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.
BACTRIM SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE OF SKIN RASH OR ANY SIGN OF ADVERSE REACTION. Clinical signs, such as rash, sore throat, fever, arthralgia, cough, shortness of breath, pallor, purpura or jaundice may be early indications of serious reactions. In rare instances a skin rash may be followed by more severe reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis or serious blood disorder. Complete blood counts should be done frequently in patients receiving sulfonamides.
BACTRIM SHOULD NOT BE USED IN THE TREATMENT OF STREPTOCOCCAL PHARYNGITIS. Clinical studies have documented that patients with group A (beta)-hemolytic streptococcal tonsillopharyngitis have a greater incidence of bacteriologic failure when treated with Bactrim than do those patients treated with penicillin, as evidenced by failure to eradicate this organism from the tonsillopharyngeal area.
Bactrim IV Infusion 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.
PRECAUTIONS
General: Bactrim should be given with caution to patients with impaired renal or hepatic function, to those with possible folate deficiency (eg, 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 doserelated.
Local irritation and inflammation due to extravascular infiltration of the infusion have been observed with Bactrim IV 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, eg, impaired kidney and/or liver function, or concomitant use of other drugs. Severe skin reactions, generalized bone marrow suppression (see WARNINGS and ADVERSE REACTIONS sections) 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 section). Use in the Treatment of 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.
Laboratory Tests: Appropriate culture and susceptibility studies should be performed before and throughout treatment. 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.
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, thus increasing free methotrexate concentrations.
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 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:
Carcinogenesis: Long-term studies in animals to evaluate carcinogenic potential have not been conducted with Bactrim IV Infusion. 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 cultured in vitro with sulfamethoxazole and trimethoprim alone or in combination; the concentrations used exceeded blood levels of these compounds following therapy with Bactrim. Observations of leukocytes obtained from patients treated with Bactrim revealed no chromosomal abnormalities. Impairment of Fertility: Bactrim IV 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 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 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, Bactrim IV 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: Bactrim IV Infusion is not recommended for infants younger than two months of age (see CONTRAINDICATIONS section).
INFORMATION FOR PATIENTS
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