Use caution and monitor for hematologic toxicity during concurrent use. Moderate Concomitant use of trimethoprim and zidovudine may result in additive hematological abnormalities. Moderate Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment.
Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. Minor Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: Taking these drugs together may also increase risk for phototoxicity. Patients should limit sunlight and UV exposure, and follow proper precautions for sunscreens and protective clothing.
Patients at risk for hypoglycemia due to sulfonamides include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. Minor QT prolongation resulting in ventricular tachycardia and torsade de pointes TdP have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
Major QT prolongation resulting in ventricular tachycardia and torsade de pointes TdP have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include alfuzosin. Major Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics.
An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. Moderate Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary.
Hyperkalemia may be more significant in patients receiving IV trimethoprim. For those patients at higher risk of hyperkalemia e. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
Moderate It is possible that an increase in the exposure of pioglitazone may occur when coadministered with other drugs that inhibit CYP2C8 such as trimethoprim. Monitor for changes in glycemic control if trimethoprim is coadministered with pioglitazone. Moderate Use caution, administration of trimethoprim may result in increased serum concentrations of amantadine.
Amantadine is primarily excreted unchanged in the urine by both glomerular filtration and tubular secretion. The mechanism is not certain. Renal elimination of amantadine may be mediated in part by one or more organic cation transporters independent of OCT2. A single case of toxic delirium has been reported in the literature after coadministration of trimethoprim and amantadine.
The clinical significance to a wider population is not known. Major Trimethoprim has a potassium-sparing effect and may induce hyperkalemia, especially in patients with pre-existing risk factors for hyperkalemia e.
Patients, especially those with renal dysfunction, should be carefully monitored for hyperkalemia during concomitant use of potassium-sparing diuretics and trimethoprim. Moderate Aminobenzoate potassium should not be administered to patients taking sulfonamides or aminosalicylate sodium, aminosalicylic acid.
Bacteria preferentially absorb aminobenzoate potassium instead of the antibacterial agents, decreasing their efficacy. Aminosalicylate sodium, Aminosalicylic acid: Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include amiodarone. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tricyclic antidepressants.
Moderate Monitor for hyperkalemia if concomitant use of an angiotensin-converting enzyme ACE inhibitors and trimethoprim is necessary.
Hyperkalemia may be more signficant in patients receiving IV trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include clarithromycin. Major Torsades de pointes TdP and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy.
Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with anagrelide include sulfamethoxazole; trimethoprim. Angiotensin II receptor antagonists: Moderate QT prolongation resulting in ventricular tachycardia and torsade de pointes TdP have been reported during post-marketing use of sulfamethoxazole; trimethoprim.
Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia SVT , ventricular tachycardia, heart block, and premature ventricular contractions PVCs have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include apomorphine.
Minor Use caution if sulfamethoxazole and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of sulfamethoxazole. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. The effects of aprepitant on tolbutamide were not considered significant.
Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include aripiprazole. Major Avoid coadministration of sulfamethoxazole; trimethoprim and arsenic trioxide. QT prolongation resulting in ventricular tachycardia and torsade de pointes TdP have been reported during post-marketing use of sulfamethoxazole; trimethoprim.
If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. QT prolongation should be expected with the administration of arsenic trioxide. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include artemether.
Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include asenapine. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include atomoxetine. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of TdP. No difference was observed in atovaquone pharmacokinetics.
This may not be of any clinical significance but should be used with caution. Major Sulfonamides can crystallize in an acidic urine. Because methenamine salts produce an acidic urine, these agents should not be used concomitantly. Moderate Azathioprine may interact with other drugs that are myelosuppressive. Drugs that may affect the production of leukocytes, including sulfamethoxazole; trimethoprim, SMX-TMP, may lead to exaggerated leukopenia, especially in patients who have received a renal transplant.
Minor Folate antagonists, such as trimethoprim, especially when used in high doses or over a prolonged period, inhibit dihydrofolate reductase and thus may inhibit the action of folic acid, vitamin B9. Minor L-methylfolate and trimethoprim should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with trimethoprim.
Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. Major Due to a possible risk for QT prolongation and torsade de pointes TdP , azithromycin and sulfamethoxazole; trimethoprim should be used together cautiously. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
In addition, there have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include bedaquiline.
Moderate Rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine products. Examples of other drugs that can cause methemoglobinemia include the sulfonamides.
Therefore, caution is warranted when combining such medications with topical or oromucosal benzocaine products. Patients using OTC benzocaine gels and liquids should be advised to seek immediate medical attention if signs or symptoms of methemoglobinemia develop. In addition, clinicians should closely monitor patients for the development of methemoglobinemia when benzocaine sprays are used during a procedure. Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: Major Potential QT prolongation has been reported in limited case reports with metronidazole; therefore, it should be used cautiously when adminstered with sulfamethoxazole; trimethoprim, which has a possible risk for QT prolongation and TdP.
Also, medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Bismuth Subsalicylate; Metronidazole; Tetracycline: Moderate Close clinical monitoring is advised when administering sulfamethoxazole with boceprevir due to an increased potential for sulfamethoxazole-related adverse events.
If sulfamethoxazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of sulfamethoxazole. Sulfamethoxazole is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated sulfamethoxazole plasma concentrations.
Moderate Sulfamethoxazole potently inhibits CYP2C9 and may theoretically lead to elevated plasma concentrations of bosentan when coadministered. Monitor for potential adverse effects of bosentan during coadministration.
Excessive bosentan dosage may result in hypotension or elevated hepatic enzymes. Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications e. Buprenorphine has also been associated with QT prolongation and has a possible risk of torsade de pointes TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
Moderate Use caution if coadministration of capecitabine with sulfamethoxazole is necessary, and monitor for an increase in sulfamethoxazole-related adverse reactions.
Megaloblastic anemia can occur when sulfamethoxazole; trimethoprim, SMX-TMP is used in patients who are taking other folate antagonists. These agents include carbamazepine. If these agents are used concomitantly, close observation of blood counts is warranted. Major Avoid coadministration of ceritinib with sulfamethoxazole due to increased sulfamethoxazole exposure; additive QT prolongation may also occur. If coadministration is unavoidable, monitor for sulfamethoxazole-related adverse reactions.
Periodically monitor electrolytes and ECGs; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Sulfamethoxazole is primarily metabolized by CYP2C9; QT prolongation resulting in ventricular tachycardia and torsade de pointes TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
These agents include chloramphenicol. Para-aminobenzoic acid, PABA, in turn, antagonizes the effects of sulfonamides.
Thus, ester-type local anesthetics should not be used in patients receiving sulfonamides. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include chloroquine. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include chlorpromazine.
Choline Salicylate; Magnesium Salicylate: Moderate Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include ciprofloxacin. Severe QT prolongation and ventricular arrhythmias, including torsade de pointes TdP and death, have been reported with cisapride.
QT prolongation resulting in ventricular tachycardia and TdP have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Because of the potential for TdP, concurrent use is contraindicated. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include citalopram.
Citric Acid; Potassium Citrate: Thus, clopidogrel could increase plasma concentrations of drugs metabolized by this isoenzyme, such as sulfamethoxazole. Although there are no in vivo data with which to predict the magnitude or clinical significance of this potential interaction, caution should be used when sulfamethoxazole is coadministered with clopidogrel. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include clozapine.
Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: Moderate Caution is warranted when elvitegravir is administered with sulfamethoxazole; trimethoprim, SMX-TMP as there is a potential for decreased sulfamethoxazole concentrations. Moderate Promethazine carries a possible risk of QT prolongation. Major Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with sulfamethoxazole; trimethoprim. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs.
Crizotinib has been associated with concentration-dependent QT prolongation. QT prolongation resulting in ventricular tachycardia and torsade de pointes TdP has also been reported during postmarketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include cyclobenzaprine.
Major Avoid the concomitant use of sulfamethoxazole; trimethoprim and cyclosporine. There have been reports of significant, but reversible nephrotoxicity with coadministration in renal transplant patients.
In addition, there are case reports of reduced exposure to cyclosporine in patients receiving concomitant sulfonamides. Monitor renal function and cyclosporine concentrations if concomitant use is required.
Major Agranulocytosis has been reported in the second to third month of weekly concomitant treatment with dapsone and other hemolytic agents such as folic acid antagonists e. These combinations increase the likelihood of adverse hematologic events.
Concurrent administration of dapsone with trimethoprim increases the plasma concentrations of both drugs. The efficacy of dapsone is increased, which may provide a therapeutic advantage in the treatment of Pneumocystis pneumonia; however, an increase in the frequency and severity of dapsone toxicity methemoglobinemia, hemolytic anemia also has been noted. Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: However, the Cmax of trimethoprim and sulfamethoxazole was not affected.
In addition, both ritonavir and sulfamethoxazole; trimethoprim are associated with QT prolongation; concomitant use increases the risk of QT prolongation. Minor According to the manufacturer, no dosage adjustments are required when trimethoprim is administered with dasabuvir; ombitasvir; paritaprevir; ritonavir; however, use of these drugs together may result in elevated dasabuvir plasma concentrations. Trimethoprim inhibits CYP2C8, an enzyme primarily responsible for the metabolism of dasabuvir.
Caution and close monitoring are advised if these drugs are administered together. Major Monitor for evidence of QT prolongation and torsade de pointes TdP during concurrent use of dasatinib and sulfamethoxazole; trimethoprim.
In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include degarelix.
Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include halogenated anesthetics. Clinically relevant QTc prolongation may occur with deutetrabenazine. QT prolongation resulting in ventricular tachycardia and torsade de pointes TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include quinidine. Moderate Anti-infectives that disrupt the normal GI flora, including sulfonamides, may potentially decrease the effectiveness of estrogen-containing oral contraceptives.
Moderate It would be prudent to recommend alternative or additional contraception when oral contraceptives OCs are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora.
One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported.
It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use.
Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives.
These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances.
Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries e. Major Because both trimethoprim and digoxin undergo tubular secretion, trimethoprim can interfere with the renal tubular secretion of digoxin when administered concomitantly. Similar changes were not noted in a single-dose study of young healthy volunteers. Patients receiving digoxin, especially the elderly, should be monitored carefully for digoxin toxicity if trimethoprim is added.
Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include disopyramide. Major The ingestion of ethanol by patients receiving disulfiram causes an extremely unpleasant reaction that can last from 30 minutes to several hours.
Intravenous sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole contains ethanol and should not be co-administered with disulfiram. This reaction would not be expected to occur with oral sulfamethoxazole; trimethoprim.
Severe The concurrent use of dofetilide with trimethoprim alone or in combination with sulfamethoxazole is contraindicated. Trimethoprim is an inhibitor of renal cationic secretion and decreases the renal tubular secretion of dofetilide.
Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include dolasetron. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include rilpivirine. Major Case reports indicate that QT prolongation and torsade de pointes TdP can occur during donepezil therapy.
Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Moderate Cationic drugs that are eliminated by renal tubular secretion, such as trimethoprim, may decrease memantine elimination by competing for common renal tubular transport systems. Moderate Cytochrome P enzyme inhibitors, such as sulfamethoxazole, may inhibit the hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
Major Use caution if coadministration of dronabinol with sulfamethoxazole is necessary, and monitor for an increase in dronabinol-related adverse reactions e. Concomitant use may result in elevated plasma concentrations of dronabinol. Severe The concomitant use of dronedarone with other drugs that prolong the QTc and that may induce torsade de pointes TdP is contraindicated.
QT prolongation resulting in ventricular tachycardia and torsade de pointes TdP have been reported during post-marketing use of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of mg twice daily the FDA-approved dose and up to 25 milliseconds at doses of mg twice daily.
Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Additionally, dronedarone is metabolized by and is an inhibitor of CYP3A.
Sulfamethoxazole is a substrate for CYP3A4. The concomitant administration of dronedarone and sulfamethoxazole may result in increased exposure of sulfamethoxazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include droperidol. Drospirenone; Ethinyl Estradiol; Levomefolate: Major Coadministration of efavirenz and sulfamethoxazole; trimethoprim may increase the risk for QT prolongation and torsade de pointes TdP.
QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP.
QT prolongation resulting in ventricular tachycardia and TdP has been reported during post-marketing use of sulfamethoxazole; trimethoprim. Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: Drugs with a possible risk for QT prolongation and torsade de pointes TdP that should be used cautiously and with close monitoring with eliglustat include sulfamethoxazole; trimethoprim, SMX-TMP.
The significance of administering inhibitors of CYP2C8, such as trimethoprim, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: Major Avoid coadministration of encorafenib and sulfamethoxazole; trimethoprim due to the potential for additive QT prolongation. Encorafenib is associated with dose-dependent prolongation of the QT interval. Moderate Both entecavir and trimethoprim are secreted by active tubular secretion. In theory, coadministration of entecavir with trimethoprim may increase the serum concentrations of either drug due to competition for the drug elimination pathway.
Moderate Monitor for decreased efficacy of sulfamethoxazole if coadministration with enzalutamide is necessary. Concomitant use may decrease sulfamethoxazole plasma concentrations. Major Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia.
Serum digoxin levels should be monitored. Increased sulfamethoxazole blood levels may occur in patients who are also receiving indomethacin. Occasional reports suggest that patients receiving pyrimethamine as malaria prophylaxis in doses exceeding 25 mg weekly may develop megaloblastic anemia if BACTRIM is prescribed. Additional monitoring of blood glucose may be warranted.
Cases of interactions with other OCT2 substrates, memantine and metformin, have also been reported. 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. Carcinogenesis, Mutagenesis, Impairment of Fertility: In vitro reverse mutation bacterial tests according to the standard protocol have not been performed with sulfamethoxazole and trimethoprim in combination. Observations of leukocytes obtained from patients treated with sulfamethoxazole and trimethoprim revealed no chromosomal abnormalities.
Sulfamethoxazole alone was positive in an in vitro reverse mutation bacterial assay and in in vitro micronucleus assays using cultured human lymphocytes. Trimethoprim alone was negative in in vitro reverse mutation bacterial assays and in in vitro chromosomal aberration assays with Chinese Hamster ovary or lung cells with or without S9 activation.
In in vitro Comet, micronucleus and chromosomal damage assays using cultured human lymphocytes, trimethoprim was positive. In mice following oral administration of trimethoprim, no DNA damage in Comet assays of liver, kidney, lung, spleen, or bone marrow was recorded.
While there are no large, well-controlled studies on the use of sulfamethoxazole and trimethoprim in pregnant women, Brumfitt and Pursell,10 in a retrospective study, reported the outcome of pregnancies during which the mother received either placebo or sulfamethoxazole and trimethoprim. The incidence of congenital abnormalities was 4. 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 sulfamethoxazole and trimethoprim at the time of conception or shortly thereafter. Because sulfamethoxazole and trimethoprim may interfere with folic acid metabolism, BACTRIM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
These studies, however, were limited by the small number of exposed cases and the lack of adjustment for multiple statistical comparisons and confounders. These studies are further limited by recall, selection, and information biases, and by limited generalizability of their findings.
Lastly, outcome measures varied between studies, limiting cross-study comparisons. These doses are approximately 5 and 6 times the recommended human total daily dose on a body surface area basis. In some rabbit studies, an overall increase in fetal loss dead and resorbed conceptuses was associated with doses of trimethoprim 6 times the human therapeutic dose based on body surface area. Caution should be exercised when BACTRIM 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.
Clinical studies of BACTRIM 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. In those concurrently receiving certain diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported.
Hematological changes indicative of folic acid deficiency may occur in elderly patients. The trimethoprim component of BACTRIM 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. Bactrim Tablets contain 1. Bactrim DS Tablets contain 3. Pharmacokinetics parameters for sulfamethoxazole were similar for geriatric subjects and younger adult subjects.
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. 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 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. When administered together, neither sulfamethoxazole nor trimethoprim affects the urinary excretion pattern of the other. Both sulfamethoxazole and trimethoprim distribute to sputum and vaginal fluid; trimethoprim also distributes to bronchial secretions, and both pass the placental barrier and are excreted in breast 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, this combination 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 this combination than with either sulfamethoxazole or trimethoprim alone. In vitro serial dilution tests have shown that the spectrum of antibacterial activity of sulfamethoxazole and trimethoprim injection 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.
Coadministration may increase the risk for QT prolongation. Monitor serum potassium levels in patients with risk factors for developing drug-induced hyperkalemia renal impairment, elderly, high-dose trimethoprim. Additionally, propylene glycol toxicity may result in acute kidney injury, CNS toxicity, and multi-organ failure. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. Dosage adjustments may be necessary in patients with hepatic impairment, however, specific dosage adjustment guidelines how not available. Moderate The half-life of phenytoin may be increased when trimethoprim is given concurrently with phenytoin, how many mg is bactrim. Hydroxychloroquine increases the QT interval and should not be administered with other erythromycin reviews for rosacea known to prolong the QT interval. Moderate Androgen deprivation therapy e. Cases of interactions with other OCT2 substrates, memantine and metformin, have also been reported. Severe The concomitant use of dronedarone with other drugs that prolong the QTc and that may induce torsade de pointes TdP is contraindicated. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. Drugs with a possible risk for QT bactrim and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include prochlorperazine. Moderate Caution is advised with the concomitant use of tamoxifen and sulfamethoxazole; trimethoprim due to an increased risk of How prolongation and torsade de pointes TdP. Prescribing this drug in the how of a proven, or strongly suspected, susceptible bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the many of the development of drug-resistant bacteria antimicrobial resistance. For Patients With Impaired Renal Function When renal function is impaired, bactrim reduced dosage should be employed using the following table: Moderate Rare and sometimes fatal many of methemoglobinemia have been reported tramadol 100 overnight the use of topical or oromucosal benzocaine products, how many mg is bactrim. Urine many of both bactrim and trimethoprim are considerably higher than are the concentrations in the blood.
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