 |
SEPTRA I.V. Infusion (trimethoprim and sulfamethoxazole), a sterile solution for intravenous infusion only, is a synthetic antibacterial combination product. Each mL contains 16 mg trimethoprim and 80 mg sulfamethoxazole compounded with 40% propylene glycol, 10% ethyl alcohol, and 0.3% diethanolamine; 1% benzyl alcohol and 0.1% sodium metabisulfite added as preservatives, Water for Injection, and pH adjusted to approximately 10 with sodium hydroxide.
Trimethoprim is 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4-pyrimidinediamine. It is a white to light yellow, odorless, bitter compound with a molecular weight of 290.32 and the molecular formula C 14 H 18 N 4 O 3 . The structural formula is:
|
|
Sulfamethoxazole is 4-amino- N -(5-methyl-3-isoxazolyl)benzenesulfonamide. It is an almost white, odorless, tasteless compound with a molecular weight of 253.28 and the molecular formula C 10 H 11 N 3 O 3 S. The structural formula is:
 |
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 lb to 165 lb (mean, 143 lb), the mean peak plasma concentrations of trimethoprim and sulfamethoxazole were 3.4 ± 0.3 mcg/mL and 46.3 ± 2.7 mcg/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 mcg/mL and 8.8 ± 0.9 mcg/mL for trimethoprim and 70.6 ± 7.3 mcg/mL and 105.6 ± 10.9 mcg/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 pediatric patients and adults suggest an age-dependent half-life of trimethoprim as indicated in the following table. 2
|
Patients with severely impaired renal function exhibit an increase in the half-lives of both components, requiring dosage regimen adjustment (see DOSAGE AND ADMINISTRATION ).
Both trimethoprim and sulfamethoxazole exist in the blood as unbound, protein-bound, and metabolized forms; sulfamethoxazole also exists as the conjugated form. The metabolism of sulfamethoxazole occurs predominately by N 4 -acetylation, although the glucuronide conjugate has been identified. The principal metabolites of trimethoprim are the 1- and 3-oxides and the 3'- and 4'-hydroxy derivatives. The free forms of 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 1,200 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 SEPTRA, 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 human 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, SEPTRA 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 SEPTRA than with trimethoprim or sulfamethoxazole alone.
In vitro serial dilution tests have shown that the spectrum of antibacterial activity of SEPTRA 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 SEPTRA I.V. Infusion in serious systemic infections due to Haemophilus influenzae and Streptococcus pneumoniae .
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Susceptibility Testing: The recommended quantitative disc susceptibility method may be used for estimating the susceptibility of bacteria to SEPTRA. 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 SEPTRA. 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 SEPTRA.
Pneumocystis Carinii Pneumonia SEPTRA I.V. Infusion is indicated in the treatment of Pneumocystis carinii pneumonia in pediatric patients and adults.
Shigellosis SEPTRA I.V. Infusion is indicated in the treatment of enteritis caused by susceptible strains of Shigella flexneri and Shigella sonnei in pediatric patients and adults.
Urinary Tract Infections: SEPTRA I.V. Infusion is indicated in the treatment of severe or complicated urinary tract infections due to susceptible strains of Escherichia coli, Klebsiella species Enterobacter species Morganella morganii , and Proteus species when oral administration of SEPTRA is not feasible and when the organism is not susceptible to single-agent antibacterials effective in the urinary tract.
Although appropriate culture and susceptibility studies should be performed, therapy may be started while awaiting the results of these studies.
SEPTRA is contraindicated in patients with a known hypersensitivity to trimethoprim or sulfonamides and in patients with documented megaloblastic anemia due to folate deficiency. SEPTRA is also contraindicated in pregnant patients at term and in nursing mothers, because sulfonamides pass the placenta and are excreted in the milk and may cause kernicterus. SEPTRA is contraindicated in pediatric patients less than 2 months of age.
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 TRIMETHOPRIM/SULFAMETHOXAZOLE, 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 the treatment of group A beta-hemolytic streptococcal infections. In an established infection, they will not eradicate the streptococcus and, therefore, will not prevent sequelae such as rheumatic fever.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including trimethoprim/sulfamethoxazole, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis."
After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug effective against C. difficile .
Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Contains benzyl alcohol. In newborn infants, benzyl alcohol has been associated with an increased incidence of neurological and other complications which are sometimes fatal.
General: SEPTRA 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 allergy or bronchial asthma. In glucose-6-phosphate dehydrogenase-deficient individuals, hemolysis may occur. This reaction is frequently dose-related. Adequate fluid intake must be maintained in order to prevent crystalluria and stone formation (see and DOSAGE AND ADMINISTRATION ).
Local irritation and inflammation due to extravascular infiltration of the infusion has been observed with SEPTRA I.V. Infusion. If these occur, the infusion should be discontinued and restarted at another site.
Use in the Elderly: 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, or concomitant use of other drugs. Severe skin reactions, or generalized bone marrow suppression (see and ADVERSE REACTIONS ), or a specific decrease in platelets (with or without purpura) 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. Appropriate dosage adjustments should be made for patients with impaired kidney function (see DOSAGE AND ADMINISTRATION ).
Use in the Treatment of Pneumocystis carinii Pneumonia in Patients with Acquired Immunodeficiency Syndrome (AIDS): The incidence of side effects, particularly rash, fever, leukopenia, and elevated aminotransferase (transaminase) values in AIDS patients who are being treated with SEPTRA for Pneumocystis carinii pneumonia has been reported to be greatly increased compared with the incidence normally associated with the use of SEPTRA in non-AIDS patients. The incidence of hyperkalemia and hyponatremia appears to be increased in AIDS patients receiving SEPTRA.
The concomitant use of leucovorin with trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection was associated with increased rates of treatment failure and morbidity in a placebo-controlled study.
Laboratory Tests: Appropriate culture and susceptibility studies should be performed before and throughout treatment. Complete blood counts should be done frequently in patients receiving SEPTRA; if a significant reduction in the count of any formed blood element is noted, SEPTRA 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.
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 SEPTRA may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin. This interaction should be kept in mind when SEPTRA is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed.
SEPTRA may inhibit the hepatic metabolism of phenytoin. SEPTRA, 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, thus increasing free methotrexate concentrations.
Drug/Laboratory Test Interactions: SEPTRA, 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 trimethoprim and sulfamethoxazole may also interfere with the Jaffé alkaline picrate reaction assay for creatinine, resulting in over-estimations of about 10% in the range of normal values.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenesis: Long-term studies in animals to evaluate carcinogenic potential have not been conducted with SEPTRA I.V. Infusion.
Mutagenesis: Bacterial mutagenic studies have not been performed with sulfamethoxazole and trimethoprim in combination. Trimethoprim was demonstrated to be non-mutagenic in the Ames assay. In studies at two laboratories, no chromosomal damage was detected in cultured Chinese hamster ovary cells at concentrations approximately 500 times human plasma levels; at concentrations approximately 1,000 times human plasma levels in these same cells, a low level of chromosomal damage was induced at one of the laboratories. No chromosomal abnormalities were observed in cultured human leukocytes at concentrations of trimethoprim up to 20 times human steady-state plasma levels. No chromosomal effects were detected in peripheral lymphocytes of human subjects receiving 320 mg of trimethoprim in combination with up to 1,600 mg of sulfamethoxazole per day for as long as 112 weeks.
Impairment of Fertility: SEPTRA I.V. Infusion has not been studied in animals for evidence of impairment of fertility. However, studies in rats at oral dosages as high as 70 mg/kg trimethoprim plus 350 mg/kg sulfamethoxazole daily showed no adverse effects on fertility or general reproductive performance.
Pregnancy Teratogenic Effects: Pregnancy Category C. In rats, oral doses of 533 mg/kg sulfamethoxazole or 200 mg/kg trimethoprim produced teratological 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 teratogenicity 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 nine 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 six times the human therapeutic dose.
While there are no large, well-controlled studies on the use of trimethoprim and sulfamethoxazole in pregnant women, Brumfitt and Pursell, 5 in a retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or oral trimethoprim and sulfamethoxazole. 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 trimethoprim and sulfamethoxazole. 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 trimethoprim and sulfamethoxazole at the time of conception or shortly thereafter.
Because trimethoprim and sulfamethoxazole may interfere with folic acid metabolism, SEPTRA I.V. Infusion 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: SEPTRA I.V. Infusion is not recommended for pediatric patients younger than 2 months of age (see CONTRAINDICATIONS ).
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, OTHER BLOOD DYSCRASIAS, AND HYPERSENSITIVITY OF THE RESPIRATORY TRACT (SEE ). Local reaction, pain, and slight irritation on I.V. administration are infrequent. Thrombophlebitis has rarely been observed.
Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia.
Allergic: Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-Schönlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, conjunctival and scleral injection, photosensitivity, 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, and crystalluria.
Metabolic: Hyperkalemia, hyponatremia.
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.
Respiratory System: Cough, shortness of breath, and pulmonary infiltrates (see ).
Miscellaneous: Weakness, fatigue, insomnia.
Acute: Since there has been no extensive experience in humans with single doses of SEPTRA I.V. Infusion in excess of 25 mL (400 mg trimethoprim and 2,000 mg sulfamethoxazole), the maximum tolerated dose in humans is unknown. 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 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 trimethoprim and sulfamethoxazole.
Chronic: Use of SEPTRA I.V. Infusion 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 leucovorin daily has been recommended by some investigators.
Animal Toxicity: The LD 50 of SEPTRA I.V. Infusion in mice is 700 mg/kg or 7.3 mL/kg; in rats and rabbits the LD 50 is >500 mg/kg or >5.2 mL/kg. The vehicle produced the same LD 50 in each of these species as the active drug.
The signs and symptoms noted in mice, rats, and rabbits with SEPTRA I.V. Infusion or its vehicle at the high I.V. doses used in acute toxicity studies included ataxia, decreased motor activity, loss of righting reflex, tremors or convulsions, and/or respiratory depression.
CONTRAINDICATED IN PEDIATRIC PATIENTS LESS THAN 2 MONTHS OF AGE. CAUTION-SEPTRA I.V. INFUSION MUST BE DILUTED IN 5% DEXTROSE IN WATER SOLUTION PRIOR TO ADMINISTRATION. DO NOT MIX SEPTRA I.V. INFUSION WITH OTHER DRUGS OR SOLUTIONS. RAPID INFUSION OR BOLUS INJECTION MUST BE AVOIDED.
Dosage: Pediatric Patients and Adults:
Pneumocystis Carinii Pneumonia: Total daily dose is 15 to 20 mg/kg (based on the trimethoprim component) given in three to four equally divided doses every 6 or 8 hours for up to 14 days. One investigator noted that a total daily dose of 10 to 15 mg/kg was sufficient in 10 adult patients with normal renal function. 6
Severe Urinary Tract Infections and Shigellosis: Total daily dose is 8 to 10 mg/kg (based on the trimethoprim component) given in two to four equally divided doses every 6, 8, or 12 hours for up to 14 days for severe urinary tract infections and 5 days for shigellosis. The maximum recommended daily dose is 60 mL per day.
For Patients with Impaired Renal Function: When renal function is impaired, a reduced dosage should be employed using the following table:
|
Method of Preparation: SEPTRA I.V. Infusion must be diluted. EACH 5 mL SHOULD BE ADDED TO 125 mL OF 5% DEXTROSE IN WATER. After diluting with 5% dextrose in water, the solution should not be refrigerated and should be used within 6 hours. If a dilution of 5 mL per 100 mL of 5% dextrose in water is desired, it should be used within 4 hours. If upon visual inspection there is cloudiness or evidence of crystallization after mixing, the solution should be discarded and a fresh solution prepared.
Multiple-Dose Vial: After initial entry into the vial, the remaining contents must be used within 48 hours.
The following infusion systems have been tested and found satisfactory: unit-dose glass containers; unit-dose polyvinyl chloride and polyolefin containers. No other systems have been tested and, therefore, no others can be recommended.
Dilution: EACH 5 mL OF SEPTRA I.V. INFUSION SHOULD BE ADDED TO 125 mL OF 5% DEXTROSE IN WATER.
NOTE: In those instances where fluid restriction is desirable, each 5 mL may be added to 75 mL of 5% dextrose in water. Under these circumstances the solution should be mixed just prior to use and should be administered within 2 hours. If upon visual inspection there is cloudiness or evidence of crystallization after mixing, the solution should be discarded and a fresh solution prepared.
DO NOT MIX SEPTRA I.V. INFUSION-5% DEXTROSE IN WATER WITH DRUGS OR SOLUTIONS IN THE SAME CONTAINER.
Administration: The solution should be given by intravenous infusion over a period of 60 to 90 minutes. Rapid infusion or bolus injections must be avoided. SEPTRA I.V. Infusion should not be given intramuscularly.
5-mL vials, containing 80 mg trimethoprim (16 mg/mL) and 400 mg sulfamethoxazole (80 mg/mL) for infusion with 5% dextrose in water. Contains benzyl alcohol (see ). Tray of 10 (NDC 61570-056-10).
10-mL multiple-dose vials, containing 160 mg trimethoprim (16 mg/mL) and 800 mg sulfamethoxazole (80 mg/mL) for infusion with 5% dextrose in water. Contains benzyl alcohol (see ). Tray of 10 (NDC 61570-054-10).
20-mL multiple-dose vials, containing 320 mg trimethoprim (16 mg/mL) and 1,600 mg sulfamethoxazole (80 mg/mL) for infusion with 5% dextrose in water. Contains benzyl alcohol (see ). Tray of 10 (NDC 61570-055-10).
Store at 15° to 25°C (59° to 77°F). DO NOT REFRIGERATE.
Also available in tablets containing 80 mg trimethoprim and 400 mg sulfamethoxazole (bottle of 100); DS (double strength) tablets containing 160 mg trimethoprim and 800 mg sulfamethoxazole (bottles of 100 and 250); and oral suspension containing 40 mg trimethoprim and 200 mg sulfamethoxazole in each 5 mL (pink, cherry-flavored: bottle of 1 pint [473 mL], 100 mL-package of 6; and purple, grape-flavored: bottle of 1 pint [473 mL]).
Distributed by: Monarch Pharmaceuticals, Inc., Bristol, TN 37620
Manufactured by: Catalytica Pharmaceuticals, Inc., Greenville, NC 27834
Rev. 1/98
595716