Sulfadiazine is an oral, intermediate-duration sulfonamide antibiotic. It is used in combination with pyrimethamine for the treatment of toxoplasmosis. Sulfadiazine is also occassionally used to treat other infections due to susceptible organisms. This drug is poorly soluble in urine and causes crystalluria more often than other sulfonamides. For this reason and because of previous problems with drug supply, sulfadiazine use is generally limited to serious infections. Sulfadiazine was approved by the FDA in 1941.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-NOTE: Wide variations in blood concentrations of sulfadiazine may occur with identical doses. The manufacturer recommends monitoring of sulfadiazine concentrations in patients with serious infections. Free sulfadiazine concentrations of 50-150 mcg/ml may be considered therapeutic for most infections and blood concentrations of 120-150 mcg/ml may be considered optimal for serious infections. Blood concentrations should generally not exceed 200 mcg/ml, since adverse reactions occur more frequently above this level.
Route-Specific Administration
Oral Administration
-Sulfadiazine is administered orally. May be administered without regard to meals.
-Fluid intake should be adequate enough to maintain a urine output of at least 1200-1500 ml/day in adults.
Numerous adverse reactions to sulfadiazine have been reported, although the incidence of many of these adverse reactions is not well documented. All sulfonamides are known to cause allergic reactions, some of which can be serious. Some of the serious allergic manifestations reported with sulfadiazine include Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, exfoliative dermatitis, allergic myocarditis, and anaphylactoid reactions. Less severe dermatologic reactions associated with sulfadiazine use include generalized skin eruptions, urticaria, photosensitivity, pruritus, and purpura. Other hypersensitivity reactions include periorbital edema, conjunctival injection, and scleral injection.
Sulfadiazine may crystallize in concentrated acidic urine, especially in patients with impaired renal function or in dehydrated patients. Compared with many newer sulfonamides, sulfadiazine is less soluble and more likely to crystallize in urine. Crystalluria can lead to acute renal failure due to renal tubular obstruction. Adequate fluid intake can help to minimize crystalluria and the subsequent development of renal failure. Nephrolithiasis, toxic nephrosis with anuria and oliguria; periarteritis nodosa, and lupus-like symptoms have also been reported with sulfadiazine.
Sulfadiazine and other sulfonamides have chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides), and oral hypoglycemic agents. It is possible that cross-sensitivity exists with these agents. Goiter production, diuresis, and hypoglycemia have occurred rarely in patients receiving sulfonamides.
Sulfadiazine and other sulfonamides have been associated with the development of potentially fatal blood dyscrasias, including agranulocytosis, aplastic anemia, hypoprothrombinemia, thrombocytopenia, leukopenia, and hemolytic anemia. Hemolysis may occur in individuals with glucose-6-phosphate dehydrogenase deficiency. This reaction appears to be dose-related. Complete blood counts should be monitored and the drug discontinued if significant bone hematologic abnormalities are documented.
A serious, but infrequent adverse effect of sulfadiazine is methemoglobinemia. This effect is seen as pale skin, bluish fingernails or lips, difficulty in breathing, fever, sore throat, tiredness, and bruising. Sulfadiazine should be discontinued in patients who manifest this syndrome.
Gastrointestinal adverse effects reported with sulfadiazine include hepatitis, abdominal pain, anorexia, diarrhea, nausea, vomiting, pancreatitis, and stomatitis.
Sulfadiazine-induced CNS effects include ataxia, depression, hallucinations, headache, insomnia, peripheral neuropathy/neuritis, seizures, tinnitus, and vertigo.
Serum sickness, arthralgia,drug fever, and chills have been reported with sulfadiazine and may be related to hypersensitivity reactions. Drug fever often develops 7-10 days after initiation of the sulfonamide.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with sulfadiazine. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate.
Due to the potential for the development of kernicterus, sulfadiazine use is contraindicated in neonates and infants less than 2 months of age, except as adjunctive therapy with pyrimethamine for the treatment of congenital toxoplasmosis. Premature infants may be especially prone to the development of hyperbilirubinemia and/or kernicterus. Sulfonamides compete with bilirubin for binding to plasma albumin. In utero, free bilirubin is cleared by the placental circulation; but after birth, this mechanism for removal of unbound bilirubin is no longer available. Unbound bilirubin can cross the blood-brain barrier, leading to kernicterus.
Sulfadiazine is contraindicated in pregnancy at term because sulfonamides may promote kernicterus in the newborn by displacing bilirubin from plasma proteins. Sulfonamides readily cross the placenta with fetal concentrations averaging 70% to 90% of maternal concentrations. In a nested, case-control study (n = 87,020 controls; 8,702 cases) within the Quebec Pregnancy Cohort, sulfonamide use during early pregnancy was associated with an increased risk of spontaneous abortion (adjusted odds ratio (aOR) 2.01; 95% CI: 1.36 to 2.97; 30 exposed cases); residual confounding by severity of infection may be a potential limitation of this study. However, other studies such as the Collaborative Perinatal Project, which included 1,455 mothers with first trimester sulfonamide exposure and 5,689 with exposure anytime during pregnancy, found no evidence to suggest a relationship between sulfonamide use and fetal malformations.
According to the manufacturer, because of the potential risk to a nursing neonate, either breast-feeding or sulfadiazine should be discontinued. Sulfadiazine is excreted into human breast milk. Sulfadiazine is contraindicated in mothers who are breast-feeding infants less than 2 months of age because sulfonamides may promote kernicterus in the newborn by displacing bilirubin from plasma proteins. Sulfadiazine may be considered for use when breast-feeding healthy infants; however, caution should be used in infants with jaundice, hyperbilirubinemia, or G-6-PD deficiency or in infants who are critically ill, stressed, or premature. Amoxicillin, ceftriaxone, and ciprofloxacin are generally considered compatible with breast-feeding by the American Academy of Pediatrics (AAP) and may be potential alternatives to consider during breast-feeding. However, site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Sulfadiazine has been associated with acute hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency). Although the development of hemolytic anemia appears to be dose-related, any dose of sulfadiazine should be used with caution in patients with G6PD deficiency. Complete blood counts should be performed frequently in patients receiving sulfadiazine.
Sulfadiazine is relatively contraindicated in patients with preexisting bone marrow suppression, blood dyscrasias, or megaloblastic anemia secondary to folate deficiency because sulfonamides can aggravate these conditions.
Sulfadiazine is contraindicated in patients with porphyria because sulfonamides can precipitate an acute attack of porphyria.
Sulfadiazine should not be used to treat group A beta-hemolytic streptococcal infection. In an established infection, sulfonamides will not eradicate streptococcus and, therefore, will not prevent sequelae such as rheumatic fever and glomerulonephritis.
Sulfadiazine is contraindicated in patients with sulfonamide hypersensitivity. Deaths associated with administration of sulfonamides have been reported from hypersensitivity reactions (see Adverse Reactions).
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, such as sulfadiazine, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Sulfadiazine may crystallize in urine, especially in patients with renal impairment or in patients with dehydration. Patients should be instructed to drink an 8 ounce (240 mL) glass of water with each dose of medication and at frequent intervals throughout the day. Patients with renal impairment may be at higher risk for drug-induced adverse reactions. Patients with renal impairment and renal failure require dosage adjustments, usually with less frequent intervals of dosing. The frequency of renal complications is considerably lower in patients receiving the more soluble sulfonamides.
Sulfadiazine should be used cautiously in patients with hepatic disease because sulfonamides are metabolized in the liver and have been associated with cholestatic hepatitis and fulminant hepatic necrosis, although these effects are relatively rare (see Adverse Reactions).
Photosensitivity can occur with sulfonamide treatment, so patients should avoid or limit sunlight (UV) exposure, including sunlamps and tanning booths. Sunscreens should be employed, but may provide limited protection for this reaction. Discontinue drug use at the first sign of erythema.
Use sulfadiazine with caution in the geriatric patient, who may be more likely to have renal impairment, dehydration, or other risk factors for adverse drug reactions and/or decreased renal solubility of the drug. Monitor urine output, renal function, and hematologic parameters during therapy.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Chlamydia trachomatis, Enterobacter sp., Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella sp., Neisseria meningitidis, Nocardia sp., Plasmodium falciparum, Proteus mirabilis, Proteus vulgaris, Staphylococcus aureus (MSSA), Toxoplasma gondii
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: Actinomyces sp., Paracoccidioides brasiliensis
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of urinary tract infection (UTI) (primarily pyelonephritis and cystitis), in the absence of obstructive uropathy or foreign bodies, due to susceptible organisms, only when more soluble sulfonamides have been unsuccessful:
Oral dosage:
Adults: 2 to 4 g PO as a loading dose, followed by 2 to 4 g/day PO, given in 3 to 6 divided doses.
Infants 3 to 11 months, Children, and Adolescents: 75 mg/kg PO or 2 g/m2 PO loading dose, followed by 150 mg/kg/day PO or 4 g/m2/day PO, given in 4 to 6 divided doses (Max: 6 g/day).
Neonates and Infants 1 to 2 months: Use is contraindicated.
For secondary rheumatic fever prophylaxis (prevention of recurrent attacks), as an alternative to penicillin:
Oral dosage:
Adults: 1 g PO once daily. Guidelines recommend secondary prophylaxis for 10 years or until age 40 years (whichever is longer) for patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease). For patients who have experienced rheumatic fever with carditis but have no residual heart disease, prophylaxis is recommended for 10 years or until age 21 years (whichever is longer). For patients who have experienced rheumatic fever without carditis, prophylaxis is recommended for 5 years or until age 21 years (whichever is longer).
Children and Adolescents weighing more than 27 kg: 1 g PO once daily. The FDA-approved dose is 500 mg PO once daily for patients weighing less than 30 kg and 1 g PO once daily for patients weighing more than 30 kg. Guidelines recommend secondary prophylaxis for 10 years or until age 40 years (whichever is longer) for patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease). For patients who have experienced rheumatic fever with carditis but have no residual heart disease, prophylaxis is recommended for 10 years or until age 21 years (whichever is longer). For patients who have experienced rheumatic fever without carditis, prophylaxis is recommended for 5 years or until age 21 years (whichever is longer).
Children weighing 27 kg or less: 500 mg PO once daily. The FDA-approved dose is 500 mg PO once daily for patients weighing less than 30 kg and 1 g PO once daily for patients weighing more than 30 kg. Guidelines recommend secondary prophylaxis for 10 years or until age 40 years (whichever is longer) for patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease). For patients who have experienced rheumatic fever with carditis but have no residual heart disease, prophylaxis is recommended for 10 years or until age 21 years (whichever is longer). For patients who have experienced rheumatic fever without carditis, prophylaxis is recommended for 5 years or until age 21 years (whichever is longer).
Infants 3 to 11 months: 500 mg PO once daily. Guidelines recommend secondary prophylaxis for 10 years or until age 40 years (whichever is longer) for patients who have experienced rheumatic fever with carditis and have residual heart disease (persistent valvular disease). For patients who have experienced rheumatic fever with carditis but have no residual heart disease, prophylaxis is recommended for 10 years or until age 21 years (whichever is longer). For patients who have experienced rheumatic fever without carditis, prophylaxis is recommended for 5 years or until age 21 years (whichever is longer).
For the treatment of nocardiosis:
Oral dosage:
Adults: 2 to 4 g PO as a loading dose, followed by 2 to 4 g/day PO, given in 3 to 6 divided doses.
Infants 3 to 11 months, Children, and Adolescents: 75 mg/kg PO or 2 g/m2 PO loading dose, followed by 150 mg/kg/day PO or 4 g/m2/day PO, given in 4 to 6 divided doses (Max: 6 g/day).
Neonates and Infants 1 to 2 months: Use is contraindicated.
For the treatment of toxoplasmosis, including toxoplasmic encephalitis:
Oral dosage:
Adults weighing more than 60 kg: 1.5 g PO every 6 hours in combination with pyrimethamine plus leucovorin, or alternatively with atovaquone is recommended by the HIV guidelines; this is followed by chronic suppressive therapy. The FDA-labeled dose is an initial 2 to 4 g PO loading dose, followed by 2 to 4 g/day PO, given in 3 to 6 divided doses. Treatment duration should be at least 6 weeks; however, a longer duration may be necessary if clinical or radiologic disease is extensive or if the response is incomplete at 6 weeks. Adjunctive corticosteroids may be administered when clinically indicated for the treatment of mass effect attributed to focal lesions or associated edema; however, discontinue as soon as possible. Anticonvulsants may be administered to patients with a seizure history during the acute treatment phase; however, they should not be used prophylactically.
Adults weighing 60 kg or less: 1 g PO every 6 hours in combination with pyrimethamine plus leucovorin, or alternatively with atovaquone is recommended by the HIV guidelines; this is followed by chronic suppressive therapy. The FDA-labeled dose an initial 2 to 4 g PO loading dose, followed by 2 to 4 g/day PO divided in 3 to 6 doses. Treatment duration should be at least 6 weeks; however, a longer duration may be necessary if clinical or radiologic disease is extensive or if the response is incomplete at 6 weeks. Adjunctive corticosteroids may be administered when clinically indicated for the treatment of mass effect attributed to focal lesions or associated edema; however, discontinue as soon as possible. Anticonvulsants may be administered to patients with a seizure history during the acute treatment phase; however, they should not be used prophylactically.
Pregnant females: 75 mg/kg PO as a single dose, followed by 50 mg/kg/dose PO twice daily (Max: 4 g/day) in combination with pyrimethamine and leucovorin is recommended by the American Academy of Pediatrics (AAP) guidelines. Treatment is recommended for women who are pregnant 18 weeks or more with suspected or confirmed acute infection acquired at or after 18 weeks of pregnancy, a positive AF PCR test, or an abnormal fetal ultrasound suggestive of congenital toxoplasmosis. The FDA-labeled dose is 2 to 4 g PO loading dose, followed by 2 to 4 g/day PO divided in 3 to 6 doses.
Adolescents weighing more than 60 kg: 1.5 g PO every 6 hours in combination with pyrimethamine plus leucovorin, or alternatively with atovaquone is recommended by the HIV guidelines; this is followed by chronic suppressive therapy. The FDA-labeled dose is 2 to 4 g PO loading dose, followed by 2 to 4 g/day PO, given in 3 to 6 divided doses. Treatment duration should be at least 6 weeks; however, a longer duration may be necessary if clinical or radiologic disease is extensive or if the response is incomplete at 6 weeks. Adjunctive corticosteroids may be administered when clinically indicated for the treatment of mass effect attributed to focal lesions or associated edema; however, discontinue as soon as possible. Anticonvulsants may be administered to patients with a seizure history during the acute treatment phase; however, they should not be used prophylactically.
Adolescents weighing 60 kg or less: 1 g PO every 6 hours in combination with pyrimethamine plus leucovorin, or alternatively with atovaquone is recommended by the HIV guidelines; this is followed by chronic suppressive therapy. The FDA-labeled dose is 2 to 4 g PO loading dose, followed by 2 to 4 g/day PO, given in 3 to 6 divided doses. Treatment duration should be at least 6 weeks; however, a longer duration may be necessary if clinical or radiologic disease is extensive or if the response is incomplete at 6 weeks. Adjunctive corticosteroids may be administered when clinically indicated for the treatment of mass effect attributed to focal lesions or associated edema; however, discontinue as soon as possible. Anticonvulsants may be administered to patients with a seizure history during the acute treatment phase; however, they should not be used prophylactically.
Infants and Children: 25 to 50 mg/kg/dose PO 4 times daily (Max: 1 to 1.5 g/dose) in combination with pyrimethamine plus leucovorin for at least 6 weeks (depending on clinical and radiologic response) is recommended by the HIV guidelines; this is followed by chronic suppressive therapy. The FDA-labeled dose is 75 mg/kg PO or 2 g/m2 PO loading dose, then 150 mg/kg/day or 4 g/m2/day PO, given in 4 to 6 divided doses (Max: 6 g/day).
-for the treatment of congenital toxoplasmosis:
Oral dosage:
Infants and Children: 75 mg/kg PO as a single dose, followed by 50 mg/kg/dose PO twice daily in combination with pyrimethamine and leucovorin is recommended for infants/older children diagnosed beyond the neonatal period with active disease (chorioretinitis) by the American Academy of Pediatrics (AAP) guidelines. Continue treatment for at least 1 to 2 weeks after resolution of signs and symptoms and for 4 to 6 weeks total.
Neonates: 50 mg/kg/dose PO twice daily in combination with pyrimethamine and leucovorin is recommended by the American Academy of Pediatrics (AAP) guidelines. Treatment is usually continued for 1 year.
For secondary toxoplasmosis prophylaxis* (chronic maintenance therapy*) after treatment of acute toxoplasmic encephalitis in HIV-infected patients:
Oral dosage:
Adults: 2 to 4 g PO daily divided in 2 to 4 doses in combination with pyrimethamine and leucovorin, or alternatively with atovaquone, is recommended by the HIV guidelines. Secondary prophylaxis may be discontinued in asymptomatic patients who have a sustained increase in their CD4 counts more than 200 cells/mm3 after highly active antiretroviral therapy for at least 6 months; however, a limited number of patients have been evaluated and recurrences have been observed. Secondary prophylaxis should be reintroduced if the CD4 count decreases to less than 200 cells/mm3.
Adolescents: 2 to 4 g PO daily divided in 2 to 4 doses in combination with pyrimethamine and leucovorin, or alternatively with atovaquone, is recommended by the HIV guidelines. Secondary prophylaxis may be discontinued in asymptomatic patients who have a sustained increase in their CD4 counts more than 200 cells/mm3 after highly active antiretroviral therapy for at least 6 months; however, a limited number of patients have been evaluated and recurrences have been observed. Secondary prophylaxis should be reintroduced if the CD4 count decreases to less than 200 cells/mm3.
Infants and Children: 85 to 120 mg/kg/day PO in 2 to 4 divided doses (Max: 2 to 4 g/day) in combination with pyrimethamine and leucovorin is recommended by the HIV guidelines. For children 1 to 5 years of age, secondary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy with a CD4 percentage of at least 15% for more than 6 consecutive months. For children at least 6 years of age, secondary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy and CD4 count more than 200 cells/mm3 for more than 6 consecutive months. Additionally, in order to safely discontinue secondary prophylaxis, children must also have completed initial therapy for toxoplasmic encephalitis and be asymptomatic.
For the treatment of malaria due to chloroquine-resistant strains of P. falciparum, when used as adjunctive therapy:
Oral dosage:
Adults: 2 to 4 g PO as a loading dose, then 2 to 4 g/day PO given in 3 to 6 divided doses.
Infants, Children, and Adolescents 3 months to 17 years: 75 mg/kg/dose PO or 2 g/m2/dose PO as a loading dose, then 150 mg/kg/day PO or 4 g/m2/day (Max: 6 g/day) PO in 4 to 6 divided doses.
For the treatment of meningococcal meningitis, when the organism has been demonstrated to be susceptible; or for the treatment of Haemophilus influenzae meningitis, as adjunctive therapy with parenteral streptomycin:
Oral dosage:
Adults: 2 to 4 g PO as a loading dose, followed by 2 to 4 g/day PO, given in 3 to 6 divided doses.
Infants 3 to 11 months, Children, and Adolescents: 75 mg/kg PO or 2 g/m2 PO as a loading dose, followed by 150 mg/kg/day PO or 4 g/m2/day PO in 4 to 6 divided doses (Max: 6 g/day).
Neonates and Infants 1 to 2 months: Use is contraindicated.
For post-exposure meningococcal infection prophylaxis when sulfonamide-sensitive group A strains are known to prevail in family groups or larger closed populations:
Oral dosage:
Adults: 2 to 4 g PO once, then 2 to 4 g/day PO divided in 3 to 6 doses. Guidelines do not include sulfadiazine.
Infants, Children, and Adolescents 3 months to 17 years: 75 mg/kg PO or 2 g/m2 PO once, then 150 mg/kg/day PO or 4 g/m2/day (Max: 6 g/day) PO divided in 4 to 6 doses. Guidelines do not include sulfadiazine.
For the treatment of chancroid due to Haemophilus ducreyi:
Oral dosage:
Adults: Sulfadiazine is not recommended by guidelines. The FDA-labeled dosage is 2 to 4 g PO as a loading dose, then 2 to 4 g/day PO, given in 3 to 6 divided doses.
Infants 3 to 11 months, Children, and Adolescents: Sulfadiazine is not recommended by guidelines. The FDA-labeled dosage is 75 mg/kg PO or 2 g/m2 PO loading dose, then 150 mg/kg/day PO or 4 g/m2/day PO in 4 to 6 divided doses (Max: 6 g/day).
For the treatment of chlamydial conjunctivitis, including trachoma (Chlamydia trachomatis serotypes A to C) and inclusion conjunctivitis (Chlamydia trachomatis serotypes D to K):
Oral dosage:
Adults: Sulfadiazine is not recommended by guidelines. The FDA-approved dosage is 2 to 4 g PO as a loading dose, followed by 2 to 4 g/day PO, given in 3 to 6 divided doses.
Infants 3 to 11 months, Children, and Adolescents: Sulfadiazine is not recommended by guidelines. The FDA-approved dosage is 75 mg/kg PO or 2 g/m2 PO as a loading dose, followed by 150 mg/kg/day PO or 4 g/m2/day PO, given in 4 to 6 divided doses (Max: 6 g/day).
For the treatment of acute otitis media due to Haemophilus influenzae, when used concomitantly with adequate doses of penicillin:
Oral dosage:
Adults: 2 to 4 g PO as a loading dose, then 2 to 4 g/day PO, given in 3 to 6 divided doses.
Infants 3 to 11 months, Children, and Adolescents: 75 mg/kg PO or 2 g/m2 PO as a loading dose, then 150 mg/kg/day PO or 4 g/m2/day PO, given in 4 to 6 divided doses (Max: 6 g/day).
Neonates and Infants 1 to 2 months: Use is contraindicated.
For the treatment of paracoccidioidomycosis* due to Paracoccidioides brasiliensis*:
Oral dosage:
Adults: 1 to 1.5 g PO every 6 hours, continued for several weeks to months until clinical and mycologic improvement is apparent. Treatment may be necessary for 3 to 5 years to avoid relapses.
Infants 3 to 11 months, Children, and Adolescents: 100 to 150 mg/kg/day PO divided every 6 hours (Max: 6 g/day), continued for several weeks to months until clinical and mycologic improvement is apparent. Treatment may be necessary for 3 to 5 years to avoid relapses.
Neonates and Infants 1 to 2 months: Use is contraindicated.
Maximum Dosage Limits:
-Adults
4 g/day PO is FDA-approved maximum dosage; however, doses up to 6 g/day PO have been used off-label.
-Geriatric
4 g/day PO is FDA-approved maximum dosage; however, doses up to 6 g/day PO have been used off-label.
-Adolescents
150 mg/kg/day PO or 4 g/m2/day PO (Max: 6 g/day).
-Children
150 mg/kg/day PO or 4 g/m2/day PO (Max: 6 g/day).
-Infants
3 to 11 months: 150 mg/kg/day PO or 4 g/m2/day PO.
1 to 2 months: Use is contraindicated in this age group except for the treatment of congenital toxoplasmosis in which doses up to 100 mg/kg/day PO have been used.
-Neonates
Use is contraindicated in this age group except for the treatment of congenital toxoplasmosis in which doses up to 100 mg/kg/day PO have been used.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
CrCl more than 50 mL/minute: No dosage adjustment needed.
CrCl 10 to 50 mL/minute: Extend dosing interval to every 12 hours.
CrCl less than 10 mL/minute: Extend dosing interval to every 24 hours.
Hemodialysis
Extend dosing interval to every 24 hours; dose after hemodialysis on dialysis days.
*non-FDA-approved indication
Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Concomitant use of sulfonamides and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Acarbose: (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.
Acetaminophen; Aspirin, ASA; Caffeine: (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; Aspirin: (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; Aspirin; Diphenhydramine: (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.
Alogliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alogliptin; Metformin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alogliptin; Pioglitazone: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Alpha-glucosidase Inhibitors: (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.
Aminolevulinic Acid: (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of photosensitizing agents used during photodynamic therapy.
Aminosalicylate sodium, Aminosalicylic acid: (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.
Amoxicillin: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Amoxicillin; Clavulanic Acid: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Ampicillin: (Minor) Sulfonamides may compete with ampicillin for renal tubular secretion, increasing ampicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Ampicillin; Sulbactam: (Minor) Sulfonamides may compete with ampicillin for renal tubular secretion, increasing ampicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Articaine; Epinephrine: (Moderate) Coadministration of articaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue articaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Aspirin, ASA: (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.
Aspirin, ASA; Butalbital; Caffeine: (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.
Aspirin, ASA; Caffeine: (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.
Aspirin, ASA; Caffeine; Orphenadrine: (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.
Aspirin, ASA; Carisoprodol; Codeine: (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.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (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.
Aspirin, ASA; Dipyridamole: (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.
Aspirin, ASA; Omeprazole: (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.
Aspirin, ASA; Oxycodone: (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.
Benzalkonium Chloride; Benzocaine: (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.
Benzocaine: (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.
Benzocaine; Butamben; Tetracaine: (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.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Sulfonamides can crystallize in an acidic urine. Because methenamine salts produce an acidic urine, these agents should not be used concomitantly. (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.
Bexagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Bismuth Subsalicylate: (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.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (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.
Bromocriptine: (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. Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., sulfonamides), which may alter their effectiveness and risk for side effects.
Bupivacaine Liposomal: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Epinephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Lidocaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Meloxicam: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Butalbital; Aspirin; Caffeine; Codeine: (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.
Canagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Chloroprocaine: (Major) Coadministration of chloroprocaine with sulfonamides may antagonize the effect of sulfonamides. Chloroprocaine is metabolized to para-aminobenzoic acid (PABA). PABA antagonized the effects of sulfonamides. Additionally, coadministration of chloroprocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Choline Salicylate; Magnesium Salicylate: (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.
Cyclosporine: (Moderate) Use caution and closely monitor cyclosporine serum concentrations when administered concurrently with sulfadiazine. Use of these drugs together may result in decreased cyclosporine serum concentrations and the potential for decreased efficacy. Cyclosporine dose adjustments may be necessary and should be guided by serum concentrations during coadministration.
Dapagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Dapsone: (Moderate) Coadministration of dapsone with sulfonamides may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Desogestrel; Ethinyl Estradiol: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Dicloxacillin: (Minor) Sulfonamides may compete with dicloxacillin for renal tubular secretion, increasing dicloxacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Dienogest; Estradiol valerate: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Diphenhydramine; Naproxen: (Minor) Naproxen is 99% bound to albumin. 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.
Drospirenone: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Drospirenone; Estetrol: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Drospirenone; Estradiol: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol; Levomefolate: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Dulaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Elagolix; Estradiol; Norethindrone acetate: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Empagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Estradiol: (Moderate) Anti-infectives that disrupt the normal GI flora, including sulfonamides, may potentially decrease the effectiveness of estrogen-containing oral contraceptives. (Moderate) Anti-infectives which disrupt the normal GI flora, including sulfonamides, may potentially decrease the effectiveness of estrogen containing oral contraceptives. Alternative or additional contraception may be advisable.
Estradiol; Levonorgestrel: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Estradiol; Norethindrone: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Estradiol; Norgestimate: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Ethinyl Estradiol; Norelgestromin: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Ethinyl Estradiol; Norethindrone Acetate: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Ethinyl Estradiol; Norgestrel: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Ethynodiol Diacetate; Ethinyl Estradiol: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Etonogestrel; Ethinyl Estradiol: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Exenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Fenoprofen: (Minor) An interaction may occur between fenoprofen and sulfonamides. Fenoprofen is 99% bound to albumin. Thus, fenoprofen may displace other highly protein bound drugs from albumin or vice versa. If fenoprofen is used concurrently with sulfonamides, monitor patients for toxicity from any of the drugs.
Fluvastatin: (Moderate) In theory, concurrent use CYP2C9 inhibitors, such as sulfonamides, and fluvastatin, a CYP2C9 substrate, may result in reduced metabolism of fluvastatin and potential for toxicity.
Glimepiride: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. 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. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. 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.
Glipizide: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. 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. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. 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.
Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. 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. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. 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.
Glyburide: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. 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. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. 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.
Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. 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. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. 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.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Sulfonamides can crystallize in an acidic urine. Because methenamine salts produce an acidic urine, these agents should not be used concomitantly. (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.
Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Aspart: (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Degludec: (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Detemir: (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine: (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glulisine: (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro: (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin, Inhaled: (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulins: (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Concomitant use of sulfonamides and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Leuprolide; Norethindrone: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Levonorgestrel: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Lidocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Epinephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Prilocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of prilocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Linagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Liraglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Lixisenatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Losartan: (Minor) Inhibitors of the hepatic CYP2C9 isoenzyme, such as sulfonamides, have potential to inhibit the conversion of losartan to its active metabolite. Monitor therapeutic response to individualize losartan dosage.
Losartan; Hydrochlorothiazide, HCTZ: (Minor) Inhibitors of the hepatic CYP2C9 isoenzyme, such as sulfonamides, have potential to inhibit the conversion of losartan to its active metabolite. Monitor therapeutic response to individualize losartan dosage.
Magnesium Salicylate: (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.
Meglitinides: (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.
Mepivacaine: (Moderate) Coadministration of mepivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue mepivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Repaglinide: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (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.
Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Methenamine: (Major) Sulfonamides can crystallize in an acidic urine. Because methenamine salts produce an acidic urine, these agents should not be used concomitantly.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Sulfonamides can crystallize in an acidic urine. Because methenamine salts produce an acidic urine, these agents should not be used concomitantly.
Methenamine; Sodium Salicylate: (Major) Sulfonamides can crystallize in an acidic urine. Because methenamine salts produce an acidic urine, these agents should not be used concomitantly. (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.
Methotrexate: (Moderate) Concurrent use of sulfadiazine and methotrexate may increase the incidence of methotrexate-related adverse events. Methotrexate is partially bound to albumin, and toxicity may be increased because of displacement by sulfonamides.
Methoxsalen: (Moderate) Use methoxsalen and sulfonamides together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Miglitol: (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.
Naproxen: (Minor) Naproxen is 99% bound to albumin. 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.
Naproxen; Esomeprazole: (Minor) Naproxen is 99% bound to albumin. 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.
Naproxen; Pseudoephedrine: (Minor) Naproxen is 99% bound to albumin. 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.
Nateglinide: (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.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Norethindrone: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Norgestimate; Ethinyl Estradiol: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Norgestrel: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Oxacillin: (Minor) Sulfonamides may compete with oxacillin for renal tubular secretion, increasing oxacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Penicillamine: (Major) Do not use penicillamine concurrently with antimalarials due to an increased risk of severe hematologic and renal adverse reactions.
Penicillin G Benzathine: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. Sulfonamides may also compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects. (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. Sulfonamides may also compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Penicillin G: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Penicillin V: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with sulfadiazine. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Photosensitizing agents (topical): (Moderate) Sulfonamides may cause photosensitization and may increase the photosensitizing effects of photosensitizing agents used during photodynamic therapy.
Pioglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. 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. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. 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.
Pioglitazone; Metformin: (Moderate) Monitor blood glucose during concomitant metformin and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant thiazolidinedione and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Piperacillin; Tazobactam: (Minor) Sulfonamides may compete with piperacillin for renal tubular secretion, increasing piperacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Porfimer: (Major) Avoid coadministration of porfimer with sulfonamides due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like sulfonamides may increase the risk of a photosensitivity reaction.
Pramlintide: (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.
Pretomanid: (Major) Avoid coadministration of pretomanid with sulfadiazine, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Prilocaine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Prilocaine; Epinephrine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Probenecid: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Probenecid; Colchicine: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Pyrimethamine: (Moderate) Concomitant use of other antifolic drugs associated with myelosuppression, including sulfonamides, may increase the risk of bone marrow suppression.
Rabies Vaccine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
Regular Insulin: (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin and sulfonamide use; an insulin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Relugolix; Estradiol; Norethindrone acetate: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Repaglinide: (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.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and sulfadiazine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Ropivacaine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Rosiglitazone: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Salicylates: (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.
Salsalate: (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.
Saxagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Segesterone Acetate; Ethinyl Estradiol: (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. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. 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.g., patches, rings) are not available.
Semaglutide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sitagliptin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sodium Iodide: (Moderate) Sulfonamides may alter sodium iodide I-131 pharmacokinetics and dynamics for up to 1 week after administrations.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Sotagliflozin: (Moderate) Monitor blood glucose during concomitant SGLT2 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sulfonylureas: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents; patients with diabetes mellitus should be closely monitored during sulfonamide treatment. 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. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. 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.
Sumatriptan; Naproxen: (Minor) Naproxen is 99% bound to albumin. 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.
Tetracaine: (Major) Coadministration of tetracaine with sulfonamides may antagonize the effect of sulfonamides. Tetracaine is metabolized to para-aminobenzoic acid (PABA). PABA antagonized the effects of sulfonamides. Additionally, coadministration of tetracaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Thiazolidinediones: (Moderate) Monitor blood glucose during concomitant thiazolidinedione and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Tirzepatide: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Typhoid Vaccine: (Major) Avoid use of sulfonamides and other antibiotics during the oral typhoid vaccination series at concurrent administration may result in a reduced immune response. In order to provided immunity, the oral typhoid vaccine requires initiation of a limited infection localized within the gastrointestinal tract. Antibiotics prevent this bacterial infection from occurring, thereby, reducing the vaccines protective immune response.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with sulfonamides is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like sulfonamides may increase the risk of a photosensitivity reaction.
Vonoprazan; Amoxicillin: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Vonoprazan; Amoxicillin; Clarithromycin: (Minor) Sulfonamides may compete with amoxicillin for renal tubular secretion, increasing amoxicillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Voriconazole: (Moderate) Voriconazole is metabolized by the CYP2C9 isoenzyme, and drugs that are known to be inhibitors of CYP2C9 may theoretically lead to elevated plasma levels of voriconazole when co-administered. Sulfonamides are known to be inhibitors of CYP2C9.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with sulfonamides is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Warfarin doses may need to be adjusted when sulfonamide therapy is discontinued. Sulfonamides, including sulfathiazole, sulfamethoxazole, and sulfisoxazole, potentiate the anticoagulant effect of warfarin. Sulfonamides are known to inhibit the hepatic metabolism of S-warfarin and have, in some cases, doubled the hypoprothrombinemic effect of warfarin. A protein-binding interaction also may be possible, with sulfonamides displacing warfarin from protein binding sites.
Zidovudine, ZDV: (Moderate) Concomitant use of sulfonamides and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
Sulfadiazine inhibits bacterial dihydropteroate synthase by competing for binding sites with p-aminobenzoic acid (PABA), a precursor required for bacterial synthesis of folic acid (pteroylglutamic acid). Folic acid is a coenzyme responsible for the transport of one-carbon fragments from one molecule to another and is essential for the synthesis of thymidine, purines, and certain amino acids. Thus, interference of folic acid synthesis inhibits bacterial growth. Sulfonamides do not affect mammalian cells or bacterial cells that use folic acid precursors or preformed (dietary) folic acid. Sulfadiazine exhibits in vitro inhibitory activity against a broad spectrum of gram-positive and gram-negative bacteria, including Enterobacter sp., Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Klebsiella sp., Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, and Staphylococcus aureus. Sulfadiazine also is active against Actinomyces sp., Chlamydia trachomatis, Nocardia sp., Paracoccidioides brasiliensis, Plasmodium falciparum, and Toxoplasma gondii. The in vitro sensitivity of sulfonamides is strongly influenced by inoculum size and the composition of the test media. Resistance to sulfonamides is widespread and increasing, especially among strains of streptococci, staphylococci, Enterobacteriaceae, and Neisseria sp.
Sulfadiazine is administered orally. In serum, the drug is 38-48% bound to serum proteins. It distributes into cerebrospinal fluid, with free drug reaching 32-65% of the concentration in blood. In blood, sulfadiazine exists in three forms - free, conjugated (acetylated and possibly others) and protein bound. Only the free drug is active. Sulfadiazine is excreted primarily in urine; concentrations in urine are usually 10-25 times greater than serum concentrations. Approximately 60-85% of a single oral dose is excreted in urine within 48-72 hours. Of the amount excreted in urine, 15-40% is in the inactive, acetyl form. Administration of alkali accelerates the renal clearance of both the free and acetylated forms of sulfadiazine by further diminishing their tubular reabsorption. The elimination half-life of sulfadiazine in patients with normal renal function is roughly 17 hours.
-Route-Specific Pharmacokinetics
Oral Route
Sulfadiazine is readily absorbed through the GI tract. After a single 2 g oral dose, a peak serum concentration of about 60 mcg/ml is reached in 4 hours, of which 46.5 mcg/ml is free drug.
-Special Populations
Renal Impairment
In patients with a CrCl < 10 ml/min, the elimination half-life is significantly prolonged (e.g., roughly 34 hours).