia may be higher.
Thrombocytopenia caused by sulfamethoxazole and trimethoprim may be immune-mediated.
Drug-induced immune-mediated thrombocytopenia with sulfamethoxazole/trimethoprim is characterized by a drug-dependent antibody that is itself nonreactive, but when soluble drug is present at pharmacologic concentrations, antibody binds tightly to specific platelet membrane glycoproteins, causing platelet destruction.
7 Serologic testing for drug-specific antibody is commercially available and may be useful for identifying the specific cause of thrombocytopenia in individual cases.
Testing is important because a patient with drug-dependent antibodies should not be re-exposed to BACTRIM (see CONTRAINDICATIONS ).
Typically, a patient with immune thrombocytopenia will have taken drug for about 1 week or intermittently over a longer period of time (possibly years) before presenting with petechiae or bruising.
Systemic symptoms, such as lightheadedness, chills, fever, nausea, and vomiting, often may precede bleeding events.
Thrombocytopenia may be severe.
Patients should have risk/benefit re-evaluated in order to continue treatment with BACTRIM.
If the drug is stopped, symptoms usually resolve within 1 or 2 days and platelet count returns to normal in less than 1 week.
If BACTRIM is not stopped, there is a risk of fatal hemorrhage.
The onset of thrombocytopenia may be more rapid upon re-exposure.
Sulfamethoxazole has also been shown to occasionally trigger the production of platelet-specific autoantibodies leading to a clinical picture indistinguishable from spontaneous autoimmune thrombocytopenia.
In such cases, autoantibodies remain present for up to 9 weeks after sulfamethoxazole has been stopped, corresponding with a marked reduction in platelet counts for the same period.
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.
DRUG INTERACTIONS
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 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 also 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 sulfamethoxazole/trimethoprim and amantadine.
In the literature, three cases of hyperkalemia in elderly patients have been reported after concomitant intake of sulfamethoxazole/trimethoprim and an angiotensin converting enzyme inhibitor.
10,11
OVERDOSAGE
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.
DESCRIPTION
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 N 1 -(5-methyl-3-isoxazolyl)sulfanilamide; the molecular formula is C 10 H 11 N 3 O 3 S.
It is an 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 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: Inactive ingredients: Docusate sodium 85%, sodium benzoate 15%, sodium starch glycolate, magnesium stearate and pregelatinized starch.
Chemical Structure Chemical Structure
HOW SUPPLIED
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 10 ( NDC 54868-0337-3 ), bottles of 20 ( NDC 54868-0337-0 ), bottles of 30 ( NDC 54868-0337-1 ).
Imprint on tablets (debossed): (front) BACTRIM DS Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room Temperature] DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.
GERIATRIC USE
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 ).
INDICATIONS AND USAGE
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 .
PEDIATRIC USE
Pediatric Use: BACTRIM is not recommended for infants younger than 2 months of age (see INDICATIONS and CONTRAINDICATIONS sections).
PREGNANCY
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 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 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, 12 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.
NUSRING MOTHERS
Nursing Mothers: See CONTRAINDICATIONS section.
INFORMATION FOR PATIENTS
Information for Patients: 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.
DOSAGE AND ADMINISTRATION
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 1 66 30 1½ 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 treatment of 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.
13 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.
14 Children: For children, the recommended dose is 750 mg/m 2 /day sulfamethoxazole with 150 mg/m 2 /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.
15 The following table is a guideline for the attainment of this dosage in children: Body Surface Area Dose–every 12 hours (m 2 ) 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.