Septra (sulfamethoxazole/trimethoprim) Disease Interactions

There are 12 disease interactions with Septra (sulfamethoxazole/trimethoprim):

Colitis Hematologic Toxicity Hypersensitivity Reactions Liver Disease Porphyria Renal Dysfunction

Folate Deficiency Crystalluria Hemodialysis Urinary Obstruction Dialysis Renal Dysfunction

Pseudomembranous colitis has been reported with most antibacterial agents and may range in severity from mild to life-threatening, with an onset of up to several weeks following cessation of therapy. Antibiotic therapy can alter the normal flora of the colon and permit overgrowth of Clostridium difficile, whose toxin is believed to be a primary cause of antibiotic-associated colitis. The colitis is usually characterized by severe, persistent diarrhea and severe abdominal cramps, and may be associated with the passage of blood and mucus. The most common culprits are clindamycin, lincomycin, the aminopenicillins (amoxicillin, ampicillin), and the cephalosporins. Therapy with broad-spectrum antibiotics and other agents with significant antibacterial activity should be administered cautiously in patients with a history of gastrointestinal diseases, particularly colitis. There is some evidence that pseudomembranous colitis, if it occurs, may run a more severe course in these patients and that it may be associated with flares in their underlying disease activity. The offending antibiotic(s) should be discontinued if significant diarrhea occurs during therapy. Stool cultures for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically. A large bowel endoscopy may be considered to establish a definitive diagnosis in cases of severe diarrhea.

The use of sulfonamides has been associated with hematologic toxicity, including methemoglobinemia, sulfhemoglobinemia, leukopenia, granulocytopenia, eosinophilia, hemolytic anemia, aplastic anemia, purpura, clotting disorder, thrombocytopenia, hypofibrinogenemia, and hypoprothrombinemia. Acute dose-related hemolytic anemia may occur during the first week of therapy due to sensitization or glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, while chronic hemolytic anemia may occur with prolonged use. Therapy with sulfonamides should be administered cautiously in patients with preexisting blood dyscrasias or bone marrow suppression. Complete blood counts should be obtained regularly, especially during prolonged therapy (>2 weeks), and patients should be instructed to immediately report any signs or symptoms suggestive of blood dyscrasia such as fever, sore throat, local infection, bleeding, pallor, dizziness, or jaundice.

The use of sulfonamides is associated with large increases in the risk of Stevens-Johnson syndrome, toxic epidermal necrolysis and other serious dermatologic reactions, although these phenomena are rare as a whole. Hepatitis, pneumonitis, and interstitial nephritis have also occurred in association with sulfonamide hypersensitivity. Therapy with sulfonamides should be administered cautiously in patients with severe allergies, bronchial asthma or AIDS, since these patients may be at increased risk for potentially severe hypersensitivity reactions. Patients should be instructed to promptly report signs and symptoms that may precede the onset of cutaneous manifestations of the Stevens-Johnson syndrome, such as high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balantitis. Sulfonamide therapy should be stopped at once if a rash develops.

Hepatotoxicity, including jaundice, diffuse hepatocellular necrosis, hypersensitivity hepatitis and hepatic failure, has rarely been reported in patients receiving sulfonamides. In addition, sulfonamides are partially metabolized by the liver and may accumulate in patients with hepatic impairment. Therapy with sulfonamides should be administered cautiously in patients with liver disease.

The use of sulfonamides is contraindicated in patients with porphyria, since these drugs can precipitate an acute attack.

Sulfonamides and their metabolites are eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from sulfonamides due to decreased drug clearance. Dosage adjustments may be necessary and modifications should be based on the degree of renal impairment and severity of infection. Additionally, sulfonamides may cause renal toxicity secondary to crystalluria, including uro- and nephrolithiasis, nephritis, toxic nephrosis, hematuria, proteinuria, and elevated BUN and creatinine. Hydration (8 oz. glass of water with each dose and throughout the day) and adequate urinary output (> 1.5 L/day) should be maintained during sulfonamide administration. Renal function tests and urinalysis should be performed weekly or as often as indicated by the patient's status. Rarely, alkalinization of the urine is necessary.

The use of trimethoprim is contraindicated in patients with documented megaloblastic anemia due to folate deficiency. Trimethoprim inhibits dihydrofolate reductase, an enzyme necessary in the synthesis of tetrahydrofolic acid, or the metabolically active form of folic acid. Thrombocytopenia, neutropenia, megaloblastic anemia, and methemoglobinemia have been reported rarely. However, the risk is increased in the presence of folate deficiency, chronic hemolytic anemia and/or renal impairment, as well as during prolonged therapy (e.g., > 6 months) with high dosages. Therapy with trimethoprim should be administered cautiously under these conditions and in patients with suspected folate depletion (e.g., elderly, alcoholic, malnourished or debilitated patients). Folic acid supplementation, if necessary, may be administered concomitantly without interfering with the antibacterial action of trimethoprim. Patients should be instructed to immediately report any signs or symptoms suggestive of hematologic toxicity such as fever, sore throat, local infection, bleeding, pallor, dizziness, or jaundice. Leucovorin (folinic acid) should be administered if bone marrow depression is detected.

Crystalluria can occur during sulfonamide therapy due to precipitation of the sulfonamide and/or its N4-acetyl metabolite in the urinary tract. Renal toxicity such as uro- and nephrolithiasis, nephritis, toxic nephrosis, hematuria, proteinuria, and elevated BUN and creatinine has been reported. Hydration (8 oz. glass of water with each dose and throughout the day) and adequate urinary output (> 1.5 L/day) should be maintained during sulfonamide administration. Patients who are dehydrated (e.g., due to severe diarrhea or vomiting) may be at increased risk for the development of crystalluria and lithiasis and should be encouraged to consume additional amounts of liquid or given intravenous fluid. Renal function tests and urinalysis should be performed weekly during prolonged therapy (> 2 weeks). Rarely, alkalinization of the urine is necessary.

The sulfonamides, sulfadiazine, sulfamethoxazole, and sulfisoxazole, are partially removed by hemodialysis and should be administered after dialysis.

Sulfonamides are excreted and concentrated in the urine. Therapy with sulfonamides should be administered cautiously in patients with urinary obstruction or retention, since excessive drug accumulation may occur. These patients may also be at increased risk for sulfonamide crystalluria, which may be associated with renal toxicity such as uro- and nephrolithiasis, nephritis, toxic nephrosis, hematuria, proteinuria, and elevated BUN and creatinine. A urinary output of at least 1.5 L/day should be maintained during sulfonamide administration. Renal function tests and urinalysis should be performed weekly, especially during prolonged therapy (> 2 weeks).

Trimethoprim is moderately removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.

Trimethoprim is primarily eliminated by the kidney. The serum concentration of trimethoprim may be increased and the half-life prolonged in patients with impaired renal function. Dosage adjustments may be necessary and modifications should be based on the degree of renal impairment as well as severity of infection. The manufacturers recommend a dosage of 50 mg every 12 hours in patients with creatinine clearance between 15 to 30 mL/min and not using the drug in patients with creatinine clearance below 15 mL/min.

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Septra (sulfamethoxazole/trimethoprim) drug Interactions

There are 198 drug interactions with Septra (sulfamethoxazole/trimethoprim)

Septra (sulfamethoxazole/trimethoprim) food/lifestyle Interactions

There is 1 food/lifestyle interaction with Septra (sulfamethoxazole/trimethoprim)

See also...

• Septra (sulfamethoxazole/trimethoprim) Side Effects
• Septra (sulfamethoxazole/trimethoprim) Consumer Information

• Drug Interactions Checker

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