Septra Information
Septra (Sulfamethoxazole)
Septra (Sulfamethoxazole) Description
Septra (Sulfamethoxazole) (trimethoprim and sulfamethoxazole) is a synthetic antibacterial combination product. Each Septra (Sulfamethoxazole) Tablet contains 80 mg trimethoprim and 400 mg sulfamethoxazole and the inactive ingredients docusate sodium (0.4 mg per tablet), FD&C Red No. 40, magnesium stearate, povidone, and sodium starch glycolate.
Each Septra (Sulfamethoxazole) DS (double strength) Tablet contains 160 mg trimethoprim and 800 mg sulfamethoxazole and the inactive ingredients docusate sodium (0.8 mg per tablet), FD&C Red No. 40, magnesium stearate, povidone, and sodium starch glycolate.
Each teaspoonful (5 mL) of Septra (Sulfamethoxazole) Suspension contains 40 mg trimethoprim and 200 mg sulfamethoxazole and the inactive ingredients alcohol 0.26%, methylparaben 0.1% and sodium benzoate 0.1% (added as preservatives), carboxymethylcellulose sodium, citric acid, FD&C Red No. 40 and Yellow No. 6, flavor, glycerin, microcrystalline cellulose, polysorbate 80, saccharin sodium, and sorbitol. Each teaspoonful (5 mL) of Septra (Sulfamethoxazole) Grape Suspension contains 40 mg trimethoprim and 200 mg sulfamethoxazole and the inactive ingredients alcohol 0.26%, methylparaben 0.1%, and sodium benzoate 0.1% (added as preservatives), carboxymethylcellulose sodium, citric acid, FD&C Red No. 40 and Blue No. 1, flavor, glycerin, microcrystalline cellulose, polysorbate 80, saccharin sodium, and sorbitol. Both tablet and suspension forms are for oral administration.
Trimethoprim is 5-[(3,4,5-trimeth-oxyphenyl)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 CHNO. 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 CHNOS. The structural formula is:
Septra (Sulfamethoxazole) Clinical Pharmacology
Septra (Sulfamethoxazole) is rapidly absorbed following oral administration. Both sulfamethoxazole and trimethoprim 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-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 sulfamethoxazole and trimethoprim 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.
Peak blood levels for the individual components occur 1 to 4 hours after oral administration. The mean serum half-lives of sulfamethoxazole and trimethoprim are 10 and 8 to 10 hours, respectively. However, patients with severely impaired renal function exhibit an increase in the half-lives of both components, requiring dosage regimen adjustment (see ). Detectable amounts of trimethoprim and sulfamethoxazole are present in the blood 24 hours after drug administration. During administration of 160 mg trimethoprim and 800 mg sulfamethoxazole b.i.d., the mean steady-state plasma concentration of trimethoprim was 1.72 mcg/mL. The steady-state minimal plasma levels of free and total sulfamethoxazole were 57.4 mcg/mL and 68.0 mcg/mL, respectively. These steady-state levels were achieved after 3 days of drug administration.
Excretion of sulfamethoxazole and trimethoprim is primarily by the kidneys through both glomerular filtration and tubular secretion. Urine concentrations of both sulfamethoxazole and trimethoprim are considerably higher than are the concentrations in the blood. The average percentage of the dose recovered in urine from 0 to 72 hours after a single oral dose is 84.5% for total sulfonamide and 66.8% for free trimethoprim. Thirty percent of the total sulfonamide is excreted as free sulfamethoxazole, with the remaining as N-acetylated metabolite. When administered together as Septra (Sulfamethoxazole) , neither sulfamethoxazole nor trimethoprim affects the urinary excretion pattern of the other.
Both trimethoprim and sulfamethoxazole distribute to sputum, vaginal fluid, and middle ear fluid; trimethoprim also distributes to bronchial secretions, and both pass the placental barrier and are excreted in human milk.
Septra (Sulfamethoxazole) Indications And Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Septra (Sulfamethoxazole) and other antibacterial drugs, Septra (Sulfamethoxazole) 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 the empiric selection of therapy.
Septra (Sulfamethoxazole) Contraindications
Septra (Sulfamethoxazole) is contraindicated in patients with a known hypersensitivity to trimethoprim or sulfonamides and in patients with documented megaloblastic anemia due to folate deficiency. Septra (Sulfamethoxazole) 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 (Sulfamethoxazole) is contraindicated in pediatric patients less than 2 months of age.
Septra (Sulfamethoxazole) Warnings
Clinical signs, such as rash, sore throat, fever, arthralgia, pallor, purpura, or jaundice may be early indications of serious reactions.
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.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of 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 may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of , and surgical evaluation should be instituted as clinically indicated.
Septra (Sulfamethoxazole) Precautions
Prescribing Septra (Sulfamethoxazole) 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.
Septra (Sulfamethoxazole) 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 (see and ).
The incidence of side effects, particularly rash, fever, leukopenia, and elevated aminotransferase (transaminase) values in AIDS patients who are being treated with Septra (Sulfamethoxazole) for pneumonia has been reported to be greatly increased compared with the incidence normally associated with the use of Septra (Sulfamethoxazole) in non-AIDS patients. The incidence of hyperkalemia and hyponatremia appears to be increased in AIDS patients receiving Septra (Sulfamethoxazole) . Adverse effects are generally less severe in patients receiving Septra (Sulfamethoxazole) for prophylaxis. A history of mild intolerance to Septra (Sulfamethoxazole) in AIDS patients does not appear to predict intolerance of subsequent secondary prophylaxis. However, if a patient develops skin rash or any sign of adverse reaction, therapy with Septra (Sulfamethoxazole) should be re-evaluated (see ).
The concomitant use of leucovorin with trimethoprim-sulfamethoxazole for the acute treatment of pneumonia in patients with HIV infection was associated with increased rates of treatment failure and morbidity in a placebo-controlled study.
Patients should be counseled that antibacterial drugs including Septra (Sulfamethoxazole) should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Septra (Sulfamethoxazole) is 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 with Septra (Sulfamethoxazole) 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.
In elderly patients concurrently receiving certain diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported. In the literature, two cases of hyperkalemia in elderly patients have been reported after concomitant intake of trimethoprim/sulfamethoxazole and an angiotensin converting enzyme inhibitor.
It has been reported that Septra (Sulfamethoxazole) may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin. This interaction should be kept in mind when Septra (Sulfamethoxazole) is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed.
Septra (Sulfamethoxazole) may inhibit the hepatic metabolism of phenytoin. Septra (Sulfamethoxazole) , 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.
Septra (Sulfamethoxazole) , 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 overestimations of about 10% in the range of normal values.
Carcinogenesis:
Mutagenesis:
Impairment of Fertility:
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, in a retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or 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 (Sulfamethoxazole) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Clinical studies of Septra (Sulfamethoxazole) 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 and 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 Septra (Sulfamethoxazole) 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 section). The trimethoprim component of Septra (Sulfamethoxazole) 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 Septra (Sulfamethoxazole) treatment is recommended to help lower potassium serum levels. Septra (Sulfamethoxazole) Tablets contain 1.8 mg (0.08 mEq) of sodium per tablet. Septra (Sulfamethoxazole) 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 trimpethoprim was lower in geriatric subjects compared with younger subjects (see : ).
Septra (Sulfamethoxazole) Adverse Reactions
The most common adverse effects are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash and urticaria).
Septra (Sulfamethoxazole) Overdosage
The amount of a single dose of Septra (Sulfamethoxazole) 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 trimethoprim and sulfamethoxazole.
Septra (Sulfamethoxazole) Dosage And Administration
Contraindicated in pediatric patients less than 2 months of age.
For the lower limit dose (15 mg/kg trimethoprim and 75 mg/kg sulfamethoxazole per 24 hours) administer 75% of the dose in the above table.
Septra (Sulfamethoxazole) How Supplied
Tablets should be stored at 15° to 25°C (59° to 77°F) in a dry place and protected from light.
Suspensions should be stored at 15° to 25°C (59° to 77°F) and protected from light.
Septra (Sulfamethoxazole) References
Rx Only.
Prescribing Information as of March 2007.
Distributed by: Monarch Pharmaceuticals, Inc., Bristol, TN 37620
(A wholly owned subsidiary of King Pharmaceuticals, Inc.)
Manufactured by: King Pharmaceuticals, Inc., Bristol, TN 37620
Septra (Sulfamethoxazole) Labelgraphics
Septra (Sulfamethoxazole) Labelgraphics
Septra (Sulfamethoxazole) Labelgraphics
Septra (Sulfamethoxazole) Labelgraphics
