Sulfonamide is a functional group (a part of a molecule) that is the basis of several groups of drugs, which are called sulphonamides, sulfa drugs or sulpha drugs.The original antibacterial sulfonamides are synthetic (nonantibiotic) antimicrobial agents that contain the sulfonamide group. Sulfamethoxazole is metabolized in humans to at least 5 metabolites: the N4-acetyl-, N4-hydroxy-, 5-methylhydroxy-, N4-acetyl-5-methylhydroxy- sulfamethoxazole metabolites and an N-glucuronide conjugate. Clinical trials have confirmed its prophylactic and therapeutic utility in cases of toxoplasmosis. In an established infection, they will not eradicate the streptococcus and, therefore, will not prevent sequelae such as rheumatic fever. The average percentage of the dose recovered in urine from 0 to 72 hours after a single oral dose of sulfamethoxazole and trimethoprim is 84.5% for total sulfonamide and 66.8% for free trimethoprim. Do not take any medicine to treat diarrhea without first checking with your doctor. What dose of co-trimoxazole is used in a patient with a UTI? Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. Trimethoprim has been noted to impair phenylalanine metabolism but this is of no significance in phenylketonuric patients on appropriate dietary restriction. Acidification of the urine will increase renal elimination of trimethoprim. This interaction should be kept in mind when sulfamethoxazole and trimethoprim is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed. Using these medicines together may cause these medicines to not work as well for you. Sulfonamides can also displace methotrexate from plasma protein binding sites and can compete with the renal transport of methotrexate, thus increasing free methotrexate concentrations. In mice following oral administration of trimethoprim, no DNA damage in Comet assays of liver, kidney, lung, spleen, or bone marrow was recorded. Approximately 70% of sulfamethoxazole and 44% of trimethoprim are bound to plasma proteins. Nursing Mothers: Levels of trimethoprim/sulfamethoxazole in breast milk are approximately 2% to 5% of the recommended daily dose for infants over 2 months of age. Wrongly Prescribing Antibiotics Sets Dangerous Pattern, Sulfamethoxazole / trimethoprim systemic 800 mg / 160 mg (H 49). Sulfamethoxazole and trimethoprim have been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section. Evaluation for hyponatremia and appropriate correction is necessary in symptomatic patients to prevent life-threatening complications. Traveler’s Diarrhea in Adults: For the treatment of traveler’s diarrhea due to susceptible strains of enterotoxigenic E. coli. Sulfamethoxazole and trimethoprim is a synthetic antibacterial combination product available in DS (double strength) tablets, each containing 800 mg sulfamethoxazole, USP and 160 mg trimethoprim, USP; in tablets, each containing 400 mg sulfamethoxazole, USP and 80 mg trimethoprim, USP for oral administration. Indications & Usage INDICATIONS AND USAGE. Sulfamethoxazole and trimethoprim potentiates the effect of oral hypoglycemics that are metabolized by CYP2C8 (e.g., pioglitazone, repaglinide, and rosiglitazone) or CYP2C9 (e.g., glipizide and glyburide) or eliminated renally via OCT2 (e.g., metformin). Signs of acute overdosage with trimethoprim include nausea, vomiting, dizziness, headache, mental depression, confusion and bone marrow depression. [4], Its use in those less than 2 months of age is not recommended due to the risk of adverse side effects. The effects of trimethoprim causes a backlog of dihydrofolate (DHF) and this backlog can work against the inhibitory effect the drug has on tetrahydrofolate biosynthesis; this is where the sulfamethoxazole comes in, its role is in depleting the excess DHF by preventing it from being synthesised in the first place. They do not treat viral infections (e.g., the common cold). These may be symptoms of a serious liver problem. Talk with your doctor if you have black, tarry stools, bleeding gums, blood in urine or stools, pinpoint red spots on the skin, unusual bleeding or bruising. Peak blood levels for the individual components occur 1 to 4 hours after oral administration. 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. Trimethoprim is metabolized in vitro to 11 different metabolites, of which, five are glutathione adducts and six are oxidative metabolites, including the major metabolites, 1- and 3-oxides and the 3- and 4-hydroxy derivatives. 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. Susceptibility Testing. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides. In addition, periarteritis nodosa and systemic lupus erythematosus have been reported. [11] It may be effective in a variety of upper and lower respiratory tract infections, kidney and urinary tract infections, gastrointestinal tract infections, skin and wound infections, sepsis, and other infections caused by sensitive organisms. Clinical trials have confirmed its efficacy in this indication. Close monitoring of serum potassium is warranted in these patients. Detectable amounts of sulfamethoxazole and trimethoprim are present in the blood 24 hours after drug administration. However, if a patient develops skin rash or any sign of adverse reaction, therapy with sulfamethoxazole and trimethoprim should be reevaluated (see WARNINGS). No interference occurs, however, if methotrexate is measured by a radioimmunoassay (RIA). It has the following structural formula: Inactive Ingredients: Magnesium stearate, povidone, pregelatinized starch and sodium starch glycolate. Do not take other medicines unless they have been discussed with your doctor. It is a white to light yellow, odorless, bitter compound with a molecular weight of 290.3. It is very important that your doctor check the progress of you or your child at regular visits to make sure that this medicine is working properly. In vitro studies suggest that trimethoprim is a substrate of P-glycoprotein, OCT1 and OCT2, and that sulfamethoxazole is not a substrate of P-glycoprotein. [2][3] It may be used both to treat and prevent pneumocystis pneumonia and toxoplasmosis in people with HIV/AIDS and other causes of immunosuppression. Co-administration of sulfamethoxazole and trimethoprim and leucovorin should be avoided with P. jiroveci pneumonia (see WARNINGS). [33], It can be given by mouth, as a tablet or suspension, or intravenously.[2][70]. This medicine may cause serious allergic reactions, including anaphylaxis. Pyrexia, hematuria and crystalluria may be noted. Because of this, you may bleed or get infections more easily. Check with your doctor right away if you have dark urine, clay-colored stools, stomach pain, or yellow eyes or skin. 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. Any use of this site constitutes your agreement to the Terms and Conditions and Privacy Policy linked below. Precautions. Just five months previously, the Japanese firm Shionogi, had registered suphamethoxazole for exactly the same purposes and licensed its use to pharmaceutical super-giant Hoffmann-La-Roche. The steady-state mean plasma levels of free and total sulfamethoxazole were 57.4 mcg/mL and 68 mcg/mL, respectively. This medicine, especially if you are receiving high doses or for a long period of time, may lower the number of platelets in your body, which are necessary for proper blood clotting. Metabolic and Nutritional: Hyperkalemia, hyponatremia (see PRECAUTIONS: Electrolyte Abnormalities). In the literature, three cases of hyperkalemia in elderly patients have been reported after concomitant intake of sulfamethoxazole/trimethoprim and an angiotensin converting enzyme inhibitor6,7. 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 (SEE WARNINGS SECTION). Sulfamethoxazole, USP is N1-(5-methyl-3-isoxazolyl) sulfanilamide; the molecular formula is C10H11N3O3S. This site complies with the HONcode standard for trustworthy health information: verify here. While there are no large, well-controlled studies on the use of sulfamethoxazole and trimethoprim in pregnant women, Brumfitt and Pursell8, in a retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or sulfamethoxazole and trimethoprim. The incidence of side effects, particularly rash, fever, leukopenia and elevated aminotransferase (transaminase) values, with sulfamethoxazole and trimethoprim therapy in AIDS patients who are being treated for P. jiroveci pneumonia has been reported to be greatly increased compared with the incidence normally associated with the use of sulfamethoxazole and trimethoprim in non-AIDS patients. Lastly, outcome measures varied between studies, limiting cross-study comparisons. Last updated on Nov 1, 2019. Pharmacokinetic values for sulfamethoxazole in geriatric subjects were similar to those observed in young adult subjects. These studies, however, were limited by the small number of exposed cases and the lack of adjustment for multiple statistical comparisons and confounders. Patients who are “slow acetylators” may be more prone to idiosyncratic reactions to sulfonamides. It does this by competing with p-aminobenzoic acid (PABA) in the biosynthesis of dihydrofolate. Available for Android and iOS devices. Miscellaneous: Weakness, fatigue, insomnia. The total daily dose should not exceed 1600 mg sulfamethoxazole and 320 mg trimethoprim11. In glucose-6-phosphate dehydrogenase deficient individuals, hemolysis may occur. Genitourinary: Renal failure, interstitial nephritis, BUN and serum creatinine elevation, toxic nephrosis with oliguria and anuria, crystalluria and nephrotoxicity in association with cyclosporine. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. C. difficile produces toxins A and B which contribute to the development of CDAD. In those concurrently receiving certain diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported. Mayo Clinic College of Medicine and Science, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic School of Continuous Professional Development, Mayo Clinic School of Graduate Medical Education, Sulfamethoxazole And Trimethoprim (Oral Route), FREE book offer – Mayo Clinic Health Letter. Co-administration of trimethoprim-sulfamethoxazole and leucovorin during treatment of Pneumocystis jiroveci pneumonia should be avoided. Copyright © 2020 IBM Watson Health. If signs of bone marrow depression occur, the patient should be given leucovorin 5 to 15 mg daily until normal hematopoiesis is restored. Tetrahydrofolate is crucial in the synthesis of purines, thymidine, and methionine which are needed for the production of DNA and proteins[31] during bacterial replication. Mutagenesis: In vitro reverse mutation bacterial tests according to the standard protocol have not been performed with sulfamethoxazole and trimethoprim in combination. Available from: MEDLINE Complete, Ipswich, MA. These steady-state levels were achieved after three days of drug administration1. Cases of interactions with other OCT2 substrates, memantine and metformin, have also been reported. Sulfamethoxazole Trimethoprim Oral Suspension, Sulfamethoxazole and Trimethoprim Injection, Sulfamethoxazole and Trimethoprim Suspension. When administered together as sulfamethoxazole and trimethoprim, neither sulfamethoxazole nor trimethoprim affects the urinary excretion pattern of the other. Serum digoxin levels should be monitored. Use an effective form of birth control to keep from getting pregnant. Information is for End User's use only and may not be sold, redistributed or otherwise used for commercial purposes. This medicine may cause electrolyte problems, such as high potassium in the blood (hyperkalemia) and low sodium in the blood (hyponatremia). Trimethoprim/sulfamethoxazole (TMP/SMX), also known as co-trimoxazole among other names, is an antibiotic used to treat a variety of bacterial infections. Urinary Tract Infections and Shigellosis in Adults and Pediatric Patients, and Acute Otitis Media in Children. Caution should be exercised when sulfamethoxazole and trimethoprim is administered to a nursing woman, especially when breastfeeding, jaundiced, ill, stressed, or premature infants because of the potential risk of bilirubin displacement and kernicterus. Sulfamethoxazole and trimethoprim tablets are not indicated for prophylactic or prolonged administration in otitis media at any age. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. Complete blood counts should be done frequently in patients receiving sulfamethoxazole and trimethoprim; if a significant reduction in the count of any formed blood element is noted, sulfamethoxazole and trimethoprim should be discontinued. 4.2. The patient should be monitored with blood counts and appropriate blood chemistries, including electrolytes. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].